Major Depressive Disorder

Low levels of serum lactate dehydrogenase were significantly associated with depression and suicide attempts in adults with major depressive disorder, based on data from more than 300 individuals.

The pathogenesis of depression is complex, and recent research has focused on the potential relationship between energy metabolism and depression, wrote Qian Yao, MD, of Wuhan University, Hubei, China, and colleagues.

Previous studies have suggested that serum lactate dehydrogenase (LDH) may be a biomarker for Parkinson’s disease, Huntington’s disease, and post-stroke depression, but the link between lactate metabolism and depression remains unclear, they said.

“We hypothesize that LDH may act as a potential biomarker for MDD, considering it represents a reduced energy metabolic status in depressive patients,” they explained.

In a study published in General Hospital Psychiatry, the researchers examined differences in serum LDH in 232 patients with major depressive disorder (MDD) and 110 healthy controls. They also examined whether LDH was predictive of suicide attempts in the MDD patients. Depression was assessed via the 24-item Hamilton Depression Scale (HAMD-24).

The mean age across both groups was 33 years; other clinical characteristics were similar between the groups.

The serum LDH level of the MDD group was significantly lower than the control group was (177.94 U/L vs. 196.50 U/L; P < .001). Analysis of blood lipid levels showed significantly lower levels of total cholesterol in the MDD group compared with controls, but no significant differences were noted in LDL cholesterol, HDL cholesterol, or triglycerides.

In a further analysis of subgroups of depression, the serum LDH in MDD patients who had attempted suicide was significantly lower compared to those without suicide attempts (169.96 vs. 181.25; P = .002), although the LDH level for the non-suicide MDD patients also was significantly lower than controls (181.25 vs. 196.50; P < .001). No significant correlation was noted between HAMD-24 score and suicide attempts.

Some gender differences also appeared. Both male and female MDD patients had significantly lower LDH levels compared with controls. However, in a regression analysis, a correlation between total cholesterol and LDL cholesterol as potential suicide markers was noted in female MDD patients, but not male MDD patients, which suggests an impact of gender on suicide risk in MDD, the researchers wrote in their discussion.

The findings were limited by several factors including the retrospective design, lack of investigation of changes in LDH isozymes in MDD patients, and lack of assessment of changes in LDH in cerebrospinal fluid, the researchers noted. However, the results “provide clear evidence that the concentration of LDH in serum is associated with early onset and clinical prognosis of depressive symptoms,” in MDD, which may inform diagnosis and guide clinical intervention, including early identification of suicide risk, they concluded.

The study was supported by the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.

Low levels of serum lactate dehydrogenase were significantly associated with depression and suicide attempts in adults with major depressive disorder, based on data from more than 300 individuals.

The pathogenesis of depression is complex, and recent research has focused on the potential relationship between energy metabolism and depression, wrote Qian Yao, MD, of Wuhan University, Hubei, China, and colleagues.

Previous studies have suggested that serum lactate dehydrogenase (LDH) may be a biomarker for Parkinson’s disease, Huntington’s disease, and post-stroke depression, but the link between lactate metabolism and depression remains unclear, they said.

“We hypothesize that LDH may act as a potential biomarker for MDD, considering it represents a reduced energy metabolic status in depressive patients,” they explained.

In a study published in General Hospital Psychiatry, the researchers examined differences in serum LDH in 232 patients with major depressive disorder (MDD) and 110 healthy controls. They also examined whether LDH was predictive of suicide attempts in the MDD patients. Depression was assessed via the 24-item Hamilton Depression Scale (HAMD-24).

The mean age across both groups was 33 years; other clinical characteristics were similar between the groups.

The serum LDH level of the MDD group was significantly lower than the control group was (177.94 U/L vs. 196.50 U/L; P < .001). Analysis of blood lipid levels showed significantly lower levels of total cholesterol in the MDD group compared with controls, but no significant differences were noted in LDL cholesterol, HDL cholesterol, or triglycerides.

In a further analysis of subgroups of depression, the serum LDH in MDD patients who had attempted suicide was significantly lower compared to those without suicide attempts (169.96 vs. 181.25; P = .002), although the LDH level for the non-suicide MDD patients also was significantly lower than controls (181.25 vs. 196.50; P < .001). No significant correlation was noted between HAMD-24 score and suicide attempts.

Some gender differences also appeared. Both male and female MDD patients had significantly lower LDH levels compared with controls. However, in a regression analysis, a correlation between total cholesterol and LDL cholesterol as potential suicide markers was noted in female MDD patients, but not male MDD patients, which suggests an impact of gender on suicide risk in MDD, the researchers wrote in their discussion.

The findings were limited by several factors including the retrospective design, lack of investigation of changes in LDH isozymes in MDD patients, and lack of assessment of changes in LDH in cerebrospinal fluid, the researchers noted. However, the results “provide clear evidence that the concentration of LDH in serum is associated with early onset and clinical prognosis of depressive symptoms,” in MDD, which may inform diagnosis and guide clinical intervention, including early identification of suicide risk, they concluded.

The study was supported by the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.

Low levels of serum lactate dehydrogenase were significantly associated with depression and suicide attempts in adults with major depressive disorder, based on data from more than 300 individuals.

The pathogenesis of depression is complex, and recent research has focused on the potential relationship between energy metabolism and depression, wrote Qian Yao, MD, of Wuhan University, Hubei, China, and colleagues.

Previous studies have suggested that serum lactate dehydrogenase (LDH) may be a biomarker for Parkinson’s disease, Huntington’s disease, and post-stroke depression, but the link between lactate metabolism and depression remains unclear, they said.

“We hypothesize that LDH may act as a potential biomarker for MDD, considering it represents a reduced energy metabolic status in depressive patients,” they explained.

In a study published in General Hospital Psychiatry, the researchers examined differences in serum LDH in 232 patients with major depressive disorder (MDD) and 110 healthy controls. They also examined whether LDH was predictive of suicide attempts in the MDD patients. Depression was assessed via the 24-item Hamilton Depression Scale (HAMD-24).

The mean age across both groups was 33 years; other clinical characteristics were similar between the groups.

The serum LDH level of the MDD group was significantly lower than the control group was (177.94 U/L vs. 196.50 U/L; P < .001). Analysis of blood lipid levels showed significantly lower levels of total cholesterol in the MDD group compared with controls, but no significant differences were noted in LDL cholesterol, HDL cholesterol, or triglycerides.

In a further analysis of subgroups of depression, the serum LDH in MDD patients who had attempted suicide was significantly lower compared to those without suicide attempts (169.96 vs. 181.25; P = .002), although the LDH level for the non-suicide MDD patients also was significantly lower than controls (181.25 vs. 196.50; P < .001). No significant correlation was noted between HAMD-24 score and suicide attempts.

Some gender differences also appeared. Both male and female MDD patients had significantly lower LDH levels compared with controls. However, in a regression analysis, a correlation between total cholesterol and LDL cholesterol as potential suicide markers was noted in female MDD patients, but not male MDD patients, which suggests an impact of gender on suicide risk in MDD, the researchers wrote in their discussion.

The findings were limited by several factors including the retrospective design, lack of investigation of changes in LDH isozymes in MDD patients, and lack of assessment of changes in LDH in cerebrospinal fluid, the researchers noted. However, the results “provide clear evidence that the concentration of LDH in serum is associated with early onset and clinical prognosis of depressive symptoms,” in MDD, which may inform diagnosis and guide clinical intervention, including early identification of suicide risk, they concluded.

The study was supported by the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.

Sleep complaints by patients with a major depressive episode (MDE) may be a red flag signaling a higher risk for developing other psychiatric disorders, new research suggests.

Investigators studied 3-year incidence rates of psychiatric disorders in almost 3,000 patients experiencing an MDE. Results showed that having a history of difficulty falling asleep, early morning awakening, and hypersomnia increased risk for incident psychiatric disorders.

“The findings of this study suggest the potential value of including insomnia and hypersomnia in clinical assessments of all psychiatric disorders,” write the investigators, led by Bénédicte Barbotin, MD, Département de Psychiatrie et d’Addictologie, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, France.

“Insomnia and hypersomnia symptoms may be prodromal transdiagnostic biomarkers and easily modifiable therapeutic targets for the prevention of psychiatric disorders,” they add.

The findings were published online recently in the Journal of Clinical Psychiatry.


 

Bidirectional association

The researchers note that sleep disturbance is “one of the most common symptoms” associated with major depressive disorder (MDD) and may be “both a consequence and a cause.”

Moreover, improving sleep disturbances for patients with an MDE “tends to improve depressive symptom and outcomes,” they add.

Although the possibility of a bidirectional association between MDEs and sleep disturbances “offers a new perspective that sleep complaints might be a predictive prodromal symptom,” the association of sleep complaints with the subsequent development of other psychiatric disorders in MDEs “remains poorly documented,” the investigators write.

The observation that sleep complaints are associated with psychiatric complications and adverse outcomes, such as suicidality and substance overdose, suggests that longitudinal studies “may help to better understand these relationships.”

To investigate these issues, the researchers examined three sleep complaints among patients with MDE: trouble falling asleep, early morning awakening, and hypersomnia. They adjusted for an array of variables, including antisocial personality disorders, use of sedatives or tranquilizers, sociodemographic characteristics, MDE severity, poverty, obesity, educational level, and stressful life events.

They also used a “bifactor latent variable approach” to “disentangle” a number of effects, including those shared by all psychiatric disorders; those specific to dimensions of psychopathology, such as internalizing dimension; and those specific to individual psychiatric disorders, such as dysthymia.

“To our knowledge, this is the most extensive prospective assessment [ever conducted] of associations between sleep complaints and incident psychiatric disorders,” the investigators write.

They drew on data from Waves 1 and 2 of the National Epidemiological Survey on Alcohol and Related Conditions, a large nationally representative survey conducted in 2001-2002 (Wave 1) and 2004-2005 (Wave 2) by the National Institute on Alcoholism and Alcohol Abuse.

The analysis included 2,864 participants who experienced MDE in the year prior to Wave 1 and who completed interviews at both waves.

Researchers assessed past-year DSM-IV Axis I disorders and baseline sleep complaints at Wave 1, as well as incident DSM-IV Axis I disorders between the two waves – including substance use, mood, and anxiety disorders.
 

Screening needed?

Results showed a wide range of incidence rates for psychiatric disorders between Wave 1 and Wave 2, ranging from 2.7% for cannabis use to 8.2% for generalized anxiety disorder.

The lifetime prevalence of sleep complaints was higher among participants who developed a psychiatric disorder between the two waves than among those who did not have sleep complaints. The range (from lowest to highest percentage) is shown in the accompanying table.

A higher number of sleep complaints was also associated with higher percentages of psychiatric disorders.

Hypersomnia, in particular, significantly increased the odds of having another psychiatric disorder. For patients with MDD who reported hypersomnia, the mean number of sleep disorders was significantly higher than for patients without hypersomnia (2.08 vs. 1.32; P < .001).

“This explains why hypersomnia appears more strongly associated with the incidence of psychiatric disorders,” the investigators write.

After adjusting for sociodemographic and clinical characteristics and antisocial personality disorder, the effects shared across all sleep complaints were “significantly associated with the incident general psychopathology factor, representing mechanisms that may lead to incidence of all psychiatric disorder in the model,” they add.

The researchers note that insomnia and hypersomnia can impair cognitive function, decision-making, problem-solving, and emotion processing networks, thereby increasing the onset of psychiatric disorders in vulnerable individuals.

Shared biological determinants, such as monoamine neurotransmitters that play a major role in depression, anxiety, substance use disorders, and the regulation of sleep stages, may also underlie both sleep disturbances and psychiatric disorders, they speculate.

“These results suggest the importance of systematically assessing insomnia and hypersomnia when evaluating psychiatric disorders and considering these symptoms as nonspecific prodromal or at-risk symptoms, also shared with suicidal behaviors,” the investigators write.

“In addition, since most individuals who developed a psychiatric disorder had at least one sleep complaint, all psychiatric disorders should be carefully screened among individuals with sleep complaints,” they add.
 

Transdiagnostic phenomenon

In a comment, Roger McIntyre, MD, professor of psychiatry and pharmacology at the University of Toronto, and head of the Mood Disorders Psychopharmacology Unit, noted that the study replicates previous observations that a bidirectional relationship exists between sleep disturbances and mental disorders and that there “seems to be a relationship between sleep disturbance and suicidality that is bidirectional.”

He added that he appreciated the fact that the investigators “took this knowledge one step further; and what they are saying is that within the syndrome of depression, it is the sleep disturbance that is predicting future problems.”

Dr. McIntyre, who is also chairman and executive director of the Brain and Cognitive Discover Foundation in Toronto, was not involved with the study.

The data suggest that, “conceptually, sleep disturbance is a transdiagnostic phenomenon that may also be the nexus when multiple comorbid mental disorders occur,” he said.

“If this is the case, clinically, there is an opportunity here to prevent incident mental disorders in persons with depression and sleep disturbance, prioritizing sleep management in any patient with a mood disorder,” Dr. McIntyre added.

He noted that “the testable hypothesis” is how this is occurring mechanistically.

“I would conjecture that it could be inflammation and/or insulin resistance that is part of sleep disturbance that could predispose and portend other mental illnesses – and likely other medical conditions too, such as obesity and diabetes,” he said.

The study received no specific funding from any funding agency, commercial, or not-for-profit sectors. The investigators’ relevant financial relationships are listed in the original article. Dr. McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; has received speaker/consultation fees from Lundbeck, Janssen, Alkermes,Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, AbbVie, and Atai Life Sciences; and is a CEO of Braxia Scientific Corp.

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

Sleep complaints by patients with a major depressive episode (MDE) may be a red flag signaling a higher risk for developing other psychiatric disorders, new research suggests.

Investigators studied 3-year incidence rates of psychiatric disorders in almost 3,000 patients experiencing an MDE. Results showed that having a history of difficulty falling asleep, early morning awakening, and hypersomnia increased risk for incident psychiatric disorders.

“The findings of this study suggest the potential value of including insomnia and hypersomnia in clinical assessments of all psychiatric disorders,” write the investigators, led by Bénédicte Barbotin, MD, Département de Psychiatrie et d’Addictologie, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, France.

“Insomnia and hypersomnia symptoms may be prodromal transdiagnostic biomarkers and easily modifiable therapeutic targets for the prevention of psychiatric disorders,” they add.

The findings were published online recently in the Journal of Clinical Psychiatry.


 

Bidirectional association

The researchers note that sleep disturbance is “one of the most common symptoms” associated with major depressive disorder (MDD) and may be “both a consequence and a cause.”

Moreover, improving sleep disturbances for patients with an MDE “tends to improve depressive symptom and outcomes,” they add.

Although the possibility of a bidirectional association between MDEs and sleep disturbances “offers a new perspective that sleep complaints might be a predictive prodromal symptom,” the association of sleep complaints with the subsequent development of other psychiatric disorders in MDEs “remains poorly documented,” the investigators write.

The observation that sleep complaints are associated with psychiatric complications and adverse outcomes, such as suicidality and substance overdose, suggests that longitudinal studies “may help to better understand these relationships.”

To investigate these issues, the researchers examined three sleep complaints among patients with MDE: trouble falling asleep, early morning awakening, and hypersomnia. They adjusted for an array of variables, including antisocial personality disorders, use of sedatives or tranquilizers, sociodemographic characteristics, MDE severity, poverty, obesity, educational level, and stressful life events.

They also used a “bifactor latent variable approach” to “disentangle” a number of effects, including those shared by all psychiatric disorders; those specific to dimensions of psychopathology, such as internalizing dimension; and those specific to individual psychiatric disorders, such as dysthymia.

“To our knowledge, this is the most extensive prospective assessment [ever conducted] of associations between sleep complaints and incident psychiatric disorders,” the investigators write.

They drew on data from Waves 1 and 2 of the National Epidemiological Survey on Alcohol and Related Conditions, a large nationally representative survey conducted in 2001-2002 (Wave 1) and 2004-2005 (Wave 2) by the National Institute on Alcoholism and Alcohol Abuse.

The analysis included 2,864 participants who experienced MDE in the year prior to Wave 1 and who completed interviews at both waves.

Researchers assessed past-year DSM-IV Axis I disorders and baseline sleep complaints at Wave 1, as well as incident DSM-IV Axis I disorders between the two waves – including substance use, mood, and anxiety disorders.
 

Screening needed?

Results showed a wide range of incidence rates for psychiatric disorders between Wave 1 and Wave 2, ranging from 2.7% for cannabis use to 8.2% for generalized anxiety disorder.

The lifetime prevalence of sleep complaints was higher among participants who developed a psychiatric disorder between the two waves than among those who did not have sleep complaints. The range (from lowest to highest percentage) is shown in the accompanying table.

A higher number of sleep complaints was also associated with higher percentages of psychiatric disorders.

Hypersomnia, in particular, significantly increased the odds of having another psychiatric disorder. For patients with MDD who reported hypersomnia, the mean number of sleep disorders was significantly higher than for patients without hypersomnia (2.08 vs. 1.32; P < .001).

“This explains why hypersomnia appears more strongly associated with the incidence of psychiatric disorders,” the investigators write.

After adjusting for sociodemographic and clinical characteristics and antisocial personality disorder, the effects shared across all sleep complaints were “significantly associated with the incident general psychopathology factor, representing mechanisms that may lead to incidence of all psychiatric disorder in the model,” they add.

The researchers note that insomnia and hypersomnia can impair cognitive function, decision-making, problem-solving, and emotion processing networks, thereby increasing the onset of psychiatric disorders in vulnerable individuals.

Shared biological determinants, such as monoamine neurotransmitters that play a major role in depression, anxiety, substance use disorders, and the regulation of sleep stages, may also underlie both sleep disturbances and psychiatric disorders, they speculate.

“These results suggest the importance of systematically assessing insomnia and hypersomnia when evaluating psychiatric disorders and considering these symptoms as nonspecific prodromal or at-risk symptoms, also shared with suicidal behaviors,” the investigators write.

“In addition, since most individuals who developed a psychiatric disorder had at least one sleep complaint, all psychiatric disorders should be carefully screened among individuals with sleep complaints,” they add.
 

Transdiagnostic phenomenon

In a comment, Roger McIntyre, MD, professor of psychiatry and pharmacology at the University of Toronto, and head of the Mood Disorders Psychopharmacology Unit, noted that the study replicates previous observations that a bidirectional relationship exists between sleep disturbances and mental disorders and that there “seems to be a relationship between sleep disturbance and suicidality that is bidirectional.”

He added that he appreciated the fact that the investigators “took this knowledge one step further; and what they are saying is that within the syndrome of depression, it is the sleep disturbance that is predicting future problems.”

Dr. McIntyre, who is also chairman and executive director of the Brain and Cognitive Discover Foundation in Toronto, was not involved with the study.

The data suggest that, “conceptually, sleep disturbance is a transdiagnostic phenomenon that may also be the nexus when multiple comorbid mental disorders occur,” he said.

“If this is the case, clinically, there is an opportunity here to prevent incident mental disorders in persons with depression and sleep disturbance, prioritizing sleep management in any patient with a mood disorder,” Dr. McIntyre added.

He noted that “the testable hypothesis” is how this is occurring mechanistically.

“I would conjecture that it could be inflammation and/or insulin resistance that is part of sleep disturbance that could predispose and portend other mental illnesses – and likely other medical conditions too, such as obesity and diabetes,” he said.

