MDedge Psychiatry

SECOND OF 2 PARTS

Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder characterized by a persistent pattern of inattention, impulsivity, and/or hyperactivity that causes functional impairment.¹ ADHD begins in childhood, continues into adulthood, and has negative consequences in many facets of adult patients’ lives, including their careers, daily functioning, and interpersonal relationships.² According to the National Institute of Health and Care Excellence’s recommendations, both pharmacotherapy and psychotherapy are advised for patients with ADHD.³ Although various pharmacotherapies are advised as first-line treatments for ADHD, they are frequently linked to unfavorable adverse effects, partial responses, chronic residual symptoms, high dropout rates, and issues with addiction.⁴ As a result, there is a need for evidence-based nonpharmacologic therapies.

In a systematic review, Nimmo-Smith et al⁵ found that certain nonpharmacologic treatments can be effective in helping patients with ADHD manage their illness. In clinical and cognitive assessments of ADHD, a recent meta-analysis found that noninvasive brain stimulation had a small but significant effect.⁶ Some evidence suggests that in addition to noninvasive brain stimulation, other nonpharmacologic interventions, including psychoeducation (PE), mindfulness, cognitive-behavioral therapy (CBT), and chronotherapy, can be effective as an adjunct treatment to pharmacotherapy, and possibly as monotherapy.

Part 1 of this 2-part article reviewed 6 randomized controlled trials (RCTs) of pharmacologic interventions for adult ADHD published within the last 5 years.⁷ Part 2 analyzes 6 RCTs of nonpharmacologic treatments for adult ADHD published within the last 5 years (Table^8-13).

1. Leffa DT, Grevet EH, Bau CHD, et al. Transcranial direct current stimulation vs sham for the treatment of inattention in adults with attention-deficit/hyperactivity disorder: the TUNED randomized clinical trial. JAMA Psychiatry. 2022;79(9):847-856. doi:10.1001/jamapsychiatry.2022.2055

Transcranial direct current stimulation (tDCS) uses noninvasive, low-intensity electrical current on the scalp to affect underlying cortical activity.¹⁴ This form of neurostimulation offers an alternative treatment option for when medications fail or are not tolerated, and can be used at home without the direct involvement of a clinician.¹⁴ tDCS as a treatment for ADHD has been increasingly researched, though many studies have been limited by short treatment periods and varied methodological approaches. In a meta-analysis, Westwood et al⁶ found a trend toward improvement on the function of processing speed but not on attention. Leffa et al⁸ examined the efficacy and safety of a 4-week course of home-based tDCS in adult patients with ADHD, specifically looking at reduction in inattention symptoms.

Study design

• This randomized, double-blind, parallel, sham-controlled clinical trial evaluated 64 participants age 18 to 60 from a single center in Brazil who met DSM-5 criteria for combined or primarily inattentive ADHD.
• Inclusion criteria included an inattention score ≥21 on the clinician-administered Adult ADHD Self-report Scale version 1.1 (CASRS). This scale assesses both inattentive symptoms (CASRS-I) and hyperactive-impulsive symptoms (CASRS-HI). Participants were not being treated with stimulants or agreed to undergo a 30-day washout of stimulants prior to the study.
• Exclusion criteria included current moderate to severe depression (Beck Depression Inventory-II [BDI] score >21), current moderate to severe anxiety (Beck Anxiety Inventory [BAI] score ≥21), diagnosis of bipolar disorder (BD) with either a manic or depressive episode in the year prior to study, diagnosis of a psychotic disorder, diagnosis of autism spectrum disorder (ASD), positive screen for substance use, unstable medical condition resulting in poor functionality, pregnant or planning on becoming pregnant within 3 months of the study, not able to use home-based equipment, history of neurosurgery, presence of ferromagnetic metal in the head or presence of implanted medical devices in head/neck region, or history of epilepsy with reported seizures in the year prior to the study.
• Participants were randomized to self-administer real or sham tDCS; the devices looked the same. Participants underwent daily 30-minute sessions using a 2-mA direct constant current for a total of 28 sessions. Sham treatment involved a 30-second ramp-up to 2-mA and a 30-second ramp-down sensation at the beginning, middle, and end of each respective session.
• The primary outcome was a change in symptoms of inattention per CASRS-I. Secondary outcomes were scores on the CASRS-HI, BDI, BAI, and Behavior Rating Inventory of Executive Functions-Adult (BRIEF-A), which evaluates executive function.

Outcomes

• A total of 53 participants used stimulant medications prior to the study and 8 required a washout. The average age was 38.3, and 53% of participants were male.
• For the 55 participants who completed 4 weeks of treatment, the mean number of sessions was 25.2 in the tDCS group and 24.8 in the sham group.
• At the end of Week 4, there was a statistically significant treatment by time interaction in CASRS-I scores in the tDCS group compared to the sham group (18.88 vs 23.63 on final CASRS-I scores; P < .001).
• There were no statistically significant differences in any of the secondary outcomes.

Conclusions/limitations

• This study showed the benefits of 4 weeks of home-based tDCS for managing inattentive symptoms in adults with ADHD. The authors noted that extended treatment of tDCS may incur greater benefit, as this study used a longer treatment course compared to others that have used a shorter duration of treatment (ie, days instead of weeks). Additionally, this study placed the anodal electrode over the right dorsolateral prefrontal cortex (DLPFC) vs over the left DLPFC, because there may be a decrease in activation in the right DLPFC in adults with ADHD undergoing attention tasks.¹⁵
• This study also showed that home-based tDCS can be an easier and more accessible way for patients to receive treatment, as opposed to needing to visit a health care facility.
• Limitations: The dropout rate (although only 2 of 7 participants who dropped out of the active group withdrew due to adverse events), lack of remote monitoring of patients, and restrictive inclusion criteria limit the generalizability of these findings. Additionally, 3 patients in the tDCS group and 7 in the sham group were taking psychotropic medications for anxiety or depression.

Continue to: #2

Previous research has shown that using mindfulness-based approaches can improve ADHD symptoms.^16,17 Hoxhaj et al⁹ looked at the effectiveness of mindfulness awareness practices (MAP) for alleviating ADHD symptoms.

Study design

• This RCT enrolled 81 adults from a German medical center who met DSM-IV criteria for ADHD, were not taking any ADHD medications, and had not undergone any psychotherapeutic treatments in the last 3 months. Participants were randomized to receive MAP (n = 41) or PE (n = 40).
• Exclusion criteria included having a previous diagnosis of schizophrenia, BD I, active substance dependence, ASD, suicidality, self-injurious behavior, or neurologic disorders.
• The MAP group underwent 8 weekly 2.5-hour sessions, plus homework involving meditation and other exercises. The PE group was given information regarding ADHD and management options, including organization and stress management skills.
• Patients were assessed 2 weeks before treatment (T1), at the completion of therapy (T2), and 6 months after the completion of therapy (T3).
• The primary outcome was the change in the blind-observer rated Conner’s Adult ADHD Rating Scales (CAARS) inattention/memory scales from T1 to T2.
• Secondary outcomes included the other CAARS subscales, the Brief Symptom Inventory (BSI), the BDI, the 36-item Short Form Health Survey, and the Five Facet Mindfulness Questionnaire (FFMQ).

Outcomes

• Baseline demographics did not differ between groups other than the MAP group having a significantly higher IQ than the PE group. However, this difference resolved after the final sample was analyzed, as there were 2 dropouts and 7 participants lost to follow-up in the MAP group and 4 dropouts and 4 participants lost to follow-up in the PE group.
• There was no significant difference between the groups in the primary outcome of observer-rated CAARS inattention/memory subscale scores, or other ADHD symptoms per the CAARS.
• However, there was a significant difference within each group on all ADHD subscales of the observer-rated CAARS at T2. Persistent, significant differences were noted for the observer-rated CAARS subscales of self-concept and DSM-IV Inattentive Symptoms, and all CAARS self-report scales to T3.
• Compared to the PE group, there was a significantly larger improvement in the MAP group on scores of the mindfulness parameters of observation and nonreactivity to inner experience.
• There were significant improvements regarding depression per the BDI and global severity per the BSI in both treatment groups, with no differences between the groups.
• At T3, in the MAP group, 3 patients received methylphenidate, 1 received atomoxetine, and 1 received antidepressant medication. In the PE group, 2 patients took methylphenidate, and 2 participants took antidepressants.
• There was a significant difference regarding sex and response, with men experiencing less overall improvement than women.

Conclusions/limitations

• MAP was not superior to PE in terms of changes on CAARS scores, although within each group, both therapies showed improvement over time.
• While there may be gender-specific differences in processing information and coping strategies, future research should examine the differences between men and women with different therapeutic approaches.
• Limitations: This study did not employ a true placebo but instead had 2 active arms. Generalizability is limited due to a lack of certain comorbidities and use of medications.

Continue to: #3

Mindfulness-based cognitive therapy (MBCT) is a form of psychotherapy that combines mindfulness with the principles of CBT. Hepark et al¹⁸ found benefits of MBCT for reducing ADHD symptoms. In a larger, multicenter, single-blind RCT, Janssen et al¹⁰ reviewed the efficacy of MBCT compared to treatment as usual (TAU).

Study design

• A total of 120 participants age ≥18 who met DSM-IV criteria for ADHD were recruited from Dutch clinics and advertisements and randomized to receive MBCT plus TAU (n = 60) or TAU alone (n = 60). There were no significant demographic differences between groups at baseline.
• Exclusion criteria included active depression with psychosis or suicidality, active manic episode, tic disorder with vocal tics, ASD, learning or other cognitive impairments, borderline or antisocial personality disorder, substance dependence, or previous participation in MBCT or other mindfulness-based interventions. Participants also had to be able to complete the questionnaires in Dutch.
• Blinded evaluations were conducted at baseline (T0), at the completion of therapy (T1), 3 months after the completion of therapy (T2), and 6 months after the completion of therapy (T3).
• MBCT included 8 weekly, 2.5-hour sessions and a 6-hour silent session between the sixth and seventh sessions. Patients participated in various meditation techniques with the addition of PE, CBT, and group discussions. They were also instructed to practice guided exercises 6 days/week, for approximately 30 minutes/day.
• The primary outcome was change in ADHD symptoms as assessed by the investigator-rated CAARS (CAARS-INV) at T1.
• Secondary outcomes included change in scores on the CAARS: Screening Version (CAARS-S:SV), BRIEF-A, Five Facet Mindfulness Questionnaire-Short Form (FFMQ-SF), Self-Compassion Scale-Short Form (SCS-SF), Mental Health Continuum-Short Form (MHC-SF), and Outcome Questionnaire (OQ 45.2).

Outcomes

• In the MBCT group, participants who dropped out (n = 9) were less likely to be using ADHD medication at baseline than those who completed the study.
• At T1, the MBCT plus TAU group had significantly less ADHD symptoms on CAARS-INV compared to TAU (d = 0.41, P = .004), with more participants in the MBCT plus TAU group experiencing a symptom reduction ≥30% (24% vs 7%, P = .001) and remission (P = .039).
• The MBCT plus TAU group also had a significant reduction in scores on CAARS-S:SV as well as significant improvement on self-compassion per SCS-SF, mindfulness skills per FFMQ-SF, and positive mental health per MHC-SF, but not on executive functioning per BRIEF-A or general functioning per OQ 45.2.
• Over 6-month follow-up, there continued to be significant improvement in CAARS-INV, CAARS-S:SV, mindfulness skills, self-compassion, and positive mental health in the MBCT plus TAU group compared to TAU. The difference in executive functioning (BRIEF-A) also became significant over time.

Conclusions/limitations

• MBCT plus TAU appears to be effective for reducing ADHD symptoms, both from a clinician-rated and self-reported perspective, with improvements lasting up to 6 months.
• There were also improvements in mindfulness, self-compassion, and positive mental health posttreatment in the MBCT plus TAU group, with improvement in executive functioning seen over the follow-up periods.
• Limitations: The sample was drawn solely from a Dutch population and did not assess the success of blinding.

Continue to: #4

Managing adult ADHD can include PE, but few studies have reviewed the effectiveness of formal clinical PE. PE is “systemic, didactic-psychotherapeutic interventions, which are adequate for informing patients and their relatives about the illness and its treatment, facilitating both an understanding and personally responsible handling of the illness and supporting those afflicted in coping with the disorder.”¹⁹ Selaskowski et al¹¹ investigated the feasibility of using smartphone-assisted PE (SAP) for adults diagnosed with ADHD.

Study design

• Participants were 60 adults age 18 to 65 who met DSM-5 diagnostic criteria for ADHD. They were required to have a working comprehension of the German language and access to an Android-powered smartphone.
• Exclusion criteria included a diagnosis of schizophrenia or other psychotic disorder, antisocial personality disorder, substance use disorder, severe affective disorder, severe neurologic disorder, or initial use or dose change of ADHD medications 2 weeks prior to baseline.
• Participants were randomized to SAP (n = 30) or brochure-assisted PE (BAP) (n = 30). The demographics at baseline were mostly balanced between the groups except for substance abuse (5 in the SAP group vs 0 in the BAP group; P = .022).
• The primary outcome was severity of total ADHD symptoms, which was assessed by blinded evaluations conducted at baseline (T0) and after 8 weekly PE sessions (T1).
• Secondary outcomes included dropout rates, improvement in depressive symptoms as measured by the German BDI-II, improvement in functional impairment as measured by the Weiss Functional Impairment Scale (WFIRS), homework performed, attendance, and obtained PE knowledge.
• Both groups attended 8 weekly 1-hour PE group sessions led by 2 therapists and comprised of 10 participants.

Outcomes

• Only 43 of the 60 initial participants completed the study; 24 in the SAP group and 19 in the BAP group.
• The SAP group experienced a significant symptom improvement of 33.4% from T0 to T1 compared to the BAP group, which experienced a symptom improvement of 17.3% (P = .019).
• ADHD core symptoms considerably decreased in both groups. There was no significant difference between groups (P = .74).
• SAP dramatically improved inattention (P = .019), improved impulsivity (P = .03), and increased completed homework (P < .001), compared to the BAP group.
• There was no significant difference in correctly answered quiz questions or in BDI-II or WFIRS scores.

Conclusions/limitations

• Both SAP and BAP appear to be effective methods for PE, but patients who participated in SAP showed greater improvements than those who participated in BAP.
• Limitations: This study lacked a control intervention that was substantially different from SAP and lacked follow-up. The sample was a mostly German population, participants were required to have smartphone access beforehand, and substance abuse was more common in the SAP group.

Continue to: #5

CBT has demonstrated long-term benefit for the core symptoms of ADHD, comorbid symptoms (anxiety and depression), and social functioning. For ADHD, pharmacotherapies have a bottom-up effect where they increase neurotransmitter concentration, leading to an effect in the prefrontal lobe, whereas psychotherapies affect behavior-related brain activity in the prefrontal lobes, leading to the release of neurotransmitters. Pan et al¹² compared the benefits of CBT plus medication (CBT + M) to CBT alone on core ADHD symptoms, social functioning, and comorbid symptoms.

Study design

• The sample consisted of 124 participants age >18 who had received a diagnosis of adult ADHD according to DSM-IV via Conner’s Adult ADHD Diagnostic Interview and were either outpatients at Peking University Sixth Hospital or participants in a previous RCT (Huang et al²⁰).
• Exclusion criteria included organic mental disorders, high suicide risk in those with major depressive disorder, acute BD episode requiring medication or severe panic disorder or psychotic disorder requiring medication, pervasive developmental disorder, previous or current involvement in other psychological therapies, IQ <90, unstable physical conditions requiring medical treatment, attending <7 CBT sessions, or having serious adverse effects from medication.
• Participants received CBT + M (n = 57) or CBT alone (n = 67); 40 (70.18%) participants in the CBT + M group received methylphenidate hydrochloride controlled-release tablets (average dose 27.45 ± 9.97 mg) and 17 (29.82%) received atomoxetine hydrochloride (average dose 46.35 ± 20.09 mg). There were no significant demographic differences between groups.
• CBT consisted of 12 weekly 2-hour sessions (8 to 12 participants in each group) that were led by 2 trained psychiatrist therapists and focused on behavioral and cognitive strategies.
• Participants in the CBT alone group were drug-naïve and those in CBT + M group were stable on medications.
• The primary outcome was change in ADHD Rating Scale (ADHD-RS) score from baseline to Week 12.
• Secondary outcomes included Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), Self-Esteem Scale (SES), executive functioning (BRIEF-A), and quality of life (World Health Organization Quality of Life-Brief version [WHOQOL-BREF]).

Outcomes

• ADHD-RS total, impulsiveness-hyperactivity subscale, and inattention subscale scores significantly improved in both groups (P < .01). The improvements were greater in the CBT + M group compared to the CBT-only group, but the differences were not statistically significant.
• There was no significant difference between groups in remission rate (P < .689).
• There was a significant improvement in SAS, SES, and SDS scores in both groups (P < .01).
• In terms of the WHOQOL-BREF, the CBT + M group experienced improvements only in the psychological and environmental domains, while the CBT-only group significantly improved across the board. The CBT-only group experienced greater improvement in the physical domain (P < .01).
• Both groups displayed considerable improvements in the Metacognition Index and Global Executive Composite for BRIEF-A. The shift, self-monitor, initiate, working memory, plan/organize, task monitor, and material organization skills significantly improved in the CBT + M group. The only areas where the CBT group significantly improved were initiate, material organization, and working memory. No significant differences in BRIEF-A effectiveness were discovered.

Conclusions/limitations

• CBT is an effective treatment for improving core ADHD symptoms.
• This study was unable to establish that CBT alone was preferable to CBT + M, particularly in terms of core symptoms, emotional symptoms, or self-esteem.
• CBT + M could lead to a greater improvement in executive function than CBT alone.
• Limitations: This study used previous databases rather than RCTs. There was no placebo in the CBT-only group. The findings may not be generalizable because participants had high education levels and IQ. The study lacked follow-up after 12 weeks.

Continue to: #6

Most individuals with ADHD have a delayed circadian rhythm.²¹ Delayed sleep phase syndrome (DSPS) is diagnosed when a persistently delayed circadian rhythm is not brought on by other diseases or medications. ADHD symptoms and circadian rhythm may both benefit from DSPS treatment. A 3-armed randomized clinical parallel-group trial by van Andel et al¹³ investigated the effects of chronotherapy on ADHD symptoms and circadian rhythm.

Study design

• Participants were Dutch-speaking individuals age 18 to 55 who were diagnosed with ADHD and DSPS. They were randomized to receive melatonin 0.5 mg/d (n = 17), placebo (n = 17), or melatonin 0.5 mg/d plus 30 minutes of timed morning bright light therapy (BLT) (n = 15) daily for 3 weeks. There were no significant differences in baseline characteristics between groups except that the melatonin plus BLT group had higher use of oral contraceptives (P = .007).
• This study was completed in the Netherlands with participants from an outpatient adult ADHD clinic.
• Exclusion criteria included epilepsy, psychotic disorders, anxiety or depression requiring acute treatment, alcohol intake >15 units/week in women or >21 units/week in men, ADHD medications, medications affecting sleep, use of drugs, mental retardation, amnestic disorder, dementia, cognitive dysfunction, crossed >2 time zones in the 2 weeks prior to the study, shift work within the previous month, having children disturbing sleep, glaucoma, retinopathy, having BLT within the previous month, pregnancy, lactation, or trying to conceive.
• The study consisted of 3-armed placebo-controlled parallel groups in which 2 were double-blind (melatonin group and placebo group).
• During the first week of treatment, medication was taken 3 hours before dim-light melatonin onset (DLMO) and later advanced to 4 and 5 hours in Week 2 and Week 3, respectively. BLT was used at 20 cm from the eyes for 30 minutes every morning between 7 am and 8 am.
• The primary outcome was DLMO in which radioimmunoassay was used to determine melatonin concentrations. DLMO was used as a marker for internal circadian rhythm.
• The secondary outcome was ADHD symptoms using the Dutch version of the ADHD Rating Scale-IV.
• Evaluations were conducted at baseline (T0), the conclusion of treatment (T1), and 2 weeks after the end of treatment (T2).

Outcomes

• Out of 51 participants, 2 dropped out of the melatonin plus BLT group before baseline, and 3 dropped out of the placebo group before T1.
• At baseline, the average DLMO was 11:43 pm ± 1 hour and 46 minutes, with 77% of participants experiencing DLMO after 11 pm. Melatonin advanced DLMO by 1 hour and 28 minutes (P = .001) and melatonin plus BLT had an advance of 1 hour and 58 minutes (P < .001). DLMO was unaffected by placebo.
• The melatonin group experienced a 14% reduction in ADHD symptoms (P = .038); the placebo and melatonin plus BLT groups did not experience a reduction.
• DLMO and ADHD symptoms returned to baseline 2 weeks after therapy ended.

Conclusions/limitations

• In patients with DSPS and ADHD, low-dose melatonin can improve internal circadian rhythm and decrease ADHD symptoms.
• Melatonin plus BLT was not effective in improving ADHD symptoms or advancing DLMO.
• Limitations: This study used self-reported measures for ADHD symptoms. The generalizability of the findings is limited because the exclusion criteria led to minimal comorbidity. The sample was comprised of a mostly Dutch population.

SECOND OF 2 PARTS

Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder characterized by a persistent pattern of inattention, impulsivity, and/or hyperactivity that causes functional impairment.¹ ADHD begins in childhood, continues into adulthood, and has negative consequences in many facets of adult patients’ lives, including their careers, daily functioning, and interpersonal relationships.² According to the National Institute of Health and Care Excellence’s recommendations, both pharmacotherapy and psychotherapy are advised for patients with ADHD.³ Although various pharmacotherapies are advised as first-line treatments for ADHD, they are frequently linked to unfavorable adverse effects, partial responses, chronic residual symptoms, high dropout rates, and issues with addiction.⁴ As a result, there is a need for evidence-based nonpharmacologic therapies.

In a systematic review, Nimmo-Smith et al⁵ found that certain nonpharmacologic treatments can be effective in helping patients with ADHD manage their illness. In clinical and cognitive assessments of ADHD, a recent meta-analysis found that noninvasive brain stimulation had a small but significant effect.⁶ Some evidence suggests that in addition to noninvasive brain stimulation, other nonpharmacologic interventions, including psychoeducation (PE), mindfulness, cognitive-behavioral therapy (CBT), and chronotherapy, can be effective as an adjunct treatment to pharmacotherapy, and possibly as monotherapy.

Part 1 of this 2-part article reviewed 6 randomized controlled trials (RCTs) of pharmacologic interventions for adult ADHD published within the last 5 years.⁷ Part 2 analyzes 6 RCTs of nonpharmacologic treatments for adult ADHD published within the last 5 years (Table^8-13).

1. Leffa DT, Grevet EH, Bau CHD, et al. Transcranial direct current stimulation vs sham for the treatment of inattention in adults with attention-deficit/hyperactivity disorder: the TUNED randomized clinical trial. JAMA Psychiatry. 2022;79(9):847-856. doi:10.1001/jamapsychiatry.2022.2055

Transcranial direct current stimulation (tDCS) uses noninvasive, low-intensity electrical current on the scalp to affect underlying cortical activity.¹⁴ This form of neurostimulation offers an alternative treatment option for when medications fail or are not tolerated, and can be used at home without the direct involvement of a clinician.¹⁴ tDCS as a treatment for ADHD has been increasingly researched, though many studies have been limited by short treatment periods and varied methodological approaches. In a meta-analysis, Westwood et al⁶ found a trend toward improvement on the function of processing speed but not on attention. Leffa et al⁸ examined the efficacy and safety of a 4-week course of home-based tDCS in adult patients with ADHD, specifically looking at reduction in inattention symptoms.

Study design

• This randomized, double-blind, parallel, sham-controlled clinical trial evaluated 64 participants age 18 to 60 from a single center in Brazil who met DSM-5 criteria for combined or primarily inattentive ADHD.
• Inclusion criteria included an inattention score ≥21 on the clinician-administered Adult ADHD Self-report Scale version 1.1 (CASRS). This scale assesses both inattentive symptoms (CASRS-I) and hyperactive-impulsive symptoms (CASRS-HI). Participants were not being treated with stimulants or agreed to undergo a 30-day washout of stimulants prior to the study.
• Exclusion criteria included current moderate to severe depression (Beck Depression Inventory-II [BDI] score >21), current moderate to severe anxiety (Beck Anxiety Inventory [BAI] score ≥21), diagnosis of bipolar disorder (BD) with either a manic or depressive episode in the year prior to study, diagnosis of a psychotic disorder, diagnosis of autism spectrum disorder (ASD), positive screen for substance use, unstable medical condition resulting in poor functionality, pregnant or planning on becoming pregnant within 3 months of the study, not able to use home-based equipment, history of neurosurgery, presence of ferromagnetic metal in the head or presence of implanted medical devices in head/neck region, or history of epilepsy with reported seizures in the year prior to the study.
• Participants were randomized to self-administer real or sham tDCS; the devices looked the same. Participants underwent daily 30-minute sessions using a 2-mA direct constant current for a total of 28 sessions. Sham treatment involved a 30-second ramp-up to 2-mA and a 30-second ramp-down sensation at the beginning, middle, and end of each respective session.
• The primary outcome was a change in symptoms of inattention per CASRS-I. Secondary outcomes were scores on the CASRS-HI, BDI, BAI, and Behavior Rating Inventory of Executive Functions-Adult (BRIEF-A), which evaluates executive function.

Outcomes

• A total of 53 participants used stimulant medications prior to the study and 8 required a washout. The average age was 38.3, and 53% of participants were male.
• For the 55 participants who completed 4 weeks of treatment, the mean number of sessions was 25.2 in the tDCS group and 24.8 in the sham group.
• At the end of Week 4, there was a statistically significant treatment by time interaction in CASRS-I scores in the tDCS group compared to the sham group (18.88 vs 23.63 on final CASRS-I scores; P < .001).
• There were no statistically significant differences in any of the secondary outcomes.

Conclusions/limitations

• This study showed the benefits of 4 weeks of home-based tDCS for managing inattentive symptoms in adults with ADHD. The authors noted that extended treatment of tDCS may incur greater benefit, as this study used a longer treatment course compared to others that have used a shorter duration of treatment (ie, days instead of weeks). Additionally, this study placed the anodal electrode over the right dorsolateral prefrontal cortex (DLPFC) vs over the left DLPFC, because there may be a decrease in activation in the right DLPFC in adults with ADHD undergoing attention tasks.¹⁵
• This study also showed that home-based tDCS can be an easier and more accessible way for patients to receive treatment, as opposed to needing to visit a health care facility.
• Limitations: The dropout rate (although only 2 of 7 participants who dropped out of the active group withdrew due to adverse events), lack of remote monitoring of patients, and restrictive inclusion criteria limit the generalizability of these findings. Additionally, 3 patients in the tDCS group and 7 in the sham group were taking psychotropic medications for anxiety or depression.

Continue to: #2

Previous research has shown that using mindfulness-based approaches can improve ADHD symptoms.^16,17 Hoxhaj et al⁹ looked at the effectiveness of mindfulness awareness practices (MAP) for alleviating ADHD symptoms.

Study design

• This RCT enrolled 81 adults from a German medical center who met DSM-IV criteria for ADHD, were not taking any ADHD medications, and had not undergone any psychotherapeutic treatments in the last 3 months. Participants were randomized to receive MAP (n = 41) or PE (n = 40).
• Exclusion criteria included having a previous diagnosis of schizophrenia, BD I, active substance dependence, ASD, suicidality, self-injurious behavior, or neurologic disorders.
• The MAP group underwent 8 weekly 2.5-hour sessions, plus homework involving meditation and other exercises. The PE group was given information regarding ADHD and management options, including organization and stress management skills.
• Patients were assessed 2 weeks before treatment (T1), at the completion of therapy (T2), and 6 months after the completion of therapy (T3).
• The primary outcome was the change in the blind-observer rated Conner’s Adult ADHD Rating Scales (CAARS) inattention/memory scales from T1 to T2.
• Secondary outcomes included the other CAARS subscales, the Brief Symptom Inventory (BSI), the BDI, the 36-item Short Form Health Survey, and the Five Facet Mindfulness Questionnaire (FFMQ).

Outcomes

• Baseline demographics did not differ between groups other than the MAP group having a significantly higher IQ than the PE group. However, this difference resolved after the final sample was analyzed, as there were 2 dropouts and 7 participants lost to follow-up in the MAP group and 4 dropouts and 4 participants lost to follow-up in the PE group.
• There was no significant difference between the groups in the primary outcome of observer-rated CAARS inattention/memory subscale scores, or other ADHD symptoms per the CAARS.
• However, there was a significant difference within each group on all ADHD subscales of the observer-rated CAARS at T2. Persistent, significant differences were noted for the observer-rated CAARS subscales of self-concept and DSM-IV Inattentive Symptoms, and all CAARS self-report scales to T3.
• Compared to the PE group, there was a significantly larger improvement in the MAP group on scores of the mindfulness parameters of observation and nonreactivity to inner experience.
• There were significant improvements regarding depression per the BDI and global severity per the BSI in both treatment groups, with no differences between the groups.
• At T3, in the MAP group, 3 patients received methylphenidate, 1 received atomoxetine, and 1 received antidepressant medication. In the PE group, 2 patients took methylphenidate, and 2 participants took antidepressants.
• There was a significant difference regarding sex and response, with men experiencing less overall improvement than women.

