Current Psychiatry

Revisiting delirious mania

After treating a young woman with delirious mania, we were compelled to comment on the case report “Confused and nearly naked after going on spending sprees” (Cases That Test Your Skills, Current Psychiatry. July 2014, p. 56-62).

A young woman with bipolar I disorder and mild intellectual disability was brought to our inpatient psychiatric unit after she disappeared from her home. Her family reported she was not compliant with her medications, and she recently showed deterioration marked by bizarre and violent behaviors for the previous month.

Although her presentation was consistent with earlier manic episodes, additional behaviors indicated an increase in severity. The patient was only oriented to name, was disrobing, had urinary and fecal incontinence, and showed purposeless hyperactivity such as continuously dancing in circles.

Because we thought she was experiencing a severe exacerbation of bipolar disorder, the patient was started on 4 different antipsychotic trials (typical and atypical) and 2 mood stabilizers, all of which did not produce adequate response. Even after augmentation with nightly long-acting benzodiazepines, the patient’s symptoms remained unchanged.

The patient received a diagnosis of delirious mania, with the underlying mechanism being severe catatonia. A literature search revealed electroconvulsive therapy (ECT) and benzodiazepines as first-line treatments, and discouraged use of typical antipsychotics because of an increased risk of neuroleptic malignant syndrome and malignant delirious mania.¹ Because ECT was not available at our facility, we initiated benzodiazepines, while continuing an atypical antipsychotic and mood stabilizer. The patient was discharged after her symptoms improved rapidly.

We agree it is prudent to rule out any medical illnesses that could cause delirium. Interestingly, in our patient a head CT revealed small calcifications suggestive of cysticercosis, which have been seen on imaging since age 13. We suggest that this finding contributed to her disinhibition, prolonged her recovery, and could explain why she did not respond adequately to medications.

Diagnosing and treating delirious mania in our patient was challenging. As mentioned by Davis et al, there is no classification of delirious mania in DSM-5. In addition, there are no large-scale studies to educate psychiatrists about the prevalence and appropriate treatment of this disorder.

Our treatment approach differed from that of Davis et al in that we chose scheduled benzodiazepines rather than antipsychotics to target the patient’s catatonia. However, both patients improved, prompting us to further question the mechanism behind this presentation.

We encourage the addition of delirious mania to the next edition of DSM. Without classification and establishment of this diagnosis, psychiatrists are unlikely to consider this serious and potentially fatal syndrome. Delirious mania is mysterious and rare and its inner workings are not fully elucidated.

Sabina Bera, MD MSc

PGY-2 Psychiatry Resident

Mohammed Molla, MD, DFAPA

Interim Joint Chair and Program Director

University of California Los Angeles-Kern

Psychiatry Training Program
Bakersfield, California

Reference

1. Jacobowski NL, Heckers S, Bobo WV. Delirious mania: detection, diagnosis, and clinical management in the acute setting. J Psychiatr Pract. 2013;19(1):15-28.

Correcting an error

In his informative guest editorial "Forget the myths and help your psychiatric patients quit smoking" (From the Editor, Current Psychiatry. October 2016, p. 23-25), Dr. Anthenelli makes a common statistical error, which may mislead readers, namely, confusing “percentage” with “percentage points.” He reports a difference in the rates of serious neuropsychiatric adverse events between a non-psychiatric cohort (2%) and a psychiatric cohort (6%) as “4%” (p. 25), when the percentage (relative) difference is 300% (ie, 3-fold). The absolute difference in rates is 4 percentage points, which may be what he wanted to report.

David A. Gorelick, MD, PhD

Professor of Psychiatry
Maryland Psychiatric Research Center
University of Maryland
Baltimore, Maryland

Revisiting delirious mania

After treating a young woman with delirious mania, we were compelled to comment on the case report “Confused and nearly naked after going on spending sprees” (Cases That Test Your Skills, Current Psychiatry. July 2014, p. 56-62).

A young woman with bipolar I disorder and mild intellectual disability was brought to our inpatient psychiatric unit after she disappeared from her home. Her family reported she was not compliant with her medications, and she recently showed deterioration marked by bizarre and violent behaviors for the previous month.

Although her presentation was consistent with earlier manic episodes, additional behaviors indicated an increase in severity. The patient was only oriented to name, was disrobing, had urinary and fecal incontinence, and showed purposeless hyperactivity such as continuously dancing in circles.

Because we thought she was experiencing a severe exacerbation of bipolar disorder, the patient was started on 4 different antipsychotic trials (typical and atypical) and 2 mood stabilizers, all of which did not produce adequate response. Even after augmentation with nightly long-acting benzodiazepines, the patient’s symptoms remained unchanged.

The patient received a diagnosis of delirious mania, with the underlying mechanism being severe catatonia. A literature search revealed electroconvulsive therapy (ECT) and benzodiazepines as first-line treatments, and discouraged use of typical antipsychotics because of an increased risk of neuroleptic malignant syndrome and malignant delirious mania.¹ Because ECT was not available at our facility, we initiated benzodiazepines, while continuing an atypical antipsychotic and mood stabilizer. The patient was discharged after her symptoms improved rapidly.