The study received no specific funding from any funding agency, commercial, or not-for-profit sectors. The investigators’ relevant financial relationships are listed in the original article. Dr. McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; has received speaker/consultation fees from Lundbeck, Janssen, Alkermes,Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, AbbVie, and Atai Life Sciences; and is a CEO of Braxia Scientific Corp.

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

Sleep complaints by patients with a major depressive episode (MDE) may be a red flag signaling a higher risk for developing other psychiatric disorders, new research suggests.

Investigators studied 3-year incidence rates of psychiatric disorders in almost 3,000 patients experiencing an MDE. Results showed that having a history of difficulty falling asleep, early morning awakening, and hypersomnia increased risk for incident psychiatric disorders.

“The findings of this study suggest the potential value of including insomnia and hypersomnia in clinical assessments of all psychiatric disorders,” write the investigators, led by Bénédicte Barbotin, MD, Département de Psychiatrie et d’Addictologie, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, France.

“Insomnia and hypersomnia symptoms may be prodromal transdiagnostic biomarkers and easily modifiable therapeutic targets for the prevention of psychiatric disorders,” they add.

The findings were published online recently in the Journal of Clinical Psychiatry.


 

Bidirectional association

The researchers note that sleep disturbance is “one of the most common symptoms” associated with major depressive disorder (MDD) and may be “both a consequence and a cause.”

Moreover, improving sleep disturbances for patients with an MDE “tends to improve depressive symptom and outcomes,” they add.

Although the possibility of a bidirectional association between MDEs and sleep disturbances “offers a new perspective that sleep complaints might be a predictive prodromal symptom,” the association of sleep complaints with the subsequent development of other psychiatric disorders in MDEs “remains poorly documented,” the investigators write.

The observation that sleep complaints are associated with psychiatric complications and adverse outcomes, such as suicidality and substance overdose, suggests that longitudinal studies “may help to better understand these relationships.”

To investigate these issues, the researchers examined three sleep complaints among patients with MDE: trouble falling asleep, early morning awakening, and hypersomnia. They adjusted for an array of variables, including antisocial personality disorders, use of sedatives or tranquilizers, sociodemographic characteristics, MDE severity, poverty, obesity, educational level, and stressful life events.

They also used a “bifactor latent variable approach” to “disentangle” a number of effects, including those shared by all psychiatric disorders; those specific to dimensions of psychopathology, such as internalizing dimension; and those specific to individual psychiatric disorders, such as dysthymia.

“To our knowledge, this is the most extensive prospective assessment [ever conducted] of associations between sleep complaints and incident psychiatric disorders,” the investigators write.

They drew on data from Waves 1 and 2 of the National Epidemiological Survey on Alcohol and Related Conditions, a large nationally representative survey conducted in 2001-2002 (Wave 1) and 2004-2005 (Wave 2) by the National Institute on Alcoholism and Alcohol Abuse.

The analysis included 2,864 participants who experienced MDE in the year prior to Wave 1 and who completed interviews at both waves.

Researchers assessed past-year DSM-IV Axis I disorders and baseline sleep complaints at Wave 1, as well as incident DSM-IV Axis I disorders between the two waves – including substance use, mood, and anxiety disorders.
 

Screening needed?

Results showed a wide range of incidence rates for psychiatric disorders between Wave 1 and Wave 2, ranging from 2.7% for cannabis use to 8.2% for generalized anxiety disorder.

The lifetime prevalence of sleep complaints was higher among participants who developed a psychiatric disorder between the two waves than among those who did not have sleep complaints. The range (from lowest to highest percentage) is shown in the accompanying table.

A higher number of sleep complaints was also associated with higher percentages of psychiatric disorders.

Hypersomnia, in particular, significantly increased the odds of having another psychiatric disorder. For patients with MDD who reported hypersomnia, the mean number of sleep disorders was significantly higher than for patients without hypersomnia (2.08 vs. 1.32; P < .001).

“This explains why hypersomnia appears more strongly associated with the incidence of psychiatric disorders,” the investigators write.

After adjusting for sociodemographic and clinical characteristics and antisocial personality disorder, the effects shared across all sleep complaints were “significantly associated with the incident general psychopathology factor, representing mechanisms that may lead to incidence of all psychiatric disorder in the model,” they add.

The researchers note that insomnia and hypersomnia can impair cognitive function, decision-making, problem-solving, and emotion processing networks, thereby increasing the onset of psychiatric disorders in vulnerable individuals.

Shared biological determinants, such as monoamine neurotransmitters that play a major role in depression, anxiety, substance use disorders, and the regulation of sleep stages, may also underlie both sleep disturbances and psychiatric disorders, they speculate.

“These results suggest the importance of systematically assessing insomnia and hypersomnia when evaluating psychiatric disorders and considering these symptoms as nonspecific prodromal or at-risk symptoms, also shared with suicidal behaviors,” the investigators write.

“In addition, since most individuals who developed a psychiatric disorder had at least one sleep complaint, all psychiatric disorders should be carefully screened among individuals with sleep complaints,” they add.
 

Transdiagnostic phenomenon

In a comment, Roger McIntyre, MD, professor of psychiatry and pharmacology at the University of Toronto, and head of the Mood Disorders Psychopharmacology Unit, noted that the study replicates previous observations that a bidirectional relationship exists between sleep disturbances and mental disorders and that there “seems to be a relationship between sleep disturbance and suicidality that is bidirectional.”

He added that he appreciated the fact that the investigators “took this knowledge one step further; and what they are saying is that within the syndrome of depression, it is the sleep disturbance that is predicting future problems.”

Dr. McIntyre, who is also chairman and executive director of the Brain and Cognitive Discover Foundation in Toronto, was not involved with the study.

The data suggest that, “conceptually, sleep disturbance is a transdiagnostic phenomenon that may also be the nexus when multiple comorbid mental disorders occur,” he said.

“If this is the case, clinically, there is an opportunity here to prevent incident mental disorders in persons with depression and sleep disturbance, prioritizing sleep management in any patient with a mood disorder,” Dr. McIntyre added.

He noted that “the testable hypothesis” is how this is occurring mechanistically.

“I would conjecture that it could be inflammation and/or insulin resistance that is part of sleep disturbance that could predispose and portend other mental illnesses – and likely other medical conditions too, such as obesity and diabetes,” he said.

The study received no specific funding from any funding agency, commercial, or not-for-profit sectors. The investigators’ relevant financial relationships are listed in the original article. Dr. McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; has received speaker/consultation fees from Lundbeck, Janssen, Alkermes,Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, AbbVie, and Atai Life Sciences; and is a CEO of Braxia Scientific Corp.

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

The administration of IV ketamine over the course of 2 months can improve treatment resistant depression (TRD) and executive function in older adults, findings from a new pilot study suggest.

Results showed nearly 50% of participants responded to ketamine and 25% achieved complete remission from TRD, as measured by scores on the Montgomery-Asberg Depression Rating Scale (MADRS).

“Our pilot study suggests that IV ketamine is well-tolerated, safe, and associated with improvement in late-life TRD,” co-investigator Marie Anne Gebara, MD, assistant professor of psychiatry at the University of Pittsburgh, told this news organization.

Dr. Gebara pointed out the treatment “may not be appropriate for all patients with TRD,” such as those with a history of psychotic symptoms or uncontrolled hypertension; but “it appears to be a promising option.”

The findings were published online in the American Journal of Geriatric Psychiatry.
 

Lack of data in seniors

Although ketamine has been shown in prior research to rapidly reduce suicidal ideation in adults, there has been a lack of data on its efficacy and safety in older adults, the current investigators note.

“Almost 50% of older adults suffering from depression have TRD, which is a leading cause of disability, excess mortality from suicide, and dementia,” Dr. Gebara said.

She added that after two failed trials of antidepressants, “older adults have few evidence-based choices: aripiprazole or bupropion augmentation, transcranial magnetic stimulation, or electroconvulsive therapy. Novel treatments with rapid benefit are needed as long-term outcomes are poor and recurrence rates are high.”

Dr. Gebara and colleagues at five sites (Columbia University, New York State Psychiatric Institute, University of Toronto, University of Pittsburgh, and Washington University in St. Louis) each enrolled five participants aged 60 and older into the pilot study between October 2020 and November 2021, for a total of 25 participants (mean age, 71 years).

Each participant was recruited from patient registries or referred by behavioral health or primary care providers and diagnosed with TRD, which was defined as an episode of major depressive disorder without psychotic features that persisted despite two or more trials of antidepressants including at least one evidence-based second-line treatment.

Participants had to take an oral antidepressant dosage for at least 1 month prior to the start of the IV ketamine infusions, and continue their antidepressant for the length of the trial.

They received IV ketamine twice weekly for 4 weeks. The dosage was weight-dependent.

At the end of the 4 weeks, participants who achieved a MADRS total score of less than 10 or had a 30% or greater reduction from their baseline MADRS score entered another 4-week phase of the trial. This phase consisted of once-weekly administration of IV ketamine.
 

Larger plans

Results showed 15 of the 25 participants (60%) experienced a 30% or higher reduction in MADRS scores in the first phase of the study. The mean change in MADRS total score from the beginning to the end of the first phase was a decrease of 9.4 points (P < .01).

At the end of the continuation phase, half (48%) met criteria for response and 27% met criteria for remission.

After ketamine administration, the researchers also found an improvement in Fluid Cognition Composite Score (Cohen’s d value = .61), indicating a medium to large effect size, and in three measures of executive function.

Overall, adverse events were rare and did not keep patients from participating in the study, the investigators note. Five of the 25 participants reported infusion-induced hypertension that was transient.

Study limitations cited include the small sample size and the absence of randomization and placebo control or comparison treatment.

“We were very pleased with these findings because they establish the safety of this novel intervention in older adults,” Dr. Gebara said.

“After establishing safety and tolerability, we can plan for larger, randomized controlled trials that will allow us to determine the effectiveness of IV ketamine for older adults with TRD,” she added.
 

Multiple mechanisms

In a comment, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University and director of the Yale Depression Research Program, New Haven, Conn., noted multiple mechanisms likely contribute to the antidepressant effects of ketamine.

Dr. Sanacora has independently researched the effects of ketamine but was not involved with the current study.

“Much of the work to date has focused on the drug’s proximal effects on the glutamatergic neurotransmitter system and the resulting enhancement of adaptive neuroplasticity in several brain regions,” he said.

“However, there is also evidence to suggest other neurotransmitter systems and possibly even neuroinflammatory regulators are also contributing to the effect,” Dr. Sanacora added.

He noted that these mechanisms are also likely amplified by the “hope, optimism, expectations, and improved medical management overall that are known to be associated with treatments that require close monitoring and follow-up with health care providers.”

Dr. Gebara noted that “internal/department funds at each site” were used to support the study. She also reported receiving support from Otsuka US. Disclosures for the other investigators are listed in the original article. Dr. Sanacora has reported having “no major direct conflicts” with the study.

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

The administration of IV ketamine over the course of 2 months can improve treatment resistant depression (TRD) and executive function in older adults, findings from a new pilot study suggest.

Results showed nearly 50% of participants responded to ketamine and 25% achieved complete remission from TRD, as measured by scores on the Montgomery-Asberg Depression Rating Scale (MADRS).

“Our pilot study suggests that IV ketamine is well-tolerated, safe, and associated with improvement in late-life TRD,” co-investigator Marie Anne Gebara, MD, assistant professor of psychiatry at the University of Pittsburgh, told this news organization.

Dr. Gebara pointed out the treatment “may not be appropriate for all patients with TRD,” such as those with a history of psychotic symptoms or uncontrolled hypertension; but “it appears to be a promising option.”

The findings were published online in the American Journal of Geriatric Psychiatry.
 

Lack of data in seniors

Although ketamine has been shown in prior research to rapidly reduce suicidal ideation in adults, there has been a lack of data on its efficacy and safety in older adults, the current investigators note.

“Almost 50% of older adults suffering from depression have TRD, which is a leading cause of disability, excess mortality from suicide, and dementia,” Dr. Gebara said.

She added that after two failed trials of antidepressants, “older adults have few evidence-based choices: aripiprazole or bupropion augmentation, transcranial magnetic stimulation, or electroconvulsive therapy. Novel treatments with rapid benefit are needed as long-term outcomes are poor and recurrence rates are high.”

Dr. Gebara and colleagues at five sites (Columbia University, New York State Psychiatric Institute, University of Toronto, University of Pittsburgh, and Washington University in St. Louis) each enrolled five participants aged 60 and older into the pilot study between October 2020 and November 2021, for a total of 25 participants (mean age, 71 years).

Each participant was recruited from patient registries or referred by behavioral health or primary care providers and diagnosed with TRD, which was defined as an episode of major depressive disorder without psychotic features that persisted despite two or more trials of antidepressants including at least one evidence-based second-line treatment.

Participants had to take an oral antidepressant dosage for at least 1 month prior to the start of the IV ketamine infusions, and continue their antidepressant for the length of the trial.

They received IV ketamine twice weekly for 4 weeks. The dosage was weight-dependent.

At the end of the 4 weeks, participants who achieved a MADRS total score of less than 10 or had a 30% or greater reduction from their baseline MADRS score entered another 4-week phase of the trial. This phase consisted of once-weekly administration of IV ketamine.
 

Larger plans

Results showed 15 of the 25 participants (60%) experienced a 30% or higher reduction in MADRS scores in the first phase of the study. The mean change in MADRS total score from the beginning to the end of the first phase was a decrease of 9.4 points (P < .01).

At the end of the continuation phase, half (48%) met criteria for response and 27% met criteria for remission.

After ketamine administration, the researchers also found an improvement in Fluid Cognition Composite Score (Cohen’s d value = .61), indicating a medium to large effect size, and in three measures of executive function.

Overall, adverse events were rare and did not keep patients from participating in the study, the investigators note. Five of the 25 participants reported infusion-induced hypertension that was transient.

Study limitations cited include the small sample size and the absence of randomization and placebo control or comparison treatment.

“We were very pleased with these findings because they establish the safety of this novel intervention in older adults,” Dr. Gebara said.

“After establishing safety and tolerability, we can plan for larger, randomized controlled trials that will allow us to determine the effectiveness of IV ketamine for older adults with TRD,” she added.
 

Multiple mechanisms

In a comment, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University and director of the Yale Depression Research Program, New Haven, Conn., noted multiple mechanisms likely contribute to the antidepressant effects of ketamine.

Dr. Sanacora has independently researched the effects of ketamine but was not involved with the current study.

“Much of the work to date has focused on the drug’s proximal effects on the glutamatergic neurotransmitter system and the resulting enhancement of adaptive neuroplasticity in several brain regions,” he said.

“However, there is also evidence to suggest other neurotransmitter systems and possibly even neuroinflammatory regulators are also contributing to the effect,” Dr. Sanacora added.

He noted that these mechanisms are also likely amplified by the “hope, optimism, expectations, and improved medical management overall that are known to be associated with treatments that require close monitoring and follow-up with health care providers.”

Dr. Gebara noted that “internal/department funds at each site” were used to support the study. She also reported receiving support from Otsuka US. Disclosures for the other investigators are listed in the original article. Dr. Sanacora has reported having “no major direct conflicts” with the study.

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

The administration of IV ketamine over the course of 2 months can improve treatment resistant depression (TRD) and executive function in older adults, findings from a new pilot study suggest.

Results showed nearly 50% of participants responded to ketamine and 25% achieved complete remission from TRD, as measured by scores on the Montgomery-Asberg Depression Rating Scale (MADRS).

“Our pilot study suggests that IV ketamine is well-tolerated, safe, and associated with improvement in late-life TRD,” co-investigator Marie Anne Gebara, MD, assistant professor of psychiatry at the University of Pittsburgh, told this news organization.

Dr. Gebara pointed out the treatment “may not be appropriate for all patients with TRD,” such as those with a history of psychotic symptoms or uncontrolled hypertension; but “it appears to be a promising option.”

The findings were published online in the American Journal of Geriatric Psychiatry.
 

Lack of data in seniors

Although ketamine has been shown in prior research to rapidly reduce suicidal ideation in adults, there has been a lack of data on its efficacy and safety in older adults, the current investigators note.

“Almost 50% of older adults suffering from depression have TRD, which is a leading cause of disability, excess mortality from suicide, and dementia,” Dr. Gebara said.

She added that after two failed trials of antidepressants, “older adults have few evidence-based choices: aripiprazole or bupropion augmentation, transcranial magnetic stimulation, or electroconvulsive therapy. Novel treatments with rapid benefit are needed as long-term outcomes are poor and recurrence rates are high.”

Dr. Gebara and colleagues at five sites (Columbia University, New York State Psychiatric Institute, University of Toronto, University of Pittsburgh, and Washington University in St. Louis) each enrolled five participants aged 60 and older into the pilot study between October 2020 and November 2021, for a total of 25 participants (mean age, 71 years).

Each participant was recruited from patient registries or referred by behavioral health or primary care providers and diagnosed with TRD, which was defined as an episode of major depressive disorder without psychotic features that persisted despite two or more trials of antidepressants including at least one evidence-based second-line treatment.

Participants had to take an oral antidepressant dosage for at least 1 month prior to the start of the IV ketamine infusions, and continue their antidepressant for the length of the trial.

They received IV ketamine twice weekly for 4 weeks. The dosage was weight-dependent.

At the end of the 4 weeks, participants who achieved a MADRS total score of less than 10 or had a 30% or greater reduction from their baseline MADRS score entered another 4-week phase of the trial. This phase consisted of once-weekly administration of IV ketamine.
 

Larger plans

Results showed 15 of the 25 participants (60%) experienced a 30% or higher reduction in MADRS scores in the first phase of the study. The mean change in MADRS total score from the beginning to the end of the first phase was a decrease of 9.4 points (P < .01).

At the end of the continuation phase, half (48%) met criteria for response and 27% met criteria for remission.

After ketamine administration, the researchers also found an improvement in Fluid Cognition Composite Score (Cohen’s d value = .61), indicating a medium to large effect size, and in three measures of executive function.

Overall, adverse events were rare and did not keep patients from participating in the study, the investigators note. Five of the 25 participants reported infusion-induced hypertension that was transient.

Study limitations cited include the small sample size and the absence of randomization and placebo control or comparison treatment.

“We were very pleased with these findings because they establish the safety of this novel intervention in older adults,” Dr. Gebara said.

“After establishing safety and tolerability, we can plan for larger, randomized controlled trials that will allow us to determine the effectiveness of IV ketamine for older adults with TRD,” she added.
 

Multiple mechanisms

In a comment, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University and director of the Yale Depression Research Program, New Haven, Conn., noted multiple mechanisms likely contribute to the antidepressant effects of ketamine.

Dr. Sanacora has independently researched the effects of ketamine but was not involved with the current study.

“Much of the work to date has focused on the drug’s proximal effects on the glutamatergic neurotransmitter system and the resulting enhancement of adaptive neuroplasticity in several brain regions,” he said.

“However, there is also evidence to suggest other neurotransmitter systems and possibly even neuroinflammatory regulators are also contributing to the effect,” Dr. Sanacora added.

He noted that these mechanisms are also likely amplified by the “hope, optimism, expectations, and improved medical management overall that are known to be associated with treatments that require close monitoring and follow-up with health care providers.”