Conclusions/limitations

• MAP was not superior to PE in terms of changes on CAARS scores, although within each group, both therapies showed improvement over time.
• While there may be gender-specific differences in processing information and coping strategies, future research should examine the differences between men and women with different therapeutic approaches.
• Limitations: This study did not employ a true placebo but instead had 2 active arms. Generalizability is limited due to a lack of certain comorbidities and use of medications.

Continue to: #3

Mindfulness-based cognitive therapy (MBCT) is a form of psychotherapy that combines mindfulness with the principles of CBT. Hepark et al¹⁸ found benefits of MBCT for reducing ADHD symptoms. In a larger, multicenter, single-blind RCT, Janssen et al¹⁰ reviewed the efficacy of MBCT compared to treatment as usual (TAU).

Study design

• A total of 120 participants age ≥18 who met DSM-IV criteria for ADHD were recruited from Dutch clinics and advertisements and randomized to receive MBCT plus TAU (n = 60) or TAU alone (n = 60). There were no significant demographic differences between groups at baseline.
• Exclusion criteria included active depression with psychosis or suicidality, active manic episode, tic disorder with vocal tics, ASD, learning or other cognitive impairments, borderline or antisocial personality disorder, substance dependence, or previous participation in MBCT or other mindfulness-based interventions. Participants also had to be able to complete the questionnaires in Dutch.
• Blinded evaluations were conducted at baseline (T0), at the completion of therapy (T1), 3 months after the completion of therapy (T2), and 6 months after the completion of therapy (T3).
• MBCT included 8 weekly, 2.5-hour sessions and a 6-hour silent session between the sixth and seventh sessions. Patients participated in various meditation techniques with the addition of PE, CBT, and group discussions. They were also instructed to practice guided exercises 6 days/week, for approximately 30 minutes/day.
• The primary outcome was change in ADHD symptoms as assessed by the investigator-rated CAARS (CAARS-INV) at T1.
• Secondary outcomes included change in scores on the CAARS: Screening Version (CAARS-S:SV), BRIEF-A, Five Facet Mindfulness Questionnaire-Short Form (FFMQ-SF), Self-Compassion Scale-Short Form (SCS-SF), Mental Health Continuum-Short Form (MHC-SF), and Outcome Questionnaire (OQ 45.2).

Outcomes

• In the MBCT group, participants who dropped out (n = 9) were less likely to be using ADHD medication at baseline than those who completed the study.
• At T1, the MBCT plus TAU group had significantly less ADHD symptoms on CAARS-INV compared to TAU (d = 0.41, P = .004), with more participants in the MBCT plus TAU group experiencing a symptom reduction ≥30% (24% vs 7%, P = .001) and remission (P = .039).
• The MBCT plus TAU group also had a significant reduction in scores on CAARS-S:SV as well as significant improvement on self-compassion per SCS-SF, mindfulness skills per FFMQ-SF, and positive mental health per MHC-SF, but not on executive functioning per BRIEF-A or general functioning per OQ 45.2.
• Over 6-month follow-up, there continued to be significant improvement in CAARS-INV, CAARS-S:SV, mindfulness skills, self-compassion, and positive mental health in the MBCT plus TAU group compared to TAU. The difference in executive functioning (BRIEF-A) also became significant over time.

Conclusions/limitations

• MBCT plus TAU appears to be effective for reducing ADHD symptoms, both from a clinician-rated and self-reported perspective, with improvements lasting up to 6 months.
• There were also improvements in mindfulness, self-compassion, and positive mental health posttreatment in the MBCT plus TAU group, with improvement in executive functioning seen over the follow-up periods.
• Limitations: The sample was drawn solely from a Dutch population and did not assess the success of blinding.

Continue to: #4

Managing adult ADHD can include PE, but few studies have reviewed the effectiveness of formal clinical PE. PE is “systemic, didactic-psychotherapeutic interventions, which are adequate for informing patients and their relatives about the illness and its treatment, facilitating both an understanding and personally responsible handling of the illness and supporting those afflicted in coping with the disorder.”¹⁹ Selaskowski et al¹¹ investigated the feasibility of using smartphone-assisted PE (SAP) for adults diagnosed with ADHD.

Study design

• Participants were 60 adults age 18 to 65 who met DSM-5 diagnostic criteria for ADHD. They were required to have a working comprehension of the German language and access to an Android-powered smartphone.
• Exclusion criteria included a diagnosis of schizophrenia or other psychotic disorder, antisocial personality disorder, substance use disorder, severe affective disorder, severe neurologic disorder, or initial use or dose change of ADHD medications 2 weeks prior to baseline.
• Participants were randomized to SAP (n = 30) or brochure-assisted PE (BAP) (n = 30). The demographics at baseline were mostly balanced between the groups except for substance abuse (5 in the SAP group vs 0 in the BAP group; P = .022).
• The primary outcome was severity of total ADHD symptoms, which was assessed by blinded evaluations conducted at baseline (T0) and after 8 weekly PE sessions (T1).
• Secondary outcomes included dropout rates, improvement in depressive symptoms as measured by the German BDI-II, improvement in functional impairment as measured by the Weiss Functional Impairment Scale (WFIRS), homework performed, attendance, and obtained PE knowledge.
• Both groups attended 8 weekly 1-hour PE group sessions led by 2 therapists and comprised of 10 participants.

Outcomes

• Only 43 of the 60 initial participants completed the study; 24 in the SAP group and 19 in the BAP group.
• The SAP group experienced a significant symptom improvement of 33.4% from T0 to T1 compared to the BAP group, which experienced a symptom improvement of 17.3% (P = .019).
• ADHD core symptoms considerably decreased in both groups. There was no significant difference between groups (P = .74).
• SAP dramatically improved inattention (P = .019), improved impulsivity (P = .03), and increased completed homework (P < .001), compared to the BAP group.
• There was no significant difference in correctly answered quiz questions or in BDI-II or WFIRS scores.

Conclusions/limitations

• Both SAP and BAP appear to be effective methods for PE, but patients who participated in SAP showed greater improvements than those who participated in BAP.
• Limitations: This study lacked a control intervention that was substantially different from SAP and lacked follow-up. The sample was a mostly German population, participants were required to have smartphone access beforehand, and substance abuse was more common in the SAP group.

Continue to: #5

CBT has demonstrated long-term benefit for the core symptoms of ADHD, comorbid symptoms (anxiety and depression), and social functioning. For ADHD, pharmacotherapies have a bottom-up effect where they increase neurotransmitter concentration, leading to an effect in the prefrontal lobe, whereas psychotherapies affect behavior-related brain activity in the prefrontal lobes, leading to the release of neurotransmitters. Pan et al¹² compared the benefits of CBT plus medication (CBT + M) to CBT alone on core ADHD symptoms, social functioning, and comorbid symptoms.

Study design

• The sample consisted of 124 participants age >18 who had received a diagnosis of adult ADHD according to DSM-IV via Conner’s Adult ADHD Diagnostic Interview and were either outpatients at Peking University Sixth Hospital or participants in a previous RCT (Huang et al²⁰).
• Exclusion criteria included organic mental disorders, high suicide risk in those with major depressive disorder, acute BD episode requiring medication or severe panic disorder or psychotic disorder requiring medication, pervasive developmental disorder, previous or current involvement in other psychological therapies, IQ <90, unstable physical conditions requiring medical treatment, attending <7 CBT sessions, or having serious adverse effects from medication.
• Participants received CBT + M (n = 57) or CBT alone (n = 67); 40 (70.18%) participants in the CBT + M group received methylphenidate hydrochloride controlled-release tablets (average dose 27.45 ± 9.97 mg) and 17 (29.82%) received atomoxetine hydrochloride (average dose 46.35 ± 20.09 mg). There were no significant demographic differences between groups.
• CBT consisted of 12 weekly 2-hour sessions (8 to 12 participants in each group) that were led by 2 trained psychiatrist therapists and focused on behavioral and cognitive strategies.
• Participants in the CBT alone group were drug-naïve and those in CBT + M group were stable on medications.
• The primary outcome was change in ADHD Rating Scale (ADHD-RS) score from baseline to Week 12.
• Secondary outcomes included Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), Self-Esteem Scale (SES), executive functioning (BRIEF-A), and quality of life (World Health Organization Quality of Life-Brief version [WHOQOL-BREF]).

Outcomes

• ADHD-RS total, impulsiveness-hyperactivity subscale, and inattention subscale scores significantly improved in both groups (P < .01). The improvements were greater in the CBT + M group compared to the CBT-only group, but the differences were not statistically significant.
• There was no significant difference between groups in remission rate (P < .689).
• There was a significant improvement in SAS, SES, and SDS scores in both groups (P < .01).
• In terms of the WHOQOL-BREF, the CBT + M group experienced improvements only in the psychological and environmental domains, while the CBT-only group significantly improved across the board. The CBT-only group experienced greater improvement in the physical domain (P < .01).
• Both groups displayed considerable improvements in the Metacognition Index and Global Executive Composite for BRIEF-A. The shift, self-monitor, initiate, working memory, plan/organize, task monitor, and material organization skills significantly improved in the CBT + M group. The only areas where the CBT group significantly improved were initiate, material organization, and working memory. No significant differences in BRIEF-A effectiveness were discovered.

Conclusions/limitations

• CBT is an effective treatment for improving core ADHD symptoms.
• This study was unable to establish that CBT alone was preferable to CBT + M, particularly in terms of core symptoms, emotional symptoms, or self-esteem.
• CBT + M could lead to a greater improvement in executive function than CBT alone.
• Limitations: This study used previous databases rather than RCTs. There was no placebo in the CBT-only group. The findings may not be generalizable because participants had high education levels and IQ. The study lacked follow-up after 12 weeks.

Continue to: #6

Most individuals with ADHD have a delayed circadian rhythm.²¹ Delayed sleep phase syndrome (DSPS) is diagnosed when a persistently delayed circadian rhythm is not brought on by other diseases or medications. ADHD symptoms and circadian rhythm may both benefit from DSPS treatment. A 3-armed randomized clinical parallel-group trial by van Andel et al¹³ investigated the effects of chronotherapy on ADHD symptoms and circadian rhythm.

Study design

• Participants were Dutch-speaking individuals age 18 to 55 who were diagnosed with ADHD and DSPS. They were randomized to receive melatonin 0.5 mg/d (n = 17), placebo (n = 17), or melatonin 0.5 mg/d plus 30 minutes of timed morning bright light therapy (BLT) (n = 15) daily for 3 weeks. There were no significant differences in baseline characteristics between groups except that the melatonin plus BLT group had higher use of oral contraceptives (P = .007).
• This study was completed in the Netherlands with participants from an outpatient adult ADHD clinic.
• Exclusion criteria included epilepsy, psychotic disorders, anxiety or depression requiring acute treatment, alcohol intake >15 units/week in women or >21 units/week in men, ADHD medications, medications affecting sleep, use of drugs, mental retardation, amnestic disorder, dementia, cognitive dysfunction, crossed >2 time zones in the 2 weeks prior to the study, shift work within the previous month, having children disturbing sleep, glaucoma, retinopathy, having BLT within the previous month, pregnancy, lactation, or trying to conceive.
• The study consisted of 3-armed placebo-controlled parallel groups in which 2 were double-blind (melatonin group and placebo group).
• During the first week of treatment, medication was taken 3 hours before dim-light melatonin onset (DLMO) and later advanced to 4 and 5 hours in Week 2 and Week 3, respectively. BLT was used at 20 cm from the eyes for 30 minutes every morning between 7 am and 8 am.
• The primary outcome was DLMO in which radioimmunoassay was used to determine melatonin concentrations. DLMO was used as a marker for internal circadian rhythm.
• The secondary outcome was ADHD symptoms using the Dutch version of the ADHD Rating Scale-IV.
• Evaluations were conducted at baseline (T0), the conclusion of treatment (T1), and 2 weeks after the end of treatment (T2).

Outcomes

• Out of 51 participants, 2 dropped out of the melatonin plus BLT group before baseline, and 3 dropped out of the placebo group before T1.
• At baseline, the average DLMO was 11:43 pm ± 1 hour and 46 minutes, with 77% of participants experiencing DLMO after 11 pm. Melatonin advanced DLMO by 1 hour and 28 minutes (P = .001) and melatonin plus BLT had an advance of 1 hour and 58 minutes (P < .001). DLMO was unaffected by placebo.
• The melatonin group experienced a 14% reduction in ADHD symptoms (P = .038); the placebo and melatonin plus BLT groups did not experience a reduction.
• DLMO and ADHD symptoms returned to baseline 2 weeks after therapy ended.

Conclusions/limitations

• In patients with DSPS and ADHD, low-dose melatonin can improve internal circadian rhythm and decrease ADHD symptoms.
• Melatonin plus BLT was not effective in improving ADHD symptoms or advancing DLMO.
• Limitations: This study used self-reported measures for ADHD symptoms. The generalizability of the findings is limited because the exclusion criteria led to minimal comorbidity. The sample was comprised of a mostly Dutch population.

SECOND OF 2 PARTS

Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder characterized by a persistent pattern of inattention, impulsivity, and/or hyperactivity that causes functional impairment.¹ ADHD begins in childhood, continues into adulthood, and has negative consequences in many facets of adult patients’ lives, including their careers, daily functioning, and interpersonal relationships.² According to the National Institute of Health and Care Excellence’s recommendations, both pharmacotherapy and psychotherapy are advised for patients with ADHD.³ Although various pharmacotherapies are advised as first-line treatments for ADHD, they are frequently linked to unfavorable adverse effects, partial responses, chronic residual symptoms, high dropout rates, and issues with addiction.⁴ As a result, there is a need for evidence-based nonpharmacologic therapies.

In a systematic review, Nimmo-Smith et al⁵ found that certain nonpharmacologic treatments can be effective in helping patients with ADHD manage their illness. In clinical and cognitive assessments of ADHD, a recent meta-analysis found that noninvasive brain stimulation had a small but significant effect.⁶ Some evidence suggests that in addition to noninvasive brain stimulation, other nonpharmacologic interventions, including psychoeducation (PE), mindfulness, cognitive-behavioral therapy (CBT), and chronotherapy, can be effective as an adjunct treatment to pharmacotherapy, and possibly as monotherapy.

Part 1 of this 2-part article reviewed 6 randomized controlled trials (RCTs) of pharmacologic interventions for adult ADHD published within the last 5 years.⁷ Part 2 analyzes 6 RCTs of nonpharmacologic treatments for adult ADHD published within the last 5 years (Table^8-13).

1. Leffa DT, Grevet EH, Bau CHD, et al. Transcranial direct current stimulation vs sham for the treatment of inattention in adults with attention-deficit/hyperactivity disorder: the TUNED randomized clinical trial. JAMA Psychiatry. 2022;79(9):847-856. doi:10.1001/jamapsychiatry.2022.2055

Transcranial direct current stimulation (tDCS) uses noninvasive, low-intensity electrical current on the scalp to affect underlying cortical activity.¹⁴ This form of neurostimulation offers an alternative treatment option for when medications fail or are not tolerated, and can be used at home without the direct involvement of a clinician.¹⁴ tDCS as a treatment for ADHD has been increasingly researched, though many studies have been limited by short treatment periods and varied methodological approaches. In a meta-analysis, Westwood et al⁶ found a trend toward improvement on the function of processing speed but not on attention. Leffa et al⁸ examined the efficacy and safety of a 4-week course of home-based tDCS in adult patients with ADHD, specifically looking at reduction in inattention symptoms.

Study design

• This randomized, double-blind, parallel, sham-controlled clinical trial evaluated 64 participants age 18 to 60 from a single center in Brazil who met DSM-5 criteria for combined or primarily inattentive ADHD.
• Inclusion criteria included an inattention score ≥21 on the clinician-administered Adult ADHD Self-report Scale version 1.1 (CASRS). This scale assesses both inattentive symptoms (CASRS-I) and hyperactive-impulsive symptoms (CASRS-HI). Participants were not being treated with stimulants or agreed to undergo a 30-day washout of stimulants prior to the study.
• Exclusion criteria included current moderate to severe depression (Beck Depression Inventory-II [BDI] score >21), current moderate to severe anxiety (Beck Anxiety Inventory [BAI] score ≥21), diagnosis of bipolar disorder (BD) with either a manic or depressive episode in the year prior to study, diagnosis of a psychotic disorder, diagnosis of autism spectrum disorder (ASD), positive screen for substance use, unstable medical condition resulting in poor functionality, pregnant or planning on becoming pregnant within 3 months of the study, not able to use home-based equipment, history of neurosurgery, presence of ferromagnetic metal in the head or presence of implanted medical devices in head/neck region, or history of epilepsy with reported seizures in the year prior to the study.
• Participants were randomized to self-administer real or sham tDCS; the devices looked the same. Participants underwent daily 30-minute sessions using a 2-mA direct constant current for a total of 28 sessions. Sham treatment involved a 30-second ramp-up to 2-mA and a 30-second ramp-down sensation at the beginning, middle, and end of each respective session.
• The primary outcome was a change in symptoms of inattention per CASRS-I. Secondary outcomes were scores on the CASRS-HI, BDI, BAI, and Behavior Rating Inventory of Executive Functions-Adult (BRIEF-A), which evaluates executive function.

Outcomes

• A total of 53 participants used stimulant medications prior to the study and 8 required a washout. The average age was 38.3, and 53% of participants were male.
• For the 55 participants who completed 4 weeks of treatment, the mean number of sessions was 25.2 in the tDCS group and 24.8 in the sham group.
• At the end of Week 4, there was a statistically significant treatment by time interaction in CASRS-I scores in the tDCS group compared to the sham group (18.88 vs 23.63 on final CASRS-I scores; P < .001).
• There were no statistically significant differences in any of the secondary outcomes.

Conclusions/limitations

• This study showed the benefits of 4 weeks of home-based tDCS for managing inattentive symptoms in adults with ADHD. The authors noted that extended treatment of tDCS may incur greater benefit, as this study used a longer treatment course compared to others that have used a shorter duration of treatment (ie, days instead of weeks). Additionally, this study placed the anodal electrode over the right dorsolateral prefrontal cortex (DLPFC) vs over the left DLPFC, because there may be a decrease in activation in the right DLPFC in adults with ADHD undergoing attention tasks.¹⁵
• This study also showed that home-based tDCS can be an easier and more accessible way for patients to receive treatment, as opposed to needing to visit a health care facility.
• Limitations: The dropout rate (although only 2 of 7 participants who dropped out of the active group withdrew due to adverse events), lack of remote monitoring of patients, and restrictive inclusion criteria limit the generalizability of these findings. Additionally, 3 patients in the tDCS group and 7 in the sham group were taking psychotropic medications for anxiety or depression.

Continue to: #2

Previous research has shown that using mindfulness-based approaches can improve ADHD symptoms.^16,17 Hoxhaj et al⁹ looked at the effectiveness of mindfulness awareness practices (MAP) for alleviating ADHD symptoms.

Study design

• This RCT enrolled 81 adults from a German medical center who met DSM-IV criteria for ADHD, were not taking any ADHD medications, and had not undergone any psychotherapeutic treatments in the last 3 months. Participants were randomized to receive MAP (n = 41) or PE (n = 40).
• Exclusion criteria included having a previous diagnosis of schizophrenia, BD I, active substance dependence, ASD, suicidality, self-injurious behavior, or neurologic disorders.
• The MAP group underwent 8 weekly 2.5-hour sessions, plus homework involving meditation and other exercises. The PE group was given information regarding ADHD and management options, including organization and stress management skills.
• Patients were assessed 2 weeks before treatment (T1), at the completion of therapy (T2), and 6 months after the completion of therapy (T3).
• The primary outcome was the change in the blind-observer rated Conner’s Adult ADHD Rating Scales (CAARS) inattention/memory scales from T1 to T2.
• Secondary outcomes included the other CAARS subscales, the Brief Symptom Inventory (BSI), the BDI, the 36-item Short Form Health Survey, and the Five Facet Mindfulness Questionnaire (FFMQ).

Outcomes

• Baseline demographics did not differ between groups other than the MAP group having a significantly higher IQ than the PE group. However, this difference resolved after the final sample was analyzed, as there were 2 dropouts and 7 participants lost to follow-up in the MAP group and 4 dropouts and 4 participants lost to follow-up in the PE group.
• There was no significant difference between the groups in the primary outcome of observer-rated CAARS inattention/memory subscale scores, or other ADHD symptoms per the CAARS.
• However, there was a significant difference within each group on all ADHD subscales of the observer-rated CAARS at T2. Persistent, significant differences were noted for the observer-rated CAARS subscales of self-concept and DSM-IV Inattentive Symptoms, and all CAARS self-report scales to T3.
• Compared to the PE group, there was a significantly larger improvement in the MAP group on scores of the mindfulness parameters of observation and nonreactivity to inner experience.
• There were significant improvements regarding depression per the BDI and global severity per the BSI in both treatment groups, with no differences between the groups.
• At T3, in the MAP group, 3 patients received methylphenidate, 1 received atomoxetine, and 1 received antidepressant medication. In the PE group, 2 patients took methylphenidate, and 2 participants took antidepressants.
• There was a significant difference regarding sex and response, with men experiencing less overall improvement than women.

Conclusions/limitations

• MAP was not superior to PE in terms of changes on CAARS scores, although within each group, both therapies showed improvement over time.
• While there may be gender-specific differences in processing information and coping strategies, future research should examine the differences between men and women with different therapeutic approaches.
• Limitations: This study did not employ a true placebo but instead had 2 active arms. Generalizability is limited due to a lack of certain comorbidities and use of medications.

Continue to: #3

Mindfulness-based cognitive therapy (MBCT) is a form of psychotherapy that combines mindfulness with the principles of CBT. Hepark et al¹⁸ found benefits of MBCT for reducing ADHD symptoms. In a larger, multicenter, single-blind RCT, Janssen et al¹⁰ reviewed the efficacy of MBCT compared to treatment as usual (TAU).

Study design

• A total of 120 participants age ≥18 who met DSM-IV criteria for ADHD were recruited from Dutch clinics and advertisements and randomized to receive MBCT plus TAU (n = 60) or TAU alone (n = 60). There were no significant demographic differences between groups at baseline.
• Exclusion criteria included active depression with psychosis or suicidality, active manic episode, tic disorder with vocal tics, ASD, learning or other cognitive impairments, borderline or antisocial personality disorder, substance dependence, or previous participation in MBCT or other mindfulness-based interventions. Participants also had to be able to complete the questionnaires in Dutch.
• Blinded evaluations were conducted at baseline (T0), at the completion of therapy (T1), 3 months after the completion of therapy (T2), and 6 months after the completion of therapy (T3).
• MBCT included 8 weekly, 2.5-hour sessions and a 6-hour silent session between the sixth and seventh sessions. Patients participated in various meditation techniques with the addition of PE, CBT, and group discussions. They were also instructed to practice guided exercises 6 days/week, for approximately 30 minutes/day.
• The primary outcome was change in ADHD symptoms as assessed by the investigator-rated CAARS (CAARS-INV) at T1.
• Secondary outcomes included change in scores on the CAARS: Screening Version (CAARS-S:SV), BRIEF-A, Five Facet Mindfulness Questionnaire-Short Form (FFMQ-SF), Self-Compassion Scale-Short Form (SCS-SF), Mental Health Continuum-Short Form (MHC-SF), and Outcome Questionnaire (OQ 45.2).

Outcomes

• In the MBCT group, participants who dropped out (n = 9) were less likely to be using ADHD medication at baseline than those who completed the study.
• At T1, the MBCT plus TAU group had significantly less ADHD symptoms on CAARS-INV compared to TAU (d = 0.41, P = .004), with more participants in the MBCT plus TAU group experiencing a symptom reduction ≥30% (24% vs 7%, P = .001) and remission (P = .039).
• The MBCT plus TAU group also had a significant reduction in scores on CAARS-S:SV as well as significant improvement on self-compassion per SCS-SF, mindfulness skills per FFMQ-SF, and positive mental health per MHC-SF, but not on executive functioning per BRIEF-A or general functioning per OQ 45.2.
• Over 6-month follow-up, there continued to be significant improvement in CAARS-INV, CAARS-S:SV, mindfulness skills, self-compassion, and positive mental health in the MBCT plus TAU group compared to TAU. The difference in executive functioning (BRIEF-A) also became significant over time.

Conclusions/limitations

• MBCT plus TAU appears to be effective for reducing ADHD symptoms, both from a clinician-rated and self-reported perspective, with improvements lasting up to 6 months.
• There were also improvements in mindfulness, self-compassion, and positive mental health posttreatment in the MBCT plus TAU group, with improvement in executive functioning seen over the follow-up periods.
• Limitations: The sample was drawn solely from a Dutch population and did not assess the success of blinding.

Continue to: #4

Managing adult ADHD can include PE, but few studies have reviewed the effectiveness of formal clinical PE. PE is “systemic, didactic-psychotherapeutic interventions, which are adequate for informing patients and their relatives about the illness and its treatment, facilitating both an understanding and personally responsible handling of the illness and supporting those afflicted in coping with the disorder.”¹⁹ Selaskowski et al¹¹ investigated the feasibility of using smartphone-assisted PE (SAP) for adults diagnosed with ADHD.

Study design

• Participants were 60 adults age 18 to 65 who met DSM-5 diagnostic criteria for ADHD. They were required to have a working comprehension of the German language and access to an Android-powered smartphone.
• Exclusion criteria included a diagnosis of schizophrenia or other psychotic disorder, antisocial personality disorder, substance use disorder, severe affective disorder, severe neurologic disorder, or initial use or dose change of ADHD medications 2 weeks prior to baseline.
• Participants were randomized to SAP (n = 30) or brochure-assisted PE (BAP) (n = 30). The demographics at baseline were mostly balanced between the groups except for substance abuse (5 in the SAP group vs 0 in the BAP group; P = .022).
• The primary outcome was severity of total ADHD symptoms, which was assessed by blinded evaluations conducted at baseline (T0) and after 8 weekly PE sessions (T1).
• Secondary outcomes included dropout rates, improvement in depressive symptoms as measured by the German BDI-II, improvement in functional impairment as measured by the Weiss Functional Impairment Scale (WFIRS), homework performed, attendance, and obtained PE knowledge.
• Both groups attended 8 weekly 1-hour PE group sessions led by 2 therapists and comprised of 10 participants.

Outcomes

• Only 43 of the 60 initial participants completed the study; 24 in the SAP group and 19 in the BAP group.
• The SAP group experienced a significant symptom improvement of 33.4% from T0 to T1 compared to the BAP group, which experienced a symptom improvement of 17.3% (P = .019).
• ADHD core symptoms considerably decreased in both groups. There was no significant difference between groups (P = .74).
• SAP dramatically improved inattention (P = .019), improved impulsivity (P = .03), and increased completed homework (P < .001), compared to the BAP group.
• There was no significant difference in correctly answered quiz questions or in BDI-II or WFIRS scores.

Conclusions/limitations

• Both SAP and BAP appear to be effective methods for PE, but patients who participated in SAP showed greater improvements than those who participated in BAP.
• Limitations: This study lacked a control intervention that was substantially different from SAP and lacked follow-up. The sample was a mostly German population, participants were required to have smartphone access beforehand, and substance abuse was more common in the SAP group.

Continue to: #5

CBT has demonstrated long-term benefit for the core symptoms of ADHD, comorbid symptoms (anxiety and depression), and social functioning. For ADHD, pharmacotherapies have a bottom-up effect where they increase neurotransmitter concentration, leading to an effect in the prefrontal lobe, whereas psychotherapies affect behavior-related brain activity in the prefrontal lobes, leading to the release of neurotransmitters. Pan et al¹² compared the benefits of CBT plus medication (CBT + M) to CBT alone on core ADHD symptoms, social functioning, and comorbid symptoms.

Study design

• The sample consisted of 124 participants age >18 who had received a diagnosis of adult ADHD according to DSM-IV via Conner’s Adult ADHD Diagnostic Interview and were either outpatients at Peking University Sixth Hospital or participants in a previous RCT (Huang et al²⁰).
• Exclusion criteria included organic mental disorders, high suicide risk in those with major depressive disorder, acute BD episode requiring medication or severe panic disorder or psychotic disorder requiring medication, pervasive developmental disorder, previous or current involvement in other psychological therapies, IQ <90, unstable physical conditions requiring medical treatment, attending <7 CBT sessions, or having serious adverse effects from medication.
• Participants received CBT + M (n = 57) or CBT alone (n = 67); 40 (70.18%) participants in the CBT + M group received methylphenidate hydrochloride controlled-release tablets (average dose 27.45 ± 9.97 mg) and 17 (29.82%) received atomoxetine hydrochloride (average dose 46.35 ± 20.09 mg). There were no significant demographic differences between groups.
• CBT consisted of 12 weekly 2-hour sessions (8 to 12 participants in each group) that were led by 2 trained psychiatrist therapists and focused on behavioral and cognitive strategies.
• Participants in the CBT alone group were drug-naïve and those in CBT + M group were stable on medications.
• The primary outcome was change in ADHD Rating Scale (ADHD-RS) score from baseline to Week 12.
• Secondary outcomes included Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), Self-Esteem Scale (SES), executive functioning (BRIEF-A), and quality of life (World Health Organization Quality of Life-Brief version [WHOQOL-BREF]).