We agree it is prudent to rule out any medical illnesses that could cause delirium. Interestingly, in our patient a head CT revealed small calcifications suggestive of cysticercosis, which have been seen on imaging since age 13. We suggest that this finding contributed to her disinhibition, prolonged her recovery, and could explain why she did not respond adequately to medications.

Diagnosing and treating delirious mania in our patient was challenging. As mentioned by Davis et al, there is no classification of delirious mania in DSM-5. In addition, there are no large-scale studies to educate psychiatrists about the prevalence and appropriate treatment of this disorder.

Our treatment approach differed from that of Davis et al in that we chose scheduled benzodiazepines rather than antipsychotics to target the patient’s catatonia. However, both patients improved, prompting us to further question the mechanism behind this presentation.

We encourage the addition of delirious mania to the next edition of DSM. Without classification and establishment of this diagnosis, psychiatrists are unlikely to consider this serious and potentially fatal syndrome. Delirious mania is mysterious and rare and its inner workings are not fully elucidated.

Sabina Bera, MD MSc

PGY-2 Psychiatry Resident

Mohammed Molla, MD, DFAPA

Interim Joint Chair and Program Director

University of California Los Angeles-Kern

Psychiatry Training Program
Bakersfield, California

Reference

1. Jacobowski NL, Heckers S, Bobo WV. Delirious mania: detection, diagnosis, and clinical management in the acute setting. J Psychiatr Pract. 2013;19(1):15-28.

Correcting an error

In his informative guest editorial "Forget the myths and help your psychiatric patients quit smoking" (From the Editor, Current Psychiatry. October 2016, p. 23-25), Dr. Anthenelli makes a common statistical error, which may mislead readers, namely, confusing “percentage” with “percentage points.” He reports a difference in the rates of serious neuropsychiatric adverse events between a non-psychiatric cohort (2%) and a psychiatric cohort (6%) as “4%” (p. 25), when the percentage (relative) difference is 300% (ie, 3-fold). The absolute difference in rates is 4 percentage points, which may be what he wanted to report.

David A. Gorelick, MD, PhD

Professor of Psychiatry
Maryland Psychiatric Research Center
University of Maryland
Baltimore, Maryland

Revisiting delirious mania

After treating a young woman with delirious mania, we were compelled to comment on the case report “Confused and nearly naked after going on spending sprees” (Cases That Test Your Skills, Current Psychiatry. July 2014, p. 56-62).

A young woman with bipolar I disorder and mild intellectual disability was brought to our inpatient psychiatric unit after she disappeared from her home. Her family reported she was not compliant with her medications, and she recently showed deterioration marked by bizarre and violent behaviors for the previous month.

Although her presentation was consistent with earlier manic episodes, additional behaviors indicated an increase in severity. The patient was only oriented to name, was disrobing, had urinary and fecal incontinence, and showed purposeless hyperactivity such as continuously dancing in circles.

Because we thought she was experiencing a severe exacerbation of bipolar disorder, the patient was started on 4 different antipsychotic trials (typical and atypical) and 2 mood stabilizers, all of which did not produce adequate response. Even after augmentation with nightly long-acting benzodiazepines, the patient’s symptoms remained unchanged.

The patient received a diagnosis of delirious mania, with the underlying mechanism being severe catatonia. A literature search revealed electroconvulsive therapy (ECT) and benzodiazepines as first-line treatments, and discouraged use of typical antipsychotics because of an increased risk of neuroleptic malignant syndrome and malignant delirious mania.¹ Because ECT was not available at our facility, we initiated benzodiazepines, while continuing an atypical antipsychotic and mood stabilizer. The patient was discharged after her symptoms improved rapidly.

We agree it is prudent to rule out any medical illnesses that could cause delirium. Interestingly, in our patient a head CT revealed small calcifications suggestive of cysticercosis, which have been seen on imaging since age 13. We suggest that this finding contributed to her disinhibition, prolonged her recovery, and could explain why she did not respond adequately to medications.

Diagnosing and treating delirious mania in our patient was challenging. As mentioned by Davis et al, there is no classification of delirious mania in DSM-5. In addition, there are no large-scale studies to educate psychiatrists about the prevalence and appropriate treatment of this disorder.

Our treatment approach differed from that of Davis et al in that we chose scheduled benzodiazepines rather than antipsychotics to target the patient’s catatonia. However, both patients improved, prompting us to further question the mechanism behind this presentation.

We encourage the addition of delirious mania to the next edition of DSM. Without classification and establishment of this diagnosis, psychiatrists are unlikely to consider this serious and potentially fatal syndrome. Delirious mania is mysterious and rare and its inner workings are not fully elucidated.

Sabina Bera, MD MSc

PGY-2 Psychiatry Resident

Mohammed Molla, MD, DFAPA

Interim Joint Chair and Program Director

University of California Los Angeles-Kern

Psychiatry Training Program
Bakersfield, California

Reference

1. Jacobowski NL, Heckers S, Bobo WV. Delirious mania: detection, diagnosis, and clinical management in the acute setting. J Psychiatr Pract. 2013;19(1):15-28.