Dr. Gebara noted that “internal/department funds at each site” were used to support the study. She also reported receiving support from Otsuka US. Disclosures for the other investigators are listed in the original article. Dr. Sanacora has reported having “no major direct conflicts” with the study.

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

Treatment-resistant depression (TRD) is significantly linked to comorbid psychiatric conditions and a higher risk for mortality and can take more than a year to be diagnosed, new research shows.

In a population study of more than 145,000 patients, participants with TRD used outpatient resources and missed work at twice the rate as patients with treatment-responsive depression. They also had a threefold higher number of days spent in hospital.

Patients with TRD also had a 23% higher risk of dying during the time they were observed, compared with their matched counterparts with non-TRD depression, and their self-harm rates were twice as high.

In addition, it took an average of 1.5 years for patients with TRD to undergo two unsuccessful treatment attempts and reach their third treatment trial, which is several months longer than is recommended for assessing the efficacy of a treatment for depression.

“It seemed like ineffective treatments were allowed to continue for longer than should be needed and what is recommended in current guidelines,” lead investigator Johan Lundberg, MD, PhD, adjunct professor of psychiatry in the department of clinical neuroscience and head of the mood disorder section at the Northern Stockholm Psychiatry Clinic, told this news organization.

“If this is true, patients would most likely benefit from a more frequent evaluation of treatment effect and, when needed, optimization of ineffective treatments,” Dr. Lundberg said.

The findings were published online in JAMA Psychiatry.
 

More anxiety, sleep disorders, substance use

Using data from the Region Stockholm’s administrative health care database and the Swedish social insurance agency, the investigators identified nearly 160,000 unipolar major depressive disorder (MDD) episodes in 145,577 patients who sought treatment between January 2012 and December 2017.

Of those episodes, 12,800 fulfilled criteria for TRD, which meant there were three or more treatment trials with antidepressants, add-on medication (aripiprazole, lithium, olanzapine, quetiapine, and/or risperidone), electroshock therapy, or repetitive transcranial magnetic stimulation.

Each new treatment had to be initiated within the MDD episode more than 28 days after previous treatment initiation.

Investigators matched each TRD episode with up to five non-TRD episodes and found that patients with TRD were more likely to have comorbid psychiatric conditions than were their non-TRD counterparts.

This included anxiety (60% vs. 44%, respectively), sleep disorders (28% vs. 19%), substance use (15% vs. 11%) or alcohol use (10% vs. 7%) disorders, and personality disorders (6% vs. 3%). Rates of intentional self-harm were also higher in the TRD group (5% vs. 2%).

Perhaps in part because of the comorbid problems, patients with TRD had a more than 50% higher mean number of outpatient physician visits 1 year before and after the index date, defined as the date of the initiation of the third treatment trial.

The most important predictor of TRD depression was the severity of depression at diagnosis on the self-rated Montgomery Åsberg Depression Rating Scale, the researchers report.
 

Not generalizable?

Patients with TRD also had three times the number of inpatient bed days as did those with depression that responded to treatment (mean, 3.9 days vs. 1.3 days, respectively) and significantly more lost workdays (132.3 days vs. 58.7 days).

Most notably, patients with TRD episodes had a 23% higher risk of dying during the time they were observed than did their non-TRD counterparts.

“This finding in itself could be a reason to focus on how to avoid putting a patient on the TRD path. This could be done through prospective studies comparing different treatment options and their risk of leading to TRD,” Dr. Lundberg said.

Interestingly, he noted that the study results may not be generalizable to other populations, such as the United States.

“The biggest difference between Stockholm and the U.S. may not be the demographics, but the access to health care,” Dr. Lundberg said.

“In Stockholm, there is a universal access health care system, meaning that these results are what you can expect if you are able to get care. In the U.S., this is not the case, meaning that people outside the health care system may fare worse than what our study suggests,” he added.
 

Quality over quantity

In a comment, Sidney Zisook, MD, distinguished professor of psychiatry at the University of California, San Diego, said that the findings “highlight the need for our field to develop better-tolerated, more effective, and sustainable treatments for major depressive disorder and for better education of clinicians so they can employ up-to-date, evidence-based treatments and integrate sound clinical guidelines into clinical practice.”

Dr. Zisook has independently researched TRD but was not involved with the current study.

He noted that it was “striking how long patients remained on the same antidepressant, apparently despite suboptimal outcomes, without taking next steps.”

However, Dr. Zisook expressed concern that the diagnosis of TRD in the study was solely on the basis of the number of treatment trials for an episode.

“Somebody might have had three different antidepressant trials because they had had three episodes with interepisode periods of recovery followed by recurrent episodes. That would not be considered treatment-resistant depression,” he said.

Dr. Zisook also noted that patients might be given a new antidepressant for reasons other than treatment resistance. “For example, they lost an initial good response – this used to be called Prozac poop out, were nonadherent, or had troublesome side effects,” he said.

“We usually define treatment-resistant depression not only on the basis of number of trials but also the quality of the trial, taking both dose and duration into account,” Dr. Zisook added.

The study was funded by Region Stockholm. Dr. Zisook reports receiving research funding from COMPASS Pathways.

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

Treatment-resistant depression (TRD) is significantly linked to comorbid psychiatric conditions and a higher risk for mortality and can take more than a year to be diagnosed, new research shows.

In a population study of more than 145,000 patients, participants with TRD used outpatient resources and missed work at twice the rate as patients with treatment-responsive depression. They also had a threefold higher number of days spent in hospital.

Patients with TRD also had a 23% higher risk of dying during the time they were observed, compared with their matched counterparts with non-TRD depression, and their self-harm rates were twice as high.

In addition, it took an average of 1.5 years for patients with TRD to undergo two unsuccessful treatment attempts and reach their third treatment trial, which is several months longer than is recommended for assessing the efficacy of a treatment for depression.

“It seemed like ineffective treatments were allowed to continue for longer than should be needed and what is recommended in current guidelines,” lead investigator Johan Lundberg, MD, PhD, adjunct professor of psychiatry in the department of clinical neuroscience and head of the mood disorder section at the Northern Stockholm Psychiatry Clinic, told this news organization.

“If this is true, patients would most likely benefit from a more frequent evaluation of treatment effect and, when needed, optimization of ineffective treatments,” Dr. Lundberg said.

The findings were published online in JAMA Psychiatry.
 

More anxiety, sleep disorders, substance use

Using data from the Region Stockholm’s administrative health care database and the Swedish social insurance agency, the investigators identified nearly 160,000 unipolar major depressive disorder (MDD) episodes in 145,577 patients who sought treatment between January 2012 and December 2017.

Of those episodes, 12,800 fulfilled criteria for TRD, which meant there were three or more treatment trials with antidepressants, add-on medication (aripiprazole, lithium, olanzapine, quetiapine, and/or risperidone), electroshock therapy, or repetitive transcranial magnetic stimulation.

Each new treatment had to be initiated within the MDD episode more than 28 days after previous treatment initiation.

Investigators matched each TRD episode with up to five non-TRD episodes and found that patients with TRD were more likely to have comorbid psychiatric conditions than were their non-TRD counterparts.

This included anxiety (60% vs. 44%, respectively), sleep disorders (28% vs. 19%), substance use (15% vs. 11%) or alcohol use (10% vs. 7%) disorders, and personality disorders (6% vs. 3%). Rates of intentional self-harm were also higher in the TRD group (5% vs. 2%).

Perhaps in part because of the comorbid problems, patients with TRD had a more than 50% higher mean number of outpatient physician visits 1 year before and after the index date, defined as the date of the initiation of the third treatment trial.

The most important predictor of TRD depression was the severity of depression at diagnosis on the self-rated Montgomery Åsberg Depression Rating Scale, the researchers report.
 

Not generalizable?

Patients with TRD also had three times the number of inpatient bed days as did those with depression that responded to treatment (mean, 3.9 days vs. 1.3 days, respectively) and significantly more lost workdays (132.3 days vs. 58.7 days).

Most notably, patients with TRD episodes had a 23% higher risk of dying during the time they were observed than did their non-TRD counterparts.

“This finding in itself could be a reason to focus on how to avoid putting a patient on the TRD path. This could be done through prospective studies comparing different treatment options and their risk of leading to TRD,” Dr. Lundberg said.

Interestingly, he noted that the study results may not be generalizable to other populations, such as the United States.

“The biggest difference between Stockholm and the U.S. may not be the demographics, but the access to health care,” Dr. Lundberg said.

“In Stockholm, there is a universal access health care system, meaning that these results are what you can expect if you are able to get care. In the U.S., this is not the case, meaning that people outside the health care system may fare worse than what our study suggests,” he added.
 

Quality over quantity

In a comment, Sidney Zisook, MD, distinguished professor of psychiatry at the University of California, San Diego, said that the findings “highlight the need for our field to develop better-tolerated, more effective, and sustainable treatments for major depressive disorder and for better education of clinicians so they can employ up-to-date, evidence-based treatments and integrate sound clinical guidelines into clinical practice.”

Dr. Zisook has independently researched TRD but was not involved with the current study.

He noted that it was “striking how long patients remained on the same antidepressant, apparently despite suboptimal outcomes, without taking next steps.”

However, Dr. Zisook expressed concern that the diagnosis of TRD in the study was solely on the basis of the number of treatment trials for an episode.

“Somebody might have had three different antidepressant trials because they had had three episodes with interepisode periods of recovery followed by recurrent episodes. That would not be considered treatment-resistant depression,” he said.

Dr. Zisook also noted that patients might be given a new antidepressant for reasons other than treatment resistance. “For example, they lost an initial good response – this used to be called Prozac poop out, were nonadherent, or had troublesome side effects,” he said.

“We usually define treatment-resistant depression not only on the basis of number of trials but also the quality of the trial, taking both dose and duration into account,” Dr. Zisook added.

The study was funded by Region Stockholm. Dr. Zisook reports receiving research funding from COMPASS Pathways.

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

Treatment-resistant depression (TRD) is significantly linked to comorbid psychiatric conditions and a higher risk for mortality and can take more than a year to be diagnosed, new research shows.

In a population study of more than 145,000 patients, participants with TRD used outpatient resources and missed work at twice the rate as patients with treatment-responsive depression. They also had a threefold higher number of days spent in hospital.

Patients with TRD also had a 23% higher risk of dying during the time they were observed, compared with their matched counterparts with non-TRD depression, and their self-harm rates were twice as high.

In addition, it took an average of 1.5 years for patients with TRD to undergo two unsuccessful treatment attempts and reach their third treatment trial, which is several months longer than is recommended for assessing the efficacy of a treatment for depression.

“It seemed like ineffective treatments were allowed to continue for longer than should be needed and what is recommended in current guidelines,” lead investigator Johan Lundberg, MD, PhD, adjunct professor of psychiatry in the department of clinical neuroscience and head of the mood disorder section at the Northern Stockholm Psychiatry Clinic, told this news organization.

“If this is true, patients would most likely benefit from a more frequent evaluation of treatment effect and, when needed, optimization of ineffective treatments,” Dr. Lundberg said.

The findings were published online in JAMA Psychiatry.
 

More anxiety, sleep disorders, substance use

Using data from the Region Stockholm’s administrative health care database and the Swedish social insurance agency, the investigators identified nearly 160,000 unipolar major depressive disorder (MDD) episodes in 145,577 patients who sought treatment between January 2012 and December 2017.

Of those episodes, 12,800 fulfilled criteria for TRD, which meant there were three or more treatment trials with antidepressants, add-on medication (aripiprazole, lithium, olanzapine, quetiapine, and/or risperidone), electroshock therapy, or repetitive transcranial magnetic stimulation.

Each new treatment had to be initiated within the MDD episode more than 28 days after previous treatment initiation.

Investigators matched each TRD episode with up to five non-TRD episodes and found that patients with TRD were more likely to have comorbid psychiatric conditions than were their non-TRD counterparts.

This included anxiety (60% vs. 44%, respectively), sleep disorders (28% vs. 19%), substance use (15% vs. 11%) or alcohol use (10% vs. 7%) disorders, and personality disorders (6% vs. 3%). Rates of intentional self-harm were also higher in the TRD group (5% vs. 2%).

Perhaps in part because of the comorbid problems, patients with TRD had a more than 50% higher mean number of outpatient physician visits 1 year before and after the index date, defined as the date of the initiation of the third treatment trial.

The most important predictor of TRD depression was the severity of depression at diagnosis on the self-rated Montgomery Åsberg Depression Rating Scale, the researchers report.
 

Not generalizable?

Patients with TRD also had three times the number of inpatient bed days as did those with depression that responded to treatment (mean, 3.9 days vs. 1.3 days, respectively) and significantly more lost workdays (132.3 days vs. 58.7 days).

Most notably, patients with TRD episodes had a 23% higher risk of dying during the time they were observed than did their non-TRD counterparts.

“This finding in itself could be a reason to focus on how to avoid putting a patient on the TRD path. This could be done through prospective studies comparing different treatment options and their risk of leading to TRD,” Dr. Lundberg said.

Interestingly, he noted that the study results may not be generalizable to other populations, such as the United States.

“The biggest difference between Stockholm and the U.S. may not be the demographics, but the access to health care,” Dr. Lundberg said.

“In Stockholm, there is a universal access health care system, meaning that these results are what you can expect if you are able to get care. In the U.S., this is not the case, meaning that people outside the health care system may fare worse than what our study suggests,” he added.
 

Quality over quantity

In a comment, Sidney Zisook, MD, distinguished professor of psychiatry at the University of California, San Diego, said that the findings “highlight the need for our field to develop better-tolerated, more effective, and sustainable treatments for major depressive disorder and for better education of clinicians so they can employ up-to-date, evidence-based treatments and integrate sound clinical guidelines into clinical practice.”

Dr. Zisook has independently researched TRD but was not involved with the current study.

He noted that it was “striking how long patients remained on the same antidepressant, apparently despite suboptimal outcomes, without taking next steps.”

However, Dr. Zisook expressed concern that the diagnosis of TRD in the study was solely on the basis of the number of treatment trials for an episode.

“Somebody might have had three different antidepressant trials because they had had three episodes with interepisode periods of recovery followed by recurrent episodes. That would not be considered treatment-resistant depression,” he said.

Dr. Zisook also noted that patients might be given a new antidepressant for reasons other than treatment resistance. “For example, they lost an initial good response – this used to be called Prozac poop out, were nonadherent, or had troublesome side effects,” he said.

“We usually define treatment-resistant depression not only on the basis of number of trials but also the quality of the trial, taking both dose and duration into account,” Dr. Zisook added.

The study was funded by Region Stockholm. Dr. Zisook reports receiving research funding from COMPASS Pathways.

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

More than a quarter of cardiologists in an international survey reported experiencing mental health conditions ranging from anxiety or anger issues to major depression or other psychiatric disorders.  

Such conditions varied in prevalence by cardiology subspecialty and years in the field, were more common in women than in men, and were closely linked to enduring hostile work environments and other strains of professional life.

The survey, conducted only months before the COVID-19 pandemic and with its share of limitations, still paints a picture that’s not pretty.

For example, mental health concerns were reported by about 42% of respondents who cited a hostile work environment, defined as workplace experience of discrimination based on age, sex, religion, race or ethnicity, or emotional or sexual harassment. Conversely, the prevalence of these concerns reached only 17% among those without such workplace conditions.

The study shows substantial overlap between cardiologists reporting hostility at work and those with mental health concerns, “and that was a significant finding,” Garima Sharma, MD, Johns Hopkins University, Baltimore, said in an interview.

Still, only 31% of male and 42% of female cardiologists (P < .001) reporting mental health concerns also said they had sought professional help either within or outside their own institutions.

That means “there is a lot of silent suffering” in the field, said Dr. Sharma, who is lead author on the study, published in the Journal of the American College of Cardiology.
 

Bringing back the conversation

The survey findings, she added, point to at least two potential ways the cardiology community can strive to diminish what may be a major underlying cause of the mental health concerns and their consequences.

“If you work towards reducing hostility at work and making mental health a priority for your workforce, then those experiencing these types of egregious conditions based on age, gender, race, ethnicity, or sexual orientation are less likely to be harmed.”

Mental health concerns among cardiologists are seldom openly discussed, so the current study can be “a way to bring them back into the conversation,” Dr. Sharma said. Clinician mental health “is extremely important because it directly impacts patient care and productivity.”

The survey’s reported mental health conditions “are an issue across the board in medicine, and amongst our medical students as well,” senior author Laxmi S. Mehta, MD, professor of internal medicine at Ohio State University, Columbus, said in an interview. The current study provides new details about their prevalence and predictors in cardiology and, she hopes, may improve the field’s awareness of and efforts to address the problem.

“We need to support those who have underlying mental health conditions, as well as improve the work environment to reduce contributory factors to mental illnesses. And we also need to work on reducing the stigma associated with seeking treatment and on reducing the barriers to receiving treatment,” said Dr. Mehta, who chairs the Workgroup on Clinician Well-Being of the ACC, which conducted the survey in 2019.
 

A global perspective

Cardiologists in Africa, the Americas, Asia, Europe, the Middle East, and Oceania – 5,890 in all – responded to mental health questions on the survey, which was novel for its global reach and insights across continents and cultures.

Respondents in South America and Central America reported the highest prevalences of mental health concerns, outliers at about 39% and 33%, respectively. Rates for most other geographic regions ranged narrowly from about 20% to 26%, the lowest reported in Asia and the Middle East.

Dr. Sharma acknowledged that the countries probably varied widely in social and cultural factors likely to influence survey responses, such as interpretation of the questionnaire’s mental health terminology or the degree to which the disorders are stigmatized.

“I think it’s hard to say how people may or may not respond culturally to a certain word or metric,” she said. But on the survey results, “whether you’re practicing in rural America, in rural India, or in the United Arab Emirates, Oceania, or Eastern Europe, there is a level of consistency, across the board, in what people are recognizing as mental health conditions.”
 

Junior vs. senior physicians

The global perspective “is a nice positive of the study, and the high rates in Central America and South America I think were something the field was not aware of and are an important contribution,” Srijan Sen, MD, PhD, said in an interview.

The psychological toll of hostile work environments is an issue throughout medicine, “but it seems greater in certain specialties, and cardiology may be one where it’s more of a problem,” observed Dr. Sen, who studies physician mental health at the University of Michigan, Ann Arbor, and wasn’t associated with the survey.

Mental health concerns in the survey were significantly more common among women than men (33.7% vs 26.3%), and for younger cardiologists, compared with older cardiologists (32.2% for those < 40 vs. 22.1% and 16.8% for those 55-69 and 70 or older, respectively).

Those findings seem to make sense, Dr. Sen observed. “Generally, cardiology and medicine broadly are hierarchical, so being more junior can be stressful.” And if there’s more hostility in the workplace, “it might fall on junior people.”

In other studies, moreover, “a high level of work-family conflict has been a real driver of depression and burnout, and that likely is affecting younger physicians, particularly young women physicians,” who may have smaller children and a greater burden of childcare than their seniors.

He pointed to the survey’s low response rate as an important limitation of the study. Of the 71,022 cardiologists invited to participate, only 5,890 (8.3%) responded and answered the queries on mental health.

With a response rate that low, a survey “can be biased in ways that we can’t predict,” Dr. Sen noted. Also, anyone concerned about the toxicity of their own workplace might be “more likely to respond to the survey than if they worked in a more pleasant place. That would provide a skewed sense of the overall experience of cardiologists.”