Outcomes

• ADHD-RS total, impulsiveness-hyperactivity subscale, and inattention subscale scores significantly improved in both groups (P < .01). The improvements were greater in the CBT + M group compared to the CBT-only group, but the differences were not statistically significant.
• There was no significant difference between groups in remission rate (P < .689).
• There was a significant improvement in SAS, SES, and SDS scores in both groups (P < .01).
• In terms of the WHOQOL-BREF, the CBT + M group experienced improvements only in the psychological and environmental domains, while the CBT-only group significantly improved across the board. The CBT-only group experienced greater improvement in the physical domain (P < .01).
• Both groups displayed considerable improvements in the Metacognition Index and Global Executive Composite for BRIEF-A. The shift, self-monitor, initiate, working memory, plan/organize, task monitor, and material organization skills significantly improved in the CBT + M group. The only areas where the CBT group significantly improved were initiate, material organization, and working memory. No significant differences in BRIEF-A effectiveness were discovered.

Conclusions/limitations

• CBT is an effective treatment for improving core ADHD symptoms.
• This study was unable to establish that CBT alone was preferable to CBT + M, particularly in terms of core symptoms, emotional symptoms, or self-esteem.
• CBT + M could lead to a greater improvement in executive function than CBT alone.
• Limitations: This study used previous databases rather than RCTs. There was no placebo in the CBT-only group. The findings may not be generalizable because participants had high education levels and IQ. The study lacked follow-up after 12 weeks.

Continue to: #6

Most individuals with ADHD have a delayed circadian rhythm.²¹ Delayed sleep phase syndrome (DSPS) is diagnosed when a persistently delayed circadian rhythm is not brought on by other diseases or medications. ADHD symptoms and circadian rhythm may both benefit from DSPS treatment. A 3-armed randomized clinical parallel-group trial by van Andel et al¹³ investigated the effects of chronotherapy on ADHD symptoms and circadian rhythm.

Study design

• Participants were Dutch-speaking individuals age 18 to 55 who were diagnosed with ADHD and DSPS. They were randomized to receive melatonin 0.5 mg/d (n = 17), placebo (n = 17), or melatonin 0.5 mg/d plus 30 minutes of timed morning bright light therapy (BLT) (n = 15) daily for 3 weeks. There were no significant differences in baseline characteristics between groups except that the melatonin plus BLT group had higher use of oral contraceptives (P = .007).
• This study was completed in the Netherlands with participants from an outpatient adult ADHD clinic.
• Exclusion criteria included epilepsy, psychotic disorders, anxiety or depression requiring acute treatment, alcohol intake >15 units/week in women or >21 units/week in men, ADHD medications, medications affecting sleep, use of drugs, mental retardation, amnestic disorder, dementia, cognitive dysfunction, crossed >2 time zones in the 2 weeks prior to the study, shift work within the previous month, having children disturbing sleep, glaucoma, retinopathy, having BLT within the previous month, pregnancy, lactation, or trying to conceive.
• The study consisted of 3-armed placebo-controlled parallel groups in which 2 were double-blind (melatonin group and placebo group).
• During the first week of treatment, medication was taken 3 hours before dim-light melatonin onset (DLMO) and later advanced to 4 and 5 hours in Week 2 and Week 3, respectively. BLT was used at 20 cm from the eyes for 30 minutes every morning between 7 am and 8 am.
• The primary outcome was DLMO in which radioimmunoassay was used to determine melatonin concentrations. DLMO was used as a marker for internal circadian rhythm.
• The secondary outcome was ADHD symptoms using the Dutch version of the ADHD Rating Scale-IV.
• Evaluations were conducted at baseline (T0), the conclusion of treatment (T1), and 2 weeks after the end of treatment (T2).

Outcomes

• Out of 51 participants, 2 dropped out of the melatonin plus BLT group before baseline, and 3 dropped out of the placebo group before T1.
• At baseline, the average DLMO was 11:43 pm ± 1 hour and 46 minutes, with 77% of participants experiencing DLMO after 11 pm. Melatonin advanced DLMO by 1 hour and 28 minutes (P = .001) and melatonin plus BLT had an advance of 1 hour and 58 minutes (P < .001). DLMO was unaffected by placebo.
• The melatonin group experienced a 14% reduction in ADHD symptoms (P = .038); the placebo and melatonin plus BLT groups did not experience a reduction.
• DLMO and ADHD symptoms returned to baseline 2 weeks after therapy ended.

Conclusions/limitations

• In patients with DSPS and ADHD, low-dose melatonin can improve internal circadian rhythm and decrease ADHD symptoms.
• Melatonin plus BLT was not effective in improving ADHD symptoms or advancing DLMO.
• Limitations: This study used self-reported measures for ADHD symptoms. The generalizability of the findings is limited because the exclusion criteria led to minimal comorbidity. The sample was comprised of a mostly Dutch population.

CASE New-onset auditory hallucinations

Ms. L, age 78, presents to our hospital with worsening anxiety due to auditory hallucinations. She has been hearing music, which she reports is worse at night and consists of songs, usually the song Jingle Bells, sometimes just melodies and other times with lyrics. Ms. L denies paranoia, visual hallucinations, or worsening mood.

Two weeks ago, Ms. L had visited another hospital, describing 5 days of right-side hearing loss accompanied by pain and burning in her ear and face, along with vesicular lesions in a dermatomal pattern extending into her auditory canal. During this visit, Ms. L’s complete blood count, urine culture, urine drug screen, electrolytes, liver panel, thyroid studies, and vitamin levels were unremarkable. A CT scan of her head showed no abnormalities.

Ms. L was diagnosed with Ramsay Hunt syndrome (herpes zoster oticus), which affects cranial nerves, because of physical examination findings with a dermatomal pattern of lesion distribution and associated pain. Ramsay Hunt syndrome can cause facial paralysis and hearing loss in the affected ear. She was discharged with prescriptions for prednisone 60 mg/d for 7 days and valacyclovir 1 g/d for 7 days and told to follow up with her primary care physician. During the present visit to our hospital, Ms. L’s home health nurse reports that she still has her entire bottles of valacyclovir and prednisone left. Ms. L also has left-side hearing loss that began 5 years ago and a history of recurrent major depressive disorder (MDD) and generalized anxiety disorder. Due to the recent onset of right-side hearing loss, her hearing impairment requires her to communicate via writing or via a voice-to-text app.

HISTORY Depressed and living alone

Ms. L was diagnosed with MDD more than 4 decades ago and has been receiving medication since then. She reports no prior psychiatric hospitalizations, suicide attempts, manic symptoms, or psychotic symptoms. For more than 20 years, she has seen a nurse practitioner, who had prescribed mirtazapine 30 mg/d for MDD, poor appetite, and sleep. Within the last 5 years, her nurse practitioner added risperidone 0.5 mg/d at night to augment the mirtazapine for tearfulness, irritability, and mood swings.

Ms. L’s medical history also includes hypertension and chronic obstructive pulmonary disease. She is a retired teacher and lives alone. She has a chore worker who visits her home for 1 hour 5 days a week to help with cleaning and lifting, and support from her son. Ms. L no longer drives and relies on others for transportation, but is able to manage her finances, activities of daily living, cooking, and walking without any assistance.

[polldaddy:12807642]

EVALUATION Identifying the cause of the music

Ms. L is alert and oriented to time and situation, her concentration is appropriate, and her recent and remote memories are preserved. A full cognitive screen is not performed, but she is able to spell WORLD forwards and backwards and adequately perform a serial 7s test. An examination of her ear does not reveal any open vesicular lesions or swelling, but she continues to report pain and tingling in the C7 dermatomal pattern. Her urine drug screen and infectious and autoimmune laboratory testing are unremarkable. She does not have electrolyte, renal function, or blood count abnormalities. An MRI of her brain that is performed to rule out intracranial pathology due to acute hearing loss shows no acute intracranial abnormalities, with some artifact effect due to motion. Because temporal lobe epilepsy can present with hallucinations,¹ an EEG is performed to rule out seizure activity; it shows a normal wake pattern.

Psychiatry is consulted for management of the auditory hallucinations because Ms. L is distressed by hearing music. Ms. L is evaluated by Neurology and Otolaryngology. Neurology recommends a repeat brain MRI in the outpatient setting after seeing an artifact in the inpatient imaging, as well as follow-up with her primary care physician. Otolaryngology believes her symptoms are secondary to Ramsay Hunt syndrome with incomplete treatment, which is consistent with the initial diagnosis from her previous hospital visit, and recommends another course of oral corticosteroids, along with Audiology and Otolaryngology follow-up.

Continue to: The authors' observations

This is the first case we have seen detailing musical hallucinations (MH) secondary to Ramsay Hunt syndrome, although musical hallucinations have been associated with other etiologies of hearing loss. MH is a “release phenomenon” believed to be caused by deprivation of stimulation of the auditory cortex.² They are categorized as complex auditory hallucinations made up of melodies and rhythms and may be present in up to 2.5% of patients with hearing impairment.¹ The condition is mostly seen in older adults because this population is more likely to experience hearing loss. MH is more common among women (70% to 80% of cases) and is highly comorbid with psychiatric disorders such as schizophrenia, obsessive-compulsive disorder, or (as was the case for Ms. L) MDD.³ Hallucinations secondary to hearing loss may be more common in left-side hearing loss.⁴ In a 2005 study, Warner et al⁵ found religious music such as hymns or Christmas carols was most commonly heard, possibly due to repetitive past exposure.

There is no consensus on treatment for MH. Current treatment guidance comes from case reports and case series. Treatment is generally most successful when the etiology of the hallucination is both apparent and treatable, such as an infectious eitiology.³ In the case of MH due to hearing loss, hallucinations may improve following treatment with hearing aids or cochlear implants,^1,3,6,7 which is what was advised for Ms. L. Table 1^7-9 outlines other possible measures for addressing musical hallucinations.

Anticholinesterases, antidepressants, and antiepileptics may provide some benefit.⁸ However, pharmacotherapy is generally less efficacious and can cause adverse effects, so environmental support and hearing aids may be a safer approach. No medications have been shown to completely cure MH.

TREATMENT Hearing loss management and follow-up

When speaking with the consulting psychiatry team, Ms. L reports her outpatient psychotropic regimen has been helpful. The team decides to continue mirtazapine 30 mg/d and risperidone 0.5 mg/d at night. We recommend that Ms. L discuss tapering off risperidone with her outpatient clinician if they feel it may be indicated to reduce the risk of adverse effects. The treatment team decides not to start corticosteroids due to the risk of steroid-induced psychotic symptoms. The team discusses hallucinations related to hearing loss with Ms. L and advise her to follow up with Audiology and Otolaryngology in the outpatient setting.

The authors’ observations

Approximately 40% of people age >60 struggle with hearing impairment^4,9; this impacts their general quality of life and how clinicians communicate with such patients.¹⁰ People with hearing loss are more likely to develop feelings of social isolation, depression, and delirium (Table 2^8,10,11).¹¹

Risk factors for hearing loss include tobacco use, metabolic syndrome, exposure to loud noises, and exposure to certain ototoxic medications such as chemotherapeutic agents.¹¹ As psychiatrists, it is important to identify patients who may be at risk for hearing loss and refer them to the appropriate medical professional. If hearing loss is new onset, refer the patient to an otolaryngologist for a full evaluation. Unilateral hearing loss should warrant further workup because this could be due to an acoustic neuroma.¹¹

When providing care for a patient who uses a hearing aid, discuss adherence, barriers to adherence, and difficulties with adjusting the hearing aid. A referral to an audiologist may help patients address these barriers. Patients with hearing impairment or loss may benefit from auditory rehabilitation programs that provide communication strategies, ways to adapt to hearing loss, and information about different assistive options.¹¹ Such programs are often run by audiologists or speech language pathologists and contain both counseling and group components.

Continue to: Is is critical for psychiatrists...

It is critical for psychiatrists to ensure appropriate communication with patients who are hearing impaired (Table 3^8-11). The use of assistive devices such as sound amplifiers, written messages, or family members to assist in communication is needed to prevent miscommunication.^9-11

OUTCOME Lack of follow-up

A home health worker visits Ms. L, communicating with her using voice-to-text. Ms. L has not yet gone to her primary care physician, audiologist, or outpatient psychiatrist for follow-up because she needs to arrange transportation. Ms. L remains distressed by the music she is hearing, which is worse at night, along with her acute hearing loss.

Bottom Line

Hearing loss can predispose a person to psychiatric disorders and symptoms, including depression, delirium, and auditory hallucinations. Psychiatrists should strive to ensure clear communication with patients who are hearing impaired and should refer such patients to appropriate resources to improve outcomes.

Related Resources

• Wang J, Patel D, Francois D. Elaborate hallucinations, but is it a psychotic disorder? Current Psychiatry. 2021;20(2):46-50. doi:10.12788/cp.0091
• Sosland MD, Pinninti N. 5 ways to quiet auditory hallucinations. Current Psychiatry. 2005;4(4):110.
• Convery E, Keidser G, McLelland M, et al. A smartphone app to facilitate remote patient-provider communication in hearing health care: usability and effect on hearing aid outcomes. Telemed E-Health. 2020;26(6):798-804. doi:10.1089/ tmj.2019.0109

Drug Brand Names

Mirtazapine • Remeron
Prednisone • Rayos
Risperidone • Risperdal
Valacyclovir • Valtrex

CASE New-onset auditory hallucinations

Ms. L, age 78, presents to our hospital with worsening anxiety due to auditory hallucinations. She has been hearing music, which she reports is worse at night and consists of songs, usually the song Jingle Bells, sometimes just melodies and other times with lyrics. Ms. L denies paranoia, visual hallucinations, or worsening mood.

Two weeks ago, Ms. L had visited another hospital, describing 5 days of right-side hearing loss accompanied by pain and burning in her ear and face, along with vesicular lesions in a dermatomal pattern extending into her auditory canal. During this visit, Ms. L’s complete blood count, urine culture, urine drug screen, electrolytes, liver panel, thyroid studies, and vitamin levels were unremarkable. A CT scan of her head showed no abnormalities.

Ms. L was diagnosed with Ramsay Hunt syndrome (herpes zoster oticus), which affects cranial nerves, because of physical examination findings with a dermatomal pattern of lesion distribution and associated pain. Ramsay Hunt syndrome can cause facial paralysis and hearing loss in the affected ear. She was discharged with prescriptions for prednisone 60 mg/d for 7 days and valacyclovir 1 g/d for 7 days and told to follow up with her primary care physician. During the present visit to our hospital, Ms. L’s home health nurse reports that she still has her entire bottles of valacyclovir and prednisone left. Ms. L also has left-side hearing loss that began 5 years ago and a history of recurrent major depressive disorder (MDD) and generalized anxiety disorder. Due to the recent onset of right-side hearing loss, her hearing impairment requires her to communicate via writing or via a voice-to-text app.

HISTORY Depressed and living alone

Ms. L was diagnosed with MDD more than 4 decades ago and has been receiving medication since then. She reports no prior psychiatric hospitalizations, suicide attempts, manic symptoms, or psychotic symptoms. For more than 20 years, she has seen a nurse practitioner, who had prescribed mirtazapine 30 mg/d for MDD, poor appetite, and sleep. Within the last 5 years, her nurse practitioner added risperidone 0.5 mg/d at night to augment the mirtazapine for tearfulness, irritability, and mood swings.

Ms. L’s medical history also includes hypertension and chronic obstructive pulmonary disease. She is a retired teacher and lives alone. She has a chore worker who visits her home for 1 hour 5 days a week to help with cleaning and lifting, and support from her son. Ms. L no longer drives and relies on others for transportation, but is able to manage her finances, activities of daily living, cooking, and walking without any assistance.

[polldaddy:12807642]

EVALUATION Identifying the cause of the music

Ms. L is alert and oriented to time and situation, her concentration is appropriate, and her recent and remote memories are preserved. A full cognitive screen is not performed, but she is able to spell WORLD forwards and backwards and adequately perform a serial 7s test. An examination of her ear does not reveal any open vesicular lesions or swelling, but she continues to report pain and tingling in the C7 dermatomal pattern. Her urine drug screen and infectious and autoimmune laboratory testing are unremarkable. She does not have electrolyte, renal function, or blood count abnormalities. An MRI of her brain that is performed to rule out intracranial pathology due to acute hearing loss shows no acute intracranial abnormalities, with some artifact effect due to motion. Because temporal lobe epilepsy can present with hallucinations,¹ an EEG is performed to rule out seizure activity; it shows a normal wake pattern.

Psychiatry is consulted for management of the auditory hallucinations because Ms. L is distressed by hearing music. Ms. L is evaluated by Neurology and Otolaryngology. Neurology recommends a repeat brain MRI in the outpatient setting after seeing an artifact in the inpatient imaging, as well as follow-up with her primary care physician. Otolaryngology believes her symptoms are secondary to Ramsay Hunt syndrome with incomplete treatment, which is consistent with the initial diagnosis from her previous hospital visit, and recommends another course of oral corticosteroids, along with Audiology and Otolaryngology follow-up.

Continue to: The authors' observations

This is the first case we have seen detailing musical hallucinations (MH) secondary to Ramsay Hunt syndrome, although musical hallucinations have been associated with other etiologies of hearing loss. MH is a “release phenomenon” believed to be caused by deprivation of stimulation of the auditory cortex.² They are categorized as complex auditory hallucinations made up of melodies and rhythms and may be present in up to 2.5% of patients with hearing impairment.¹ The condition is mostly seen in older adults because this population is more likely to experience hearing loss. MH is more common among women (70% to 80% of cases) and is highly comorbid with psychiatric disorders such as schizophrenia, obsessive-compulsive disorder, or (as was the case for Ms. L) MDD.³ Hallucinations secondary to hearing loss may be more common in left-side hearing loss.⁴ In a 2005 study, Warner et al⁵ found religious music such as hymns or Christmas carols was most commonly heard, possibly due to repetitive past exposure.

There is no consensus on treatment for MH. Current treatment guidance comes from case reports and case series. Treatment is generally most successful when the etiology of the hallucination is both apparent and treatable, such as an infectious eitiology.³ In the case of MH due to hearing loss, hallucinations may improve following treatment with hearing aids or cochlear implants,^1,3,6,7 which is what was advised for Ms. L. Table 1^7-9 outlines other possible measures for addressing musical hallucinations.

Anticholinesterases, antidepressants, and antiepileptics may provide some benefit.⁸ However, pharmacotherapy is generally less efficacious and can cause adverse effects, so environmental support and hearing aids may be a safer approach. No medications have been shown to completely cure MH.

TREATMENT Hearing loss management and follow-up

When speaking with the consulting psychiatry team, Ms. L reports her outpatient psychotropic regimen has been helpful. The team decides to continue mirtazapine 30 mg/d and risperidone 0.5 mg/d at night. We recommend that Ms. L discuss tapering off risperidone with her outpatient clinician if they feel it may be indicated to reduce the risk of adverse effects. The treatment team decides not to start corticosteroids due to the risk of steroid-induced psychotic symptoms. The team discusses hallucinations related to hearing loss with Ms. L and advise her to follow up with Audiology and Otolaryngology in the outpatient setting.

The authors’ observations

Approximately 40% of people age >60 struggle with hearing impairment^4,9; this impacts their general quality of life and how clinicians communicate with such patients.¹⁰ People with hearing loss are more likely to develop feelings of social isolation, depression, and delirium (Table 2^8,10,11).¹¹

Risk factors for hearing loss include tobacco use, metabolic syndrome, exposure to loud noises, and exposure to certain ototoxic medications such as chemotherapeutic agents.¹¹ As psychiatrists, it is important to identify patients who may be at risk for hearing loss and refer them to the appropriate medical professional. If hearing loss is new onset, refer the patient to an otolaryngologist for a full evaluation. Unilateral hearing loss should warrant further workup because this could be due to an acoustic neuroma.¹¹

When providing care for a patient who uses a hearing aid, discuss adherence, barriers to adherence, and difficulties with adjusting the hearing aid. A referral to an audiologist may help patients address these barriers. Patients with hearing impairment or loss may benefit from auditory rehabilitation programs that provide communication strategies, ways to adapt to hearing loss, and information about different assistive options.¹¹ Such programs are often run by audiologists or speech language pathologists and contain both counseling and group components.

Continue to: Is is critical for psychiatrists...

It is critical for psychiatrists to ensure appropriate communication with patients who are hearing impaired (Table 3^8-11). The use of assistive devices such as sound amplifiers, written messages, or family members to assist in communication is needed to prevent miscommunication.^9-11

OUTCOME Lack of follow-up

A home health worker visits Ms. L, communicating with her using voice-to-text. Ms. L has not yet gone to her primary care physician, audiologist, or outpatient psychiatrist for follow-up because she needs to arrange transportation. Ms. L remains distressed by the music she is hearing, which is worse at night, along with her acute hearing loss.

Bottom Line

Hearing loss can predispose a person to psychiatric disorders and symptoms, including depression, delirium, and auditory hallucinations. Psychiatrists should strive to ensure clear communication with patients who are hearing impaired and should refer such patients to appropriate resources to improve outcomes.

Related Resources

• Wang J, Patel D, Francois D. Elaborate hallucinations, but is it a psychotic disorder? Current Psychiatry. 2021;20(2):46-50. doi:10.12788/cp.0091
• Sosland MD, Pinninti N. 5 ways to quiet auditory hallucinations. Current Psychiatry. 2005;4(4):110.
• Convery E, Keidser G, McLelland M, et al. A smartphone app to facilitate remote patient-provider communication in hearing health care: usability and effect on hearing aid outcomes. Telemed E-Health. 2020;26(6):798-804. doi:10.1089/ tmj.2019.0109

Drug Brand Names

Mirtazapine • Remeron
Prednisone • Rayos
Risperidone • Risperdal
Valacyclovir • Valtrex

CASE New-onset auditory hallucinations

Ms. L, age 78, presents to our hospital with worsening anxiety due to auditory hallucinations. She has been hearing music, which she reports is worse at night and consists of songs, usually the song Jingle Bells, sometimes just melodies and other times with lyrics. Ms. L denies paranoia, visual hallucinations, or worsening mood.

Two weeks ago, Ms. L had visited another hospital, describing 5 days of right-side hearing loss accompanied by pain and burning in her ear and face, along with vesicular lesions in a dermatomal pattern extending into her auditory canal. During this visit, Ms. L’s complete blood count, urine culture, urine drug screen, electrolytes, liver panel, thyroid studies, and vitamin levels were unremarkable. A CT scan of her head showed no abnormalities.

Ms. L was diagnosed with Ramsay Hunt syndrome (herpes zoster oticus), which affects cranial nerves, because of physical examination findings with a dermatomal pattern of lesion distribution and associated pain. Ramsay Hunt syndrome can cause facial paralysis and hearing loss in the affected ear. She was discharged with prescriptions for prednisone 60 mg/d for 7 days and valacyclovir 1 g/d for 7 days and told to follow up with her primary care physician. During the present visit to our hospital, Ms. L’s home health nurse reports that she still has her entire bottles of valacyclovir and prednisone left. Ms. L also has left-side hearing loss that began 5 years ago and a history of recurrent major depressive disorder (MDD) and generalized anxiety disorder. Due to the recent onset of right-side hearing loss, her hearing impairment requires her to communicate via writing or via a voice-to-text app.

HISTORY Depressed and living alone

Ms. L was diagnosed with MDD more than 4 decades ago and has been receiving medication since then. She reports no prior psychiatric hospitalizations, suicide attempts, manic symptoms, or psychotic symptoms. For more than 20 years, she has seen a nurse practitioner, who had prescribed mirtazapine 30 mg/d for MDD, poor appetite, and sleep. Within the last 5 years, her nurse practitioner added risperidone 0.5 mg/d at night to augment the mirtazapine for tearfulness, irritability, and mood swings.

Ms. L’s medical history also includes hypertension and chronic obstructive pulmonary disease. She is a retired teacher and lives alone. She has a chore worker who visits her home for 1 hour 5 days a week to help with cleaning and lifting, and support from her son. Ms. L no longer drives and relies on others for transportation, but is able to manage her finances, activities of daily living, cooking, and walking without any assistance.

[polldaddy:12807642]

EVALUATION Identifying the cause of the music

Ms. L is alert and oriented to time and situation, her concentration is appropriate, and her recent and remote memories are preserved. A full cognitive screen is not performed, but she is able to spell WORLD forwards and backwards and adequately perform a serial 7s test. An examination of her ear does not reveal any open vesicular lesions or swelling, but she continues to report pain and tingling in the C7 dermatomal pattern. Her urine drug screen and infectious and autoimmune laboratory testing are unremarkable. She does not have electrolyte, renal function, or blood count abnormalities. An MRI of her brain that is performed to rule out intracranial pathology due to acute hearing loss shows no acute intracranial abnormalities, with some artifact effect due to motion. Because temporal lobe epilepsy can present with hallucinations,¹ an EEG is performed to rule out seizure activity; it shows a normal wake pattern.

Psychiatry is consulted for management of the auditory hallucinations because Ms. L is distressed by hearing music. Ms. L is evaluated by Neurology and Otolaryngology. Neurology recommends a repeat brain MRI in the outpatient setting after seeing an artifact in the inpatient imaging, as well as follow-up with her primary care physician. Otolaryngology believes her symptoms are secondary to Ramsay Hunt syndrome with incomplete treatment, which is consistent with the initial diagnosis from her previous hospital visit, and recommends another course of oral corticosteroids, along with Audiology and Otolaryngology follow-up.

Continue to: The authors' observations

This is the first case we have seen detailing musical hallucinations (MH) secondary to Ramsay Hunt syndrome, although musical hallucinations have been associated with other etiologies of hearing loss. MH is a “release phenomenon” believed to be caused by deprivation of stimulation of the auditory cortex.² They are categorized as complex auditory hallucinations made up of melodies and rhythms and may be present in up to 2.5% of patients with hearing impairment.¹ The condition is mostly seen in older adults because this population is more likely to experience hearing loss. MH is more common among women (70% to 80% of cases) and is highly comorbid with psychiatric disorders such as schizophrenia, obsessive-compulsive disorder, or (as was the case for Ms. L) MDD.³ Hallucinations secondary to hearing loss may be more common in left-side hearing loss.⁴ In a 2005 study, Warner et al⁵ found religious music such as hymns or Christmas carols was most commonly heard, possibly due to repetitive past exposure.

There is no consensus on treatment for MH. Current treatment guidance comes from case reports and case series. Treatment is generally most successful when the etiology of the hallucination is both apparent and treatable, such as an infectious eitiology.³ In the case of MH due to hearing loss, hallucinations may improve following treatment with hearing aids or cochlear implants,^1,3,6,7 which is what was advised for Ms. L. Table 1^7-9 outlines other possible measures for addressing musical hallucinations.

Anticholinesterases, antidepressants, and antiepileptics may provide some benefit.⁸ However, pharmacotherapy is generally less efficacious and can cause adverse effects, so environmental support and hearing aids may be a safer approach. No medications have been shown to completely cure MH.

TREATMENT Hearing loss management and follow-up

When speaking with the consulting psychiatry team, Ms. L reports her outpatient psychotropic regimen has been helpful. The team decides to continue mirtazapine 30 mg/d and risperidone 0.5 mg/d at night. We recommend that Ms. L discuss tapering off risperidone with her outpatient clinician if they feel it may be indicated to reduce the risk of adverse effects. The treatment team decides not to start corticosteroids due to the risk of steroid-induced psychotic symptoms. The team discusses hallucinations related to hearing loss with Ms. L and advise her to follow up with Audiology and Otolaryngology in the outpatient setting.

The authors’ observations

Approximately 40% of people age >60 struggle with hearing impairment^4,9; this impacts their general quality of life and how clinicians communicate with such patients.¹⁰ People with hearing loss are more likely to develop feelings of social isolation, depression, and delirium (Table 2^8,10,11).¹¹

Risk factors for hearing loss include tobacco use, metabolic syndrome, exposure to loud noises, and exposure to certain ototoxic medications such as chemotherapeutic agents.¹¹ As psychiatrists, it is important to identify patients who may be at risk for hearing loss and refer them to the appropriate medical professional. If hearing loss is new onset, refer the patient to an otolaryngologist for a full evaluation. Unilateral hearing loss should warrant further workup because this could be due to an acoustic neuroma.¹¹

When providing care for a patient who uses a hearing aid, discuss adherence, barriers to adherence, and difficulties with adjusting the hearing aid. A referral to an audiologist may help patients address these barriers. Patients with hearing impairment or loss may benefit from auditory rehabilitation programs that provide communication strategies, ways to adapt to hearing loss, and information about different assistive options.¹¹ Such programs are often run by audiologists or speech language pathologists and contain both counseling and group components.

Continue to: Is is critical for psychiatrists...

It is critical for psychiatrists to ensure appropriate communication with patients who are hearing impaired (Table 3^8-11). The use of assistive devices such as sound amplifiers, written messages, or family members to assist in communication is needed to prevent miscommunication.^9-11

OUTCOME Lack of follow-up

A home health worker visits Ms. L, communicating with her using voice-to-text. Ms. L has not yet gone to her primary care physician, audiologist, or outpatient psychiatrist for follow-up because she needs to arrange transportation. Ms. L remains distressed by the music she is hearing, which is worse at night, along with her acute hearing loss.

Bottom Line

Hearing loss can predispose a person to psychiatric disorders and symptoms, including depression, delirium, and auditory hallucinations. Psychiatrists should strive to ensure clear communication with patients who are hearing impaired and should refer such patients to appropriate resources to improve outcomes.

Related Resources

• Wang J, Patel D, Francois D. Elaborate hallucinations, but is it a psychotic disorder? Current Psychiatry. 2021;20(2):46-50. doi:10.12788/cp.0091
• Sosland MD, Pinninti N. 5 ways to quiet auditory hallucinations. Current Psychiatry. 2005;4(4):110.
• Convery E, Keidser G, McLelland M, et al. A smartphone app to facilitate remote patient-provider communication in hearing health care: usability and effect on hearing aid outcomes. Telemed E-Health. 2020;26(6):798-804. doi:10.1089/ tmj.2019.0109

Drug Brand Names

Mirtazapine • Remeron
Prednisone • Rayos
Risperidone • Risperdal
Valacyclovir • Valtrex

When used to treat anxiety or depressive disorders, antidepressants can cause a variety of adverse effects, including emotional blunting. Emotional blunting has been described as emotional numbness, indifference, decreased responsiveness, or numbing. In a study of 669 patients who had been receiving antidepressants (selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs], or other antidepressants), 46% said they had experienced emotional blunting.¹ A 2019 study found that approximately one-third of patients with unipolar depression or bipolar depression stopped taking their antidepressant due to emotional blunting.²

Historically, there has been difficulty parsing out emotional blunting (a general decrease of all range of emotions) from anhedonia (a restriction of positive emotions). Additionally, some researchers have questioned if the blunting of emotions is part of depressive symptomatology. In a study of 38 adults, most felt able to differentiate emotional blunting due to antidepressants by considering the resolution of other depressive symptoms and timeline of onset.³

A significant limitation has been how clinicians measure or assess emotional blunting. The Oxford Depression Questionnaire (ODQ), previously known as the Oxford Questionnaire on the Emotional Side-effects of Antidepressants, was created based on a qualitative survey of patients who endorsed emotional blunting.⁴ A validated scale, the ODQ divides emotional blunting into 4 dimensions:

• general reduction in emotions
• reduction in positive emotions
• emotional detachment from others
• not caring.⁴

The sections of ODQ focus on exploring specific aspects of patients’ emotional experiences, comparing experiences in the past week to before the development of illness/emotional blunting, and patients’ opinions about antidepressants. Example statements from the ODQ (Table⁴) may help clinicians better understand and explore emotional blunting with their patients.

There are 2 leading theories behind the mechanism of emotional blunting on antidepressants, both focused on serotonin. The first theory offers that SSRIs alter frontal lobe activity through serotonergic effects. The second theory is focused on the downward effects of serotonin on dopamine in reward pathways.⁵ 

Treatment options: Limited evidence

Data on how to address antidepressant-induced emotional blunting are limited and based largely on case reports. One open-label study (N = 143) found that patients experiencing emotional blunting while taking SSRIs and SNRIs who were switched to vortioxetine had a statistically significant decrease in ODQ total score; 50% reported no emotional blunting.⁶ Options to address emotional blunting include decreasing the antidepressant dose, augmenting with or switching to another agent, or considering other treatments such as neuromodulation.⁵ Further research is necessary to clarify which intervention is best.

Clinicians will encounter emotional blunting in patients who are taking antidepressants. It is important to recognize and address these symptoms to help improve patients’ adherence and overall quality of life. 

When used to treat anxiety or depressive disorders, antidepressants can cause a variety of adverse effects, including emotional blunting. Emotional blunting has been described as emotional numbness, indifference, decreased responsiveness, or numbing. In a study of 669 patients who had been receiving antidepressants (selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs], or other antidepressants), 46% said they had experienced emotional blunting.¹ A 2019 study found that approximately one-third of patients with unipolar depression or bipolar depression stopped taking their antidepressant due to emotional blunting.²

Historically, there has been difficulty parsing out emotional blunting (a general decrease of all range of emotions) from anhedonia (a restriction of positive emotions). Additionally, some researchers have questioned if the blunting of emotions is part of depressive symptomatology. In a study of 38 adults, most felt able to differentiate emotional blunting due to antidepressants by considering the resolution of other depressive symptoms and timeline of onset.³

A significant limitation has been how clinicians measure or assess emotional blunting. The Oxford Depression Questionnaire (ODQ), previously known as the Oxford Questionnaire on the Emotional Side-effects of Antidepressants, was created based on a qualitative survey of patients who endorsed emotional blunting.⁴ A validated scale, the ODQ divides emotional blunting into 4 dimensions:

• general reduction in emotions
• reduction in positive emotions
• emotional detachment from others
• not caring.⁴

The sections of ODQ focus on exploring specific aspects of patients’ emotional experiences, comparing experiences in the past week to before the development of illness/emotional blunting, and patients’ opinions about antidepressants. Example statements from the ODQ (Table⁴) may help clinicians better understand and explore emotional blunting with their patients.

There are 2 leading theories behind the mechanism of emotional blunting on antidepressants, both focused on serotonin. The first theory offers that SSRIs alter frontal lobe activity through serotonergic effects. The second theory is focused on the downward effects of serotonin on dopamine in reward pathways.⁵ 

Treatment options: Limited evidence

Data on how to address antidepressant-induced emotional blunting are limited and based largely on case reports. One open-label study (N = 143) found that patients experiencing emotional blunting while taking SSRIs and SNRIs who were switched to vortioxetine had a statistically significant decrease in ODQ total score; 50% reported no emotional blunting.⁶ Options to address emotional blunting include decreasing the antidepressant dose, augmenting with or switching to another agent, or considering other treatments such as neuromodulation.⁵ Further research is necessary to clarify which intervention is best.

Clinicians will encounter emotional blunting in patients who are taking antidepressants. It is important to recognize and address these symptoms to help improve patients’ adherence and overall quality of life. 

When used to treat anxiety or depressive disorders, antidepressants can cause a variety of adverse effects, including emotional blunting. Emotional blunting has been described as emotional numbness, indifference, decreased responsiveness, or numbing. In a study of 669 patients who had been receiving antidepressants (selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs], or other antidepressants), 46% said they had experienced emotional blunting.¹ A 2019 study found that approximately one-third of patients with unipolar depression or bipolar depression stopped taking their antidepressant due to emotional blunting.²

Historically, there has been difficulty parsing out emotional blunting (a general decrease of all range of emotions) from anhedonia (a restriction of positive emotions). Additionally, some researchers have questioned if the blunting of emotions is part of depressive symptomatology. In a study of 38 adults, most felt able to differentiate emotional blunting due to antidepressants by considering the resolution of other depressive symptoms and timeline of onset.³

A significant limitation has been how clinicians measure or assess emotional blunting. The Oxford Depression Questionnaire (ODQ), previously known as the Oxford Questionnaire on the Emotional Side-effects of Antidepressants, was created based on a qualitative survey of patients who endorsed emotional blunting.⁴ A validated scale, the ODQ divides emotional blunting into 4 dimensions:

• general reduction in emotions
• reduction in positive emotions
• emotional detachment from others
• not caring.⁴

The sections of ODQ focus on exploring specific aspects of patients’ emotional experiences, comparing experiences in the past week to before the development of illness/emotional blunting, and patients’ opinions about antidepressants. Example statements from the ODQ (Table⁴) may help clinicians better understand and explore emotional blunting with their patients.

There are 2 leading theories behind the mechanism of emotional blunting on antidepressants, both focused on serotonin. The first theory offers that SSRIs alter frontal lobe activity through serotonergic effects. The second theory is focused on the downward effects of serotonin on dopamine in reward pathways.⁵ 

Treatment options: Limited evidence

Data on how to address antidepressant-induced emotional blunting are limited and based largely on case reports. One open-label study (N = 143) found that patients experiencing emotional blunting while taking SSRIs and SNRIs who were switched to vortioxetine had a statistically significant decrease in ODQ total score; 50% reported no emotional blunting.⁶ Options to address emotional blunting include decreasing the antidepressant dose, augmenting with or switching to another agent, or considering other treatments such as neuromodulation.⁵ Further research is necessary to clarify which intervention is best.

Clinicians will encounter emotional blunting in patients who are taking antidepressants. It is important to recognize and address these symptoms to help improve patients’ adherence and overall quality of life. 

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact [email protected].

Throughout my psychiatric clerkship, I (JWF) participated in street medicine, the practice of providing care to patients (typically those who are homeless) at the location they currently reside, such as in a homeless encampment or community shelter. Our clinical team drove to locations that provided housing for patients diagnosed with schizophrenia, where we assisted with medications and blood draws. I remember pulling up the first day and seeing someone outside smoking a cigarette. I soon learned that many people living in such situations were smokers, and that among the substances they used, tobacco was the most common.

One patient said the cigarettes helped him manage the “voices in his head” as well as some of the adverse effects from medication, such as parkinsonism and akathisia. I asked my attending physician about this and she explained that for some patients, using tobacco was a way to mitigate the positive symptoms of schizophrenia and make the adverse effects of their therapy, particularly extrapyramidal symptoms (EPS), more bearable. By the end of my 2-week rotation, I was sure of a trend: our patients with schizophrenia smoked incessantly. Near the end of my rotation, I asked a patient, “Why do you smoke”? The patient looked at me, puzzled, and replied: “I just do.” This exchange only piqued my curiosity, and I could not help but wonder: what is the relationship between tobacco use and schizophrenia? How is tobacco use related to the pathophysiology of schizophrenia? Does tobacco use among patients with schizophrenia ameliorate aspects of their psychosis? Street medicine offered me a window into a biomedically intriguing question, and I wanted to learn more.

What smoking does for patients with schizophrenia

The high prevalence of smoking among patients with schizophrenia (50% to 88%) greatly exceeds the rates of smoking among patients with other psychiatric illnesses.^1,2 The role of smoking in relation to schizophrenia and other psychoses is multidimensional, and evidence implicates smoking as a risk factor for schizophrenia.^3,4

Two mechanisms may help explain tobacco use in patients with schizophrenia: reducing the adverse effects of antipsychotic medications and promoting neural transmission of dopamine. Second-generation antipsychotics (SGAs) are a first-line treatment, but they can produce EPS, metabolic dysregulation, and blood disorders such as hyponatremia and (rarely) agranulocytosis (1% with clozapine).⁵ Compared to those who are nonsmokers, patients with schizophrenia who smoke are more likely to experience more severe symptoms (eg, hallucinations and delusions) and less severe EPS.^5,6 Research suggests that exposure to polycyclic aromatic hydrocarbons released during smoking induces cytochrome P450 1A2, an enzyme that metabolizes antipsychotic medications such as haloperidol, clozapine, and olanzapine. Increased metabolism results in lower serum concentrations of antipsychotics, lower efficacy, and more severe positive symptoms.^5,6

Additionally, tobacco is an activator of nicotinic acetylcholine receptors (nAChR).⁶ When these receptors become activated, dopamine is released. Dopamine serves as a mediator of reward for nicotine use. In the context of schizophrenia, tobacco use opposes the mechanism of action of SGAs, which is to block neural transmission of dopamine.⁶ The etiology of EPS is related to the blockade of postsynaptic dopamine release in the striatum.⁶ By activating nAChR, smoking induces a downstream release of dopamine that can alleviate iatrogenic EPS by restoring neural transmission of dopamine.⁶ Nicotine may also modulate alpha-7 nicotinic receptor dysfunction, and improve the ability to filter out irrelevant environmental stimuli (impaired sensory gating), which can be overwhelming for patients with schizophrenia. It also can improve cognitive dysfunction and attention by inducing the release of dopamine in mesocortical pathways.⁷ The implications of this neural pathway are significant because smoking is significantly greater in tobacco users who are diagnosed with schizophrenia compared to tobacco users who lack a psychiatric diagnosis.^6,7 Smoking may enhance dopaminergic neural transmission to a far greater extent in tobacco users with schizophrenia compared to tobacco users who do not develop schizophrenia, which suggests intrinsic differences at the neuronal level. Neural differences between tobacco users with or without schizophrenia may synergize with smoking in clinically and biologically meaningful ways. These pathways require further research to support or disprove these hypotheses.

Aside from the dopaminergic system, mechanisms influencing tobacco use among patients with schizophrenia may also be related to nicotine’s mild antidepressant effects. Evidence suggests a clinically meaningful association between nicotine dependence and mood disorders, and this association may be due to the antidepressant effects of nicotine.^8-13 Patients with schizophrenia may experience respite from depressive symptoms through their tobacco use, eventually leading to nicotine dependence.

Continue to: Treatment of schizophrenia...

Treatment of schizophrenia involves multimodal management of a patient’s life, including reducing maladaptive habits that are harmful to health. Chronic smoking in patients with schizophrenia is associated not only with atherosclerosis and cardiovascular disease, but also with poor neurologic functioning, such as significant impairment in attention, working memory, learning, executive function, reasoning, problem-solving and speed of processing.¹⁴ One study found that in patients with schizophrenia, smoking increased the 20-year cardiovascular mortality risk by 86%.¹⁵

Despite challenges to abstinence, smoking cessation should be discussed with these patients, especially given the high prevalence of smoking among this vulnerable population. Bupropion and varenicline have been studied in the context of smoking cessation among patients with schizophrenia. Data on varenicline are mixed. Smokers with schizophrenia who received bupropion showed higher rates of abstinence from smoking compared to those who received placebo.¹⁶

As part of the biopsychosocial model of clinical care, sociodemographic factors must be considered in assessing the relationship between tobacco use and schizophrenia, because a large proportion of patients diagnosed with schizophrenia are members of underrepresented minority groups.¹⁷ A PubMed database search using keywords “African American” or “Black,” “tobacco,” and “schizophrenia” located only 12 studies, most of which lacked relevance to this question. Han et al¹⁸ is 1 of the few studies to investigate sociodemographic factors as they relate to tobacco use among adults with psychoses. Social determinants of health and other confounding variables also need defining to truly distinguish causation from correlation, especially regarding tobacco use and its association with other health risk behaviors.¹⁹

Without the street medicine component of the medical school training I received, the pattern of smoking among patients with schizophrenia may have remained invisible or insignificant to me, as tobacco use is not permitted in the inpatient and outpatient academic settings. This experience not only raised insightful questions, but also emphasized the clinical value of seeing patients within their living environment.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact [email protected].

Throughout my psychiatric clerkship, I (JWF) participated in street medicine, the practice of providing care to patients (typically those who are homeless) at the location they currently reside, such as in a homeless encampment or community shelter. Our clinical team drove to locations that provided housing for patients diagnosed with schizophrenia, where we assisted with medications and blood draws. I remember pulling up the first day and seeing someone outside smoking a cigarette. I soon learned that many people living in such situations were smokers, and that among the substances they used, tobacco was the most common.

One patient said the cigarettes helped him manage the “voices in his head” as well as some of the adverse effects from medication, such as parkinsonism and akathisia. I asked my attending physician about this and she explained that for some patients, using tobacco was a way to mitigate the positive symptoms of schizophrenia and make the adverse effects of their therapy, particularly extrapyramidal symptoms (EPS), more bearable. By the end of my 2-week rotation, I was sure of a trend: our patients with schizophrenia smoked incessantly. Near the end of my rotation, I asked a patient, “Why do you smoke”? The patient looked at me, puzzled, and replied: “I just do.” This exchange only piqued my curiosity, and I could not help but wonder: what is the relationship between tobacco use and schizophrenia? How is tobacco use related to the pathophysiology of schizophrenia? Does tobacco use among patients with schizophrenia ameliorate aspects of their psychosis? Street medicine offered me a window into a biomedically intriguing question, and I wanted to learn more.

What smoking does for patients with schizophrenia

The high prevalence of smoking among patients with schizophrenia (50% to 88%) greatly exceeds the rates of smoking among patients with other psychiatric illnesses.^1,2 The role of smoking in relation to schizophrenia and other psychoses is multidimensional, and evidence implicates smoking as a risk factor for schizophrenia.^3,4

Two mechanisms may help explain tobacco use in patients with schizophrenia: reducing the adverse effects of antipsychotic medications and promoting neural transmission of dopamine. Second-generation antipsychotics (SGAs) are a first-line treatment, but they can produce EPS, metabolic dysregulation, and blood disorders such as hyponatremia and (rarely) agranulocytosis (1% with clozapine).⁵ Compared to those who are nonsmokers, patients with schizophrenia who smoke are more likely to experience more severe symptoms (eg, hallucinations and delusions) and less severe EPS.^5,6 Research suggests that exposure to polycyclic aromatic hydrocarbons released during smoking induces cytochrome P450 1A2, an enzyme that metabolizes antipsychotic medications such as haloperidol, clozapine, and olanzapine. Increased metabolism results in lower serum concentrations of antipsychotics, lower efficacy, and more severe positive symptoms.^5,6

Additionally, tobacco is an activator of nicotinic acetylcholine receptors (nAChR).⁶ When these receptors become activated, dopamine is released. Dopamine serves as a mediator of reward for nicotine use. In the context of schizophrenia, tobacco use opposes the mechanism of action of SGAs, which is to block neural transmission of dopamine.⁶ The etiology of EPS is related to the blockade of postsynaptic dopamine release in the striatum.⁶ By activating nAChR, smoking induces a downstream release of dopamine that can alleviate iatrogenic EPS by restoring neural transmission of dopamine.⁶ Nicotine may also modulate alpha-7 nicotinic receptor dysfunction, and improve the ability to filter out irrelevant environmental stimuli (impaired sensory gating), which can be overwhelming for patients with schizophrenia. It also can improve cognitive dysfunction and attention by inducing the release of dopamine in mesocortical pathways.⁷ The implications of this neural pathway are significant because smoking is significantly greater in tobacco users who are diagnosed with schizophrenia compared to tobacco users who lack a psychiatric diagnosis.^6,7 Smoking may enhance dopaminergic neural transmission to a far greater extent in tobacco users with schizophrenia compared to tobacco users who do not develop schizophrenia, which suggests intrinsic differences at the neuronal level. Neural differences between tobacco users with or without schizophrenia may synergize with smoking in clinically and biologically meaningful ways. These pathways require further research to support or disprove these hypotheses.

Aside from the dopaminergic system, mechanisms influencing tobacco use among patients with schizophrenia may also be related to nicotine’s mild antidepressant effects. Evidence suggests a clinically meaningful association between nicotine dependence and mood disorders, and this association may be due to the antidepressant effects of nicotine.^8-13 Patients with schizophrenia may experience respite from depressive symptoms through their tobacco use, eventually leading to nicotine dependence.

Continue to: Treatment of schizophrenia...

Treatment of schizophrenia involves multimodal management of a patient’s life, including reducing maladaptive habits that are harmful to health. Chronic smoking in patients with schizophrenia is associated not only with atherosclerosis and cardiovascular disease, but also with poor neurologic functioning, such as significant impairment in attention, working memory, learning, executive function, reasoning, problem-solving and speed of processing.¹⁴ One study found that in patients with schizophrenia, smoking increased the 20-year cardiovascular mortality risk by 86%.¹⁵

Despite challenges to abstinence, smoking cessation should be discussed with these patients, especially given the high prevalence of smoking among this vulnerable population. Bupropion and varenicline have been studied in the context of smoking cessation among patients with schizophrenia. Data on varenicline are mixed. Smokers with schizophrenia who received bupropion showed higher rates of abstinence from smoking compared to those who received placebo.¹⁶

As part of the biopsychosocial model of clinical care, sociodemographic factors must be considered in assessing the relationship between tobacco use and schizophrenia, because a large proportion of patients diagnosed with schizophrenia are members of underrepresented minority groups.¹⁷ A PubMed database search using keywords “African American” or “Black,” “tobacco,” and “schizophrenia” located only 12 studies, most of which lacked relevance to this question. Han et al¹⁸ is 1 of the few studies to investigate sociodemographic factors as they relate to tobacco use among adults with psychoses. Social determinants of health and other confounding variables also need defining to truly distinguish causation from correlation, especially regarding tobacco use and its association with other health risk behaviors.¹⁹

Without the street medicine component of the medical school training I received, the pattern of smoking among patients with schizophrenia may have remained invisible or insignificant to me, as tobacco use is not permitted in the inpatient and outpatient academic settings. This experience not only raised insightful questions, but also emphasized the clinical value of seeing patients within their living environment.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact [email protected].

Throughout my psychiatric clerkship, I (JWF) participated in street medicine, the practice of providing care to patients (typically those who are homeless) at the location they currently reside, such as in a homeless encampment or community shelter. Our clinical team drove to locations that provided housing for patients diagnosed with schizophrenia, where we assisted with medications and blood draws. I remember pulling up the first day and seeing someone outside smoking a cigarette. I soon learned that many people living in such situations were smokers, and that among the substances they used, tobacco was the most common.

One patient said the cigarettes helped him manage the “voices in his head” as well as some of the adverse effects from medication, such as parkinsonism and akathisia. I asked my attending physician about this and she explained that for some patients, using tobacco was a way to mitigate the positive symptoms of schizophrenia and make the adverse effects of their therapy, particularly extrapyramidal symptoms (EPS), more bearable. By the end of my 2-week rotation, I was sure of a trend: our patients with schizophrenia smoked incessantly. Near the end of my rotation, I asked a patient, “Why do you smoke”? The patient looked at me, puzzled, and replied: “I just do.” This exchange only piqued my curiosity, and I could not help but wonder: what is the relationship between tobacco use and schizophrenia? How is tobacco use related to the pathophysiology of schizophrenia? Does tobacco use among patients with schizophrenia ameliorate aspects of their psychosis? Street medicine offered me a window into a biomedically intriguing question, and I wanted to learn more.

What smoking does for patients with schizophrenia

The high prevalence of smoking among patients with schizophrenia (50% to 88%) greatly exceeds the rates of smoking among patients with other psychiatric illnesses.^1,2 The role of smoking in relation to schizophrenia and other psychoses is multidimensional, and evidence implicates smoking as a risk factor for schizophrenia.^3,4

Two mechanisms may help explain tobacco use in patients with schizophrenia: reducing the adverse effects of antipsychotic medications and promoting neural transmission of dopamine. Second-generation antipsychotics (SGAs) are a first-line treatment, but they can produce EPS, metabolic dysregulation, and blood disorders such as hyponatremia and (rarely) agranulocytosis (1% with clozapine).⁵ Compared to those who are nonsmokers, patients with schizophrenia who smoke are more likely to experience more severe symptoms (eg, hallucinations and delusions) and less severe EPS.^5,6 Research suggests that exposure to polycyclic aromatic hydrocarbons released during smoking induces cytochrome P450 1A2, an enzyme that metabolizes antipsychotic medications such as haloperidol, clozapine, and olanzapine. Increased metabolism results in lower serum concentrations of antipsychotics, lower efficacy, and more severe positive symptoms.^5,6

Additionally, tobacco is an activator of nicotinic acetylcholine receptors (nAChR).⁶ When these receptors become activated, dopamine is released. Dopamine serves as a mediator of reward for nicotine use. In the context of schizophrenia, tobacco use opposes the mechanism of action of SGAs, which is to block neural transmission of dopamine.⁶ The etiology of EPS is related to the blockade of postsynaptic dopamine release in the striatum.⁶ By activating nAChR, smoking induces a downstream release of dopamine that can alleviate iatrogenic EPS by restoring neural transmission of dopamine.⁶ Nicotine may also modulate alpha-7 nicotinic receptor dysfunction, and improve the ability to filter out irrelevant environmental stimuli (impaired sensory gating), which can be overwhelming for patients with schizophrenia. It also can improve cognitive dysfunction and attention by inducing the release of dopamine in mesocortical pathways.⁷ The implications of this neural pathway are significant because smoking is significantly greater in tobacco users who are diagnosed with schizophrenia compared to tobacco users who lack a psychiatric diagnosis.^6,7 Smoking may enhance dopaminergic neural transmission to a far greater extent in tobacco users with schizophrenia compared to tobacco users who do not develop schizophrenia, which suggests intrinsic differences at the neuronal level. Neural differences between tobacco users with or without schizophrenia may synergize with smoking in clinically and biologically meaningful ways. These pathways require further research to support or disprove these hypotheses.

Aside from the dopaminergic system, mechanisms influencing tobacco use among patients with schizophrenia may also be related to nicotine’s mild antidepressant effects. Evidence suggests a clinically meaningful association between nicotine dependence and mood disorders, and this association may be due to the antidepressant effects of nicotine.^8-13 Patients with schizophrenia may experience respite from depressive symptoms through their tobacco use, eventually leading to nicotine dependence.

Continue to: Treatment of schizophrenia...

Treatment of schizophrenia involves multimodal management of a patient’s life, including reducing maladaptive habits that are harmful to health. Chronic smoking in patients with schizophrenia is associated not only with atherosclerosis and cardiovascular disease, but also with poor neurologic functioning, such as significant impairment in attention, working memory, learning, executive function, reasoning, problem-solving and speed of processing.¹⁴ One study found that in patients with schizophrenia, smoking increased the 20-year cardiovascular mortality risk by 86%.¹⁵

Despite challenges to abstinence, smoking cessation should be discussed with these patients, especially given the high prevalence of smoking among this vulnerable population. Bupropion and varenicline have been studied in the context of smoking cessation among patients with schizophrenia. Data on varenicline are mixed. Smokers with schizophrenia who received bupropion showed higher rates of abstinence from smoking compared to those who received placebo.¹⁶

As part of the biopsychosocial model of clinical care, sociodemographic factors must be considered in assessing the relationship between tobacco use and schizophrenia, because a large proportion of patients diagnosed with schizophrenia are members of underrepresented minority groups.¹⁷ A PubMed database search using keywords “African American” or “Black,” “tobacco,” and “schizophrenia” located only 12 studies, most of which lacked relevance to this question. Han et al¹⁸ is 1 of the few studies to investigate sociodemographic factors as they relate to tobacco use among adults with psychoses. Social determinants of health and other confounding variables also need defining to truly distinguish causation from correlation, especially regarding tobacco use and its association with other health risk behaviors.¹⁹

Without the street medicine component of the medical school training I received, the pattern of smoking among patients with schizophrenia may have remained invisible or insignificant to me, as tobacco use is not permitted in the inpatient and outpatient academic settings. This experience not only raised insightful questions, but also emphasized the clinical value of seeing patients within their living environment.

Thank you very much to Drs. Vincent, Good, and El-Mallakh for their guest editorial on interventional psychiatry (“Interventional psychiatry: What are the next steps?” Current Psychiatry, July 2023, p. 7-9, doi:10.12788/cp.0378). Your addressing the “gap in training” regarding “evidence the growth of interventional psychiatry has exceeded the capacity of the current training infrastructure to provide trainees with adequate exposure to these procedures” is right on the mark, as is the observation that the Accreditation Council for Graduate Medical Education (ACGME) Psychiatry Milestones “do not indicate how competency in these therapies can be achieved.”

The Clinical Transcranial Magnetic Stimulation Society (CTMSS) is well aware of these issues and is actively addressing them:

1. We have increased the number of PULSES courses—designed to serve as intensive, introductory courses on TMS—we provide, and increased the number of members on our PULSES team to address this. We have also increased the number of PULSES scholarships for psychiatry residents that cover the costs of the conference and materials.

2. We created a standing Resident Subcommittee of our Education Committee that is focused on psychiatry resident training. We realize not all psychiatric residency programs have active TMS programs or attendings who are trained in TMS. Last year we presented lectures aimed at introducing TMS to PGY-1 and PGY-2 psychiatry residents. These were recorded and are available for free on the CTMSS website (www.clinicaltmssociety.org).

3. The Resident Subcommittee presented the American Association of Directors of Psychiatric Residency Training with a curriculum submission that was accepted and will be available to all psychiatric residents across the country free of charge. (Current Psychiatry Associate Editor Phillip G. Janicak, MD was very helpful to our subcommittee with this project.)

4. The topic of resident/fellow training in all forms of neuromodulation was discussed during our monthly Grand Rounds webinar and at our annual meeting.

5. The issue of having a broader base of knowledge and training in neuromodulation was a topic at a recent Education Committee meeting, and this year we are adding lectures on electroconvulsive therapy and esketamine to our Grand Rounds webinars. Many CTMSS members are trained and knowledgeable in multiple neuromodulation modalities.

Continue to: 6. Many CTMSS members...

6. Many CTMSS members are involved in academic programs or are invited to training programs to teach psychiatric residents as guest lecturers.