Those issues might not be a concern with the current survey, however, “because the results are consistent with other studies with higher response rates.”
 

‘Sobering report’

An accompanying editorial said Dr. Sharm and colleagues have provided “a sobering report on the global prevalence and potential contributors to mental health concerns” in the surveyed population.

Based on its lessons, Andrew J. Sauer, MD, Saint Luke’s Mid America Heart Institute, Kansas City, Mo., proposed several potential “interventions” the field could enact.

It could “selectively promote leaders who strive to mitigate implicit bias, discrimination, and harassment while advancing diversity, equity, and inclusion within the broad ranks of cardiologists.”

Also, he continued, “we must eliminate the stigmatization of mental illness among physicians. We need to handle mental health concerns with compassion and without blaming, like how we strive to treat our veterans who suffer from posttraumatic stress disorder.”

Lastly, Dr. Sauer wrote, “mentorship programs should be formalized to assist the cardiologist in transition zones from early to mid-career, with particular attention to women and those experiencing a simultaneously increased load of family burdens that compound existing workplace contributors to burnout and psychological distress.”
 

Years in practice

Of the cardiologists who responded to the survey’s mental health questions, 28% reported they have experienced mental health issues that could include alcohol/drug use disorder, suicidal tendencies, psychological distress (including anxiety, irritability, or anger), “other psychiatric disorders” (such as panic disorder, posttraumatic stress, or eating disorders) or major psychiatric disorders such as major depression, bipolar disorder, or schizophrenia.

Cardiologists with 5-10 years of practice post-training were more likely than cardiologists practicing for at least 20 years to have mental health concerns (31.9% vs. 22.6%, P < .001).

Mental health concerns were cited by 42% of respondents who cited “any type of discrimination” based on age, sex, race or ethnicity, or sexual orientation, the report noted.

Among those reporting any mental health concern, 2.7% considered suicide within the past year and 2.9% considered suicide more than 12 months previously. Women were more likely than men to consider suicide within the past year (3.8% vs. 2.3%) but were also more likely to seek help (42.3% vs. 31.1%; P < .001 for both differences), the authors wrote.

In multivariate analysis, predictors of mental health concerns included emotional harassment, 2.81 (odds ratio, 2.81; 95% confidence interval, 2.46-3.20), any discrimination (OR, 1.85; 95% CI, 1.61-2.12), being divorced (OR, 1.73; 95% CI, 1.26-2.36, age less than 55 years (OR, 1.43; 95% CI, 1.24-1.66), and being mid-career versus late (OR, 1.36; 95% CI, 1.14-1.62).

Because the survey was conducted from September to October 2019, before the pandemic’s traumatic effects unfolded on health care nearly everywhere, “I think there needs to be a follow-up at some point when everything has leveled out,” Dr. Sharma said. The current study is “a baseline, and not a healthy baseline,” for the field’s state of mental health that has likely grown worse during the pandemic.

But even without such a follow-up, the current study “is actionable enough that it forces us to do something about it right now.”

Dr. Sharma, Dr. Mehta, their coauthors, Dr. Sen, and Dr. Sauer reported no relevant disclosures.

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

More than a quarter of cardiologists in an international survey reported experiencing mental health conditions ranging from anxiety or anger issues to major depression or other psychiatric disorders.  

Such conditions varied in prevalence by cardiology subspecialty and years in the field, were more common in women than in men, and were closely linked to enduring hostile work environments and other strains of professional life.

The survey, conducted only months before the COVID-19 pandemic and with its share of limitations, still paints a picture that’s not pretty.

For example, mental health concerns were reported by about 42% of respondents who cited a hostile work environment, defined as workplace experience of discrimination based on age, sex, religion, race or ethnicity, or emotional or sexual harassment. Conversely, the prevalence of these concerns reached only 17% among those without such workplace conditions.

The study shows substantial overlap between cardiologists reporting hostility at work and those with mental health concerns, “and that was a significant finding,” Garima Sharma, MD, Johns Hopkins University, Baltimore, said in an interview.

Still, only 31% of male and 42% of female cardiologists (P < .001) reporting mental health concerns also said they had sought professional help either within or outside their own institutions.

That means “there is a lot of silent suffering” in the field, said Dr. Sharma, who is lead author on the study, published in the Journal of the American College of Cardiology.
 

Bringing back the conversation

The survey findings, she added, point to at least two potential ways the cardiology community can strive to diminish what may be a major underlying cause of the mental health concerns and their consequences.

“If you work towards reducing hostility at work and making mental health a priority for your workforce, then those experiencing these types of egregious conditions based on age, gender, race, ethnicity, or sexual orientation are less likely to be harmed.”

Mental health concerns among cardiologists are seldom openly discussed, so the current study can be “a way to bring them back into the conversation,” Dr. Sharma said. Clinician mental health “is extremely important because it directly impacts patient care and productivity.”

The survey’s reported mental health conditions “are an issue across the board in medicine, and amongst our medical students as well,” senior author Laxmi S. Mehta, MD, professor of internal medicine at Ohio State University, Columbus, said in an interview. The current study provides new details about their prevalence and predictors in cardiology and, she hopes, may improve the field’s awareness of and efforts to address the problem.

“We need to support those who have underlying mental health conditions, as well as improve the work environment to reduce contributory factors to mental illnesses. And we also need to work on reducing the stigma associated with seeking treatment and on reducing the barriers to receiving treatment,” said Dr. Mehta, who chairs the Workgroup on Clinician Well-Being of the ACC, which conducted the survey in 2019.
 

A global perspective

Cardiologists in Africa, the Americas, Asia, Europe, the Middle East, and Oceania – 5,890 in all – responded to mental health questions on the survey, which was novel for its global reach and insights across continents and cultures.

Respondents in South America and Central America reported the highest prevalences of mental health concerns, outliers at about 39% and 33%, respectively. Rates for most other geographic regions ranged narrowly from about 20% to 26%, the lowest reported in Asia and the Middle East.

Dr. Sharma acknowledged that the countries probably varied widely in social and cultural factors likely to influence survey responses, such as interpretation of the questionnaire’s mental health terminology or the degree to which the disorders are stigmatized.

“I think it’s hard to say how people may or may not respond culturally to a certain word or metric,” she said. But on the survey results, “whether you’re practicing in rural America, in rural India, or in the United Arab Emirates, Oceania, or Eastern Europe, there is a level of consistency, across the board, in what people are recognizing as mental health conditions.”
 

Junior vs. senior physicians

The global perspective “is a nice positive of the study, and the high rates in Central America and South America I think were something the field was not aware of and are an important contribution,” Srijan Sen, MD, PhD, said in an interview.

The psychological toll of hostile work environments is an issue throughout medicine, “but it seems greater in certain specialties, and cardiology may be one where it’s more of a problem,” observed Dr. Sen, who studies physician mental health at the University of Michigan, Ann Arbor, and wasn’t associated with the survey.

Mental health concerns in the survey were significantly more common among women than men (33.7% vs 26.3%), and for younger cardiologists, compared with older cardiologists (32.2% for those < 40 vs. 22.1% and 16.8% for those 55-69 and 70 or older, respectively).

Those findings seem to make sense, Dr. Sen observed. “Generally, cardiology and medicine broadly are hierarchical, so being more junior can be stressful.” And if there’s more hostility in the workplace, “it might fall on junior people.”

In other studies, moreover, “a high level of work-family conflict has been a real driver of depression and burnout, and that likely is affecting younger physicians, particularly young women physicians,” who may have smaller children and a greater burden of childcare than their seniors.

He pointed to the survey’s low response rate as an important limitation of the study. Of the 71,022 cardiologists invited to participate, only 5,890 (8.3%) responded and answered the queries on mental health.

With a response rate that low, a survey “can be biased in ways that we can’t predict,” Dr. Sen noted. Also, anyone concerned about the toxicity of their own workplace might be “more likely to respond to the survey than if they worked in a more pleasant place. That would provide a skewed sense of the overall experience of cardiologists.”

Those issues might not be a concern with the current survey, however, “because the results are consistent with other studies with higher response rates.”
 

‘Sobering report’

An accompanying editorial said Dr. Sharm and colleagues have provided “a sobering report on the global prevalence and potential contributors to mental health concerns” in the surveyed population.

Based on its lessons, Andrew J. Sauer, MD, Saint Luke’s Mid America Heart Institute, Kansas City, Mo., proposed several potential “interventions” the field could enact.

It could “selectively promote leaders who strive to mitigate implicit bias, discrimination, and harassment while advancing diversity, equity, and inclusion within the broad ranks of cardiologists.”

Also, he continued, “we must eliminate the stigmatization of mental illness among physicians. We need to handle mental health concerns with compassion and without blaming, like how we strive to treat our veterans who suffer from posttraumatic stress disorder.”

Lastly, Dr. Sauer wrote, “mentorship programs should be formalized to assist the cardiologist in transition zones from early to mid-career, with particular attention to women and those experiencing a simultaneously increased load of family burdens that compound existing workplace contributors to burnout and psychological distress.”
 

Years in practice

Of the cardiologists who responded to the survey’s mental health questions, 28% reported they have experienced mental health issues that could include alcohol/drug use disorder, suicidal tendencies, psychological distress (including anxiety, irritability, or anger), “other psychiatric disorders” (such as panic disorder, posttraumatic stress, or eating disorders) or major psychiatric disorders such as major depression, bipolar disorder, or schizophrenia.

Cardiologists with 5-10 years of practice post-training were more likely than cardiologists practicing for at least 20 years to have mental health concerns (31.9% vs. 22.6%, P < .001).

Mental health concerns were cited by 42% of respondents who cited “any type of discrimination” based on age, sex, race or ethnicity, or sexual orientation, the report noted.

Among those reporting any mental health concern, 2.7% considered suicide within the past year and 2.9% considered suicide more than 12 months previously. Women were more likely than men to consider suicide within the past year (3.8% vs. 2.3%) but were also more likely to seek help (42.3% vs. 31.1%; P < .001 for both differences), the authors wrote.

In multivariate analysis, predictors of mental health concerns included emotional harassment, 2.81 (odds ratio, 2.81; 95% confidence interval, 2.46-3.20), any discrimination (OR, 1.85; 95% CI, 1.61-2.12), being divorced (OR, 1.73; 95% CI, 1.26-2.36, age less than 55 years (OR, 1.43; 95% CI, 1.24-1.66), and being mid-career versus late (OR, 1.36; 95% CI, 1.14-1.62).

Because the survey was conducted from September to October 2019, before the pandemic’s traumatic effects unfolded on health care nearly everywhere, “I think there needs to be a follow-up at some point when everything has leveled out,” Dr. Sharma said. The current study is “a baseline, and not a healthy baseline,” for the field’s state of mental health that has likely grown worse during the pandemic.

But even without such a follow-up, the current study “is actionable enough that it forces us to do something about it right now.”

Dr. Sharma, Dr. Mehta, their coauthors, Dr. Sen, and Dr. Sauer reported no relevant disclosures.

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

More than a quarter of cardiologists in an international survey reported experiencing mental health conditions ranging from anxiety or anger issues to major depression or other psychiatric disorders.  

Such conditions varied in prevalence by cardiology subspecialty and years in the field, were more common in women than in men, and were closely linked to enduring hostile work environments and other strains of professional life.

The survey, conducted only months before the COVID-19 pandemic and with its share of limitations, still paints a picture that’s not pretty.

For example, mental health concerns were reported by about 42% of respondents who cited a hostile work environment, defined as workplace experience of discrimination based on age, sex, religion, race or ethnicity, or emotional or sexual harassment. Conversely, the prevalence of these concerns reached only 17% among those without such workplace conditions.

The study shows substantial overlap between cardiologists reporting hostility at work and those with mental health concerns, “and that was a significant finding,” Garima Sharma, MD, Johns Hopkins University, Baltimore, said in an interview.

Still, only 31% of male and 42% of female cardiologists (P < .001) reporting mental health concerns also said they had sought professional help either within or outside their own institutions.

That means “there is a lot of silent suffering” in the field, said Dr. Sharma, who is lead author on the study, published in the Journal of the American College of Cardiology.
 

Bringing back the conversation

The survey findings, she added, point to at least two potential ways the cardiology community can strive to diminish what may be a major underlying cause of the mental health concerns and their consequences.

“If you work towards reducing hostility at work and making mental health a priority for your workforce, then those experiencing these types of egregious conditions based on age, gender, race, ethnicity, or sexual orientation are less likely to be harmed.”

Mental health concerns among cardiologists are seldom openly discussed, so the current study can be “a way to bring them back into the conversation,” Dr. Sharma said. Clinician mental health “is extremely important because it directly impacts patient care and productivity.”

The survey’s reported mental health conditions “are an issue across the board in medicine, and amongst our medical students as well,” senior author Laxmi S. Mehta, MD, professor of internal medicine at Ohio State University, Columbus, said in an interview. The current study provides new details about their prevalence and predictors in cardiology and, she hopes, may improve the field’s awareness of and efforts to address the problem.

“We need to support those who have underlying mental health conditions, as well as improve the work environment to reduce contributory factors to mental illnesses. And we also need to work on reducing the stigma associated with seeking treatment and on reducing the barriers to receiving treatment,” said Dr. Mehta, who chairs the Workgroup on Clinician Well-Being of the ACC, which conducted the survey in 2019.
 

A global perspective

Cardiologists in Africa, the Americas, Asia, Europe, the Middle East, and Oceania – 5,890 in all – responded to mental health questions on the survey, which was novel for its global reach and insights across continents and cultures.

Respondents in South America and Central America reported the highest prevalences of mental health concerns, outliers at about 39% and 33%, respectively. Rates for most other geographic regions ranged narrowly from about 20% to 26%, the lowest reported in Asia and the Middle East.

Dr. Sharma acknowledged that the countries probably varied widely in social and cultural factors likely to influence survey responses, such as interpretation of the questionnaire’s mental health terminology or the degree to which the disorders are stigmatized.

“I think it’s hard to say how people may or may not respond culturally to a certain word or metric,” she said. But on the survey results, “whether you’re practicing in rural America, in rural India, or in the United Arab Emirates, Oceania, or Eastern Europe, there is a level of consistency, across the board, in what people are recognizing as mental health conditions.”
 

Junior vs. senior physicians

The global perspective “is a nice positive of the study, and the high rates in Central America and South America I think were something the field was not aware of and are an important contribution,” Srijan Sen, MD, PhD, said in an interview.

The psychological toll of hostile work environments is an issue throughout medicine, “but it seems greater in certain specialties, and cardiology may be one where it’s more of a problem,” observed Dr. Sen, who studies physician mental health at the University of Michigan, Ann Arbor, and wasn’t associated with the survey.

Mental health concerns in the survey were significantly more common among women than men (33.7% vs 26.3%), and for younger cardiologists, compared with older cardiologists (32.2% for those < 40 vs. 22.1% and 16.8% for those 55-69 and 70 or older, respectively).

Those findings seem to make sense, Dr. Sen observed. “Generally, cardiology and medicine broadly are hierarchical, so being more junior can be stressful.” And if there’s more hostility in the workplace, “it might fall on junior people.”

In other studies, moreover, “a high level of work-family conflict has been a real driver of depression and burnout, and that likely is affecting younger physicians, particularly young women physicians,” who may have smaller children and a greater burden of childcare than their seniors.

He pointed to the survey’s low response rate as an important limitation of the study. Of the 71,022 cardiologists invited to participate, only 5,890 (8.3%) responded and answered the queries on mental health.

With a response rate that low, a survey “can be biased in ways that we can’t predict,” Dr. Sen noted. Also, anyone concerned about the toxicity of their own workplace might be “more likely to respond to the survey than if they worked in a more pleasant place. That would provide a skewed sense of the overall experience of cardiologists.”

Those issues might not be a concern with the current survey, however, “because the results are consistent with other studies with higher response rates.”
 

‘Sobering report’

An accompanying editorial said Dr. Sharm and colleagues have provided “a sobering report on the global prevalence and potential contributors to mental health concerns” in the surveyed population.

Based on its lessons, Andrew J. Sauer, MD, Saint Luke’s Mid America Heart Institute, Kansas City, Mo., proposed several potential “interventions” the field could enact.

It could “selectively promote leaders who strive to mitigate implicit bias, discrimination, and harassment while advancing diversity, equity, and inclusion within the broad ranks of cardiologists.”

Also, he continued, “we must eliminate the stigmatization of mental illness among physicians. We need to handle mental health concerns with compassion and without blaming, like how we strive to treat our veterans who suffer from posttraumatic stress disorder.”

Lastly, Dr. Sauer wrote, “mentorship programs should be formalized to assist the cardiologist in transition zones from early to mid-career, with particular attention to women and those experiencing a simultaneously increased load of family burdens that compound existing workplace contributors to burnout and psychological distress.”
 

Years in practice

Of the cardiologists who responded to the survey’s mental health questions, 28% reported they have experienced mental health issues that could include alcohol/drug use disorder, suicidal tendencies, psychological distress (including anxiety, irritability, or anger), “other psychiatric disorders” (such as panic disorder, posttraumatic stress, or eating disorders) or major psychiatric disorders such as major depression, bipolar disorder, or schizophrenia.

Cardiologists with 5-10 years of practice post-training were more likely than cardiologists practicing for at least 20 years to have mental health concerns (31.9% vs. 22.6%, P < .001).

Mental health concerns were cited by 42% of respondents who cited “any type of discrimination” based on age, sex, race or ethnicity, or sexual orientation, the report noted.

Among those reporting any mental health concern, 2.7% considered suicide within the past year and 2.9% considered suicide more than 12 months previously. Women were more likely than men to consider suicide within the past year (3.8% vs. 2.3%) but were also more likely to seek help (42.3% vs. 31.1%; P < .001 for both differences), the authors wrote.

In multivariate analysis, predictors of mental health concerns included emotional harassment, 2.81 (odds ratio, 2.81; 95% confidence interval, 2.46-3.20), any discrimination (OR, 1.85; 95% CI, 1.61-2.12), being divorced (OR, 1.73; 95% CI, 1.26-2.36, age less than 55 years (OR, 1.43; 95% CI, 1.24-1.66), and being mid-career versus late (OR, 1.36; 95% CI, 1.14-1.62).

Because the survey was conducted from September to October 2019, before the pandemic’s traumatic effects unfolded on health care nearly everywhere, “I think there needs to be a follow-up at some point when everything has leveled out,” Dr. Sharma said. The current study is “a baseline, and not a healthy baseline,” for the field’s state of mental health that has likely grown worse during the pandemic.

But even without such a follow-up, the current study “is actionable enough that it forces us to do something about it right now.”

Dr. Sharma, Dr. Mehta, their coauthors, Dr. Sen, and Dr. Sauer reported no relevant disclosures.

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

A common refrain in psychiatry is that the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision, (DSM-5-TR), published in 2022, is the best we can do.

Since the DSM-III was released in 1980, the American Psychiatric Association, which publishes the manual, has espoused the position that we should list symptoms, in a manner that is reminiscent of a checklist. For example, having a depressed mood on most days for a 2-week period, or a loss of interest in pleasurable things, as well as 4 additional symptoms – among them changes in appetite, changes in sleep, changes in psychomotor activity, fatigue, worthlessness, poor concentration, or thoughts of death – can lead to a diagnosis of a major depressive episode as part of a major depressive disorder.