7. The UK's Royal College of Psychiatrists has requested access to our prerecorded lectures, and CTMSS members are working on translating our lectures into Spanish.

Resident education is a key component of the main goals of the CTMSS. Our Board of Directors is fully committed to resident education and has directed the Education Committee to address it. We look forward to moving forward on educating psychiatric residents, with the hope of eventually engaging the ACGME to acknowledge TMS by name in the ACGME guidelines, provide residents with at least basic information on TMS, and clarify how competency in these therapies can be achieved.

Thank you very much to Drs. Vincent, Good, and El-Mallakh for their guest editorial on interventional psychiatry (“Interventional psychiatry: What are the next steps?” Current Psychiatry, July 2023, p. 7-9, doi:10.12788/cp.0378). Your addressing the “gap in training” regarding “evidence the growth of interventional psychiatry has exceeded the capacity of the current training infrastructure to provide trainees with adequate exposure to these procedures” is right on the mark, as is the observation that the Accreditation Council for Graduate Medical Education (ACGME) Psychiatry Milestones “do not indicate how competency in these therapies can be achieved.”

The Clinical Transcranial Magnetic Stimulation Society (CTMSS) is well aware of these issues and is actively addressing them:

1. We have increased the number of PULSES courses—designed to serve as intensive, introductory courses on TMS—we provide, and increased the number of members on our PULSES team to address this. We have also increased the number of PULSES scholarships for psychiatry residents that cover the costs of the conference and materials.

2. We created a standing Resident Subcommittee of our Education Committee that is focused on psychiatry resident training. We realize not all psychiatric residency programs have active TMS programs or attendings who are trained in TMS. Last year we presented lectures aimed at introducing TMS to PGY-1 and PGY-2 psychiatry residents. These were recorded and are available for free on the CTMSS website (www.clinicaltmssociety.org).

3. The Resident Subcommittee presented the American Association of Directors of Psychiatric Residency Training with a curriculum submission that was accepted and will be available to all psychiatric residents across the country free of charge. (Current Psychiatry Associate Editor Phillip G. Janicak, MD was very helpful to our subcommittee with this project.)

4. The topic of resident/fellow training in all forms of neuromodulation was discussed during our monthly Grand Rounds webinar and at our annual meeting.

5. The issue of having a broader base of knowledge and training in neuromodulation was a topic at a recent Education Committee meeting, and this year we are adding lectures on electroconvulsive therapy and esketamine to our Grand Rounds webinars. Many CTMSS members are trained and knowledgeable in multiple neuromodulation modalities.

Continue to: 6. Many CTMSS members...

6. Many CTMSS members are involved in academic programs or are invited to training programs to teach psychiatric residents as guest lecturers.

7. The UK's Royal College of Psychiatrists has requested access to our prerecorded lectures, and CTMSS members are working on translating our lectures into Spanish.

Resident education is a key component of the main goals of the CTMSS. Our Board of Directors is fully committed to resident education and has directed the Education Committee to address it. We look forward to moving forward on educating psychiatric residents, with the hope of eventually engaging the ACGME to acknowledge TMS by name in the ACGME guidelines, provide residents with at least basic information on TMS, and clarify how competency in these therapies can be achieved.

Thank you very much to Drs. Vincent, Good, and El-Mallakh for their guest editorial on interventional psychiatry (“Interventional psychiatry: What are the next steps?” Current Psychiatry, July 2023, p. 7-9, doi:10.12788/cp.0378). Your addressing the “gap in training” regarding “evidence the growth of interventional psychiatry has exceeded the capacity of the current training infrastructure to provide trainees with adequate exposure to these procedures” is right on the mark, as is the observation that the Accreditation Council for Graduate Medical Education (ACGME) Psychiatry Milestones “do not indicate how competency in these therapies can be achieved.”

The Clinical Transcranial Magnetic Stimulation Society (CTMSS) is well aware of these issues and is actively addressing them:

1. We have increased the number of PULSES courses—designed to serve as intensive, introductory courses on TMS—we provide, and increased the number of members on our PULSES team to address this. We have also increased the number of PULSES scholarships for psychiatry residents that cover the costs of the conference and materials.

2. We created a standing Resident Subcommittee of our Education Committee that is focused on psychiatry resident training. We realize not all psychiatric residency programs have active TMS programs or attendings who are trained in TMS. Last year we presented lectures aimed at introducing TMS to PGY-1 and PGY-2 psychiatry residents. These were recorded and are available for free on the CTMSS website (www.clinicaltmssociety.org).

3. The Resident Subcommittee presented the American Association of Directors of Psychiatric Residency Training with a curriculum submission that was accepted and will be available to all psychiatric residents across the country free of charge. (Current Psychiatry Associate Editor Phillip G. Janicak, MD was very helpful to our subcommittee with this project.)

4. The topic of resident/fellow training in all forms of neuromodulation was discussed during our monthly Grand Rounds webinar and at our annual meeting.

5. The issue of having a broader base of knowledge and training in neuromodulation was a topic at a recent Education Committee meeting, and this year we are adding lectures on electroconvulsive therapy and esketamine to our Grand Rounds webinars. Many CTMSS members are trained and knowledgeable in multiple neuromodulation modalities.

Continue to: 6. Many CTMSS members...

6. Many CTMSS members are involved in academic programs or are invited to training programs to teach psychiatric residents as guest lecturers.

7. The UK's Royal College of Psychiatrists has requested access to our prerecorded lectures, and CTMSS members are working on translating our lectures into Spanish.

Resident education is a key component of the main goals of the CTMSS. Our Board of Directors is fully committed to resident education and has directed the Education Committee to address it. We look forward to moving forward on educating psychiatric residents, with the hope of eventually engaging the ACGME to acknowledge TMS by name in the ACGME guidelines, provide residents with at least basic information on TMS, and clarify how competency in these therapies can be achieved.

Parkinson’s disease (PD) is a neurodegenerative condition diagnosed pathologically by alpha synuclein–containing Lewy bodies and dopaminergic cell loss in the substantia nigra pars compacta of the midbrain. Loss of dopaminergic input to the caudate and putamen disrupts the direct and indirect basal ganglia pathways for motor control and contributes to the motor symptoms of PD.¹ According to the Movement Disorder Society criteria, PD is diagnosed clinically by bradykinesia (slowness of movement) plus resting tremor and/or rigidity in the presence of supportive criteria, such as levodopa responsiveness and hyposmia, and in the absence of exclusion criteria and red flags that would suggest atypical parkinsonism or an alternative diagnosis.²

Although the diagnosis and treatment of PD focus heavily on the motor symptoms, nonmotor symptoms can arise decades before the onset of motor symptoms and continue throughout the lifespan. Nonmotor symptoms affect patients from head (ie, cognition and mood) to toe (ie, striatal toe pain) and multiple organ systems in between, including the olfactory, integumentary, cardiovascular, gastrointestinal, genitourinary, and autonomic nervous systems. Thus, it is not surprising that nonmotor symptoms of PD impact health-related quality of life more substantially than motor symptoms.³ A helpful analogy is to consider the motor symptoms of PD as the tip of the iceberg and the nonmotor symptoms as the larger, submerged portions of the iceberg.⁴

Nonmotor symptoms can negatively impact the treatment of motor symptoms. For example, imagine a patient who is very rigid and dyscoordinated in the arms and legs, which limits their ability to dress and walk. If this patient also suffers from nonmotor symptoms of orthostatic hypotension and psychosis—both of which can be exacerbated by levodopa—dose escalation of levodopa for the rigidity and dyscoordination could be compromised, rendering the patient undertreated and less mobile.

In this review, we focus on identifying and managing nonmotor symptoms of PD that are relevant to psychiatric practice, including mood and motivational disorders, anxiety disorders, psychosis, cognitive disorders, and disorders related to the pharmacologic and surgical treatment of PD (Figure 1).

Mood and motivational disorders

Depression

Depression is a common symptom in PD that can occur in the prodromal period years to decades before the onset of motor symptoms, as well as throughout the disease course.⁵ The prevalence of depression in PD varies from 3% to 90%, depending on the methods of assessment, clinical setting of assessment, motor symptom severity, and other factors; clinically significant depression likely affects approximately 35% to 38% of patients.^5,6 How depression in patients with PD differs from depression in the general population is not entirely understood, but there does seem to be less guilt and suicidal ideation and a substantial component of negative affect, including dysphoria and anxiety.⁷ Practically speaking, depression is treated similarly in PD and general populations, with a few considerations.

Despite limited randomized controlled trials (RCTs) for efficacy specifically in patients with PD, selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are generally considered first-line treatments. There is also evidence for tricyclic antidepressants (TCAs), but due to potential worsening of orthostatic hypotension and cognition, TCAs may not be a favorable option for certain patients with PD.^8,9 All antidepressants have the potential to worsen tremor. Theoretically, SNRIs, with noradrenergic activity, may be less tolerable than SSRIs in patients with PD. However, worsening tremor generally has not been a clinically significant adverse event reported in PD depression clinical trials, although it was seen in 17% of patients receiving paroxetine and 21% of patients receiving venlafaxine compared to 7% of patients receiving placebo.^9-11 If tremor worsens, mirtazapine could be considered because it has been reported to cause less tremor than SSRIs or TCAs.¹²

Among medications for PD, pramipexole, a dopamine agonist, may have a beneficial effect on depression.¹³ Additionally, some evidence supports rasagiline, a monoamine oxidase type B inhibitor, as an adjunctive medication for depression in PD.¹⁴ Nevertheless, antidepressant medications remain the standard pharmacologic treatment for PD depression.

Continue to: In terms of nonpharmacologic options...

In terms of nonpharmacologic options, cognitive-behavioral therapy (CBT) is likely efficacious, exercise (especially yoga) is likely efficacious, and repetitive transcranial magnetic stimulation may be efficacious.^15,16 While further high-quality trials are needed, these treatments are low-risk and can be considered, especially for patients who cannot tolerate medications.

Apathy

Apathy—a loss of motivation and goal-directed behavior—can occur in up to 30% of patients during the prodromal period of PD, and in up to 70% of patients throughout the disease course.¹⁷ Apathy can coexist with depression, which can make apathy difficult to diagnose.¹⁷ Given the time constraints of a clinic visit, a practical approach would be to first screen for depression and cognitive impairment. If there is continued suspicion of apathy, the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale part I question (“In the past week have you felt indifferent to doing activities or being with people?”) can be used to screen for apathy, and more detailed scales, such as the Apathy Scale (AS) or Lille Apathy Rating Scale (LARS), could be used if indicated.¹⁸

There are limited high-quality positive trials of apathy-specific treatments in PD. In an RCT of patients with PD who did not have depression or dementia, rivastigmine improved LARS scores compared to placebo.¹⁵ Piribedil, a D2/D3 receptor agonist, improved apathy in patients who underwent subthalamic nucleus deep brain stimulation (STN DBS).¹⁵ Exercise such as individualized physical therapy programs, dance, and Nordic walking as well as mindfulness interventions were shown to significantly reduce apathy scale scores.¹⁹ SSRIs, SNRIs, and rotigotine showed a trend toward reducing AS scores in RCTs.^10,20

Larger, high-quality studies are needed to clarify the treatment of apathy in PD. In the meantime, a reasonable approach is to first treat any comorbid psychiatric or cognitive disorders, since apathy can be associated with these conditions, and to optimize antiparkinsonian medications for motor symptoms, motor fluctuations, and nonmotor fluctuations. Then, the investigational apathy treatments described in this section could be considered on an individual basis.

Anxiety disorders

Anxiety is seen throughout the disease course of PD in approximately 30% to 50% of patients.²¹ It can manifest as generalized anxiety disorder, panic disorder, and other anxiety disorders. There are no high-quality RCTs of pharmacologic treatments of anxiety specifically in patients with PD, except for a negative safety and tolerability study of buspirone in which one-half of patients experienced worsening motor symptoms.^15,22 Thus, the treatment of anxiety in patients with PD is similar to treatments in the general population. SSRIs and SNRIs are typically considered first-line, benzodiazepines are sometimes used with caution (although cognitive adverse effects and fall risk need to be considered), and nonpharma­cologic treatments such as mindfulness yoga, exercise, CBT, and psycho­therapy can be effective.^16,21,23

Continue to: Because there is the lack...

Because there is the lack of evidence-based treatments for anxiety in PD, we highlight 2 PD-specific anxiety disorders: internal tremor, and nonmotor “off” anxiety.

Internal tremor

Internal tremor is a sense of vibration in the axial and/or appendicular muscles that cannot be seen externally by the patient or examiner. It is not yet fully understood if this phenomenon is sensory, anxiety-related, related to subclinical tremor, or the result of a combination of these factors (ie, sensory awareness of a subclinical tremor that triggers or is worsened by anxiety). There is some evidence for subclinical tremor on electromyography, but internal tremor does not respond to antiparkinsonian medications in 70% of patients.²⁴ More electrophysiological research is needed to clarify this phenomenon. Internal tremor has been associated with anxiety in 64% of patients and often improves with anxiolytic therapies.²⁴

Although poorly understood, internal tremor is a documented phenomenon in 33% to 44% of patients with PD, and in some cases, it may be an initial symptom that motivates a patient to seek medical attention for the first time.^24,25 Internal tremor has also been reported in patients with essential tremor and multiple sclerosis.²⁵ Therefore, physicians should be aware of internal tremor because this symptom could herald an underlying neurological disease.

Nonmotor ‘off’ anxiety

Patients with PD are commonly prescribed carbidopa-levodopa, a dopamine precursor, at least 3 times daily. Initially, this medication controls motor symptoms well from 1 dose to the next. However, as the disease progresses, some patients report motor fluctuations in which an individual dose of carbidopa-levodopa may wear off early, take longer than usual to take effect, or not take effect at all. Patients describe these periods as an “off” state in which they do not feel their medications are working. Such motor fluctuations can lead to anxiety and avoidance behaviors, because patients fear being in public at times when the medication does not adequately control their motor symptoms.

In addition to these motor symptom fluctuations and related anxiety, patients can also experience nonmotor symptom fluctuations. A wide variety of nonmotor symptoms, such as mood, cognitive, and behavioral symptoms, have been reported to fluctuate in parallel with motor symptoms.^26,27 One study reported fluctuating restlessness in 39% of patients with PD, excessive worry in 17%, shortness of breath in 13%, excessive sweating and fear in 12%, and palpitations in 10%.²⁷ A patient with fluctuating shortness of breath, sweating, and palpitations (for example) may repeatedly present to the emergency department with a negative cardiac workup and eventually be diagnosed with panic disorder, whereas the patient is truly experiencing nonmotor “off” symptoms. Thus, it is important to be aware of nonmotor fluctuations so this diagnosis can be made and the symptoms appropriately treated. The first step in treating nonmotor fluctuations is to optimize the antiparkinsonian regimen to minimize fluctuations. If “off” anxiety symptoms persist, anxiolytic medications can be prescribed.²¹

Continue to: Psychosis

Psychosis can occur in prodromal and early PD but is most common in advanced PD.²⁸ One study reported that 60% of patients developed hallucinations or delusions after 12 years of follow-up.²⁹ Disease duration, disease severity, dementia, and rapid eye movement sleep behavior disorder are significant risk factors for psychosis in PD.³⁰ Well-formed visual hallucinations are the most common manifestation of psychosis in patients with PD. Auditory hallucinations and delusions are less common. Delusions are usually seen in patients with dementia and are often paranoid delusions, such as of spousal infidelity.³⁰ Sensory hallucinations can occur, but should not be mistaken with formication, a central pain syndrome in PD that can represent a nonmotor “off” symptom that may respond to dopaminergic medication.³¹ Other more mild psychotic symptoms include illusions or misinterpretation of stimuli, false sense of presence, and passage hallucinations of fleeting figures in the peripheral vision.³⁰

The pathophysiology of PD psychosis is not entirely understood but differs from psychosis in other disorders. It can occur in the absence of antiparkinsonian medication exposure and is thought to be a consequence of the underlying disease process of PD involving neurodegeneration in certain brain regions and aberrant neurotransmission of not only dopamine but also serotonin, acetylcholine, and glutamate.³⁰

Figure 2 outlines the management of psychosis in PD. After addressing medical and medication-related causes, it is important to determine if the psychotic symptom is sufficiently bothersome to and/or potentially dangerous for the patient to warrant treatment. If treatment is indicated, pimavanserin and clozapine are efficacious for psychosis in PD without worsening motor symptoms, and quetiapine is possibly efficacious with a low risk of worsening motor symptoms.¹⁵ Other antipsychotics, such as olanzapine, risperidone, and haloperidol, can substantially worsen motor symptoms.¹⁵ Both second-generation antipsychotics and pimavanserin have an FDA black-box warning for a higher risk of all-cause mortality in older patients with dementia; however, because psychosis is associated with early mortality in PD, the risk/benefit ratio should be discussed with the patient and family for shared decision-making.³⁰ If the patient also has dementia, rivastigmine—which is FDA-approved for PD dementia (PDD)—may also improve hallucinations.³²

Cognitive disorders

This section focuses on PD mild cognitive impairment (PD-MCI) and PDD. When a patient with PD reports cognitive concerns, the approach outlined in Figure 3 can be used to diagnose the cognitive disorder. A detailed history, medication review, and physical examination can identify any medical or psychiatric conditions that could affect cognition. The American Academy of Neurology recommends screening for depression, obtaining blood levels of vitamin B12 and thyroid-stimulating hormone, and obtaining a CT or MRI of the brain to rule out reversible causes of dementia.³³ A validated screening test such as the Montreal Cognitive Assessment, which has higher sensitivity for PD-MCI than the Mini-Mental State Examination, is used to identify and quantify cognitive impairment.³⁴ Neuropsychological testing is the gold standard and can be used to confirm and/or better quantify the degree and domains of cognitive impairment.³⁵ Typically, cognitive deficits in PD affect executive function, attention, and/or visuospatial domains more than memory and language early on, and deficits in visuospatial and language domains have the highest sensitivity for predicting progression to PDD.³⁶

Once reversible causes of dementia are addressed or ruled out and cognitive testing is completed, the Movement Disorder Society (MDS) criteria for PD-MCI and PDD summarized in Figure 3 can be used to diagnose the cognitive disorder.^37,38 The MDS criteria for PDD require a diagnosis of PD for ≥1 year prior to the onset of dementia to differentiate PDD from dementia with Lewy bodies (DLB). If the dementia starts within 1 year of the onset of parkinsonism, the diagnosis would be DLB. PDD and DLB are on the spectrum of Lewy body dementia, with the same Lewy body pathology in different temporal and spatial distributions in the brain.³⁸

Continue to: PD-MCI is present in...

PD-MCI is present in approximately 25% of patients.³⁵ PD-MCI does not always progress to dementia but increases the risk of dementia 6-fold. The prevalence of PDD increases with disease duration; it is present in approximately 50% of patients at 10 years and 80% of patients at 20 years of disease.³⁵ Rivastigmine is the only FDA-approved medication to slow progression of PDD. There is insufficient evidence for other acetylcholinesterase inhibitors and memantine.¹⁵ Unfortunately, RCTs of pharmacotherapy for PD-MCI have failed to show efficacy. However, exercise, cognitive rehabilitation, and neuromodulation are being studied. In the meantime, addressing modifiable risk factors (such as vascular risk factors and alcohol consumption) and treating comorbid orthostatic hypotension, obstructive sleep apnea, and depression may improve cognition.^35,39

Treatment-related disorders

Impulse control disorders

Impulse control disorders (ICDs) are an important medication-related consideration in patients with PD. The ICDs seen in PD include pathological gambling, binge eating, excessive shopping, hypersexual behaviors, and dopamine dysregulation syndrome (Table). These disorders are more common in younger patients with a history of impulsive personality traits and addictive behaviors (eg, history of tobacco or alcohol abuse), and are most strongly associated with dopaminergic therapies, particularly the dopamine agonists.^40,41 In the DOMINION study, the odds of ICDs were 2- to 3.5-fold higher in patients taking dopamine agonists.⁴² This is mainly thought to be due to stimulation of D2/D3 receptors in the mesolimbic system.⁴⁰ High doses of levodopa, monoamine oxidase inhibitors, and amantadine are also associated with ICDs.^40-42

The first step in managing ICDs is diagnosing them, which can be difficult because patients often are not forthcoming about these problems due to embarrassment or failure to recognize that the ICD is related to PD medications. If a family member accompanies the patient at the visit, the patient may not want to disclose the amount of money they spend or the extent to which the behavior is a problem. Thus, a screening questionnaire, such as the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP) can be a helpful way for patients to alert the clinician to the issue.⁴¹ Education for the patient and family is crucial before the ICD causes significant financial, health, or relationship problems.

The mainstay of treatment is to reduce or taper off the dopamine agonist or other offending agent while monitoring for worsening motor symptoms and dopamine withdrawal syndrome. If this is unsuccessful, there is very limited evidence for further treatment strategies (Table), including antidepressants, antipsychotics, and mood stabilizers.^40,43,44 There is insufficient evidence for naltrexone based on an RCT that failed to meet its primary endpoint, although naltrexone did significantly reduce QUIP scores.^15,44 There is also insufficient evidence for amantadine, which showed benefit in some studies but was associated with ICDs in the DOMINION study.^15,40,42 In terms of nonpharmacologic treatments, CBT is likely efficacious.^15,40 There are mixed results for STN DBS. Some studies showed improvement in the ICD, due at least in part to dopaminergic medication reduction postoperatively, but this treatment has also been reported to increase impulsivity.^40,45

Deep brain stimulation–related disorders

For patients with PD, the ideal lead location for STN DBS is the dorsolateral aspect of the STN, as this is the motor region of the nucleus. The STN functions in indirect and hyperdirect pathways to put the brake on certain motor programs so only the desired movement can be executed. Its function is clinically demonstrated by patients with STN stroke who develop excessive ballistic movements. Adjacent to the motor region of the STN is a centrally located associative region and a medially located limbic region. Thus, when stimulating the dorsolateral STN, current can spread to those regions as well, and the STN’s ability to put the brake on behavioral and emotional programs can be affected.⁴⁶ Stimulation of the STN has been associated with mania, euphoria, new-onset ICDs, decreased verbal fluency, and executive dysfunction. Depression, apathy, and anxiety can also occur, but more commonly result from rapid withdrawal of antiparkinsonian medications after DBS surgery.^46,47 Therefore, for PD patients with DBS with new or worsening psychiatric or cognitive symptoms, it is important to inquire about any recent programming sessions with neurology as well as recent self-increases in stimulation by the patient using their controller. Collaboration with neurology is important to troubleshoot whether stimulation could be contributing to the patient’s psychiatric or cognitive symptoms.

Continue to: Bottom Line

Mood, anxiety, psychotic, and cognitive symptoms and disorders are common psychiatric manifestations associated with Parkinson’s disease (PD). In addition, patients with PD may experience impulsive control disorders and other symptoms related to treatments they receive for PD. Careful assessment and collaboration with neurology is crucial to alleviating the effects of these conditions.

Related Resources

• Weintraub D, Aarsland D, Chaudhuri KR, et al. The neuropsychiatry of Parkinson’s disease: advances and challenges. Lancet Neurology. 2022;21(1):89-102. doi:10.1016/S1474-4422(21)00330-6
• Goldman JG, Guerra CM. Treatment of nonmotor symptoms associated with Parkinson disease. Neurologic Clinics. 2020;38(2):269-292. doi:10.1016/j.ncl.2019.12.003
• Castrioto A, Lhommee E, Moro E et al. Mood and behavioral effects of subthalamic stimulation in Parkinson’s disease. Lancet Neurology. 2014;13(3):287-305. doi:10.1016/ S1474-4422(13)70294-1

Drug Brand Names

Amantadine • Gocovri
Carbidopa-levodopa • Sinemet
Clozapine • Clozaril
Haloperidol • Haldol
Memantine • Namenda
Mirtazapine • Remeron
Naltrexone • Vivitrol
Olanzapine • Zyprexa
Paroxetine • Paxil
Pimavanserin • Nuplazid
Piribedil • Pronoran
Pramipexole • Mirapex
Quetiapine • Seroquel
Rasagiline • Azilect
Risperidone • Risperdal
Rivastigmine • Exelon
Ropinirole • Requip
Rotigotine • Neupro
Venlafaxine • Effexor
Zonisamide • Zonegran

Parkinson’s disease (PD) is a neurodegenerative condition diagnosed pathologically by alpha synuclein–containing Lewy bodies and dopaminergic cell loss in the substantia nigra pars compacta of the midbrain. Loss of dopaminergic input to the caudate and putamen disrupts the direct and indirect basal ganglia pathways for motor control and contributes to the motor symptoms of PD.¹ According to the Movement Disorder Society criteria, PD is diagnosed clinically by bradykinesia (slowness of movement) plus resting tremor and/or rigidity in the presence of supportive criteria, such as levodopa responsiveness and hyposmia, and in the absence of exclusion criteria and red flags that would suggest atypical parkinsonism or an alternative diagnosis.²

Although the diagnosis and treatment of PD focus heavily on the motor symptoms, nonmotor symptoms can arise decades before the onset of motor symptoms and continue throughout the lifespan. Nonmotor symptoms affect patients from head (ie, cognition and mood) to toe (ie, striatal toe pain) and multiple organ systems in between, including the olfactory, integumentary, cardiovascular, gastrointestinal, genitourinary, and autonomic nervous systems. Thus, it is not surprising that nonmotor symptoms of PD impact health-related quality of life more substantially than motor symptoms.³ A helpful analogy is to consider the motor symptoms of PD as the tip of the iceberg and the nonmotor symptoms as the larger, submerged portions of the iceberg.⁴

Nonmotor symptoms can negatively impact the treatment of motor symptoms. For example, imagine a patient who is very rigid and dyscoordinated in the arms and legs, which limits their ability to dress and walk. If this patient also suffers from nonmotor symptoms of orthostatic hypotension and psychosis—both of which can be exacerbated by levodopa—dose escalation of levodopa for the rigidity and dyscoordination could be compromised, rendering the patient undertreated and less mobile.

In this review, we focus on identifying and managing nonmotor symptoms of PD that are relevant to psychiatric practice, including mood and motivational disorders, anxiety disorders, psychosis, cognitive disorders, and disorders related to the pharmacologic and surgical treatment of PD (Figure 1).

Mood and motivational disorders

Depression

Depression is a common symptom in PD that can occur in the prodromal period years to decades before the onset of motor symptoms, as well as throughout the disease course.⁵ The prevalence of depression in PD varies from 3% to 90%, depending on the methods of assessment, clinical setting of assessment, motor symptom severity, and other factors; clinically significant depression likely affects approximately 35% to 38% of patients.^5,6 How depression in patients with PD differs from depression in the general population is not entirely understood, but there does seem to be less guilt and suicidal ideation and a substantial component of negative affect, including dysphoria and anxiety.⁷ Practically speaking, depression is treated similarly in PD and general populations, with a few considerations.

Despite limited randomized controlled trials (RCTs) for efficacy specifically in patients with PD, selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are generally considered first-line treatments. There is also evidence for tricyclic antidepressants (TCAs), but due to potential worsening of orthostatic hypotension and cognition, TCAs may not be a favorable option for certain patients with PD.^8,9 All antidepressants have the potential to worsen tremor. Theoretically, SNRIs, with noradrenergic activity, may be less tolerable than SSRIs in patients with PD. However, worsening tremor generally has not been a clinically significant adverse event reported in PD depression clinical trials, although it was seen in 17% of patients receiving paroxetine and 21% of patients receiving venlafaxine compared to 7% of patients receiving placebo.^9-11 If tremor worsens, mirtazapine could be considered because it has been reported to cause less tremor than SSRIs or TCAs.¹²

Among medications for PD, pramipexole, a dopamine agonist, may have a beneficial effect on depression.¹³ Additionally, some evidence supports rasagiline, a monoamine oxidase type B inhibitor, as an adjunctive medication for depression in PD.¹⁴ Nevertheless, antidepressant medications remain the standard pharmacologic treatment for PD depression.

Continue to: In terms of nonpharmacologic options...

In terms of nonpharmacologic options, cognitive-behavioral therapy (CBT) is likely efficacious, exercise (especially yoga) is likely efficacious, and repetitive transcranial magnetic stimulation may be efficacious.^15,16 While further high-quality trials are needed, these treatments are low-risk and can be considered, especially for patients who cannot tolerate medications.

Apathy

Apathy—a loss of motivation and goal-directed behavior—can occur in up to 30% of patients during the prodromal period of PD, and in up to 70% of patients throughout the disease course.¹⁷ Apathy can coexist with depression, which can make apathy difficult to diagnose.¹⁷ Given the time constraints of a clinic visit, a practical approach would be to first screen for depression and cognitive impairment. If there is continued suspicion of apathy, the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale part I question (“In the past week have you felt indifferent to doing activities or being with people?”) can be used to screen for apathy, and more detailed scales, such as the Apathy Scale (AS) or Lille Apathy Rating Scale (LARS), could be used if indicated.¹⁸

There are limited high-quality positive trials of apathy-specific treatments in PD. In an RCT of patients with PD who did not have depression or dementia, rivastigmine improved LARS scores compared to placebo.¹⁵ Piribedil, a D2/D3 receptor agonist, improved apathy in patients who underwent subthalamic nucleus deep brain stimulation (STN DBS).¹⁵ Exercise such as individualized physical therapy programs, dance, and Nordic walking as well as mindfulness interventions were shown to significantly reduce apathy scale scores.¹⁹ SSRIs, SNRIs, and rotigotine showed a trend toward reducing AS scores in RCTs.^10,20

Larger, high-quality studies are needed to clarify the treatment of apathy in PD. In the meantime, a reasonable approach is to first treat any comorbid psychiatric or cognitive disorders, since apathy can be associated with these conditions, and to optimize antiparkinsonian medications for motor symptoms, motor fluctuations, and nonmotor fluctuations. Then, the investigational apathy treatments described in this section could be considered on an individual basis.