Criticisms of this approach can be apparent. Patients subjected to such checklists, including being repeatedly asked to complete the Patient Health Questionnaire 9 (PHQ-9), which closely follows those criteria, can feel lost and even alienated by their providers. After all, one can ask all those questions and make a diagnosis of depression without even knowing about the patient’s stressors, their history, or their social context.

The DSM permits the diagnosis of psychiatric disorders without an understanding of the narrative of the patient. In its defense, the DSM is not a textbook of psychiatry, it is a guide on how to diagnose individuals. The DSM does not demand that psychiatrists only ask about the symptoms on the checklists; it is the providers who can choose to dismiss asking about the important facets of one’s life.

Yet every time we attend a lecture that starts by enumerating the DSM symptoms of the disorder being discussed, we are left with the dissatisfying impression that a specialist of this disorder should have a more nuanced and interesting description of their disorder of study. This feeling of discontent is compounded when we see a movie that encompasses so much of what is missing in today’s psychiatric parlance, and even more so if that movie is ostensibly made for children. Movies, by design, are particularly adept at encapsulating the narrative of someone’s life in a way that psychiatry can learn from.

Other than the embarrassment of not knowing a patient outside the checklist, the importance of narrative cannot be understated. Dr. Erik Erikson rightfully suggested that the point of life is “the acceptance of one’s one and only life cycle”¹ or rather to know it was okay to have been oneself without additions or substitutions. Therefore, one must know what it has meant to be themselves to reconcile this question and achieve Ego Integrity rather than disgust and despair. Narrative is the way in which we understand who we are and what it has meant to be ourselves. An understanding of our personal narrative presents a unique opportunity in expressing what is missing in the DSM. Below, we provide two of our favorite examples in Disney films, among many.
 

‘Ratatouille’ (2007)

One of the missing features of the DSM is its inability to explain to patients the intrapsychic processes that guide us. One of these processes is how our values can lead us to a deep sense of guilt, shame, and the resulting feelings of alienation. It is extremely common for patients to enter our clinical practice feeling shackled by beliefs that they should accomplish more and be more than they are.

The animated film “Ratatouille” does an excellent job at addressing this feeling. The film follows Remy, the protagonist rat, and his adventures as he explores his passion for cooking. Remy teams up with the inept but good-natured human Alfredo Linguini and guides him through cooking while hiding under his chef’s hat. The primary antagonist, Anton Ego, is a particularly harsh food critic. His presence and appearance are somber. He exudes disdain. His trim physique and scarf suggest a man that will break and react to anything, and his skull-shaped typewriter in his coffin-shaped office informs the viewer that he is out to kill with his cruel words. Anton Ego serves as our projected super-ego. He is not an external judge but the judgment deep inside ourselves, goading us to be better with such severity that we are ultimately left feeling condemned.

Remy is the younger of two siblings. He is less physically adept but more intellectual than his older brother, who does not understand why Remy isn’t content eating scraps from the garbage like the rest of their rat clan. Remy is the creative part within us that wants to challenge the status quo and try something new. Remy also represents our shame and guilt for leaving our home. On one hand, we want to dare greatly, in this case at being an extraordinary chef, but on the other we are shy and cook in secret, hiding within the hat of another person. Remy struggles with the deep feeling that we do not deserve our success, that our family will leave us for being who we are, and that we are better off isolating and segregating from our challenges.

The movie concludes that through talent and hard work, our critics will accept us. Furthermore, once accepted for what we do, we can be further accepted for who we are. The movie ends with Remy cooking the eponymous dish ratatouille. He prepares it so remarkably well, the dish transports Anton Ego back to a sublime experience of eating ratatouille as a child, a touching moment which not only underscores food’s evocative link to memory but gives a glimpse at Anton Ego’s own narrative.

Ego is first won over by the dish, and only afterward learns of Remy’s true identity. Remy’s talent is undeniable though, and even the stuffy Ego must accept the film’s theme that “Anyone can cook,” even a rat – the rat that we all sometimes feel we are deep inside, rotten to the core but trying so hard to be accepted by others, and ultimately by ourselves. In the end, we overcome the disgust inherent in the imagery of a rat in a kitchen and instead embrace our hero’s achievement of ego integrity as he combines his identities as a member of a clan of rats, and one of Paris’s finest chefs.

While modern psychiatry can favor looking at people through the lens of biology rather than narrative, “Ratatouille” can serve as a reminder of the powerful unconscious forces that guide our lives. “Ratatouille” is not a successful movie only because of the compelling narrative, but also because the narrative matches the important psychic paradigms that psychiatry once embraced.
 

‘Inside Out’ (2015)

Another missing feature of the DSM is its inability to explain how symptoms feel and manifest psychologically. One such feeling is that of control – whether one is in control of one’s life, feelings, and action or rather a victim of external forces. It is extremely common for patients to enter our clinical practice feeling traumatized by the life they’ve lived and powerless to produce any change. Part of our role is to guide them through this journey from the object of their lives to the subject of their lives.

In the animated feature “Inside Out,” Riley, a preteen girl, goes through the tribulation of growing up and learning about herself. This seemingly happy child, content playing hockey with her best friend, Meg, on the picturesque frozen lakes of Minnesota, reaches her inevitable conflict. Her parents uproot her life, moving the family to San Francisco. By doing so, they disconnect her from her school, her friends, and her hobbies. While all this is happening, we spend time inside Riley’s psyche with the personified characters of Riley’s emotions as they affect her decisions and daily actions amidst the backdrop of her core memories and islands of personality.

During the move, her parents seemingly change and ultimately destroy every facet of Riley’s sense of self, which is animated as the collapse of her personality islands. Her best friend engages Riley in a video call just to inform her that she has a new friend who plays hockey equally well. Her parents do not hear Riley’s concerns and are portrayed as distracted by their adult problems. Riley feels ridiculed in her new school and unable to share her feelings with her parents, who ask her to still be their “happy girl” and indirectly ask her to fake pleasure to alleviate their own anxiety.

The climax of the movie is when Riley decides to run away from San Francisco and her parents, to return to her perceived true home, Minnesota. The climax is resolved when Riley realizes that her parents’ love, representing the connection we have to others, transcends her need for control. To some degree, we are all powerless in the face of the tremendous forces of life and share the difficult task of accepting the cards we were dealt, thus making the story of Riley so compelling.

Additionally, the climax is further resolved by another argument that psychiatry (and the DSM) should consider embracing. Emotions are not all symptoms and living without negative emotion is not the goal of life. Riley grows from preteen to teenager, and from object to subject of her life, by realizing that her symptoms/feelings are not just nuisances to avoid and hide, but the key to meaning. Our anger drives us to try hard. Our fear protects us from harm. Our sadness attracts the warmth and care of others. Our disgust protects us physically from noxious material (symbolized as a dreaded broccoli floret for preteen Riley) and socially by encouraging us to share societal norms. Similarly, patients and people in general would benefit by being taught that, while symptoms may permit the better assessment of psychiatric conditions using the DSM, life is much more than that.

It is unfair to blame the DSM for things it was not designed to do. The DSM doesn’t advertise itself as a guidebook of all behaviors, at all times. However, for a variety of reasons, it has become the main way psychiatry describes people. While we commend the APA for its effort and do not know that we could make it any better, we are frequently happily reminded that in about 90 minutes, filmmakers are able to display an empathic understanding of personal narratives that biologic psychiatry can miss.

Dr. Pulido is a psychiatry resident at the University of California, San Diego. She is interested in women’s mental health, medical education, and outpatient psychiatry. Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. He has no conflicts of interest.

References

1. Erikson, EH. Childhood and society (New York: WW Norton, 1950).

A common refrain in psychiatry is that the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision, (DSM-5-TR), published in 2022, is the best we can do.

Since the DSM-III was released in 1980, the American Psychiatric Association, which publishes the manual, has espoused the position that we should list symptoms, in a manner that is reminiscent of a checklist. For example, having a depressed mood on most days for a 2-week period, or a loss of interest in pleasurable things, as well as 4 additional symptoms – among them changes in appetite, changes in sleep, changes in psychomotor activity, fatigue, worthlessness, poor concentration, or thoughts of death – can lead to a diagnosis of a major depressive episode as part of a major depressive disorder.

Criticisms of this approach can be apparent. Patients subjected to such checklists, including being repeatedly asked to complete the Patient Health Questionnaire 9 (PHQ-9), which closely follows those criteria, can feel lost and even alienated by their providers. After all, one can ask all those questions and make a diagnosis of depression without even knowing about the patient’s stressors, their history, or their social context.

The DSM permits the diagnosis of psychiatric disorders without an understanding of the narrative of the patient. In its defense, the DSM is not a textbook of psychiatry, it is a guide on how to diagnose individuals. The DSM does not demand that psychiatrists only ask about the symptoms on the checklists; it is the providers who can choose to dismiss asking about the important facets of one’s life.

Yet every time we attend a lecture that starts by enumerating the DSM symptoms of the disorder being discussed, we are left with the dissatisfying impression that a specialist of this disorder should have a more nuanced and interesting description of their disorder of study. This feeling of discontent is compounded when we see a movie that encompasses so much of what is missing in today’s psychiatric parlance, and even more so if that movie is ostensibly made for children. Movies, by design, are particularly adept at encapsulating the narrative of someone’s life in a way that psychiatry can learn from.

Other than the embarrassment of not knowing a patient outside the checklist, the importance of narrative cannot be understated. Dr. Erik Erikson rightfully suggested that the point of life is “the acceptance of one’s one and only life cycle”¹ or rather to know it was okay to have been oneself without additions or substitutions. Therefore, one must know what it has meant to be themselves to reconcile this question and achieve Ego Integrity rather than disgust and despair. Narrative is the way in which we understand who we are and what it has meant to be ourselves. An understanding of our personal narrative presents a unique opportunity in expressing what is missing in the DSM. Below, we provide two of our favorite examples in Disney films, among many.
 

‘Ratatouille’ (2007)

One of the missing features of the DSM is its inability to explain to patients the intrapsychic processes that guide us. One of these processes is how our values can lead us to a deep sense of guilt, shame, and the resulting feelings of alienation. It is extremely common for patients to enter our clinical practice feeling shackled by beliefs that they should accomplish more and be more than they are.

The animated film “Ratatouille” does an excellent job at addressing this feeling. The film follows Remy, the protagonist rat, and his adventures as he explores his passion for cooking. Remy teams up with the inept but good-natured human Alfredo Linguini and guides him through cooking while hiding under his chef’s hat. The primary antagonist, Anton Ego, is a particularly harsh food critic. His presence and appearance are somber. He exudes disdain. His trim physique and scarf suggest a man that will break and react to anything, and his skull-shaped typewriter in his coffin-shaped office informs the viewer that he is out to kill with his cruel words. Anton Ego serves as our projected super-ego. He is not an external judge but the judgment deep inside ourselves, goading us to be better with such severity that we are ultimately left feeling condemned.

Remy is the younger of two siblings. He is less physically adept but more intellectual than his older brother, who does not understand why Remy isn’t content eating scraps from the garbage like the rest of their rat clan. Remy is the creative part within us that wants to challenge the status quo and try something new. Remy also represents our shame and guilt for leaving our home. On one hand, we want to dare greatly, in this case at being an extraordinary chef, but on the other we are shy and cook in secret, hiding within the hat of another person. Remy struggles with the deep feeling that we do not deserve our success, that our family will leave us for being who we are, and that we are better off isolating and segregating from our challenges.

The movie concludes that through talent and hard work, our critics will accept us. Furthermore, once accepted for what we do, we can be further accepted for who we are. The movie ends with Remy cooking the eponymous dish ratatouille. He prepares it so remarkably well, the dish transports Anton Ego back to a sublime experience of eating ratatouille as a child, a touching moment which not only underscores food’s evocative link to memory but gives a glimpse at Anton Ego’s own narrative.

Ego is first won over by the dish, and only afterward learns of Remy’s true identity. Remy’s talent is undeniable though, and even the stuffy Ego must accept the film’s theme that “Anyone can cook,” even a rat – the rat that we all sometimes feel we are deep inside, rotten to the core but trying so hard to be accepted by others, and ultimately by ourselves. In the end, we overcome the disgust inherent in the imagery of a rat in a kitchen and instead embrace our hero’s achievement of ego integrity as he combines his identities as a member of a clan of rats, and one of Paris’s finest chefs.

While modern psychiatry can favor looking at people through the lens of biology rather than narrative, “Ratatouille” can serve as a reminder of the powerful unconscious forces that guide our lives. “Ratatouille” is not a successful movie only because of the compelling narrative, but also because the narrative matches the important psychic paradigms that psychiatry once embraced.
 

‘Inside Out’ (2015)

Another missing feature of the DSM is its inability to explain how symptoms feel and manifest psychologically. One such feeling is that of control – whether one is in control of one’s life, feelings, and action or rather a victim of external forces. It is extremely common for patients to enter our clinical practice feeling traumatized by the life they’ve lived and powerless to produce any change. Part of our role is to guide them through this journey from the object of their lives to the subject of their lives.

In the animated feature “Inside Out,” Riley, a preteen girl, goes through the tribulation of growing up and learning about herself. This seemingly happy child, content playing hockey with her best friend, Meg, on the picturesque frozen lakes of Minnesota, reaches her inevitable conflict. Her parents uproot her life, moving the family to San Francisco. By doing so, they disconnect her from her school, her friends, and her hobbies. While all this is happening, we spend time inside Riley’s psyche with the personified characters of Riley’s emotions as they affect her decisions and daily actions amidst the backdrop of her core memories and islands of personality.

During the move, her parents seemingly change and ultimately destroy every facet of Riley’s sense of self, which is animated as the collapse of her personality islands. Her best friend engages Riley in a video call just to inform her that she has a new friend who plays hockey equally well. Her parents do not hear Riley’s concerns and are portrayed as distracted by their adult problems. Riley feels ridiculed in her new school and unable to share her feelings with her parents, who ask her to still be their “happy girl” and indirectly ask her to fake pleasure to alleviate their own anxiety.

The climax of the movie is when Riley decides to run away from San Francisco and her parents, to return to her perceived true home, Minnesota. The climax is resolved when Riley realizes that her parents’ love, representing the connection we have to others, transcends her need for control. To some degree, we are all powerless in the face of the tremendous forces of life and share the difficult task of accepting the cards we were dealt, thus making the story of Riley so compelling.

Additionally, the climax is further resolved by another argument that psychiatry (and the DSM) should consider embracing. Emotions are not all symptoms and living without negative emotion is not the goal of life. Riley grows from preteen to teenager, and from object to subject of her life, by realizing that her symptoms/feelings are not just nuisances to avoid and hide, but the key to meaning. Our anger drives us to try hard. Our fear protects us from harm. Our sadness attracts the warmth and care of others. Our disgust protects us physically from noxious material (symbolized as a dreaded broccoli floret for preteen Riley) and socially by encouraging us to share societal norms. Similarly, patients and people in general would benefit by being taught that, while symptoms may permit the better assessment of psychiatric conditions using the DSM, life is much more than that.

It is unfair to blame the DSM for things it was not designed to do. The DSM doesn’t advertise itself as a guidebook of all behaviors, at all times. However, for a variety of reasons, it has become the main way psychiatry describes people. While we commend the APA for its effort and do not know that we could make it any better, we are frequently happily reminded that in about 90 minutes, filmmakers are able to display an empathic understanding of personal narratives that biologic psychiatry can miss.

Dr. Pulido is a psychiatry resident at the University of California, San Diego. She is interested in women’s mental health, medical education, and outpatient psychiatry. Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. He has no conflicts of interest.

References

1. Erikson, EH. Childhood and society (New York: WW Norton, 1950).

A common refrain in psychiatry is that the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision, (DSM-5-TR), published in 2022, is the best we can do.

Since the DSM-III was released in 1980, the American Psychiatric Association, which publishes the manual, has espoused the position that we should list symptoms, in a manner that is reminiscent of a checklist. For example, having a depressed mood on most days for a 2-week period, or a loss of interest in pleasurable things, as well as 4 additional symptoms – among them changes in appetite, changes in sleep, changes in psychomotor activity, fatigue, worthlessness, poor concentration, or thoughts of death – can lead to a diagnosis of a major depressive episode as part of a major depressive disorder.

Criticisms of this approach can be apparent. Patients subjected to such checklists, including being repeatedly asked to complete the Patient Health Questionnaire 9 (PHQ-9), which closely follows those criteria, can feel lost and even alienated by their providers. After all, one can ask all those questions and make a diagnosis of depression without even knowing about the patient’s stressors, their history, or their social context.

The DSM permits the diagnosis of psychiatric disorders without an understanding of the narrative of the patient. In its defense, the DSM is not a textbook of psychiatry, it is a guide on how to diagnose individuals. The DSM does not demand that psychiatrists only ask about the symptoms on the checklists; it is the providers who can choose to dismiss asking about the important facets of one’s life.

Yet every time we attend a lecture that starts by enumerating the DSM symptoms of the disorder being discussed, we are left with the dissatisfying impression that a specialist of this disorder should have a more nuanced and interesting description of their disorder of study. This feeling of discontent is compounded when we see a movie that encompasses so much of what is missing in today’s psychiatric parlance, and even more so if that movie is ostensibly made for children. Movies, by design, are particularly adept at encapsulating the narrative of someone’s life in a way that psychiatry can learn from.

Other than the embarrassment of not knowing a patient outside the checklist, the importance of narrative cannot be understated. Dr. Erik Erikson rightfully suggested that the point of life is “the acceptance of one’s one and only life cycle”¹ or rather to know it was okay to have been oneself without additions or substitutions. Therefore, one must know what it has meant to be themselves to reconcile this question and achieve Ego Integrity rather than disgust and despair. Narrative is the way in which we understand who we are and what it has meant to be ourselves. An understanding of our personal narrative presents a unique opportunity in expressing what is missing in the DSM. Below, we provide two of our favorite examples in Disney films, among many.
 

‘Ratatouille’ (2007)

One of the missing features of the DSM is its inability to explain to patients the intrapsychic processes that guide us. One of these processes is how our values can lead us to a deep sense of guilt, shame, and the resulting feelings of alienation. It is extremely common for patients to enter our clinical practice feeling shackled by beliefs that they should accomplish more and be more than they are.

The animated film “Ratatouille” does an excellent job at addressing this feeling. The film follows Remy, the protagonist rat, and his adventures as he explores his passion for cooking. Remy teams up with the inept but good-natured human Alfredo Linguini and guides him through cooking while hiding under his chef’s hat. The primary antagonist, Anton Ego, is a particularly harsh food critic. His presence and appearance are somber. He exudes disdain. His trim physique and scarf suggest a man that will break and react to anything, and his skull-shaped typewriter in his coffin-shaped office informs the viewer that he is out to kill with his cruel words. Anton Ego serves as our projected super-ego. He is not an external judge but the judgment deep inside ourselves, goading us to be better with such severity that we are ultimately left feeling condemned.

Remy is the younger of two siblings. He is less physically adept but more intellectual than his older brother, who does not understand why Remy isn’t content eating scraps from the garbage like the rest of their rat clan. Remy is the creative part within us that wants to challenge the status quo and try something new. Remy also represents our shame and guilt for leaving our home. On one hand, we want to dare greatly, in this case at being an extraordinary chef, but on the other we are shy and cook in secret, hiding within the hat of another person. Remy struggles with the deep feeling that we do not deserve our success, that our family will leave us for being who we are, and that we are better off isolating and segregating from our challenges.