Anxiety disorders

Anxiety is seen throughout the disease course of PD in approximately 30% to 50% of patients.²¹ It can manifest as generalized anxiety disorder, panic disorder, and other anxiety disorders. There are no high-quality RCTs of pharmacologic treatments of anxiety specifically in patients with PD, except for a negative safety and tolerability study of buspirone in which one-half of patients experienced worsening motor symptoms.^15,22 Thus, the treatment of anxiety in patients with PD is similar to treatments in the general population. SSRIs and SNRIs are typically considered first-line, benzodiazepines are sometimes used with caution (although cognitive adverse effects and fall risk need to be considered), and nonpharma­cologic treatments such as mindfulness yoga, exercise, CBT, and psycho­therapy can be effective.^16,21,23

Continue to: Because there is the lack...

Because there is the lack of evidence-based treatments for anxiety in PD, we highlight 2 PD-specific anxiety disorders: internal tremor, and nonmotor “off” anxiety.

Internal tremor

Internal tremor is a sense of vibration in the axial and/or appendicular muscles that cannot be seen externally by the patient or examiner. It is not yet fully understood if this phenomenon is sensory, anxiety-related, related to subclinical tremor, or the result of a combination of these factors (ie, sensory awareness of a subclinical tremor that triggers or is worsened by anxiety). There is some evidence for subclinical tremor on electromyography, but internal tremor does not respond to antiparkinsonian medications in 70% of patients.²⁴ More electrophysiological research is needed to clarify this phenomenon. Internal tremor has been associated with anxiety in 64% of patients and often improves with anxiolytic therapies.²⁴

Although poorly understood, internal tremor is a documented phenomenon in 33% to 44% of patients with PD, and in some cases, it may be an initial symptom that motivates a patient to seek medical attention for the first time.^24,25 Internal tremor has also been reported in patients with essential tremor and multiple sclerosis.²⁵ Therefore, physicians should be aware of internal tremor because this symptom could herald an underlying neurological disease.

Nonmotor ‘off’ anxiety

Patients with PD are commonly prescribed carbidopa-levodopa, a dopamine precursor, at least 3 times daily. Initially, this medication controls motor symptoms well from 1 dose to the next. However, as the disease progresses, some patients report motor fluctuations in which an individual dose of carbidopa-levodopa may wear off early, take longer than usual to take effect, or not take effect at all. Patients describe these periods as an “off” state in which they do not feel their medications are working. Such motor fluctuations can lead to anxiety and avoidance behaviors, because patients fear being in public at times when the medication does not adequately control their motor symptoms.

In addition to these motor symptom fluctuations and related anxiety, patients can also experience nonmotor symptom fluctuations. A wide variety of nonmotor symptoms, such as mood, cognitive, and behavioral symptoms, have been reported to fluctuate in parallel with motor symptoms.^26,27 One study reported fluctuating restlessness in 39% of patients with PD, excessive worry in 17%, shortness of breath in 13%, excessive sweating and fear in 12%, and palpitations in 10%.²⁷ A patient with fluctuating shortness of breath, sweating, and palpitations (for example) may repeatedly present to the emergency department with a negative cardiac workup and eventually be diagnosed with panic disorder, whereas the patient is truly experiencing nonmotor “off” symptoms. Thus, it is important to be aware of nonmotor fluctuations so this diagnosis can be made and the symptoms appropriately treated. The first step in treating nonmotor fluctuations is to optimize the antiparkinsonian regimen to minimize fluctuations. If “off” anxiety symptoms persist, anxiolytic medications can be prescribed.²¹

Continue to: Psychosis

Psychosis can occur in prodromal and early PD but is most common in advanced PD.²⁸ One study reported that 60% of patients developed hallucinations or delusions after 12 years of follow-up.²⁹ Disease duration, disease severity, dementia, and rapid eye movement sleep behavior disorder are significant risk factors for psychosis in PD.³⁰ Well-formed visual hallucinations are the most common manifestation of psychosis in patients with PD. Auditory hallucinations and delusions are less common. Delusions are usually seen in patients with dementia and are often paranoid delusions, such as of spousal infidelity.³⁰ Sensory hallucinations can occur, but should not be mistaken with formication, a central pain syndrome in PD that can represent a nonmotor “off” symptom that may respond to dopaminergic medication.³¹ Other more mild psychotic symptoms include illusions or misinterpretation of stimuli, false sense of presence, and passage hallucinations of fleeting figures in the peripheral vision.³⁰

The pathophysiology of PD psychosis is not entirely understood but differs from psychosis in other disorders. It can occur in the absence of antiparkinsonian medication exposure and is thought to be a consequence of the underlying disease process of PD involving neurodegeneration in certain brain regions and aberrant neurotransmission of not only dopamine but also serotonin, acetylcholine, and glutamate.³⁰

Figure 2 outlines the management of psychosis in PD. After addressing medical and medication-related causes, it is important to determine if the psychotic symptom is sufficiently bothersome to and/or potentially dangerous for the patient to warrant treatment. If treatment is indicated, pimavanserin and clozapine are efficacious for psychosis in PD without worsening motor symptoms, and quetiapine is possibly efficacious with a low risk of worsening motor symptoms.¹⁵ Other antipsychotics, such as olanzapine, risperidone, and haloperidol, can substantially worsen motor symptoms.¹⁵ Both second-generation antipsychotics and pimavanserin have an FDA black-box warning for a higher risk of all-cause mortality in older patients with dementia; however, because psychosis is associated with early mortality in PD, the risk/benefit ratio should be discussed with the patient and family for shared decision-making.³⁰ If the patient also has dementia, rivastigmine—which is FDA-approved for PD dementia (PDD)—may also improve hallucinations.³²

Cognitive disorders

This section focuses on PD mild cognitive impairment (PD-MCI) and PDD. When a patient with PD reports cognitive concerns, the approach outlined in Figure 3 can be used to diagnose the cognitive disorder. A detailed history, medication review, and physical examination can identify any medical or psychiatric conditions that could affect cognition. The American Academy of Neurology recommends screening for depression, obtaining blood levels of vitamin B12 and thyroid-stimulating hormone, and obtaining a CT or MRI of the brain to rule out reversible causes of dementia.³³ A validated screening test such as the Montreal Cognitive Assessment, which has higher sensitivity for PD-MCI than the Mini-Mental State Examination, is used to identify and quantify cognitive impairment.³⁴ Neuropsychological testing is the gold standard and can be used to confirm and/or better quantify the degree and domains of cognitive impairment.³⁵ Typically, cognitive deficits in PD affect executive function, attention, and/or visuospatial domains more than memory and language early on, and deficits in visuospatial and language domains have the highest sensitivity for predicting progression to PDD.³⁶

Once reversible causes of dementia are addressed or ruled out and cognitive testing is completed, the Movement Disorder Society (MDS) criteria for PD-MCI and PDD summarized in Figure 3 can be used to diagnose the cognitive disorder.^37,38 The MDS criteria for PDD require a diagnosis of PD for ≥1 year prior to the onset of dementia to differentiate PDD from dementia with Lewy bodies (DLB). If the dementia starts within 1 year of the onset of parkinsonism, the diagnosis would be DLB. PDD and DLB are on the spectrum of Lewy body dementia, with the same Lewy body pathology in different temporal and spatial distributions in the brain.³⁸

Continue to: PD-MCI is present in...

PD-MCI is present in approximately 25% of patients.³⁵ PD-MCI does not always progress to dementia but increases the risk of dementia 6-fold. The prevalence of PDD increases with disease duration; it is present in approximately 50% of patients at 10 years and 80% of patients at 20 years of disease.³⁵ Rivastigmine is the only FDA-approved medication to slow progression of PDD. There is insufficient evidence for other acetylcholinesterase inhibitors and memantine.¹⁵ Unfortunately, RCTs of pharmacotherapy for PD-MCI have failed to show efficacy. However, exercise, cognitive rehabilitation, and neuromodulation are being studied. In the meantime, addressing modifiable risk factors (such as vascular risk factors and alcohol consumption) and treating comorbid orthostatic hypotension, obstructive sleep apnea, and depression may improve cognition.^35,39

Treatment-related disorders

Impulse control disorders

Impulse control disorders (ICDs) are an important medication-related consideration in patients with PD. The ICDs seen in PD include pathological gambling, binge eating, excessive shopping, hypersexual behaviors, and dopamine dysregulation syndrome (Table). These disorders are more common in younger patients with a history of impulsive personality traits and addictive behaviors (eg, history of tobacco or alcohol abuse), and are most strongly associated with dopaminergic therapies, particularly the dopamine agonists.^40,41 In the DOMINION study, the odds of ICDs were 2- to 3.5-fold higher in patients taking dopamine agonists.⁴² This is mainly thought to be due to stimulation of D2/D3 receptors in the mesolimbic system.⁴⁰ High doses of levodopa, monoamine oxidase inhibitors, and amantadine are also associated with ICDs.^40-42

The first step in managing ICDs is diagnosing them, which can be difficult because patients often are not forthcoming about these problems due to embarrassment or failure to recognize that the ICD is related to PD medications. If a family member accompanies the patient at the visit, the patient may not want to disclose the amount of money they spend or the extent to which the behavior is a problem. Thus, a screening questionnaire, such as the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP) can be a helpful way for patients to alert the clinician to the issue.⁴¹ Education for the patient and family is crucial before the ICD causes significant financial, health, or relationship problems.

The mainstay of treatment is to reduce or taper off the dopamine agonist or other offending agent while monitoring for worsening motor symptoms and dopamine withdrawal syndrome. If this is unsuccessful, there is very limited evidence for further treatment strategies (Table), including antidepressants, antipsychotics, and mood stabilizers.^40,43,44 There is insufficient evidence for naltrexone based on an RCT that failed to meet its primary endpoint, although naltrexone did significantly reduce QUIP scores.^15,44 There is also insufficient evidence for amantadine, which showed benefit in some studies but was associated with ICDs in the DOMINION study.^15,40,42 In terms of nonpharmacologic treatments, CBT is likely efficacious.^15,40 There are mixed results for STN DBS. Some studies showed improvement in the ICD, due at least in part to dopaminergic medication reduction postoperatively, but this treatment has also been reported to increase impulsivity.^40,45

Deep brain stimulation–related disorders

For patients with PD, the ideal lead location for STN DBS is the dorsolateral aspect of the STN, as this is the motor region of the nucleus. The STN functions in indirect and hyperdirect pathways to put the brake on certain motor programs so only the desired movement can be executed. Its function is clinically demonstrated by patients with STN stroke who develop excessive ballistic movements. Adjacent to the motor region of the STN is a centrally located associative region and a medially located limbic region. Thus, when stimulating the dorsolateral STN, current can spread to those regions as well, and the STN’s ability to put the brake on behavioral and emotional programs can be affected.⁴⁶ Stimulation of the STN has been associated with mania, euphoria, new-onset ICDs, decreased verbal fluency, and executive dysfunction. Depression, apathy, and anxiety can also occur, but more commonly result from rapid withdrawal of antiparkinsonian medications after DBS surgery.^46,47 Therefore, for PD patients with DBS with new or worsening psychiatric or cognitive symptoms, it is important to inquire about any recent programming sessions with neurology as well as recent self-increases in stimulation by the patient using their controller. Collaboration with neurology is important to troubleshoot whether stimulation could be contributing to the patient’s psychiatric or cognitive symptoms.

Continue to: Bottom Line

Mood, anxiety, psychotic, and cognitive symptoms and disorders are common psychiatric manifestations associated with Parkinson’s disease (PD). In addition, patients with PD may experience impulsive control disorders and other symptoms related to treatments they receive for PD. Careful assessment and collaboration with neurology is crucial to alleviating the effects of these conditions.

Related Resources

• Weintraub D, Aarsland D, Chaudhuri KR, et al. The neuropsychiatry of Parkinson’s disease: advances and challenges. Lancet Neurology. 2022;21(1):89-102. doi:10.1016/S1474-4422(21)00330-6
• Goldman JG, Guerra CM. Treatment of nonmotor symptoms associated with Parkinson disease. Neurologic Clinics. 2020;38(2):269-292. doi:10.1016/j.ncl.2019.12.003
• Castrioto A, Lhommee E, Moro E et al. Mood and behavioral effects of subthalamic stimulation in Parkinson’s disease. Lancet Neurology. 2014;13(3):287-305. doi:10.1016/ S1474-4422(13)70294-1

Drug Brand Names

Amantadine • Gocovri
Carbidopa-levodopa • Sinemet
Clozapine • Clozaril
Haloperidol • Haldol
Memantine • Namenda
Mirtazapine • Remeron
Naltrexone • Vivitrol
Olanzapine • Zyprexa
Paroxetine • Paxil
Pimavanserin • Nuplazid
Piribedil • Pronoran
Pramipexole • Mirapex
Quetiapine • Seroquel
Rasagiline • Azilect
Risperidone • Risperdal
Rivastigmine • Exelon
Ropinirole • Requip
Rotigotine • Neupro
Venlafaxine • Effexor
Zonisamide • Zonegran

Parkinson’s disease (PD) is a neurodegenerative condition diagnosed pathologically by alpha synuclein–containing Lewy bodies and dopaminergic cell loss in the substantia nigra pars compacta of the midbrain. Loss of dopaminergic input to the caudate and putamen disrupts the direct and indirect basal ganglia pathways for motor control and contributes to the motor symptoms of PD.¹ According to the Movement Disorder Society criteria, PD is diagnosed clinically by bradykinesia (slowness of movement) plus resting tremor and/or rigidity in the presence of supportive criteria, such as levodopa responsiveness and hyposmia, and in the absence of exclusion criteria and red flags that would suggest atypical parkinsonism or an alternative diagnosis.²

Although the diagnosis and treatment of PD focus heavily on the motor symptoms, nonmotor symptoms can arise decades before the onset of motor symptoms and continue throughout the lifespan. Nonmotor symptoms affect patients from head (ie, cognition and mood) to toe (ie, striatal toe pain) and multiple organ systems in between, including the olfactory, integumentary, cardiovascular, gastrointestinal, genitourinary, and autonomic nervous systems. Thus, it is not surprising that nonmotor symptoms of PD impact health-related quality of life more substantially than motor symptoms.³ A helpful analogy is to consider the motor symptoms of PD as the tip of the iceberg and the nonmotor symptoms as the larger, submerged portions of the iceberg.⁴

Nonmotor symptoms can negatively impact the treatment of motor symptoms. For example, imagine a patient who is very rigid and dyscoordinated in the arms and legs, which limits their ability to dress and walk. If this patient also suffers from nonmotor symptoms of orthostatic hypotension and psychosis—both of which can be exacerbated by levodopa—dose escalation of levodopa for the rigidity and dyscoordination could be compromised, rendering the patient undertreated and less mobile.

In this review, we focus on identifying and managing nonmotor symptoms of PD that are relevant to psychiatric practice, including mood and motivational disorders, anxiety disorders, psychosis, cognitive disorders, and disorders related to the pharmacologic and surgical treatment of PD (Figure 1).

Mood and motivational disorders

Depression

Depression is a common symptom in PD that can occur in the prodromal period years to decades before the onset of motor symptoms, as well as throughout the disease course.⁵ The prevalence of depression in PD varies from 3% to 90%, depending on the methods of assessment, clinical setting of assessment, motor symptom severity, and other factors; clinically significant depression likely affects approximately 35% to 38% of patients.^5,6 How depression in patients with PD differs from depression in the general population is not entirely understood, but there does seem to be less guilt and suicidal ideation and a substantial component of negative affect, including dysphoria and anxiety.⁷ Practically speaking, depression is treated similarly in PD and general populations, with a few considerations.

Despite limited randomized controlled trials (RCTs) for efficacy specifically in patients with PD, selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are generally considered first-line treatments. There is also evidence for tricyclic antidepressants (TCAs), but due to potential worsening of orthostatic hypotension and cognition, TCAs may not be a favorable option for certain patients with PD.^8,9 All antidepressants have the potential to worsen tremor. Theoretically, SNRIs, with noradrenergic activity, may be less tolerable than SSRIs in patients with PD. However, worsening tremor generally has not been a clinically significant adverse event reported in PD depression clinical trials, although it was seen in 17% of patients receiving paroxetine and 21% of patients receiving venlafaxine compared to 7% of patients receiving placebo.^9-11 If tremor worsens, mirtazapine could be considered because it has been reported to cause less tremor than SSRIs or TCAs.¹²

Among medications for PD, pramipexole, a dopamine agonist, may have a beneficial effect on depression.¹³ Additionally, some evidence supports rasagiline, a monoamine oxidase type B inhibitor, as an adjunctive medication for depression in PD.¹⁴ Nevertheless, antidepressant medications remain the standard pharmacologic treatment for PD depression.

Continue to: In terms of nonpharmacologic options...

In terms of nonpharmacologic options, cognitive-behavioral therapy (CBT) is likely efficacious, exercise (especially yoga) is likely efficacious, and repetitive transcranial magnetic stimulation may be efficacious.^15,16 While further high-quality trials are needed, these treatments are low-risk and can be considered, especially for patients who cannot tolerate medications.

Apathy

Apathy—a loss of motivation and goal-directed behavior—can occur in up to 30% of patients during the prodromal period of PD, and in up to 70% of patients throughout the disease course.¹⁷ Apathy can coexist with depression, which can make apathy difficult to diagnose.¹⁷ Given the time constraints of a clinic visit, a practical approach would be to first screen for depression and cognitive impairment. If there is continued suspicion of apathy, the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale part I question (“In the past week have you felt indifferent to doing activities or being with people?”) can be used to screen for apathy, and more detailed scales, such as the Apathy Scale (AS) or Lille Apathy Rating Scale (LARS), could be used if indicated.¹⁸

There are limited high-quality positive trials of apathy-specific treatments in PD. In an RCT of patients with PD who did not have depression or dementia, rivastigmine improved LARS scores compared to placebo.¹⁵ Piribedil, a D2/D3 receptor agonist, improved apathy in patients who underwent subthalamic nucleus deep brain stimulation (STN DBS).¹⁵ Exercise such as individualized physical therapy programs, dance, and Nordic walking as well as mindfulness interventions were shown to significantly reduce apathy scale scores.¹⁹ SSRIs, SNRIs, and rotigotine showed a trend toward reducing AS scores in RCTs.^10,20

Larger, high-quality studies are needed to clarify the treatment of apathy in PD. In the meantime, a reasonable approach is to first treat any comorbid psychiatric or cognitive disorders, since apathy can be associated with these conditions, and to optimize antiparkinsonian medications for motor symptoms, motor fluctuations, and nonmotor fluctuations. Then, the investigational apathy treatments described in this section could be considered on an individual basis.

Anxiety disorders

Anxiety is seen throughout the disease course of PD in approximately 30% to 50% of patients.²¹ It can manifest as generalized anxiety disorder, panic disorder, and other anxiety disorders. There are no high-quality RCTs of pharmacologic treatments of anxiety specifically in patients with PD, except for a negative safety and tolerability study of buspirone in which one-half of patients experienced worsening motor symptoms.^15,22 Thus, the treatment of anxiety in patients with PD is similar to treatments in the general population. SSRIs and SNRIs are typically considered first-line, benzodiazepines are sometimes used with caution (although cognitive adverse effects and fall risk need to be considered), and nonpharma­cologic treatments such as mindfulness yoga, exercise, CBT, and psycho­therapy can be effective.^16,21,23

Continue to: Because there is the lack...

Because there is the lack of evidence-based treatments for anxiety in PD, we highlight 2 PD-specific anxiety disorders: internal tremor, and nonmotor “off” anxiety.

Internal tremor

Internal tremor is a sense of vibration in the axial and/or appendicular muscles that cannot be seen externally by the patient or examiner. It is not yet fully understood if this phenomenon is sensory, anxiety-related, related to subclinical tremor, or the result of a combination of these factors (ie, sensory awareness of a subclinical tremor that triggers or is worsened by anxiety). There is some evidence for subclinical tremor on electromyography, but internal tremor does not respond to antiparkinsonian medications in 70% of patients.²⁴ More electrophysiological research is needed to clarify this phenomenon. Internal tremor has been associated with anxiety in 64% of patients and often improves with anxiolytic therapies.²⁴

Although poorly understood, internal tremor is a documented phenomenon in 33% to 44% of patients with PD, and in some cases, it may be an initial symptom that motivates a patient to seek medical attention for the first time.^24,25 Internal tremor has also been reported in patients with essential tremor and multiple sclerosis.²⁵ Therefore, physicians should be aware of internal tremor because this symptom could herald an underlying neurological disease.

Nonmotor ‘off’ anxiety

Patients with PD are commonly prescribed carbidopa-levodopa, a dopamine precursor, at least 3 times daily. Initially, this medication controls motor symptoms well from 1 dose to the next. However, as the disease progresses, some patients report motor fluctuations in which an individual dose of carbidopa-levodopa may wear off early, take longer than usual to take effect, or not take effect at all. Patients describe these periods as an “off” state in which they do not feel their medications are working. Such motor fluctuations can lead to anxiety and avoidance behaviors, because patients fear being in public at times when the medication does not adequately control their motor symptoms.

In addition to these motor symptom fluctuations and related anxiety, patients can also experience nonmotor symptom fluctuations. A wide variety of nonmotor symptoms, such as mood, cognitive, and behavioral symptoms, have been reported to fluctuate in parallel with motor symptoms.^26,27 One study reported fluctuating restlessness in 39% of patients with PD, excessive worry in 17%, shortness of breath in 13%, excessive sweating and fear in 12%, and palpitations in 10%.²⁷ A patient with fluctuating shortness of breath, sweating, and palpitations (for example) may repeatedly present to the emergency department with a negative cardiac workup and eventually be diagnosed with panic disorder, whereas the patient is truly experiencing nonmotor “off” symptoms. Thus, it is important to be aware of nonmotor fluctuations so this diagnosis can be made and the symptoms appropriately treated. The first step in treating nonmotor fluctuations is to optimize the antiparkinsonian regimen to minimize fluctuations. If “off” anxiety symptoms persist, anxiolytic medications can be prescribed.²¹

Continue to: Psychosis

Psychosis can occur in prodromal and early PD but is most common in advanced PD.²⁸ One study reported that 60% of patients developed hallucinations or delusions after 12 years of follow-up.²⁹ Disease duration, disease severity, dementia, and rapid eye movement sleep behavior disorder are significant risk factors for psychosis in PD.³⁰ Well-formed visual hallucinations are the most common manifestation of psychosis in patients with PD. Auditory hallucinations and delusions are less common. Delusions are usually seen in patients with dementia and are often paranoid delusions, such as of spousal infidelity.³⁰ Sensory hallucinations can occur, but should not be mistaken with formication, a central pain syndrome in PD that can represent a nonmotor “off” symptom that may respond to dopaminergic medication.³¹ Other more mild psychotic symptoms include illusions or misinterpretation of stimuli, false sense of presence, and passage hallucinations of fleeting figures in the peripheral vision.³⁰

The pathophysiology of PD psychosis is not entirely understood but differs from psychosis in other disorders. It can occur in the absence of antiparkinsonian medication exposure and is thought to be a consequence of the underlying disease process of PD involving neurodegeneration in certain brain regions and aberrant neurotransmission of not only dopamine but also serotonin, acetylcholine, and glutamate.³⁰

Figure 2 outlines the management of psychosis in PD. After addressing medical and medication-related causes, it is important to determine if the psychotic symptom is sufficiently bothersome to and/or potentially dangerous for the patient to warrant treatment. If treatment is indicated, pimavanserin and clozapine are efficacious for psychosis in PD without worsening motor symptoms, and quetiapine is possibly efficacious with a low risk of worsening motor symptoms.¹⁵ Other antipsychotics, such as olanzapine, risperidone, and haloperidol, can substantially worsen motor symptoms.¹⁵ Both second-generation antipsychotics and pimavanserin have an FDA black-box warning for a higher risk of all-cause mortality in older patients with dementia; however, because psychosis is associated with early mortality in PD, the risk/benefit ratio should be discussed with the patient and family for shared decision-making.³⁰ If the patient also has dementia, rivastigmine—which is FDA-approved for PD dementia (PDD)—may also improve hallucinations.³²

Cognitive disorders

This section focuses on PD mild cognitive impairment (PD-MCI) and PDD. When a patient with PD reports cognitive concerns, the approach outlined in Figure 3 can be used to diagnose the cognitive disorder. A detailed history, medication review, and physical examination can identify any medical or psychiatric conditions that could affect cognition. The American Academy of Neurology recommends screening for depression, obtaining blood levels of vitamin B12 and thyroid-stimulating hormone, and obtaining a CT or MRI of the brain to rule out reversible causes of dementia.³³ A validated screening test such as the Montreal Cognitive Assessment, which has higher sensitivity for PD-MCI than the Mini-Mental State Examination, is used to identify and quantify cognitive impairment.³⁴ Neuropsychological testing is the gold standard and can be used to confirm and/or better quantify the degree and domains of cognitive impairment.³⁵ Typically, cognitive deficits in PD affect executive function, attention, and/or visuospatial domains more than memory and language early on, and deficits in visuospatial and language domains have the highest sensitivity for predicting progression to PDD.³⁶

Once reversible causes of dementia are addressed or ruled out and cognitive testing is completed, the Movement Disorder Society (MDS) criteria for PD-MCI and PDD summarized in Figure 3 can be used to diagnose the cognitive disorder.^37,38 The MDS criteria for PDD require a diagnosis of PD for ≥1 year prior to the onset of dementia to differentiate PDD from dementia with Lewy bodies (DLB). If the dementia starts within 1 year of the onset of parkinsonism, the diagnosis would be DLB. PDD and DLB are on the spectrum of Lewy body dementia, with the same Lewy body pathology in different temporal and spatial distributions in the brain.³⁸

Continue to: PD-MCI is present in...

PD-MCI is present in approximately 25% of patients.³⁵ PD-MCI does not always progress to dementia but increases the risk of dementia 6-fold. The prevalence of PDD increases with disease duration; it is present in approximately 50% of patients at 10 years and 80% of patients at 20 years of disease.³⁵ Rivastigmine is the only FDA-approved medication to slow progression of PDD. There is insufficient evidence for other acetylcholinesterase inhibitors and memantine.¹⁵ Unfortunately, RCTs of pharmacotherapy for PD-MCI have failed to show efficacy. However, exercise, cognitive rehabilitation, and neuromodulation are being studied. In the meantime, addressing modifiable risk factors (such as vascular risk factors and alcohol consumption) and treating comorbid orthostatic hypotension, obstructive sleep apnea, and depression may improve cognition.^35,39

Treatment-related disorders

Impulse control disorders

Impulse control disorders (ICDs) are an important medication-related consideration in patients with PD. The ICDs seen in PD include pathological gambling, binge eating, excessive shopping, hypersexual behaviors, and dopamine dysregulation syndrome (Table). These disorders are more common in younger patients with a history of impulsive personality traits and addictive behaviors (eg, history of tobacco or alcohol abuse), and are most strongly associated with dopaminergic therapies, particularly the dopamine agonists.^40,41 In the DOMINION study, the odds of ICDs were 2- to 3.5-fold higher in patients taking dopamine agonists.⁴² This is mainly thought to be due to stimulation of D2/D3 receptors in the mesolimbic system.⁴⁰ High doses of levodopa, monoamine oxidase inhibitors, and amantadine are also associated with ICDs.^40-42

The first step in managing ICDs is diagnosing them, which can be difficult because patients often are not forthcoming about these problems due to embarrassment or failure to recognize that the ICD is related to PD medications. If a family member accompanies the patient at the visit, the patient may not want to disclose the amount of money they spend or the extent to which the behavior is a problem. Thus, a screening questionnaire, such as the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP) can be a helpful way for patients to alert the clinician to the issue.⁴¹ Education for the patient and family is crucial before the ICD causes significant financial, health, or relationship problems.

The mainstay of treatment is to reduce or taper off the dopamine agonist or other offending agent while monitoring for worsening motor symptoms and dopamine withdrawal syndrome. If this is unsuccessful, there is very limited evidence for further treatment strategies (Table), including antidepressants, antipsychotics, and mood stabilizers.^40,43,44 There is insufficient evidence for naltrexone based on an RCT that failed to meet its primary endpoint, although naltrexone did significantly reduce QUIP scores.^15,44 There is also insufficient evidence for amantadine, which showed benefit in some studies but was associated with ICDs in the DOMINION study.^15,40,42 In terms of nonpharmacologic treatments, CBT is likely efficacious.^15,40 There are mixed results for STN DBS. Some studies showed improvement in the ICD, due at least in part to dopaminergic medication reduction postoperatively, but this treatment has also been reported to increase impulsivity.^40,45

Deep brain stimulation–related disorders

For patients with PD, the ideal lead location for STN DBS is the dorsolateral aspect of the STN, as this is the motor region of the nucleus. The STN functions in indirect and hyperdirect pathways to put the brake on certain motor programs so only the desired movement can be executed. Its function is clinically demonstrated by patients with STN stroke who develop excessive ballistic movements. Adjacent to the motor region of the STN is a centrally located associative region and a medially located limbic region. Thus, when stimulating the dorsolateral STN, current can spread to those regions as well, and the STN’s ability to put the brake on behavioral and emotional programs can be affected.⁴⁶ Stimulation of the STN has been associated with mania, euphoria, new-onset ICDs, decreased verbal fluency, and executive dysfunction. Depression, apathy, and anxiety can also occur, but more commonly result from rapid withdrawal of antiparkinsonian medications after DBS surgery.^46,47 Therefore, for PD patients with DBS with new or worsening psychiatric or cognitive symptoms, it is important to inquire about any recent programming sessions with neurology as well as recent self-increases in stimulation by the patient using their controller. Collaboration with neurology is important to troubleshoot whether stimulation could be contributing to the patient’s psychiatric or cognitive symptoms.

Continue to: Bottom Line

Mood, anxiety, psychotic, and cognitive symptoms and disorders are common psychiatric manifestations associated with Parkinson’s disease (PD). In addition, patients with PD may experience impulsive control disorders and other symptoms related to treatments they receive for PD. Careful assessment and collaboration with neurology is crucial to alleviating the effects of these conditions.

Related Resources

• Weintraub D, Aarsland D, Chaudhuri KR, et al. The neuropsychiatry of Parkinson’s disease: advances and challenges. Lancet Neurology. 2022;21(1):89-102. doi:10.1016/S1474-4422(21)00330-6
• Goldman JG, Guerra CM. Treatment of nonmotor symptoms associated with Parkinson disease. Neurologic Clinics. 2020;38(2):269-292. doi:10.1016/j.ncl.2019.12.003
• Castrioto A, Lhommee E, Moro E et al. Mood and behavioral effects of subthalamic stimulation in Parkinson’s disease. Lancet Neurology. 2014;13(3):287-305. doi:10.1016/ S1474-4422(13)70294-1

Drug Brand Names

Amantadine • Gocovri
Carbidopa-levodopa • Sinemet
Clozapine • Clozaril
Haloperidol • Haldol
Memantine • Namenda
Mirtazapine • Remeron
Naltrexone • Vivitrol
Olanzapine • Zyprexa
Paroxetine • Paxil
Pimavanserin • Nuplazid
Piribedil • Pronoran
Pramipexole • Mirapex
Quetiapine • Seroquel
Rasagiline • Azilect
Risperidone • Risperdal
Rivastigmine • Exelon
Ropinirole • Requip
Rotigotine • Neupro
Venlafaxine • Effexor
Zonisamide • Zonegran

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study.

If you run into a health care provider these days and ask, “How are you doing?” you’re likely to get a response like this one: “You know, hanging in there.” You smile and move on. But it may be time to go a step further. If you ask that next question – “No, really, how are you doing?” Well, you might need to carve out some time.

It’s been a rough few years for those of us in the health care professions. Our lives, dominated by COVID-related concerns at home, were equally dominated by COVID concerns at work. On the job, there were fewer and fewer of us around as exploitation and COVID-related stressors led doctors, nurses, and others to leave the profession entirely or take early retirement. Even now, I’m not sure we’ve recovered. Staffing in the hospitals is still a huge problem, and the persistence of impersonal meetings via teleconference – which not only prevent any sort of human connection but, audaciously, run from one into another without a break – robs us of even the subtle joy of walking from one hallway to another for 5 minutes of reflection before sitting down to view the next hastily cobbled together PowerPoint.

I’m speaking in generalities, of course.

I’m talking about how bad things are now because, in truth, they’ve never been great. And that may be why health care workers – people with jobs focused on serving others – are nevertheless at substantially increased risk for suicide.

Analyses through the years have shown that physicians tend to have higher rates of death from suicide than the general population. There are reasons for this that may not entirely be because of work-related stress. Doctors’ suicide attempts are more often lethal – we know what is likely to work, after all.

But a focus on physicians fails to acknowledge the much larger population of people who work in health care, are less well-compensated, have less autonomy, and do not hold as respected a position in society. And, according to this paper in JAMA, it is those people who may be suffering most of all.

The study is a nationally representative sample based on the 2008 American Community Survey. Records were linked to the National Death Index through 2019.

Survey respondents were classified into five categories of health care worker, as you can see here. And 1,666,000 non–health care workers served as the control group.

Dr. F. Perry Wilson

Dr. F. Perry Wilson

JAMA

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study.

If you run into a health care provider these days and ask, “How are you doing?” you’re likely to get a response like this one: “You know, hanging in there.” You smile and move on. But it may be time to go a step further. If you ask that next question – “No, really, how are you doing?” Well, you might need to carve out some time.

It’s been a rough few years for those of us in the health care professions. Our lives, dominated by COVID-related concerns at home, were equally dominated by COVID concerns at work. On the job, there were fewer and fewer of us around as exploitation and COVID-related stressors led doctors, nurses, and others to leave the profession entirely or take early retirement. Even now, I’m not sure we’ve recovered. Staffing in the hospitals is still a huge problem, and the persistence of impersonal meetings via teleconference – which not only prevent any sort of human connection but, audaciously, run from one into another without a break – robs us of even the subtle joy of walking from one hallway to another for 5 minutes of reflection before sitting down to view the next hastily cobbled together PowerPoint.

I’m speaking in generalities, of course.

I’m talking about how bad things are now because, in truth, they’ve never been great. And that may be why health care workers – people with jobs focused on serving others – are nevertheless at substantially increased risk for suicide.

Analyses through the years have shown that physicians tend to have higher rates of death from suicide than the general population. There are reasons for this that may not entirely be because of work-related stress. Doctors’ suicide attempts are more often lethal – we know what is likely to work, after all.

But a focus on physicians fails to acknowledge the much larger population of people who work in health care, are less well-compensated, have less autonomy, and do not hold as respected a position in society. And, according to this paper in JAMA, it is those people who may be suffering most of all.

The study is a nationally representative sample based on the 2008 American Community Survey. Records were linked to the National Death Index through 2019.

Survey respondents were classified into five categories of health care worker, as you can see here. And 1,666,000 non–health care workers served as the control group.

Dr. F. Perry Wilson

Dr. F. Perry Wilson

JAMA

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study.

If you run into a health care provider these days and ask, “How are you doing?” you’re likely to get a response like this one: “You know, hanging in there.” You smile and move on. But it may be time to go a step further. If you ask that next question – “No, really, how are you doing?” Well, you might need to carve out some time.

It’s been a rough few years for those of us in the health care professions. Our lives, dominated by COVID-related concerns at home, were equally dominated by COVID concerns at work. On the job, there were fewer and fewer of us around as exploitation and COVID-related stressors led doctors, nurses, and others to leave the profession entirely or take early retirement. Even now, I’m not sure we’ve recovered. Staffing in the hospitals is still a huge problem, and the persistence of impersonal meetings via teleconference – which not only prevent any sort of human connection but, audaciously, run from one into another without a break – robs us of even the subtle joy of walking from one hallway to another for 5 minutes of reflection before sitting down to view the next hastily cobbled together PowerPoint.

I’m speaking in generalities, of course.

I’m talking about how bad things are now because, in truth, they’ve never been great. And that may be why health care workers – people with jobs focused on serving others – are nevertheless at substantially increased risk for suicide.

Analyses through the years have shown that physicians tend to have higher rates of death from suicide than the general population. There are reasons for this that may not entirely be because of work-related stress. Doctors’ suicide attempts are more often lethal – we know what is likely to work, after all.

But a focus on physicians fails to acknowledge the much larger population of people who work in health care, are less well-compensated, have less autonomy, and do not hold as respected a position in society. And, according to this paper in JAMA, it is those people who may be suffering most of all.

The study is a nationally representative sample based on the 2008 American Community Survey. Records were linked to the National Death Index through 2019.

Survey respondents were classified into five categories of health care worker, as you can see here. And 1,666,000 non–health care workers served as the control group.

Dr. F. Perry Wilson

Dr. F. Perry Wilson

JAMA

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

I’m standing atop the Klein Matterhorn, staring out at the Alps, their moonscape peaks forming a jagged, terrifying, glorious white horizon.

I am small. But the emotions are huge. The joy: I get to be a part of all this today. The fear: It could kill me. More than kill me, it could consume me.

That’s what I always used to feel when training in Zermatt, Switzerland.

I was lucky. As a former U.S. Ski Team athlete, I was regularly able to experience such magnificent scenescapes – and feel the tactile insanity of it, too, the rise and fall of helicopters or trams taking us up the mountains, the slicing, frigid air at the summit, and the lurking on-edge feeling that you, tiny human, really aren’t meant to be standing where you are standing.

“Awe puts things in perspective,” said Craig Anderson, PhD, postdoctoral scholar at Washington University at St. Louis, and researcher of emotions and behavior. “It’s about feeling connected with people and part of the larger collective – and that makes it okay to feel small.”

Our modern world is at odds with awe. We tend to shrink into our daily lives, our problems, our devices, and the real-time emotional reactions to those things, especially anger.

It doesn’t have to be that way. A rising pile of research has shown how awe affects our brains and opens our minds – and we don’t have to be standing at the top of the Matterhorn to get the benefits.
 

‘In the upper reaches of pleasure and on the boundary of fear’

That’s how New York University ethical leadership professor Jonathan Haidt, PhD, and psychology professor Dacher Keltner, PhD, of the University of California, Berkeley, defined awe in a seminal report from 2003.

The feeling is composed of two elements: perceived vastness (sensing something larger than ourselves) and accommodation (our need to process and understand that vastness). The researchers also wrote that awe could “change the course of life in profound and permanent ways.”

“There’s a correlation between people who are happier and those who report more feelings of awe,” said David Yaden, PhD, assistant professor in the department of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, and coauthor of “The Varieties of Spiritual Experience.” “It’s unclear, though, which way the causality runs. Is it that having more awe experiences makes people happier? Or that happy people have more awe. But there is a correlation.”

One aspect about awe that’s clear: When people experience it, they report feeling more connected. And that sense of connection can lead to prosocial behavior – such as serving others and engaging with one’s community.

“Feelings of isolation are quite difficult, and we’re social creatures, so when we feel connected, we can benefit from it,” Dr. Yaden said.

A 2022 study published in the Journal of Personality and Social Psychology revealed that awe “awakens self-transcendence, which in turn invigorates pursuit of the authentic self.”

While these effects can be seen as one individual’s benefits, the researchers posited that they also lead to prosocial behaviors. Another study conducted by the same scientists showed that awe led to greater-good behavior during the pandemic, to the tune of an increased willingness to donate blood. In this study, researchers also cited a correlation between feelings of awe and increased empathy.
 

The awe experience

Dr. Yaden joined Dr. Keltner and other researchers in creating a scale for the “awe experience,” and found six related factors: a feeling that time momentarily slows; a sense of self-diminishment (your sense of self becomes smaller); a sense of connectedness; feeling in the presence of something grand; the need to mentally process the experience; and physical changes, like goosebumps or feeling your jaw slightly drop.

“Any of these factors can be large or small,” Dr. Yaden noted, adding that awe can also feel positive or negative. A hurricane can instill awe, for example, and the experience might not be pleasant.

However, “it’s more common for the awe experience to be positive,” Dr. Yaden said.
 

How your brain processes awe

Functional MRI, by which brain activity is measured through blood flow, allows researchers to see what’s happening in the brain after an awe experience.

One study that was conducted in the Netherlands and was published in the journal Human Brain Mapping suggested that certain parts of the brain that are responsible for self-reflection were less “activated” when participants watched awe-inspiring videos.

The researchers posit that the “captivating nature of awe stimuli” could be responsible for such reductions, meaning participants’ brains were geared more toward feelings of connection with others or something greater – and a smaller sense of self.

Another study published in the journal Emotion revealed a link between awe and lower levels of inflammatory cytokines, so awe could have positive and potentially protective health benefits, as well.

And of course there are the physical and emotional benefits of nature, as dozens of studies reveal. Dr. Anderson’s research in the journal Emotion showed that nature “experiences” led to more feelings of awe and that the effects of nature also reduced stress and increased well-being.
 

Why we turn away from awe

The world we inhabit day to day isn’t conducive to experiencing awe – indoors, seated, reacting negatively to work or social media. The mentalities we forge because of this sometimes work against experiencing any form of awe.

Example: Some people don’t like to feel small. That requires a capacity for humility.

“That [feeling] can be threatening,” noted Dr. Anderson, who earned his doctorate studying as part of Dr. Keltner’s “Project Awe” research team at UC Berkeley.

The pandemic and politics and rise in angry Internet culture also contribute. And if you didn’t know, humans have a “negativity bias.”

“Our responses to stress tend to be stronger in magnitude than responses to positive things,” Dr. Anderson said. “Browsing the Internet and seeing negative things can hijack our responses. Anger really narrows our attention on what makes us angry.”

In that sense, anger is the antithesis of awe. As Dr. Anderson puts it: Awe broadens our attention to the world and “opens us up to other people and possibilities,” he said. “When we’re faced with daily hassles, when we experience something vast and awe-inspiring, those other problems aren’t as big of a deal.”
 

We crave awe in spite of ourselves

An awful lot of us are out there seeking awe, knowingly or not.

People have been stopping at scenic overlooks and climbing local peaks since forever, but let’s start with record-setting attendance at the most basic and accessible source of natural awe we have in the United States: national parks.

In 2022, 68% of the 312 million visitors sought out nature-based or recreational park activities (as opposed to historical or cultural activities). Even though a rise in national park visits in 2021 and 2022 could be attributed to pandemic-related behavior (the need for social distancing and/or the desire to get outside), people were flocking to parks prior to COVID-19. In fact, 33 parks set visitation records in 2019; 12 did so in 2022.

We also seek awe in man-made spectacle. Consider annual visitor numbers for the following:

• Golden Gate Bridge: 10 million
• : 4 million
• : 1.62 million

And what about the most awe-inducing experience ever manufactured: Space tourism. While catering to the wealthy for now, flying to space allows untrained people to enjoy something only a chosen few astronauts have been able to feel: the “overview effect,” a term coined by author Frank White for the shift in perspective that occurs in people who see Earth from space.

Upon his return from his Blue Origin flight, actor William Shatner was candid about his emotional experience. “I was crying,” he told NPR. “I didn’t know what I was crying about. It was the death that I saw in space and the lifeforce that I saw coming from the planet – the blue, the beige, and the white. And I realized one was death and the other was life.”

We want awe. We want to feel this way.
 

Adding everyday awe to your life

It may seem counterintuitive: Most awe-inspiring places are special occasion destinations, but in truth it’s possible to find awe each day. Outdoors and indoors.

Park Rx America, led by Robert Zarr, MD, MPH, boasts a network of nearly 1500 healthcare providers ready to “prescribe” walks or time in nature as part of healing. “Our growing community of ‘nature prescribers’ incorporate nature as a treatment option for their willing clients and patients,” Dr. Zarr said.

He also noted that awe is all about where you look, including in small places.

“Something as simple as going for a walk and stopping to notice the complexity of fractal patterns in the leaves, for example, leaves me with a sense of awe,” he said. “Although difficult to measure, there is no doubt that an important part of our health is intricately linked to these daily awe-filled moments.”

Nature is not the only way. Dr. Yaden suggested that going to a museum to see art or sporting events is also a way to experience the feeling.

An unexpected source of man-made awe: Screens. A study published in Nature showed that immersive video experiences (in this case, one achieved by virtual reality) were effective in eliciting an awe response in participants.

While virtual reality isn’t ubiquitous, immersive film experiences are. IMAX screens were created for just this purpose (as anyone who saw the Avatar films in this format can attest).

Is it perfect? No. But whether you’re witnessing a birth, hiking an autumn trail bathed in orange, or letting off a little gasp when you see Oppenheimer’s nuclear explosion in 70 mm, it all counts.

Because it’s not about the thing. It’s about your openness to be awed by the thing.

I’m a little like Dr. Zarr in that I can find wonder in the crystalline structures of a snowflake. And I also love to hike and inhale expansive views. If you can get to Switzerland, and specifically Zermatt, take the old red tram to the top. I highly recommend it.

A version of this article appeared on Medscape.com.

I’m standing atop the Klein Matterhorn, staring out at the Alps, their moonscape peaks forming a jagged, terrifying, glorious white horizon.

I am small. But the emotions are huge. The joy: I get to be a part of all this today. The fear: It could kill me. More than kill me, it could consume me.

That’s what I always used to feel when training in Zermatt, Switzerland.

I was lucky. As a former U.S. Ski Team athlete, I was regularly able to experience such magnificent scenescapes – and feel the tactile insanity of it, too, the rise and fall of helicopters or trams taking us up the mountains, the slicing, frigid air at the summit, and the lurking on-edge feeling that you, tiny human, really aren’t meant to be standing where you are standing.

“Awe puts things in perspective,” said Craig Anderson, PhD, postdoctoral scholar at Washington University at St. Louis, and researcher of emotions and behavior. “It’s about feeling connected with people and part of the larger collective – and that makes it okay to feel small.”

Our modern world is at odds with awe. We tend to shrink into our daily lives, our problems, our devices, and the real-time emotional reactions to those things, especially anger.

It doesn’t have to be that way. A rising pile of research has shown how awe affects our brains and opens our minds – and we don’t have to be standing at the top of the Matterhorn to get the benefits.
 

‘In the upper reaches of pleasure and on the boundary of fear’

That’s how New York University ethical leadership professor Jonathan Haidt, PhD, and psychology professor Dacher Keltner, PhD, of the University of California, Berkeley, defined awe in a seminal report from 2003.

The feeling is composed of two elements: perceived vastness (sensing something larger than ourselves) and accommodation (our need to process and understand that vastness). The researchers also wrote that awe could “change the course of life in profound and permanent ways.”

“There’s a correlation between people who are happier and those who report more feelings of awe,” said David Yaden, PhD, assistant professor in the department of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, and coauthor of “The Varieties of Spiritual Experience.” “It’s unclear, though, which way the causality runs. Is it that having more awe experiences makes people happier? Or that happy people have more awe. But there is a correlation.”

One aspect about awe that’s clear: When people experience it, they report feeling more connected. And that sense of connection can lead to prosocial behavior – such as serving others and engaging with one’s community.

“Feelings of isolation are quite difficult, and we’re social creatures, so when we feel connected, we can benefit from it,” Dr. Yaden said.

A 2022 study published in the Journal of Personality and Social Psychology revealed that awe “awakens self-transcendence, which in turn invigorates pursuit of the authentic self.”

While these effects can be seen as one individual’s benefits, the researchers posited that they also lead to prosocial behaviors. Another study conducted by the same scientists showed that awe led to greater-good behavior during the pandemic, to the tune of an increased willingness to donate blood. In this study, researchers also cited a correlation between feelings of awe and increased empathy.
 

The awe experience

Dr. Yaden joined Dr. Keltner and other researchers in creating a scale for the “awe experience,” and found six related factors: a feeling that time momentarily slows; a sense of self-diminishment (your sense of self becomes smaller); a sense of connectedness; feeling in the presence of something grand; the need to mentally process the experience; and physical changes, like goosebumps or feeling your jaw slightly drop.

“Any of these factors can be large or small,” Dr. Yaden noted, adding that awe can also feel positive or negative. A hurricane can instill awe, for example, and the experience might not be pleasant.

However, “it’s more common for the awe experience to be positive,” Dr. Yaden said.
 

How your brain processes awe

Functional MRI, by which brain activity is measured through blood flow, allows researchers to see what’s happening in the brain after an awe experience.

One study that was conducted in the Netherlands and was published in the journal Human Brain Mapping suggested that certain parts of the brain that are responsible for self-reflection were less “activated” when participants watched awe-inspiring videos.

The researchers posit that the “captivating nature of awe stimuli” could be responsible for such reductions, meaning participants’ brains were geared more toward feelings of connection with others or something greater – and a smaller sense of self.

Another study published in the journal Emotion revealed a link between awe and lower levels of inflammatory cytokines, so awe could have positive and potentially protective health benefits, as well.

And of course there are the physical and emotional benefits of nature, as dozens of studies reveal. Dr. Anderson’s research in the journal Emotion showed that nature “experiences” led to more feelings of awe and that the effects of nature also reduced stress and increased well-being.
 

Why we turn away from awe

The world we inhabit day to day isn’t conducive to experiencing awe – indoors, seated, reacting negatively to work or social media. The mentalities we forge because of this sometimes work against experiencing any form of awe.

Example: Some people don’t like to feel small. That requires a capacity for humility.

“That [feeling] can be threatening,” noted Dr. Anderson, who earned his doctorate studying as part of Dr. Keltner’s “Project Awe” research team at UC Berkeley.

The pandemic and politics and rise in angry Internet culture also contribute. And if you didn’t know, humans have a “negativity bias.”

“Our responses to stress tend to be stronger in magnitude than responses to positive things,” Dr. Anderson said. “Browsing the Internet and seeing negative things can hijack our responses. Anger really narrows our attention on what makes us angry.”

In that sense, anger is the antithesis of awe. As Dr. Anderson puts it: Awe broadens our attention to the world and “opens us up to other people and possibilities,” he said. “When we’re faced with daily hassles, when we experience something vast and awe-inspiring, those other problems aren’t as big of a deal.”
 

We crave awe in spite of ourselves

An awful lot of us are out there seeking awe, knowingly or not.

People have been stopping at scenic overlooks and climbing local peaks since forever, but let’s start with record-setting attendance at the most basic and accessible source of natural awe we have in the United States: national parks.

In 2022, 68% of the 312 million visitors sought out nature-based or recreational park activities (as opposed to historical or cultural activities). Even though a rise in national park visits in 2021 and 2022 could be attributed to pandemic-related behavior (the need for social distancing and/or the desire to get outside), people were flocking to parks prior to COVID-19. In fact, 33 parks set visitation records in 2019; 12 did so in 2022.

We also seek awe in man-made spectacle. Consider annual visitor numbers for the following:

• Golden Gate Bridge: 10 million
• : 4 million
• : 1.62 million

And what about the most awe-inducing experience ever manufactured: Space tourism. While catering to the wealthy for now, flying to space allows untrained people to enjoy something only a chosen few astronauts have been able to feel: the “overview effect,” a term coined by author Frank White for the shift in perspective that occurs in people who see Earth from space.

Upon his return from his Blue Origin flight, actor William Shatner was candid about his emotional experience. “I was crying,” he told NPR. “I didn’t know what I was crying about. It was the death that I saw in space and the lifeforce that I saw coming from the planet – the blue, the beige, and the white. And I realized one was death and the other was life.”

We want awe. We want to feel this way.
 

Adding everyday awe to your life

It may seem counterintuitive: Most awe-inspiring places are special occasion destinations, but in truth it’s possible to find awe each day. Outdoors and indoors.

Park Rx America, led by Robert Zarr, MD, MPH, boasts a network of nearly 1500 healthcare providers ready to “prescribe” walks or time in nature as part of healing. “Our growing community of ‘nature prescribers’ incorporate nature as a treatment option for their willing clients and patients,” Dr. Zarr said.

He also noted that awe is all about where you look, including in small places.

“Something as simple as going for a walk and stopping to notice the complexity of fractal patterns in the leaves, for example, leaves me with a sense of awe,” he said. “Although difficult to measure, there is no doubt that an important part of our health is intricately linked to these daily awe-filled moments.”

Nature is not the only way. Dr. Yaden suggested that going to a museum to see art or sporting events is also a way to experience the feeling.

An unexpected source of man-made awe: Screens. A study published in Nature showed that immersive video experiences (in this case, one achieved by virtual reality) were effective in eliciting an awe response in participants.

While virtual reality isn’t ubiquitous, immersive film experiences are. IMAX screens were created for just this purpose (as anyone who saw the Avatar films in this format can attest).

Is it perfect? No. But whether you’re witnessing a birth, hiking an autumn trail bathed in orange, or letting off a little gasp when you see Oppenheimer’s nuclear explosion in 70 mm, it all counts.

Because it’s not about the thing. It’s about your openness to be awed by the thing.

I’m a little like Dr. Zarr in that I can find wonder in the crystalline structures of a snowflake. And I also love to hike and inhale expansive views. If you can get to Switzerland, and specifically Zermatt, take the old red tram to the top. I highly recommend it.

A version of this article appeared on Medscape.com.

I’m standing atop the Klein Matterhorn, staring out at the Alps, their moonscape peaks forming a jagged, terrifying, glorious white horizon.

I am small. But the emotions are huge. The joy: I get to be a part of all this today. The fear: It could kill me. More than kill me, it could consume me.

That’s what I always used to feel when training in Zermatt, Switzerland.

I was lucky. As a former U.S. Ski Team athlete, I was regularly able to experience such magnificent scenescapes – and feel the tactile insanity of it, too, the rise and fall of helicopters or trams taking us up the mountains, the slicing, frigid air at the summit, and the lurking on-edge feeling that you, tiny human, really aren’t meant to be standing where you are standing.

“Awe puts things in perspective,” said Craig Anderson, PhD, postdoctoral scholar at Washington University at St. Louis, and researcher of emotions and behavior. “It’s about feeling connected with people and part of the larger collective – and that makes it okay to feel small.”

Our modern world is at odds with awe. We tend to shrink into our daily lives, our problems, our devices, and the real-time emotional reactions to those things, especially anger.

It doesn’t have to be that way. A rising pile of research has shown how awe affects our brains and opens our minds – and we don’t have to be standing at the top of the Matterhorn to get the benefits.
 

‘In the upper reaches of pleasure and on the boundary of fear’

That’s how New York University ethical leadership professor Jonathan Haidt, PhD, and psychology professor Dacher Keltner, PhD, of the University of California, Berkeley, defined awe in a seminal report from 2003.

The feeling is composed of two elements: perceived vastness (sensing something larger than ourselves) and accommodation (our need to process and understand that vastness). The researchers also wrote that awe could “change the course of life in profound and permanent ways.”

“There’s a correlation between people who are happier and those who report more feelings of awe,” said David Yaden, PhD, assistant professor in the department of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, and coauthor of “The Varieties of Spiritual Experience.” “It’s unclear, though, which way the causality runs. Is it that having more awe experiences makes people happier? Or that happy people have more awe. But there is a correlation.”

One aspect about awe that’s clear: When people experience it, they report feeling more connected. And that sense of connection can lead to prosocial behavior – such as serving others and engaging with one’s community.

“Feelings of isolation are quite difficult, and we’re social creatures, so when we feel connected, we can benefit from it,” Dr. Yaden said.

A 2022 study published in the Journal of Personality and Social Psychology revealed that awe “awakens self-transcendence, which in turn invigorates pursuit of the authentic self.”

While these effects can be seen as one individual’s benefits, the researchers posited that they also lead to prosocial behaviors. Another study conducted by the same scientists showed that awe led to greater-good behavior during the pandemic, to the tune of an increased willingness to donate blood. In this study, researchers also cited a correlation between feelings of awe and increased empathy.
 

The awe experience

Dr. Yaden joined Dr. Keltner and other researchers in creating a scale for the “awe experience,” and found six related factors: a feeling that time momentarily slows; a sense of self-diminishment (your sense of self becomes smaller); a sense of connectedness; feeling in the presence of something grand; the need to mentally process the experience; and physical changes, like goosebumps or feeling your jaw slightly drop.

“Any of these factors can be large or small,” Dr. Yaden noted, adding that awe can also feel positive or negative. A hurricane can instill awe, for example, and the experience might not be pleasant.

However, “it’s more common for the awe experience to be positive,” Dr. Yaden said.
 

How your brain processes awe

Functional MRI, by which brain activity is measured through blood flow, allows researchers to see what’s happening in the brain after an awe experience.

One study that was conducted in the Netherlands and was published in the journal Human Brain Mapping suggested that certain parts of the brain that are responsible for self-reflection were less “activated” when participants watched awe-inspiring videos.

The researchers posit that the “captivating nature of awe stimuli” could be responsible for such reductions, meaning participants’ brains were geared more toward feelings of connection with others or something greater – and a smaller sense of self.

Another study published in the journal Emotion revealed a link between awe and lower levels of inflammatory cytokines, so awe could have positive and potentially protective health benefits, as well.

And of course there are the physical and emotional benefits of nature, as dozens of studies reveal. Dr. Anderson’s research in the journal Emotion showed that nature “experiences” led to more feelings of awe and that the effects of nature also reduced stress and increased well-being.
 

Why we turn away from awe

The world we inhabit day to day isn’t conducive to experiencing awe – indoors, seated, reacting negatively to work or social media. The mentalities we forge because of this sometimes work against experiencing any form of awe.