The movie concludes that through talent and hard work, our critics will accept us. Furthermore, once accepted for what we do, we can be further accepted for who we are. The movie ends with Remy cooking the eponymous dish ratatouille. He prepares it so remarkably well, the dish transports Anton Ego back to a sublime experience of eating ratatouille as a child, a touching moment which not only underscores food’s evocative link to memory but gives a glimpse at Anton Ego’s own narrative.

Ego is first won over by the dish, and only afterward learns of Remy’s true identity. Remy’s talent is undeniable though, and even the stuffy Ego must accept the film’s theme that “Anyone can cook,” even a rat – the rat that we all sometimes feel we are deep inside, rotten to the core but trying so hard to be accepted by others, and ultimately by ourselves. In the end, we overcome the disgust inherent in the imagery of a rat in a kitchen and instead embrace our hero’s achievement of ego integrity as he combines his identities as a member of a clan of rats, and one of Paris’s finest chefs.

While modern psychiatry can favor looking at people through the lens of biology rather than narrative, “Ratatouille” can serve as a reminder of the powerful unconscious forces that guide our lives. “Ratatouille” is not a successful movie only because of the compelling narrative, but also because the narrative matches the important psychic paradigms that psychiatry once embraced.
 

‘Inside Out’ (2015)

Another missing feature of the DSM is its inability to explain how symptoms feel and manifest psychologically. One such feeling is that of control – whether one is in control of one’s life, feelings, and action or rather a victim of external forces. It is extremely common for patients to enter our clinical practice feeling traumatized by the life they’ve lived and powerless to produce any change. Part of our role is to guide them through this journey from the object of their lives to the subject of their lives.

In the animated feature “Inside Out,” Riley, a preteen girl, goes through the tribulation of growing up and learning about herself. This seemingly happy child, content playing hockey with her best friend, Meg, on the picturesque frozen lakes of Minnesota, reaches her inevitable conflict. Her parents uproot her life, moving the family to San Francisco. By doing so, they disconnect her from her school, her friends, and her hobbies. While all this is happening, we spend time inside Riley’s psyche with the personified characters of Riley’s emotions as they affect her decisions and daily actions amidst the backdrop of her core memories and islands of personality.

During the move, her parents seemingly change and ultimately destroy every facet of Riley’s sense of self, which is animated as the collapse of her personality islands. Her best friend engages Riley in a video call just to inform her that she has a new friend who plays hockey equally well. Her parents do not hear Riley’s concerns and are portrayed as distracted by their adult problems. Riley feels ridiculed in her new school and unable to share her feelings with her parents, who ask her to still be their “happy girl” and indirectly ask her to fake pleasure to alleviate their own anxiety.

The climax of the movie is when Riley decides to run away from San Francisco and her parents, to return to her perceived true home, Minnesota. The climax is resolved when Riley realizes that her parents’ love, representing the connection we have to others, transcends her need for control. To some degree, we are all powerless in the face of the tremendous forces of life and share the difficult task of accepting the cards we were dealt, thus making the story of Riley so compelling.

Additionally, the climax is further resolved by another argument that psychiatry (and the DSM) should consider embracing. Emotions are not all symptoms and living without negative emotion is not the goal of life. Riley grows from preteen to teenager, and from object to subject of her life, by realizing that her symptoms/feelings are not just nuisances to avoid and hide, but the key to meaning. Our anger drives us to try hard. Our fear protects us from harm. Our sadness attracts the warmth and care of others. Our disgust protects us physically from noxious material (symbolized as a dreaded broccoli floret for preteen Riley) and socially by encouraging us to share societal norms. Similarly, patients and people in general would benefit by being taught that, while symptoms may permit the better assessment of psychiatric conditions using the DSM, life is much more than that.

It is unfair to blame the DSM for things it was not designed to do. The DSM doesn’t advertise itself as a guidebook of all behaviors, at all times. However, for a variety of reasons, it has become the main way psychiatry describes people. While we commend the APA for its effort and do not know that we could make it any better, we are frequently happily reminded that in about 90 minutes, filmmakers are able to display an empathic understanding of personal narratives that biologic psychiatry can miss.

Dr. Pulido is a psychiatry resident at the University of California, San Diego. She is interested in women’s mental health, medical education, and outpatient psychiatry. Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. He has no conflicts of interest.

References

1. Erikson, EH. Childhood and society (New York: WW Norton, 1950).

“It is one of life’s most self-evident truths that everything fades, that we fear the fading, and that we must live, nonetheless, in the face of the fear.” – Irvin D. Yalom, MD, Existential Psychotherapy, 1980

The email was titled simply, “A sorrowful note,” and I knew that someone had died. I held my breath and read as Dr. Jimmy Potash informed our entire department that Dr. Cait McFarland died in a car accident on December 7 while driving to work at West Cecil Health Center, Conowingo, Md., where she was director of psychiatry.

Sadness swelled as I remembered the outspoken resident who was interested in LGBTQ issues. Cait graduated from the Johns Hopkins residency program in 2020, she had recently married a social worker in the department, and the plan was for her to return to Hopkins full-time in July 2023 to be director of a clinic focused on mental health for people who are transgendered.

Sudden deaths are tragic and jarring and they call to the surface our losses from the past. These deaths don’t stand alone – I found myself thinking of my editor at Medscape, Dr. Bret Stetka, who died unexpectedly in August 2022, and then of Dr. Lidia Palcan Wenz, a psychiatrist I trained with, who died in a motor vehicle accident in 2004. Lidia’s husband also died in the accident, while their two young children in the back seat survived – this tragedy haunted me for some time. None of these people was close to me, but I am no stranger to the impact of unexpected death: My parents and brother all died from cardiac events, and any sudden death is a reminder of those losses.

Julia Riddle, MD, trained with Cait McFarland and was her close friend for years. “I don’t have a belief in ‘the afterlife’ but do like to think of the people that I have lost together in my memory – as if they are all suddenly in a new room together. And, with each loss, all the other occupants of that room come freshly to life again,” Dr. Riddle said.

Death is our shared destination in life, but sudden and unexpected deaths carry their own weight. There is no chance to tie up loose ends, to repair riffs, to say goodbye. Nothing is put in order, and the life that was to be lived goes on for some time as bills arrive, social and work events go unattended, vacations are canceled, and there is the awkward moment of running into someone who didn’t know your loved one has died.

Roger Lewin, MD, is a psychiatrist and writer in Towson, Md. He has both personal and professional experience with sudden death. “There is no way to prepare beforehand, so we have to get ready for what has already happened, and that is hard,” he said. “We invent a life for ourselves and others that extends into the future, and that gets interrupted.”

Most people become ill and die on a vaguely predictable schedule. There may be a chance to plan, to know and honor the wishes of the individual, and often there is the opportunity for loved ones to begin the grieving process gradually as death approaches. For those who are elderly, there may be a sense that this is the natural order of things – which may or may not temper the intensity of the grief for those who remain. If the person has suffered, the end may come with relief.

Still, I sometimes find myself surprised at the length and intensity of anguish that some people experience after losing a loved one who has lived a long and full life, who declined and suffered, but whose absence remains a gaping wound that takes years to form a scar.

Sudden death is not rare; accidents, homicide, and suicide are the top killers among young people, and cardiovascular deaths are number one among those who are older. Natural disasters and terrorist attacks can cause catastrophic numbers of sudden deaths and leave survivors to grieve not only the dead, but the loss of all that was familiar to them.

Psychiatry has been a bit lost as to how we approach grief. We often hear patients talk about anxiety surrounding death and illness, be it a fear of death or a longing for it. These fears can seem irrational – I am reminded of a patient who was afraid to eat romaine because of news reports that it was responsible for food poisoning in other states, but not Maryland, where the person lived. I found it odd that he worried about eating lettuce, but not about smoking two packs of cigarettes a day.

But our fears are like that – they move to what the media sensationalizes, or to what may be remote, because otherwise no one would get in a car or clear their walkway of snow. Life is most easily lived with a bit of denial: We shut out the reality that we can be here one moment, overscheduled and overwhelmed, with deadlines, mortgage payments, and summer vacation plans, oblivious to the fact that life may end at any moment. The early months of COVID-19 felt like a global game of Russian roulette, with each venture out a pull of the trigger and everyone’s defenses stripped bare.

While death belongs to us all, we relegate it to the disciplines of religion, philosophy, the arts, and psychology. Religion offers answers – whether a heaven, a hell, or continual reincarnation until the individual attains enlightenment, there is a destination. Perhaps it will be pleasant, perhaps not, and for some there is the hope that one gets to be the driver by having the right beliefs or doing good deeds, while others are comforted by the hope of being reunited with loved ones.

“The suddenness endures and the shock lasts – it’s like a meteor that creates a crater and we revisit it in different ways from different angles,” Dr. Lewin said. “It may leap on us unexpectedly, often many years later.”

Patients talk about death, and when their fears seem unrealistic we may long to reassure them, yet there is no reassurance and psychiatry grasps for how to help. Psychiatry has looked to draw lines for when normal grief crosses to abnormal. Is it an adjustment disorder, complicated grief, “prolonged” grief, pathology in need of medication and medicalization, or something one experiences individually, sometimes for a very long time even with treatment?

One justification for pathologizing “prolonged” reactions includes the fact that insurers will pay for treatment only if there is a diagnosis code, and shouldn’t people in distress be entitled to psychotherapy or medication? Yet there is something offensive about telling someone that they are mentally ill if they don’t grieve along a prescribed timeline, as much as there is about denying them the possible benefits of therapy or medication if they seek it, but are suffering in all the “right” ways. Psychiatry’s approach to death is inelegant at best.

In his poignant podcast series, All There Is, Anderson Cooper is tasked with sorting through his mother’s apartment after her death at age 95. In the course of packing up her belongings, he brings on other guests to talk about their emotional reactions to death. Mr. Cooper’s mother, Gloria Vanderbilt, died at an advanced age, but his father died after a brief cardiac illness when Mr. Cooper was a child, and his brother died by suicide when he was 21. He uses these experiences as a springboard to examine childhood losses, the aftermath of suicide, and the loneliness of grief.

“Loss and grief is this universal experience that we will all go through multiple times in our lives,” Mr. Cooper says, “And yet it leaves us feeling so alone and so separated from other people. At least it does me and has my entire life.”

When we talk about grief and loss, we talk about “getting over it,” or “moving on.” But loss doesn’t work that way – time usually eases the pain, leaving scars that are part of the road map for who we are on the journey that defines us.

Sudden death is hard, and the unexpected death of a young person is tragic. For Cait McFarland, there are the decades she won’t get to experience. For her family and friends, it may be excruciating, and for all the patients who have lost a psychiatrist, may time bring healing and peace.

The Dr. Caitlin McFarland Educational Fund for LGBTQI+ Mental Health is being established, and donations are being accepted at https://www.gofundme.com/f/in-memory-of-cait-mcfarland.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. She has disclosed no relevant financial relationships.

“It is one of life’s most self-evident truths that everything fades, that we fear the fading, and that we must live, nonetheless, in the face of the fear.” – Irvin D. Yalom, MD, Existential Psychotherapy, 1980

The email was titled simply, “A sorrowful note,” and I knew that someone had died. I held my breath and read as Dr. Jimmy Potash informed our entire department that Dr. Cait McFarland died in a car accident on December 7 while driving to work at West Cecil Health Center, Conowingo, Md., where she was director of psychiatry.

Sadness swelled as I remembered the outspoken resident who was interested in LGBTQ issues. Cait graduated from the Johns Hopkins residency program in 2020, she had recently married a social worker in the department, and the plan was for her to return to Hopkins full-time in July 2023 to be director of a clinic focused on mental health for people who are transgendered.

Sudden deaths are tragic and jarring and they call to the surface our losses from the past. These deaths don’t stand alone – I found myself thinking of my editor at Medscape, Dr. Bret Stetka, who died unexpectedly in August 2022, and then of Dr. Lidia Palcan Wenz, a psychiatrist I trained with, who died in a motor vehicle accident in 2004. Lidia’s husband also died in the accident, while their two young children in the back seat survived – this tragedy haunted me for some time. None of these people was close to me, but I am no stranger to the impact of unexpected death: My parents and brother all died from cardiac events, and any sudden death is a reminder of those losses.

Julia Riddle, MD, trained with Cait McFarland and was her close friend for years. “I don’t have a belief in ‘the afterlife’ but do like to think of the people that I have lost together in my memory – as if they are all suddenly in a new room together. And, with each loss, all the other occupants of that room come freshly to life again,” Dr. Riddle said.

Death is our shared destination in life, but sudden and unexpected deaths carry their own weight. There is no chance to tie up loose ends, to repair riffs, to say goodbye. Nothing is put in order, and the life that was to be lived goes on for some time as bills arrive, social and work events go unattended, vacations are canceled, and there is the awkward moment of running into someone who didn’t know your loved one has died.

Roger Lewin, MD, is a psychiatrist and writer in Towson, Md. He has both personal and professional experience with sudden death. “There is no way to prepare beforehand, so we have to get ready for what has already happened, and that is hard,” he said. “We invent a life for ourselves and others that extends into the future, and that gets interrupted.”

Most people become ill and die on a vaguely predictable schedule. There may be a chance to plan, to know and honor the wishes of the individual, and often there is the opportunity for loved ones to begin the grieving process gradually as death approaches. For those who are elderly, there may be a sense that this is the natural order of things – which may or may not temper the intensity of the grief for those who remain. If the person has suffered, the end may come with relief.

Still, I sometimes find myself surprised at the length and intensity of anguish that some people experience after losing a loved one who has lived a long and full life, who declined and suffered, but whose absence remains a gaping wound that takes years to form a scar.

Sudden death is not rare; accidents, homicide, and suicide are the top killers among young people, and cardiovascular deaths are number one among those who are older. Natural disasters and terrorist attacks can cause catastrophic numbers of sudden deaths and leave survivors to grieve not only the dead, but the loss of all that was familiar to them.

Psychiatry has been a bit lost as to how we approach grief. We often hear patients talk about anxiety surrounding death and illness, be it a fear of death or a longing for it. These fears can seem irrational – I am reminded of a patient who was afraid to eat romaine because of news reports that it was responsible for food poisoning in other states, but not Maryland, where the person lived. I found it odd that he worried about eating lettuce, but not about smoking two packs of cigarettes a day.

But our fears are like that – they move to what the media sensationalizes, or to what may be remote, because otherwise no one would get in a car or clear their walkway of snow. Life is most easily lived with a bit of denial: We shut out the reality that we can be here one moment, overscheduled and overwhelmed, with deadlines, mortgage payments, and summer vacation plans, oblivious to the fact that life may end at any moment. The early months of COVID-19 felt like a global game of Russian roulette, with each venture out a pull of the trigger and everyone’s defenses stripped bare.

While death belongs to us all, we relegate it to the disciplines of religion, philosophy, the arts, and psychology. Religion offers answers – whether a heaven, a hell, or continual reincarnation until the individual attains enlightenment, there is a destination. Perhaps it will be pleasant, perhaps not, and for some there is the hope that one gets to be the driver by having the right beliefs or doing good deeds, while others are comforted by the hope of being reunited with loved ones.

“The suddenness endures and the shock lasts – it’s like a meteor that creates a crater and we revisit it in different ways from different angles,” Dr. Lewin said. “It may leap on us unexpectedly, often many years later.”

Patients talk about death, and when their fears seem unrealistic we may long to reassure them, yet there is no reassurance and psychiatry grasps for how to help. Psychiatry has looked to draw lines for when normal grief crosses to abnormal. Is it an adjustment disorder, complicated grief, “prolonged” grief, pathology in need of medication and medicalization, or something one experiences individually, sometimes for a very long time even with treatment?

One justification for pathologizing “prolonged” reactions includes the fact that insurers will pay for treatment only if there is a diagnosis code, and shouldn’t people in distress be entitled to psychotherapy or medication? Yet there is something offensive about telling someone that they are mentally ill if they don’t grieve along a prescribed timeline, as much as there is about denying them the possible benefits of therapy or medication if they seek it, but are suffering in all the “right” ways. Psychiatry’s approach to death is inelegant at best.

In his poignant podcast series, All There Is, Anderson Cooper is tasked with sorting through his mother’s apartment after her death at age 95. In the course of packing up her belongings, he brings on other guests to talk about their emotional reactions to death. Mr. Cooper’s mother, Gloria Vanderbilt, died at an advanced age, but his father died after a brief cardiac illness when Mr. Cooper was a child, and his brother died by suicide when he was 21. He uses these experiences as a springboard to examine childhood losses, the aftermath of suicide, and the loneliness of grief.

“Loss and grief is this universal experience that we will all go through multiple times in our lives,” Mr. Cooper says, “And yet it leaves us feeling so alone and so separated from other people. At least it does me and has my entire life.”

When we talk about grief and loss, we talk about “getting over it,” or “moving on.” But loss doesn’t work that way – time usually eases the pain, leaving scars that are part of the road map for who we are on the journey that defines us.

Sudden death is hard, and the unexpected death of a young person is tragic. For Cait McFarland, there are the decades she won’t get to experience. For her family and friends, it may be excruciating, and for all the patients who have lost a psychiatrist, may time bring healing and peace.

The Dr. Caitlin McFarland Educational Fund for LGBTQI+ Mental Health is being established, and donations are being accepted at https://www.gofundme.com/f/in-memory-of-cait-mcfarland.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. She has disclosed no relevant financial relationships.

“It is one of life’s most self-evident truths that everything fades, that we fear the fading, and that we must live, nonetheless, in the face of the fear.” – Irvin D. Yalom, MD, Existential Psychotherapy, 1980

The email was titled simply, “A sorrowful note,” and I knew that someone had died. I held my breath and read as Dr. Jimmy Potash informed our entire department that Dr. Cait McFarland died in a car accident on December 7 while driving to work at West Cecil Health Center, Conowingo, Md., where she was director of psychiatry.

Sadness swelled as I remembered the outspoken resident who was interested in LGBTQ issues. Cait graduated from the Johns Hopkins residency program in 2020, she had recently married a social worker in the department, and the plan was for her to return to Hopkins full-time in July 2023 to be director of a clinic focused on mental health for people who are transgendered.

Sudden deaths are tragic and jarring and they call to the surface our losses from the past. These deaths don’t stand alone – I found myself thinking of my editor at Medscape, Dr. Bret Stetka, who died unexpectedly in August 2022, and then of Dr. Lidia Palcan Wenz, a psychiatrist I trained with, who died in a motor vehicle accident in 2004. Lidia’s husband also died in the accident, while their two young children in the back seat survived – this tragedy haunted me for some time. None of these people was close to me, but I am no stranger to the impact of unexpected death: My parents and brother all died from cardiac events, and any sudden death is a reminder of those losses.

Julia Riddle, MD, trained with Cait McFarland and was her close friend for years. “I don’t have a belief in ‘the afterlife’ but do like to think of the people that I have lost together in my memory – as if they are all suddenly in a new room together. And, with each loss, all the other occupants of that room come freshly to life again,” Dr. Riddle said.

Death is our shared destination in life, but sudden and unexpected deaths carry their own weight. There is no chance to tie up loose ends, to repair riffs, to say goodbye. Nothing is put in order, and the life that was to be lived goes on for some time as bills arrive, social and work events go unattended, vacations are canceled, and there is the awkward moment of running into someone who didn’t know your loved one has died.

Roger Lewin, MD, is a psychiatrist and writer in Towson, Md. He has both personal and professional experience with sudden death. “There is no way to prepare beforehand, so we have to get ready for what has already happened, and that is hard,” he said. “We invent a life for ourselves and others that extends into the future, and that gets interrupted.”

Most people become ill and die on a vaguely predictable schedule. There may be a chance to plan, to know and honor the wishes of the individual, and often there is the opportunity for loved ones to begin the grieving process gradually as death approaches. For those who are elderly, there may be a sense that this is the natural order of things – which may or may not temper the intensity of the grief for those who remain. If the person has suffered, the end may come with relief.

Still, I sometimes find myself surprised at the length and intensity of anguish that some people experience after losing a loved one who has lived a long and full life, who declined and suffered, but whose absence remains a gaping wound that takes years to form a scar.

Sudden death is not rare; accidents, homicide, and suicide are the top killers among young people, and cardiovascular deaths are number one among those who are older. Natural disasters and terrorist attacks can cause catastrophic numbers of sudden deaths and leave survivors to grieve not only the dead, but the loss of all that was familiar to them.

Psychiatry has been a bit lost as to how we approach grief. We often hear patients talk about anxiety surrounding death and illness, be it a fear of death or a longing for it. These fears can seem irrational – I am reminded of a patient who was afraid to eat romaine because of news reports that it was responsible for food poisoning in other states, but not Maryland, where the person lived. I found it odd that he worried about eating lettuce, but not about smoking two packs of cigarettes a day.

But our fears are like that – they move to what the media sensationalizes, or to what may be remote, because otherwise no one would get in a car or clear their walkway of snow. Life is most easily lived with a bit of denial: We shut out the reality that we can be here one moment, overscheduled and overwhelmed, with deadlines, mortgage payments, and summer vacation plans, oblivious to the fact that life may end at any moment. The early months of COVID-19 felt like a global game of Russian roulette, with each venture out a pull of the trigger and everyone’s defenses stripped bare.

While death belongs to us all, we relegate it to the disciplines of religion, philosophy, the arts, and psychology. Religion offers answers – whether a heaven, a hell, or continual reincarnation until the individual attains enlightenment, there is a destination. Perhaps it will be pleasant, perhaps not, and for some there is the hope that one gets to be the driver by having the right beliefs or doing good deeds, while others are comforted by the hope of being reunited with loved ones.

“The suddenness endures and the shock lasts – it’s like a meteor that creates a crater and we revisit it in different ways from different angles,” Dr. Lewin said. “It may leap on us unexpectedly, often many years later.”

Patients talk about death, and when their fears seem unrealistic we may long to reassure them, yet there is no reassurance and psychiatry grasps for how to help. Psychiatry has looked to draw lines for when normal grief crosses to abnormal. Is it an adjustment disorder, complicated grief, “prolonged” grief, pathology in need of medication and medicalization, or something one experiences individually, sometimes for a very long time even with treatment?

One justification for pathologizing “prolonged” reactions includes the fact that insurers will pay for treatment only if there is a diagnosis code, and shouldn’t people in distress be entitled to psychotherapy or medication? Yet there is something offensive about telling someone that they are mentally ill if they don’t grieve along a prescribed timeline, as much as there is about denying them the possible benefits of therapy or medication if they seek it, but are suffering in all the “right” ways. Psychiatry’s approach to death is inelegant at best.

In his poignant podcast series, All There Is, Anderson Cooper is tasked with sorting through his mother’s apartment after her death at age 95. In the course of packing up her belongings, he brings on other guests to talk about their emotional reactions to death. Mr. Cooper’s mother, Gloria Vanderbilt, died at an advanced age, but his father died after a brief cardiac illness when Mr. Cooper was a child, and his brother died by suicide when he was 21. He uses these experiences as a springboard to examine childhood losses, the aftermath of suicide, and the loneliness of grief.

“Loss and grief is this universal experience that we will all go through multiple times in our lives,” Mr. Cooper says, “And yet it leaves us feeling so alone and so separated from other people. At least it does me and has my entire life.”

When we talk about grief and loss, we talk about “getting over it,” or “moving on.” But loss doesn’t work that way – time usually eases the pain, leaving scars that are part of the road map for who we are on the journey that defines us.

Sudden death is hard, and the unexpected death of a young person is tragic. For Cait McFarland, there are the decades she won’t get to experience. For her family and friends, it may be excruciating, and for all the patients who have lost a psychiatrist, may time bring healing and peace.

The Dr. Caitlin McFarland Educational Fund for LGBTQI+ Mental Health is being established, and donations are being accepted at https://www.gofundme.com/f/in-memory-of-cait-mcfarland.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. She has disclosed no relevant financial relationships.

In the treatment of depression, clinicians are commonly dealing with a mix of comorbidities that are more complex than just depression, and as such, effective treatment options may likewise require thinking outside of the box – and beyond the definitions of the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision).

“The DSM-5 isn’t handed to us on tablets from Mount Sinai,” said Charles B. Nemeroff, MD, PhD, professor and chair in the department of psychiatry and behavioral sciences at the Mulva Clinic for the Neurosciences at the University of Texas at Austin. He spoke at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

“Our patients don’t fall into these very convenient buckets,” Dr. Nemeroff said. “The problem with depression is patients have very high rates of morbidity and comorbidity.”

The array of potential psychiatric comorbidities that are common in depression is somewhat staggering: As many as 70% of patients also have social anxiety disorder; 67% of patients have obsessive-compulsive disorder (OCD); up to 65% of patients have panic disorder; 48% of patients have posttraumatic stress disorder (PTSD); and 42% have generalized anxiety disorder, Dr. Nemeroff said.

And while the DSM-5 may have all those bases covered, in real world clinical practice, cracking the code of each patient’s unique and often more complicated psychiatric profile – and how to best manage it – can be a challenge. But Dr. Nemeroff said important clues can guide the clinician’s path.

A key starting point is making sure to gauge the severity of the patient’s core depression with one of the validated depression scales – whether it’s the self-reported Beck Depression Inventory, the clinician-rated Hamilton Rating Scale for Depression, the clinician-rated Montgomery Asberg Depression Rating Scale, or the Inventory of Depressive Symptoms, clinicians should pick one and track the score with each visit, Dr. Nemeroff advised.

“It doesn’t matter which tool you prefer – most tend to like the Beck Depression Scale, but the bottom line is that you have to get a measure of severity at every visit,” he said.

Among the most important comorbidities to identify as soon as possible is bipolar disorder, due to the potential worsening of the condition that can occur among those patients if treated with antidepressants, Dr. Nemeroff said.

“The question of whether the patient is bipolar should always be in the back of your mind,” he cautioned. “And if patients have been started on antidepressants, the clues may become evident very quickly.”

The most important indicator that the patient has bipolar disorder “is if they tell you that they were prescribed an antidepressant and it resulted in an increase in what we know to be hypomania – they may describe it as agitation or an inability to sleep,” Dr. Nemeroff said.

Of note, the effect is much more common with SNRIs [serotonin norepinephrine reuptake inhibitors] than SSRIs [selective serotonin reuptake inhibitors], he said.

“The effect is particularly notable with venlafaxine,” he said. “But SNRIs all have the propensity to switch people with depression into hypomania, but only patients who have bipolar disorder.”

“If you give a patient 150 mg of venlafaxine and they switch to developing hypomania, you now have the diagnosis of bipolar disorder, and you can treat them appropriately.”

Other important clues of bipolarity in depressed patients include:

• Family history: Most cases are genetically driven.
• Earlier age of onset (younger than age 25): “If the patient tells you they were depressed prepuberty, you should be thinking about the possibility of bipolar disorder, as it often presents as depression in childhood.”
• Psychotic features: As many as 80% of patients with psychotic depression end up being bipolar, Dr. Nemeroff said.
• Atypical depression: For example, depression with hypersomnia, or having an increased appetite instead of decreased, or a high amount of anxiety.

Remission should be the goal of treatment, and Dr. Nemeroff said that in efforts to accomplish that with the help of medications, psychiatrists may need to think “outside of the box” – or beyond the label.

“Many practitioners become slaves to the PDR [Physicians’ Desk Reference],” he said. “It is only a guide to what the clinical trials show, and not a mandate in terms of dosing.”

“There’s often strong data in the literature that supports going to a higher dose, if necessary, and I have [plenty] of patients, for instance, on 450 or 600 mg of venlafaxine who had not responded to 150 or even 300 mg.”
 

Treatment resistance

When patients continue to fail to respond, regardless of dosing or medication adjustments, Dr. Nemeroff suggested that clinicians should consider the potential important reasons. For instance, in addition to comorbid psychiatric conditions, practitioners should determine if there are medical conditions that they are not aware of.

“Does the patient have an underlying medical condition, such as thyroid dysfunction, early Parkinson’s disease, or even something like cancer?” he said.

There is also the inevitable question of whether the patient is indeed taking the medication. “We know that 30% of our patients do not follow their prescriptions, so of course that’s an important question to ask,” Dr. Nemeroff said.

Finally, while some pharmacogenomic tests are emerging with the suggestion of identifying which patients may or may not respond to certain drugs, Dr. Nemeroff says he’s seen little convincing evidence of their benefits.

“We have a problem in this field in that we don’t have the kinds of markers that they do in oncology, so we’re left with having to generally play trial and error,” he said.

“But when it comes to these pharmacogenomic tests, there’s just no ‘there there’,” he asserted. “From what I’ve seen so far, it’s frankly neuro-mythology.”

Dr. Nemeroff disclosed that he receives grant/research support from the National Institutes of Health and serves as a consultant for and/or on the advisory boards of multiple pharmaceutical companies.

The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.

In the treatment of depression, clinicians are commonly dealing with a mix of comorbidities that are more complex than just depression, and as such, effective treatment options may likewise require thinking outside of the box – and beyond the definitions of the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision).

“The DSM-5 isn’t handed to us on tablets from Mount Sinai,” said Charles B. Nemeroff, MD, PhD, professor and chair in the department of psychiatry and behavioral sciences at the Mulva Clinic for the Neurosciences at the University of Texas at Austin. He spoke at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

“Our patients don’t fall into these very convenient buckets,” Dr. Nemeroff said. “The problem with depression is patients have very high rates of morbidity and comorbidity.”

The array of potential psychiatric comorbidities that are common in depression is somewhat staggering: As many as 70% of patients also have social anxiety disorder; 67% of patients have obsessive-compulsive disorder (OCD); up to 65% of patients have panic disorder; 48% of patients have posttraumatic stress disorder (PTSD); and 42% have generalized anxiety disorder, Dr. Nemeroff said.

And while the DSM-5 may have all those bases covered, in real world clinical practice, cracking the code of each patient’s unique and often more complicated psychiatric profile – and how to best manage it – can be a challenge. But Dr. Nemeroff said important clues can guide the clinician’s path.

A key starting point is making sure to gauge the severity of the patient’s core depression with one of the validated depression scales – whether it’s the self-reported Beck Depression Inventory, the clinician-rated Hamilton Rating Scale for Depression, the clinician-rated Montgomery Asberg Depression Rating Scale, or the Inventory of Depressive Symptoms, clinicians should pick one and track the score with each visit, Dr. Nemeroff advised.

“It doesn’t matter which tool you prefer – most tend to like the Beck Depression Scale, but the bottom line is that you have to get a measure of severity at every visit,” he said.

Among the most important comorbidities to identify as soon as possible is bipolar disorder, due to the potential worsening of the condition that can occur among those patients if treated with antidepressants, Dr. Nemeroff said.

“The question of whether the patient is bipolar should always be in the back of your mind,” he cautioned. “And if patients have been started on antidepressants, the clues may become evident very quickly.”

The most important indicator that the patient has bipolar disorder “is if they tell you that they were prescribed an antidepressant and it resulted in an increase in what we know to be hypomania – they may describe it as agitation or an inability to sleep,” Dr. Nemeroff said.

Of note, the effect is much more common with SNRIs [serotonin norepinephrine reuptake inhibitors] than SSRIs [selective serotonin reuptake inhibitors], he said.

“The effect is particularly notable with venlafaxine,” he said. “But SNRIs all have the propensity to switch people with depression into hypomania, but only patients who have bipolar disorder.”

“If you give a patient 150 mg of venlafaxine and they switch to developing hypomania, you now have the diagnosis of bipolar disorder, and you can treat them appropriately.”

Other important clues of bipolarity in depressed patients include:

• Family history: Most cases are genetically driven.
• Earlier age of onset (younger than age 25): “If the patient tells you they were depressed prepuberty, you should be thinking about the possibility of bipolar disorder, as it often presents as depression in childhood.”
• Psychotic features: As many as 80% of patients with psychotic depression end up being bipolar, Dr. Nemeroff said.
• Atypical depression: For example, depression with hypersomnia, or having an increased appetite instead of decreased, or a high amount of anxiety.

Remission should be the goal of treatment, and Dr. Nemeroff said that in efforts to accomplish that with the help of medications, psychiatrists may need to think “outside of the box” – or beyond the label.

“Many practitioners become slaves to the PDR [Physicians’ Desk Reference],” he said. “It is only a guide to what the clinical trials show, and not a mandate in terms of dosing.”

“There’s often strong data in the literature that supports going to a higher dose, if necessary, and I have [plenty] of patients, for instance, on 450 or 600 mg of venlafaxine who had not responded to 150 or even 300 mg.”
 

Treatment resistance

When patients continue to fail to respond, regardless of dosing or medication adjustments, Dr. Nemeroff suggested that clinicians should consider the potential important reasons. For instance, in addition to comorbid psychiatric conditions, practitioners should determine if there are medical conditions that they are not aware of.

“Does the patient have an underlying medical condition, such as thyroid dysfunction, early Parkinson’s disease, or even something like cancer?” he said.

There is also the inevitable question of whether the patient is indeed taking the medication. “We know that 30% of our patients do not follow their prescriptions, so of course that’s an important question to ask,” Dr. Nemeroff said.

Finally, while some pharmacogenomic tests are emerging with the suggestion of identifying which patients may or may not respond to certain drugs, Dr. Nemeroff says he’s seen little convincing evidence of their benefits.

“We have a problem in this field in that we don’t have the kinds of markers that they do in oncology, so we’re left with having to generally play trial and error,” he said.

“But when it comes to these pharmacogenomic tests, there’s just no ‘there there’,” he asserted. “From what I’ve seen so far, it’s frankly neuro-mythology.”

Dr. Nemeroff disclosed that he receives grant/research support from the National Institutes of Health and serves as a consultant for and/or on the advisory boards of multiple pharmaceutical companies.

The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.

In the treatment of depression, clinicians are commonly dealing with a mix of comorbidities that are more complex than just depression, and as such, effective treatment options may likewise require thinking outside of the box – and beyond the definitions of the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision).

“The DSM-5 isn’t handed to us on tablets from Mount Sinai,” said Charles B. Nemeroff, MD, PhD, professor and chair in the department of psychiatry and behavioral sciences at the Mulva Clinic for the Neurosciences at the University of Texas at Austin. He spoke at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

“Our patients don’t fall into these very convenient buckets,” Dr. Nemeroff said. “The problem with depression is patients have very high rates of morbidity and comorbidity.”

The array of potential psychiatric comorbidities that are common in depression is somewhat staggering: As many as 70% of patients also have social anxiety disorder; 67% of patients have obsessive-compulsive disorder (OCD); up to 65% of patients have panic disorder; 48% of patients have posttraumatic stress disorder (PTSD); and 42% have generalized anxiety disorder, Dr. Nemeroff said.

And while the DSM-5 may have all those bases covered, in real world clinical practice, cracking the code of each patient’s unique and often more complicated psychiatric profile – and how to best manage it – can be a challenge. But Dr. Nemeroff said important clues can guide the clinician’s path.

A key starting point is making sure to gauge the severity of the patient’s core depression with one of the validated depression scales – whether it’s the self-reported Beck Depression Inventory, the clinician-rated Hamilton Rating Scale for Depression, the clinician-rated Montgomery Asberg Depression Rating Scale, or the Inventory of Depressive Symptoms, clinicians should pick one and track the score with each visit, Dr. Nemeroff advised.

“It doesn’t matter which tool you prefer – most tend to like the Beck Depression Scale, but the bottom line is that you have to get a measure of severity at every visit,” he said.

Among the most important comorbidities to identify as soon as possible is bipolar disorder, due to the potential worsening of the condition that can occur among those patients if treated with antidepressants, Dr. Nemeroff said.

“The question of whether the patient is bipolar should always be in the back of your mind,” he cautioned. “And if patients have been started on antidepressants, the clues may become evident very quickly.”

The most important indicator that the patient has bipolar disorder “is if they tell you that they were prescribed an antidepressant and it resulted in an increase in what we know to be hypomania – they may describe it as agitation or an inability to sleep,” Dr. Nemeroff said.

Of note, the effect is much more common with SNRIs [serotonin norepinephrine reuptake inhibitors] than SSRIs [selective serotonin reuptake inhibitors], he said.

“The effect is particularly notable with venlafaxine,” he said. “But SNRIs all have the propensity to switch people with depression into hypomania, but only patients who have bipolar disorder.”

“If you give a patient 150 mg of venlafaxine and they switch to developing hypomania, you now have the diagnosis of bipolar disorder, and you can treat them appropriately.”

Other important clues of bipolarity in depressed patients include:

• Family history: Most cases are genetically driven.
• Earlier age of onset (younger than age 25): “If the patient tells you they were depressed prepuberty, you should be thinking about the possibility of bipolar disorder, as it often presents as depression in childhood.”
• Psychotic features: As many as 80% of patients with psychotic depression end up being bipolar, Dr. Nemeroff said.
• Atypical depression: For example, depression with hypersomnia, or having an increased appetite instead of decreased, or a high amount of anxiety.

Remission should be the goal of treatment, and Dr. Nemeroff said that in efforts to accomplish that with the help of medications, psychiatrists may need to think “outside of the box” – or beyond the label.

“Many practitioners become slaves to the PDR [Physicians’ Desk Reference],” he said. “It is only a guide to what the clinical trials show, and not a mandate in terms of dosing.”

“There’s often strong data in the literature that supports going to a higher dose, if necessary, and I have [plenty] of patients, for instance, on 450 or 600 mg of venlafaxine who had not responded to 150 or even 300 mg.”
 

Treatment resistance

When patients continue to fail to respond, regardless of dosing or medication adjustments, Dr. Nemeroff suggested that clinicians should consider the potential important reasons. For instance, in addition to comorbid psychiatric conditions, practitioners should determine if there are medical conditions that they are not aware of.

“Does the patient have an underlying medical condition, such as thyroid dysfunction, early Parkinson’s disease, or even something like cancer?” he said.

There is also the inevitable question of whether the patient is indeed taking the medication. “We know that 30% of our patients do not follow their prescriptions, so of course that’s an important question to ask,” Dr. Nemeroff said.

Finally, while some pharmacogenomic tests are emerging with the suggestion of identifying which patients may or may not respond to certain drugs, Dr. Nemeroff says he’s seen little convincing evidence of their benefits.

“We have a problem in this field in that we don’t have the kinds of markers that they do in oncology, so we’re left with having to generally play trial and error,” he said.