Example: Some people don’t like to feel small. That requires a capacity for humility.

“That [feeling] can be threatening,” noted Dr. Anderson, who earned his doctorate studying as part of Dr. Keltner’s “Project Awe” research team at UC Berkeley.

The pandemic and politics and rise in angry Internet culture also contribute. And if you didn’t know, humans have a “negativity bias.”

“Our responses to stress tend to be stronger in magnitude than responses to positive things,” Dr. Anderson said. “Browsing the Internet and seeing negative things can hijack our responses. Anger really narrows our attention on what makes us angry.”

In that sense, anger is the antithesis of awe. As Dr. Anderson puts it: Awe broadens our attention to the world and “opens us up to other people and possibilities,” he said. “When we’re faced with daily hassles, when we experience something vast and awe-inspiring, those other problems aren’t as big of a deal.”
 

We crave awe in spite of ourselves

An awful lot of us are out there seeking awe, knowingly or not.

People have been stopping at scenic overlooks and climbing local peaks since forever, but let’s start with record-setting attendance at the most basic and accessible source of natural awe we have in the United States: national parks.

In 2022, 68% of the 312 million visitors sought out nature-based or recreational park activities (as opposed to historical or cultural activities). Even though a rise in national park visits in 2021 and 2022 could be attributed to pandemic-related behavior (the need for social distancing and/or the desire to get outside), people were flocking to parks prior to COVID-19. In fact, 33 parks set visitation records in 2019; 12 did so in 2022.

We also seek awe in man-made spectacle. Consider annual visitor numbers for the following:

• Golden Gate Bridge: 10 million
• : 4 million
• : 1.62 million

And what about the most awe-inducing experience ever manufactured: Space tourism. While catering to the wealthy for now, flying to space allows untrained people to enjoy something only a chosen few astronauts have been able to feel: the “overview effect,” a term coined by author Frank White for the shift in perspective that occurs in people who see Earth from space.

Upon his return from his Blue Origin flight, actor William Shatner was candid about his emotional experience. “I was crying,” he told NPR. “I didn’t know what I was crying about. It was the death that I saw in space and the lifeforce that I saw coming from the planet – the blue, the beige, and the white. And I realized one was death and the other was life.”

We want awe. We want to feel this way.
 

Adding everyday awe to your life

It may seem counterintuitive: Most awe-inspiring places are special occasion destinations, but in truth it’s possible to find awe each day. Outdoors and indoors.

Park Rx America, led by Robert Zarr, MD, MPH, boasts a network of nearly 1500 healthcare providers ready to “prescribe” walks or time in nature as part of healing. “Our growing community of ‘nature prescribers’ incorporate nature as a treatment option for their willing clients and patients,” Dr. Zarr said.

He also noted that awe is all about where you look, including in small places.

“Something as simple as going for a walk and stopping to notice the complexity of fractal patterns in the leaves, for example, leaves me with a sense of awe,” he said. “Although difficult to measure, there is no doubt that an important part of our health is intricately linked to these daily awe-filled moments.”

Nature is not the only way. Dr. Yaden suggested that going to a museum to see art or sporting events is also a way to experience the feeling.

An unexpected source of man-made awe: Screens. A study published in Nature showed that immersive video experiences (in this case, one achieved by virtual reality) were effective in eliciting an awe response in participants.

While virtual reality isn’t ubiquitous, immersive film experiences are. IMAX screens were created for just this purpose (as anyone who saw the Avatar films in this format can attest).

Is it perfect? No. But whether you’re witnessing a birth, hiking an autumn trail bathed in orange, or letting off a little gasp when you see Oppenheimer’s nuclear explosion in 70 mm, it all counts.

Because it’s not about the thing. It’s about your openness to be awed by the thing.

I’m a little like Dr. Zarr in that I can find wonder in the crystalline structures of a snowflake. And I also love to hike and inhale expansive views. If you can get to Switzerland, and specifically Zermatt, take the old red tram to the top. I highly recommend it.

A version of this article appeared on Medscape.com.

The death of a patient comes with many challenges for physicians, including a range of emotional and professional issues. Beyond those concerns, some physicians and their practices must also consider how to collect on any outstanding bill that might go unpaid after a patient’s death.

“When a patient passes away, obviously there is, unfortunately, a lot of paperwork and stress for families, and it’s a very difficult situation,” says Shikha Jain, MD, an oncologist and associate professor of medicine at the University of Illinois at Chicago. “Talking about finances in that moment can be difficult and uncomfortable, and one thing I’d recommend is that the physicians themselves not get involved.”

Instead, Dr. Jain said, someone in the billing department in the practice or the hospital should take a lead on dealing with any outstanding debts.

“That doctor-patient relationship is a very precious relationship, so you don’t want to mix that financial aspect of providing care with the doctor-patient relationship,” Dr. Jain said. “That’s one thing that’s really important.”

The best approach in such situations is for practices to have a standing policy in place that dictates how to handle bills once a patient has died.

In most cases, the executor of the patient’s will must inform all creditors, including doctors, that the decedent has died, but sometimes there’s a delay.
 

Hoping the doctor’s office writes it off

“Even though the person in charge of the estate is supposed to contact the doctor’s office and let them know when a patient has passed, that doesn’t always happen,” says Hope Wen, head of billing at practice management platform Soundry Health. “It can be very challenging to track down that information, and sometimes they’re just crossing their fingers hoping that the doctor’s office will just write off the balance, which they often do.”

Some offices use a service that compares accounts receivable lists to Social Security death files and state records to identify deaths more quickly. Some physicians might also use a debt collection agency or an attorney who has experience collecting decedent debts and dealing with executors and probate courts.

Once the practice becomes aware that a patient has died, it can no longer send communications to the name and address on file, although it can continue to go through the billing process with the insurer for any bills incurred up to the date of the death.

At that point, the estate becomes responsible for the debt, and all communication must go to the executor of the estate (in some states, this might be called a personal representative). The office can reach out to any contacts on file to see if they are able to identify the executor.

“You want to do that in a compassionate way,” says Jack Brown III, JD, MBA, president of Gulf Coast Collection Bureau. “You’ll tell them you’re sorry for their loss, but you’re wondering who is responsible for the estate. Once you’ve identified that person and gotten their letter of administration from the probate court or a power of attorney, then you can speak with that person as if they were the patient.”

The names of executors are also public record and are available through the probate court (sometimes called the surrogate court) in the county where the decedent lived.

“Even if there’s no will or no executive named, the court will appoint an administrator for the estate, which is usually a family member,” said Robert Bernstein, an estate lawyer in Parsippany, N.J. “Their information will be on file in the court.”
 

Insurance coverage

Typically, insurance will pay for treatment (after deductibles and copays) up until the date of the patient’s death. But, of course, it can take months for some insurance companies to make their final payments, allowing physicians to know exactly how much they’re owed by that estate. In such cases, it’s important for physicians to know the rules in the decedent’s state for how long they have to file a claim.

Most states require that claims occur within 6-9 months of the person’s death. However, in some states, claimants can continue to file for much longer if the estate has not yet paid out all of its assets.

“Sometimes there is real estate to sell or a business to wind down, and it can take years for the estate to distribute all of the assets,” Mr. Bernstein says. “If it’s a year later and they still haven’t distributed the assets, the physician can still file the claim and should be paid.”

In some cases, especially if the decedent received compassionate, quality care, their family will want to make good on any outstanding debts to the health care providers who took care of their loved ones in their final days. In other cases, especially when a family member has had a long illness, their assets have been depleted over time or were transferred to other family members so that there is little left in the estate itself when the patient dies.

Regardless of other circumstances, the estate alone is responsible for such payments, and family members, including spouses and children, typically have no liability. (Though rarely enforced, some states do have filial responsibility laws that could hold children responsible for their parents’ debts, including unpaid medical bills. In addition, states with community property laws might require a surviving spouse to cover their partner’s debt, even after death.)

The probate process varies from state to state, but in general, the probate system and the executor will gather all existing assets and then notify all creditors about how to submit a claim. Typically, the claim will need to include information about how much is owed and documentation, such as bills and an explanation of benefits to back up the claim. It should be borne in mind that even those who’ve passed away have privacy protections under the Health Insurance Portability and Accountability Act, so practices must be careful as to how much information they’re sharing through their claim.

Once the estate has received all the claims, the executor will follow a priority of claims, starting with secured creditors. Typically, medical bills, especially those incurred in the last 90 days of the decedent’s life, have priority in the probate process, Mr. Brown says.
 

How to minimize losses

In that case, the practice would write off the unpaid debt as a business loss. If there are not enough assets in the estate to pay all claims, the executor will follow a state schedule that apportions those assets that are available.

There are some steps that practices can take to protect themselves from incurring such losses. For example, before beginning treatment, practices might consider asking patients to name a guarantor, who will essentially promise to cover any outstanding debts that the patient incurs.

To be binding, the office will need a signature from both the patient and the guarantor. Some offices may also keep a patient credit card number on file with written authorization that they can use to pay bills that are past due, although this payment method would no longer be valid after a patient dies.

While it’s important for all physicians to document and verify the financial information for their patients, oncologists often must consider an additional layer of fiduciary responsibility when it comes to their patients. Ms. Wen suggests that oncology offices check in with insurance companies to determine whether a patient has exhausted their benefits.

“That can happen with cancer patients, depending on how long they’ve been receiving treatment and what type of treatment they’ve been getting,” she said. “Some of the clinical trials, insurance will pay for them, but they’re really expensive and can get toward that max. So knowing where they are with their insurance coverage is big.”

When time is of the essence, some patients will choose to go forward with a treatment before receiving insurance approval. In those cases, the office must have an additional conversation in which the costs of the treatment are discussed. The office should obtain written confirmation of who will pay if the insurer does not, Ms. Wen said. While it’s the patient’s responsibility to keep track of their insurance benefits, oncology practices and hospitals must also exercise due diligence in monitoring the benefits that are available.

“That’s part of their contract with insurance companies if they’re in network, helping patients understand their benefits,” Ms. Wen saids.

It’s also important for practices to keep clear, consistent records to make it easier to identify outstanding bills and the correct contact information for them. If bills had gone unpaid prior to a patient’s death and the office started legal action and received a judgment, that claim would typically go ahead of other creditors’ claims.

Dr. Jain says that some practices might also consider keeping a financial adviser or social worker on staff who can assist patients and their families with understanding their out-of-pocket costs for treatment.

“Financial toxicity in oncology and medical care is a very real problem,” she says. “At the beginning of the relationship, I recommend that my patients get set up with a financial specialist that can help them navigate that aspect, not only when a patient passes away but during the process of receiving treatment, so they’re not shocked by the bills.”

A version of this article first appeared on Medscape.com.

The death of a patient comes with many challenges for physicians, including a range of emotional and professional issues. Beyond those concerns, some physicians and their practices must also consider how to collect on any outstanding bill that might go unpaid after a patient’s death.

“When a patient passes away, obviously there is, unfortunately, a lot of paperwork and stress for families, and it’s a very difficult situation,” says Shikha Jain, MD, an oncologist and associate professor of medicine at the University of Illinois at Chicago. “Talking about finances in that moment can be difficult and uncomfortable, and one thing I’d recommend is that the physicians themselves not get involved.”

Instead, Dr. Jain said, someone in the billing department in the practice or the hospital should take a lead on dealing with any outstanding debts.

“That doctor-patient relationship is a very precious relationship, so you don’t want to mix that financial aspect of providing care with the doctor-patient relationship,” Dr. Jain said. “That’s one thing that’s really important.”

The best approach in such situations is for practices to have a standing policy in place that dictates how to handle bills once a patient has died.

In most cases, the executor of the patient’s will must inform all creditors, including doctors, that the decedent has died, but sometimes there’s a delay.
 

Hoping the doctor’s office writes it off

“Even though the person in charge of the estate is supposed to contact the doctor’s office and let them know when a patient has passed, that doesn’t always happen,” says Hope Wen, head of billing at practice management platform Soundry Health. “It can be very challenging to track down that information, and sometimes they’re just crossing their fingers hoping that the doctor’s office will just write off the balance, which they often do.”

Some offices use a service that compares accounts receivable lists to Social Security death files and state records to identify deaths more quickly. Some physicians might also use a debt collection agency or an attorney who has experience collecting decedent debts and dealing with executors and probate courts.

Once the practice becomes aware that a patient has died, it can no longer send communications to the name and address on file, although it can continue to go through the billing process with the insurer for any bills incurred up to the date of the death.

At that point, the estate becomes responsible for the debt, and all communication must go to the executor of the estate (in some states, this might be called a personal representative). The office can reach out to any contacts on file to see if they are able to identify the executor.

“You want to do that in a compassionate way,” says Jack Brown III, JD, MBA, president of Gulf Coast Collection Bureau. “You’ll tell them you’re sorry for their loss, but you’re wondering who is responsible for the estate. Once you’ve identified that person and gotten their letter of administration from the probate court or a power of attorney, then you can speak with that person as if they were the patient.”

The names of executors are also public record and are available through the probate court (sometimes called the surrogate court) in the county where the decedent lived.

“Even if there’s no will or no executive named, the court will appoint an administrator for the estate, which is usually a family member,” said Robert Bernstein, an estate lawyer in Parsippany, N.J. “Their information will be on file in the court.”
 

Insurance coverage

Typically, insurance will pay for treatment (after deductibles and copays) up until the date of the patient’s death. But, of course, it can take months for some insurance companies to make their final payments, allowing physicians to know exactly how much they’re owed by that estate. In such cases, it’s important for physicians to know the rules in the decedent’s state for how long they have to file a claim.

Most states require that claims occur within 6-9 months of the person’s death. However, in some states, claimants can continue to file for much longer if the estate has not yet paid out all of its assets.

“Sometimes there is real estate to sell or a business to wind down, and it can take years for the estate to distribute all of the assets,” Mr. Bernstein says. “If it’s a year later and they still haven’t distributed the assets, the physician can still file the claim and should be paid.”

In some cases, especially if the decedent received compassionate, quality care, their family will want to make good on any outstanding debts to the health care providers who took care of their loved ones in their final days. In other cases, especially when a family member has had a long illness, their assets have been depleted over time or were transferred to other family members so that there is little left in the estate itself when the patient dies.

Regardless of other circumstances, the estate alone is responsible for such payments, and family members, including spouses and children, typically have no liability. (Though rarely enforced, some states do have filial responsibility laws that could hold children responsible for their parents’ debts, including unpaid medical bills. In addition, states with community property laws might require a surviving spouse to cover their partner’s debt, even after death.)

The probate process varies from state to state, but in general, the probate system and the executor will gather all existing assets and then notify all creditors about how to submit a claim. Typically, the claim will need to include information about how much is owed and documentation, such as bills and an explanation of benefits to back up the claim. It should be borne in mind that even those who’ve passed away have privacy protections under the Health Insurance Portability and Accountability Act, so practices must be careful as to how much information they’re sharing through their claim.

Once the estate has received all the claims, the executor will follow a priority of claims, starting with secured creditors. Typically, medical bills, especially those incurred in the last 90 days of the decedent’s life, have priority in the probate process, Mr. Brown says.
 

How to minimize losses

In that case, the practice would write off the unpaid debt as a business loss. If there are not enough assets in the estate to pay all claims, the executor will follow a state schedule that apportions those assets that are available.

There are some steps that practices can take to protect themselves from incurring such losses. For example, before beginning treatment, practices might consider asking patients to name a guarantor, who will essentially promise to cover any outstanding debts that the patient incurs.

To be binding, the office will need a signature from both the patient and the guarantor. Some offices may also keep a patient credit card number on file with written authorization that they can use to pay bills that are past due, although this payment method would no longer be valid after a patient dies.

While it’s important for all physicians to document and verify the financial information for their patients, oncologists often must consider an additional layer of fiduciary responsibility when it comes to their patients. Ms. Wen suggests that oncology offices check in with insurance companies to determine whether a patient has exhausted their benefits.

“That can happen with cancer patients, depending on how long they’ve been receiving treatment and what type of treatment they’ve been getting,” she said. “Some of the clinical trials, insurance will pay for them, but they’re really expensive and can get toward that max. So knowing where they are with their insurance coverage is big.”

When time is of the essence, some patients will choose to go forward with a treatment before receiving insurance approval. In those cases, the office must have an additional conversation in which the costs of the treatment are discussed. The office should obtain written confirmation of who will pay if the insurer does not, Ms. Wen said. While it’s the patient’s responsibility to keep track of their insurance benefits, oncology practices and hospitals must also exercise due diligence in monitoring the benefits that are available.

“That’s part of their contract with insurance companies if they’re in network, helping patients understand their benefits,” Ms. Wen saids.

It’s also important for practices to keep clear, consistent records to make it easier to identify outstanding bills and the correct contact information for them. If bills had gone unpaid prior to a patient’s death and the office started legal action and received a judgment, that claim would typically go ahead of other creditors’ claims.

Dr. Jain says that some practices might also consider keeping a financial adviser or social worker on staff who can assist patients and their families with understanding their out-of-pocket costs for treatment.

“Financial toxicity in oncology and medical care is a very real problem,” she says. “At the beginning of the relationship, I recommend that my patients get set up with a financial specialist that can help them navigate that aspect, not only when a patient passes away but during the process of receiving treatment, so they’re not shocked by the bills.”

A version of this article first appeared on Medscape.com.

The death of a patient comes with many challenges for physicians, including a range of emotional and professional issues. Beyond those concerns, some physicians and their practices must also consider how to collect on any outstanding bill that might go unpaid after a patient’s death.

“When a patient passes away, obviously there is, unfortunately, a lot of paperwork and stress for families, and it’s a very difficult situation,” says Shikha Jain, MD, an oncologist and associate professor of medicine at the University of Illinois at Chicago. “Talking about finances in that moment can be difficult and uncomfortable, and one thing I’d recommend is that the physicians themselves not get involved.”

Instead, Dr. Jain said, someone in the billing department in the practice or the hospital should take a lead on dealing with any outstanding debts.

“That doctor-patient relationship is a very precious relationship, so you don’t want to mix that financial aspect of providing care with the doctor-patient relationship,” Dr. Jain said. “That’s one thing that’s really important.”

The best approach in such situations is for practices to have a standing policy in place that dictates how to handle bills once a patient has died.

In most cases, the executor of the patient’s will must inform all creditors, including doctors, that the decedent has died, but sometimes there’s a delay.
 

Hoping the doctor’s office writes it off

“Even though the person in charge of the estate is supposed to contact the doctor’s office and let them know when a patient has passed, that doesn’t always happen,” says Hope Wen, head of billing at practice management platform Soundry Health. “It can be very challenging to track down that information, and sometimes they’re just crossing their fingers hoping that the doctor’s office will just write off the balance, which they often do.”

Some offices use a service that compares accounts receivable lists to Social Security death files and state records to identify deaths more quickly. Some physicians might also use a debt collection agency or an attorney who has experience collecting decedent debts and dealing with executors and probate courts.

Once the practice becomes aware that a patient has died, it can no longer send communications to the name and address on file, although it can continue to go through the billing process with the insurer for any bills incurred up to the date of the death.

At that point, the estate becomes responsible for the debt, and all communication must go to the executor of the estate (in some states, this might be called a personal representative). The office can reach out to any contacts on file to see if they are able to identify the executor.

“You want to do that in a compassionate way,” says Jack Brown III, JD, MBA, president of Gulf Coast Collection Bureau. “You’ll tell them you’re sorry for their loss, but you’re wondering who is responsible for the estate. Once you’ve identified that person and gotten their letter of administration from the probate court or a power of attorney, then you can speak with that person as if they were the patient.”

The names of executors are also public record and are available through the probate court (sometimes called the surrogate court) in the county where the decedent lived.

“Even if there’s no will or no executive named, the court will appoint an administrator for the estate, which is usually a family member,” said Robert Bernstein, an estate lawyer in Parsippany, N.J. “Their information will be on file in the court.”
 

Insurance coverage

Typically, insurance will pay for treatment (after deductibles and copays) up until the date of the patient’s death. But, of course, it can take months for some insurance companies to make their final payments, allowing physicians to know exactly how much they’re owed by that estate. In such cases, it’s important for physicians to know the rules in the decedent’s state for how long they have to file a claim.

Most states require that claims occur within 6-9 months of the person’s death. However, in some states, claimants can continue to file for much longer if the estate has not yet paid out all of its assets.

“Sometimes there is real estate to sell or a business to wind down, and it can take years for the estate to distribute all of the assets,” Mr. Bernstein says. “If it’s a year later and they still haven’t distributed the assets, the physician can still file the claim and should be paid.”

In some cases, especially if the decedent received compassionate, quality care, their family will want to make good on any outstanding debts to the health care providers who took care of their loved ones in their final days. In other cases, especially when a family member has had a long illness, their assets have been depleted over time or were transferred to other family members so that there is little left in the estate itself when the patient dies.

Regardless of other circumstances, the estate alone is responsible for such payments, and family members, including spouses and children, typically have no liability. (Though rarely enforced, some states do have filial responsibility laws that could hold children responsible for their parents’ debts, including unpaid medical bills. In addition, states with community property laws might require a surviving spouse to cover their partner’s debt, even after death.)

The probate process varies from state to state, but in general, the probate system and the executor will gather all existing assets and then notify all creditors about how to submit a claim. Typically, the claim will need to include information about how much is owed and documentation, such as bills and an explanation of benefits to back up the claim. It should be borne in mind that even those who’ve passed away have privacy protections under the Health Insurance Portability and Accountability Act, so practices must be careful as to how much information they’re sharing through their claim.

Once the estate has received all the claims, the executor will follow a priority of claims, starting with secured creditors. Typically, medical bills, especially those incurred in the last 90 days of the decedent’s life, have priority in the probate process, Mr. Brown says.
 

How to minimize losses

In that case, the practice would write off the unpaid debt as a business loss. If there are not enough assets in the estate to pay all claims, the executor will follow a state schedule that apportions those assets that are available.

There are some steps that practices can take to protect themselves from incurring such losses. For example, before beginning treatment, practices might consider asking patients to name a guarantor, who will essentially promise to cover any outstanding debts that the patient incurs.

To be binding, the office will need a signature from both the patient and the guarantor. Some offices may also keep a patient credit card number on file with written authorization that they can use to pay bills that are past due, although this payment method would no longer be valid after a patient dies.

While it’s important for all physicians to document and verify the financial information for their patients, oncologists often must consider an additional layer of fiduciary responsibility when it comes to their patients. Ms. Wen suggests that oncology offices check in with insurance companies to determine whether a patient has exhausted their benefits.

“That can happen with cancer patients, depending on how long they’ve been receiving treatment and what type of treatment they’ve been getting,” she said. “Some of the clinical trials, insurance will pay for them, but they’re really expensive and can get toward that max. So knowing where they are with their insurance coverage is big.”

When time is of the essence, some patients will choose to go forward with a treatment before receiving insurance approval. In those cases, the office must have an additional conversation in which the costs of the treatment are discussed. The office should obtain written confirmation of who will pay if the insurer does not, Ms. Wen said. While it’s the patient’s responsibility to keep track of their insurance benefits, oncology practices and hospitals must also exercise due diligence in monitoring the benefits that are available.

“That’s part of their contract with insurance companies if they’re in network, helping patients understand their benefits,” Ms. Wen saids.

It’s also important for practices to keep clear, consistent records to make it easier to identify outstanding bills and the correct contact information for them. If bills had gone unpaid prior to a patient’s death and the office started legal action and received a judgment, that claim would typically go ahead of other creditors’ claims.

Dr. Jain says that some practices might also consider keeping a financial adviser or social worker on staff who can assist patients and their families with understanding their out-of-pocket costs for treatment.

“Financial toxicity in oncology and medical care is a very real problem,” she says. “At the beginning of the relationship, I recommend that my patients get set up with a financial specialist that can help them navigate that aspect, not only when a patient passes away but during the process of receiving treatment, so they’re not shocked by the bills.”

A version of this article first appeared on Medscape.com.

People with long COVID have specific biomarkers in their blood, according to results of a study published in Nature. 

The findings may be a step toward creating blood tests to positively identify people with long COVID so specialized treatments can be employed, researchers said.

 “This is a decisive step forward in the development of valid and reliable blood testing protocols for long COVID,” said David Putrino, PhD., lead author and professor of rehabilitation and human performance and director of the Abilities Research Center at Icahn Mount Sinai Health System, New York.

Researchers from the Icahn School of Medicine at Mount Sinai and Yale School of Medicine looked at blood samples from about 270 people between January 2021 and June 2022. The people had never been infected with COVID, had fully recovered from an infection, or still showed symptoms at least four months after infection.

Using machine learning, the research teams were able to differentiate between people with and without long COVID with 96% accuracy based on distinctive features in the blood samples, according to a news release from Mount Sinai.

People with long COVID had abnormal T-cell activity and low levels of the hormone cortisol. Cortisol helps people feel alert and awake, which would explain why people with long COVID often report fatigue, NBC News said in a report on the study.

“It was one of the findings that most definitively separated the folks with long Covid from the people without long Covid,” Dr. Putrino told NBC News.

The study also found that long COVID appears to reactivate latent viruses including Epstein-Barr and mononucleosis, the study said.

The blood tests could allow doctors to come up with specialized treatments in people who report a wide variety of long COVID symptoms, Dr. Putrino said. 

“There is no ‘silver bullet’ for treating long COVID, because it is an illness that infiltrates complex systems such as the immune and hormonal regulation,” he said.

The Centers for Disease Control and Prevention says about one in five Americans who had COVID still have long COVID. Symptoms include fatigue, brain fog, dizziness, digestive problems, and loss of smell and taste.

A version of this article appeared on WebMD.com.

People with long COVID have specific biomarkers in their blood, according to results of a study published in Nature. 

The findings may be a step toward creating blood tests to positively identify people with long COVID so specialized treatments can be employed, researchers said.

 “This is a decisive step forward in the development of valid and reliable blood testing protocols for long COVID,” said David Putrino, PhD., lead author and professor of rehabilitation and human performance and director of the Abilities Research Center at Icahn Mount Sinai Health System, New York.

Researchers from the Icahn School of Medicine at Mount Sinai and Yale School of Medicine looked at blood samples from about 270 people between January 2021 and June 2022. The people had never been infected with COVID, had fully recovered from an infection, or still showed symptoms at least four months after infection.

Using machine learning, the research teams were able to differentiate between people with and without long COVID with 96% accuracy based on distinctive features in the blood samples, according to a news release from Mount Sinai.

People with long COVID had abnormal T-cell activity and low levels of the hormone cortisol. Cortisol helps people feel alert and awake, which would explain why people with long COVID often report fatigue, NBC News said in a report on the study.

“It was one of the findings that most definitively separated the folks with long Covid from the people without long Covid,” Dr. Putrino told NBC News.

The study also found that long COVID appears to reactivate latent viruses including Epstein-Barr and mononucleosis, the study said.

The blood tests could allow doctors to come up with specialized treatments in people who report a wide variety of long COVID symptoms, Dr. Putrino said. 

“There is no ‘silver bullet’ for treating long COVID, because it is an illness that infiltrates complex systems such as the immune and hormonal regulation,” he said.

The Centers for Disease Control and Prevention says about one in five Americans who had COVID still have long COVID. Symptoms include fatigue, brain fog, dizziness, digestive problems, and loss of smell and taste.

A version of this article appeared on WebMD.com.

People with long COVID have specific biomarkers in their blood, according to results of a study published in Nature. 

The findings may be a step toward creating blood tests to positively identify people with long COVID so specialized treatments can be employed, researchers said.

 “This is a decisive step forward in the development of valid and reliable blood testing protocols for long COVID,” said David Putrino, PhD., lead author and professor of rehabilitation and human performance and director of the Abilities Research Center at Icahn Mount Sinai Health System, New York.

Researchers from the Icahn School of Medicine at Mount Sinai and Yale School of Medicine looked at blood samples from about 270 people between January 2021 and June 2022. The people had never been infected with COVID, had fully recovered from an infection, or still showed symptoms at least four months after infection.

Using machine learning, the research teams were able to differentiate between people with and without long COVID with 96% accuracy based on distinctive features in the blood samples, according to a news release from Mount Sinai.

People with long COVID had abnormal T-cell activity and low levels of the hormone cortisol. Cortisol helps people feel alert and awake, which would explain why people with long COVID often report fatigue, NBC News said in a report on the study.

“It was one of the findings that most definitively separated the folks with long Covid from the people without long Covid,” Dr. Putrino told NBC News.

The study also found that long COVID appears to reactivate latent viruses including Epstein-Barr and mononucleosis, the study said.

The blood tests could allow doctors to come up with specialized treatments in people who report a wide variety of long COVID symptoms, Dr. Putrino said. 

“There is no ‘silver bullet’ for treating long COVID, because it is an illness that infiltrates complex systems such as the immune and hormonal regulation,” he said.

The Centers for Disease Control and Prevention says about one in five Americans who had COVID still have long COVID. Symptoms include fatigue, brain fog, dizziness, digestive problems, and loss of smell and taste.

A version of this article appeared on WebMD.com.