“But when it comes to these pharmacogenomic tests, there’s just no ‘there there’,” he asserted. “From what I’ve seen so far, it’s frankly neuro-mythology.”

Dr. Nemeroff disclosed that he receives grant/research support from the National Institutes of Health and serves as a consultant for and/or on the advisory boards of multiple pharmaceutical companies.

The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.

The antidepressant vortioxetine (Trintellix) improved cognition, memory, and depressive symptoms in patients with comorbid major depressive disorder (MDD) and dementia.

The results of the 12-week open-label, single-group study are positive, study investigator Michael Cronquist Christensen, MPA, DrPH, a director with the Lundbeck pharmaceutical company, told this news organization before presenting the results in a poster at the 15th Clinical Trials on Alzheimer’s Disease conference.

“The study confirms earlier findings of improvement in both depressive symptoms and cognitive performance with vortioxetine in patients with depression and dementia and adds to this research that these clinical effects also extend to improvement in health-related quality of life and patients’ daily functioning,” Dr. Christensen said.

“It also demonstrates that patients with depression and comorbid dementia can be safely treated with 20 mg vortioxetine – starting dose of 5 mg for the first week and up-titration to 10 mg at day 8,” he added.

However, he reported that Lundbeck doesn’t plan to seek approval from the U.S. Food and Drug Administration for a new indication. Vortioxetine received FDA approval in 2013 to treat MDD, but 3 years later the agency rejected an expansion of its indication to include cognitive dysfunction.

“Vortioxetine is approved for MDD, but the product can be used in patients with MDD who have other diseases, including other mental illnesses,” Dr. Christensen said.

Potential neurotransmission modulator

Vortioxetine is a selective serotonin reuptake inhibitor and serotonin receptor modulator. According to Dr. Christensen, evidence suggests the drug’s receptor targets “have the potential to modulate neurotransmitter systems that are essential for regulation of cognitive function.”

The researchers recruited 83 individuals aged 55-85 with recurrent MDD that had started before the age of 55. All had MDD episodes within the previous 6 months and comorbid dementia for at least 6 months.

Of the participants, 65.9% were female. In addition, 42.7% had Alzheimer’s disease, 26.8% had mixed-type dementia, and the rest had other types of dementia.

The daily oral dose of vortioxetine started at 5 mg for up to week 1 and then was increased to 10 mg. It was then increased to 20 mg or decreased to 5 mg “based on investigator judgment and patient response.” The average daily dose was 12.3 mg.

In regard to the primary outcome, at week 12 (n = 70), scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) fell by a mean of –12.4 (.78, P < .0001), which researchers deemed to be a significant reduction in severe symptoms.

“A significant and clinically meaningful effect was observed from week 1,” the researchers reported.

“As a basis for comparison, we typically see an improvement around 13-14 points during 8 weeks of antidepressant treatment in adults with MDD who do not have dementia,” Dr. Christensen added.

More than a third of patients (35.7%) saw a reduction in MADRS score by more than 50% at week 12, and 17.2% were considered to have reached MDD depression remission, defined as a MADRS score at or under 10.

For secondary outcomes, the total Digit Symbol Substitution test score grew by 0.65 (standardized effect size) by week 12, showing significant improvement (P < .0001). In addition, participants improved on some other cognitive measures, and Dr. Christensen noted that “significant improvement was also observed in the patients’ health-related quality of life and daily functioning.”

A third of patients had drug-related treatment-emergent adverse events.

Vortioxetine is one of the most expensive antidepressants: It has a list price of $444 a month, and no generic version is currently available.

Small trial, open-label design

In a comment, Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer’s Association, said the study “reflects a valuable aspect of treatment research because of the close connection between depression and dementia. Depression is a known risk factor for dementia, including Alzheimer’s disease, and those who have dementia may experience depression.”

Alzheimer’s Association

She cautioned, however, that the trial was small and had an open-label design instead of the “gold standard” of a double-blinded trial with a control group.

The study was funded by Lundbeck, where Dr. Christensen is an employee. Another author is a Lundbeck employee, and a third author reported various disclosures. Dr. Sexton reported no disclosures.

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

The antidepressant vortioxetine (Trintellix) improved cognition, memory, and depressive symptoms in patients with comorbid major depressive disorder (MDD) and dementia.

The results of the 12-week open-label, single-group study are positive, study investigator Michael Cronquist Christensen, MPA, DrPH, a director with the Lundbeck pharmaceutical company, told this news organization before presenting the results in a poster at the 15th Clinical Trials on Alzheimer’s Disease conference.

“The study confirms earlier findings of improvement in both depressive symptoms and cognitive performance with vortioxetine in patients with depression and dementia and adds to this research that these clinical effects also extend to improvement in health-related quality of life and patients’ daily functioning,” Dr. Christensen said.

“It also demonstrates that patients with depression and comorbid dementia can be safely treated with 20 mg vortioxetine – starting dose of 5 mg for the first week and up-titration to 10 mg at day 8,” he added.

However, he reported that Lundbeck doesn’t plan to seek approval from the U.S. Food and Drug Administration for a new indication. Vortioxetine received FDA approval in 2013 to treat MDD, but 3 years later the agency rejected an expansion of its indication to include cognitive dysfunction.

“Vortioxetine is approved for MDD, but the product can be used in patients with MDD who have other diseases, including other mental illnesses,” Dr. Christensen said.

Potential neurotransmission modulator

Vortioxetine is a selective serotonin reuptake inhibitor and serotonin receptor modulator. According to Dr. Christensen, evidence suggests the drug’s receptor targets “have the potential to modulate neurotransmitter systems that are essential for regulation of cognitive function.”

The researchers recruited 83 individuals aged 55-85 with recurrent MDD that had started before the age of 55. All had MDD episodes within the previous 6 months and comorbid dementia for at least 6 months.

Of the participants, 65.9% were female. In addition, 42.7% had Alzheimer’s disease, 26.8% had mixed-type dementia, and the rest had other types of dementia.

The daily oral dose of vortioxetine started at 5 mg for up to week 1 and then was increased to 10 mg. It was then increased to 20 mg or decreased to 5 mg “based on investigator judgment and patient response.” The average daily dose was 12.3 mg.

In regard to the primary outcome, at week 12 (n = 70), scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) fell by a mean of –12.4 (.78, P < .0001), which researchers deemed to be a significant reduction in severe symptoms.

“A significant and clinically meaningful effect was observed from week 1,” the researchers reported.

“As a basis for comparison, we typically see an improvement around 13-14 points during 8 weeks of antidepressant treatment in adults with MDD who do not have dementia,” Dr. Christensen added.

More than a third of patients (35.7%) saw a reduction in MADRS score by more than 50% at week 12, and 17.2% were considered to have reached MDD depression remission, defined as a MADRS score at or under 10.

For secondary outcomes, the total Digit Symbol Substitution test score grew by 0.65 (standardized effect size) by week 12, showing significant improvement (P < .0001). In addition, participants improved on some other cognitive measures, and Dr. Christensen noted that “significant improvement was also observed in the patients’ health-related quality of life and daily functioning.”

A third of patients had drug-related treatment-emergent adverse events.

Vortioxetine is one of the most expensive antidepressants: It has a list price of $444 a month, and no generic version is currently available.

Small trial, open-label design

In a comment, Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer’s Association, said the study “reflects a valuable aspect of treatment research because of the close connection between depression and dementia. Depression is a known risk factor for dementia, including Alzheimer’s disease, and those who have dementia may experience depression.”

Alzheimer’s Association

She cautioned, however, that the trial was small and had an open-label design instead of the “gold standard” of a double-blinded trial with a control group.

The study was funded by Lundbeck, where Dr. Christensen is an employee. Another author is a Lundbeck employee, and a third author reported various disclosures. Dr. Sexton reported no disclosures.

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

The antidepressant vortioxetine (Trintellix) improved cognition, memory, and depressive symptoms in patients with comorbid major depressive disorder (MDD) and dementia.

The results of the 12-week open-label, single-group study are positive, study investigator Michael Cronquist Christensen, MPA, DrPH, a director with the Lundbeck pharmaceutical company, told this news organization before presenting the results in a poster at the 15th Clinical Trials on Alzheimer’s Disease conference.

“The study confirms earlier findings of improvement in both depressive symptoms and cognitive performance with vortioxetine in patients with depression and dementia and adds to this research that these clinical effects also extend to improvement in health-related quality of life and patients’ daily functioning,” Dr. Christensen said.

“It also demonstrates that patients with depression and comorbid dementia can be safely treated with 20 mg vortioxetine – starting dose of 5 mg for the first week and up-titration to 10 mg at day 8,” he added.

However, he reported that Lundbeck doesn’t plan to seek approval from the U.S. Food and Drug Administration for a new indication. Vortioxetine received FDA approval in 2013 to treat MDD, but 3 years later the agency rejected an expansion of its indication to include cognitive dysfunction.

“Vortioxetine is approved for MDD, but the product can be used in patients with MDD who have other diseases, including other mental illnesses,” Dr. Christensen said.

Potential neurotransmission modulator

Vortioxetine is a selective serotonin reuptake inhibitor and serotonin receptor modulator. According to Dr. Christensen, evidence suggests the drug’s receptor targets “have the potential to modulate neurotransmitter systems that are essential for regulation of cognitive function.”

The researchers recruited 83 individuals aged 55-85 with recurrent MDD that had started before the age of 55. All had MDD episodes within the previous 6 months and comorbid dementia for at least 6 months.

Of the participants, 65.9% were female. In addition, 42.7% had Alzheimer’s disease, 26.8% had mixed-type dementia, and the rest had other types of dementia.

The daily oral dose of vortioxetine started at 5 mg for up to week 1 and then was increased to 10 mg. It was then increased to 20 mg or decreased to 5 mg “based on investigator judgment and patient response.” The average daily dose was 12.3 mg.

In regard to the primary outcome, at week 12 (n = 70), scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) fell by a mean of –12.4 (.78, P < .0001), which researchers deemed to be a significant reduction in severe symptoms.

“A significant and clinically meaningful effect was observed from week 1,” the researchers reported.

“As a basis for comparison, we typically see an improvement around 13-14 points during 8 weeks of antidepressant treatment in adults with MDD who do not have dementia,” Dr. Christensen added.

More than a third of patients (35.7%) saw a reduction in MADRS score by more than 50% at week 12, and 17.2% were considered to have reached MDD depression remission, defined as a MADRS score at or under 10.

For secondary outcomes, the total Digit Symbol Substitution test score grew by 0.65 (standardized effect size) by week 12, showing significant improvement (P < .0001). In addition, participants improved on some other cognitive measures, and Dr. Christensen noted that “significant improvement was also observed in the patients’ health-related quality of life and daily functioning.”

A third of patients had drug-related treatment-emergent adverse events.

Vortioxetine is one of the most expensive antidepressants: It has a list price of $444 a month, and no generic version is currently available.

Small trial, open-label design

In a comment, Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer’s Association, said the study “reflects a valuable aspect of treatment research because of the close connection between depression and dementia. Depression is a known risk factor for dementia, including Alzheimer’s disease, and those who have dementia may experience depression.”

Alzheimer’s Association

She cautioned, however, that the trial was small and had an open-label design instead of the “gold standard” of a double-blinded trial with a control group.

The study was funded by Lundbeck, where Dr. Christensen is an employee. Another author is a Lundbeck employee, and a third author reported various disclosures. Dr. Sexton reported no disclosures.

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

Being male, being older, and having a clear intent to die were among the key independent predictors of psychiatric hospital admission after self-harm, based on data from more than 1,800 individuals.

Clinicians who assess suicidal patients in the emergency department setting face the challenge of whether to admit the patient to inpatient or outpatient care, and data on predictors of compulsory admission are limited, wrote Laurent Michaud, MD, of the University of Lausanne, Switzerland, and colleagues.

To better identify predictors of hospitalization after self-harm, the researchers reviewed data from 1,832 patients aged 18 years and older admitted to four emergency departments in Switzerland between December 2016 and November 2019 .

Self-harm (SH) was defined in this study as “all nonfatal intentional acts of self-poisoning or self-injury, irrespective of degree of suicidal intent or other types of motivation,” the researchers noted. The study included 2,142 episodes of self-harm.

The researchers conducted two analyses. They compared episodes followed by any hospitalization and those with outpatient follow-up (1,083 episodes vs. 1,059 episodes) and episodes followed by compulsory hospitalization (357 episodes) with all other episodes followed by either outpatient care or voluntary hospitalization (1,785 episodes).

Overall, women were significantly more likely to be referred to outpatient follow-up compared with men (61.8% vs. 38.1%), and hospitalized patients were significantly older than outpatients (mean age of 41 years vs. 36 years, P < .001 for both).

“Not surprisingly, major psychopathological conditions such as depression, mania, dementia, and schizophrenia were predictive of hospitalization,” the researchers noted.

Other sociodemographic factors associated with hospitalization included living alone, no children, problematic socioeconomic status, and unemployment. Clinical factors associated with hospitalization included physical pain, more lethal suicide attempt method, and clear intent to die.

In a multivariate analysis, independent predictors of any hospitalization included male gender, older age, assessment in the Neuchatel location vs. Lausanne, depression vs. personality disorders, substance use, or anxiety disorder, difficult socioeconomic status, a clear vs. unclear intent to die, and a serious suicide attempt vs. less serious.

Differences in hospitalization based on hospital setting was a striking finding, the researchers wrote in their discussion. These differences may be largely explained by the organization of local mental health services and specific institutional cultures; the workload of staff and availability of beds also may have played a role in decisions to hospitalize, they said.

The findings were limited by several factors including the lack of data on the realization level of a self-harm episode and significant events such as a breakup, the researchers explained. Other limitations included missing data, multiple analyses that could increase the risk of false positives, the reliance on clinical diagnosis rather than formal instruments, and the cross-sectional study design, they said.

However, the results have clinical implications, as the clinical factors identified could be used to target subgroups of suicidal populations and refine treatment strategies, they concluded.

The study was supported by institutional funding and the Swiss Federal Office of Public Health. The researchers had no financial conflicts to disclose.

Being male, being older, and having a clear intent to die were among the key independent predictors of psychiatric hospital admission after self-harm, based on data from more than 1,800 individuals.

Clinicians who assess suicidal patients in the emergency department setting face the challenge of whether to admit the patient to inpatient or outpatient care, and data on predictors of compulsory admission are limited, wrote Laurent Michaud, MD, of the University of Lausanne, Switzerland, and colleagues.

To better identify predictors of hospitalization after self-harm, the researchers reviewed data from 1,832 patients aged 18 years and older admitted to four emergency departments in Switzerland between December 2016 and November 2019 .

Self-harm (SH) was defined in this study as “all nonfatal intentional acts of self-poisoning or self-injury, irrespective of degree of suicidal intent or other types of motivation,” the researchers noted. The study included 2,142 episodes of self-harm.

The researchers conducted two analyses. They compared episodes followed by any hospitalization and those with outpatient follow-up (1,083 episodes vs. 1,059 episodes) and episodes followed by compulsory hospitalization (357 episodes) with all other episodes followed by either outpatient care or voluntary hospitalization (1,785 episodes).

Overall, women were significantly more likely to be referred to outpatient follow-up compared with men (61.8% vs. 38.1%), and hospitalized patients were significantly older than outpatients (mean age of 41 years vs. 36 years, P < .001 for both).

“Not surprisingly, major psychopathological conditions such as depression, mania, dementia, and schizophrenia were predictive of hospitalization,” the researchers noted.

Other sociodemographic factors associated with hospitalization included living alone, no children, problematic socioeconomic status, and unemployment. Clinical factors associated with hospitalization included physical pain, more lethal suicide attempt method, and clear intent to die.

In a multivariate analysis, independent predictors of any hospitalization included male gender, older age, assessment in the Neuchatel location vs. Lausanne, depression vs. personality disorders, substance use, or anxiety disorder, difficult socioeconomic status, a clear vs. unclear intent to die, and a serious suicide attempt vs. less serious.

Differences in hospitalization based on hospital setting was a striking finding, the researchers wrote in their discussion. These differences may be largely explained by the organization of local mental health services and specific institutional cultures; the workload of staff and availability of beds also may have played a role in decisions to hospitalize, they said.

The findings were limited by several factors including the lack of data on the realization level of a self-harm episode and significant events such as a breakup, the researchers explained. Other limitations included missing data, multiple analyses that could increase the risk of false positives, the reliance on clinical diagnosis rather than formal instruments, and the cross-sectional study design, they said.

However, the results have clinical implications, as the clinical factors identified could be used to target subgroups of suicidal populations and refine treatment strategies, they concluded.

The study was supported by institutional funding and the Swiss Federal Office of Public Health. The researchers had no financial conflicts to disclose.

Being male, being older, and having a clear intent to die were among the key independent predictors of psychiatric hospital admission after self-harm, based on data from more than 1,800 individuals.

Clinicians who assess suicidal patients in the emergency department setting face the challenge of whether to admit the patient to inpatient or outpatient care, and data on predictors of compulsory admission are limited, wrote Laurent Michaud, MD, of the University of Lausanne, Switzerland, and colleagues.

To better identify predictors of hospitalization after self-harm, the researchers reviewed data from 1,832 patients aged 18 years and older admitted to four emergency departments in Switzerland between December 2016 and November 2019 .

Self-harm (SH) was defined in this study as “all nonfatal intentional acts of self-poisoning or self-injury, irrespective of degree of suicidal intent or other types of motivation,” the researchers noted. The study included 2,142 episodes of self-harm.

The researchers conducted two analyses. They compared episodes followed by any hospitalization and those with outpatient follow-up (1,083 episodes vs. 1,059 episodes) and episodes followed by compulsory hospitalization (357 episodes) with all other episodes followed by either outpatient care or voluntary hospitalization (1,785 episodes).

Overall, women were significantly more likely to be referred to outpatient follow-up compared with men (61.8% vs. 38.1%), and hospitalized patients were significantly older than outpatients (mean age of 41 years vs. 36 years, P < .001 for both).

“Not surprisingly, major psychopathological conditions such as depression, mania, dementia, and schizophrenia were predictive of hospitalization,” the researchers noted.

Other sociodemographic factors associated with hospitalization included living alone, no children, problematic socioeconomic status, and unemployment. Clinical factors associated with hospitalization included physical pain, more lethal suicide attempt method, and clear intent to die.

In a multivariate analysis, independent predictors of any hospitalization included male gender, older age, assessment in the Neuchatel location vs. Lausanne, depression vs. personality disorders, substance use, or anxiety disorder, difficult socioeconomic status, a clear vs. unclear intent to die, and a serious suicide attempt vs. less serious.

Differences in hospitalization based on hospital setting was a striking finding, the researchers wrote in their discussion. These differences may be largely explained by the organization of local mental health services and specific institutional cultures; the workload of staff and availability of beds also may have played a role in decisions to hospitalize, they said.

The findings were limited by several factors including the lack of data on the realization level of a self-harm episode and significant events such as a breakup, the researchers explained. Other limitations included missing data, multiple analyses that could increase the risk of false positives, the reliance on clinical diagnosis rather than formal instruments, and the cross-sectional study design, they said.

However, the results have clinical implications, as the clinical factors identified could be used to target subgroups of suicidal populations and refine treatment strategies, they concluded.

The study was supported by institutional funding and the Swiss Federal Office of Public Health. The researchers had no financial conflicts to disclose.