Correcting an error

In his informative guest editorial "Forget the myths and help your psychiatric patients quit smoking" (From the Editor, Current Psychiatry. October 2016, p. 23-25), Dr. Anthenelli makes a common statistical error, which may mislead readers, namely, confusing “percentage” with “percentage points.” He reports a difference in the rates of serious neuropsychiatric adverse events between a non-psychiatric cohort (2%) and a psychiatric cohort (6%) as “4%” (p. 25), when the percentage (relative) difference is 300% (ie, 3-fold). The absolute difference in rates is 4 percentage points, which may be what he wanted to report.

David A. Gorelick, MD, PhD

Professor of Psychiatry
Maryland Psychiatric Research Center
University of Maryland
Baltimore, Maryland

CASE Confusion, hallucinations

Mr. G, age 57, is brought to the emergency department (ED) from a hospice care facility for worsening agitation and psychosis over 2 days. His wife, who accompanies him, describes a 2-month onset of “confusion” with occasional visual hallucinations. She says that at baseline Mr. G was alert and oriented and able to engage appropriately in conversations. The hospice facility administered emergency medications, including unknown dosages of haloperidol and chlorpromazine, the morning before transfer to the ED.

Mr. G has a history of posttraumatic stress disorder (PTSD), anxiety, and depression that has been managed for 6 years with several trials of antidepressant monotherapy, including fluoxetine, citalopram, mirtazapine, bupropion, and augmentation using aripiprazole, risperidone, topiramate, and zolpidem. At the time of this hospital presentation, his symptoms are controlled on clonazepam, 2 mg/d, and trazodone, 50 mg/d. For his pain attributed to non-small cell lung cancer (NSCLC), he receives methadone, 25 mg, 6 times a day, and hydromorphone, 8 mg, every 4 hours as needed, for breakthrough pain. Mr. G underwent a right upper lobectomy 5 years ago and neurosurgery with a right suboccipital craniectomy for right-sided cerebellar metastatic tumor measuring 2 × 1 × 0.6 cm, along with chemotherapy and radiation for metastasis in the brain 1 year ago. His last chemotherapy session was 3 months ago.

In the ED, Mr. G is sedated and oriented only to person and his wife. He is observed mumbling incoherently. Abnormal vital signs and laboratory findings are elevated pulse, 97 beats per minute; mild anemia, 13.5 g/dL hemoglobin and 40.8% hematocrit; an elevated glucose of 136 mg/dL; and small amounts of blood, trace ketones, and hyaline casts in urinalysis. Vital signs, laboratory results, and physical examination are unremarkable, with no focal or sensory neurologic deficits noted.

In addition to psychotropic and pain medication, Mr. G is taking cyclobenzaprine, 5 mg, every 6 hours as needed, for muscle spasms; docusate, 200 mg/d; enoxaparin, 100 mg/1mL, every 12 hours; folic acid, 1 mg/d; gabapentin, 600 mg, 3 times daily; lidocaine ointment, twice daily as needed, for pain; omeprazole, 80 mg/d; ondansetron, 4 mg, every 8 hours as needed, for nausea; and tamsulosin, 0.4 mg/d.

What is your differential diagnosis for Mr. G?

a) brain metastases
b) infection
c) PTSD
d) polypharmacy
e) benzodiazepine withdrawal

The authors’ observations

Altered mental status (AMS), or acute confusional state, describes an individual who fails to interact with environmental stimuli in an appropriate, anticipated manner. The disturbance usually is acute and transient.¹ Often providers struggle to obtain relevant facts about a patient’s history of illness and must use laboratory and diagnostic data to determine the underlying cause of the patient’s disorientation.

Mental status includes 2 components: arousal and awareness. Arousal refers to a person’s wakeful state and how an individual responds to his (her) surroundings. Impairment in arousal can result in variable states including lethargy, drowsiness, and even coma. Awareness, on the other hand, is an individual’s perception of his environment, including orientation to surroundings, executive functioning, and memory. Although arousal level is controlled by the reticular activating system of the brainstem, awareness of consciousness is mediated at the cortical level. Mr. G experienced increased arousal and AMS with a clear change in behavior from his baseline. With increasing frequency of hallucinations and agitated behaviors, several tests must be ordered to determine the etiology of his altered mentation (Table 1).

Which test would you order next?

a) urine drug screen (UDS)
b) chest CT with pulmonary embolism protocol
c) CT of the head
d) blood cultures
e) chest radiography

EVALUATION Awake, still confused

The ED physician orders a UDS, non-contrasted CT of the head, and chest radiography for preliminary workup investigating the cause of Mr. G’s AMS. UDS is negative for illicit substances. The non-contrasted CT of the head shows a stable, right cerebellar hemisphere lesion from a prior lung metastasis. Mr. G’s chest radiography reading describes an ill-defined opacity at the left lung base.

Mr. G is admitted to the medical service and is started on dexamethasone, 8 mg/d, for his NSCLC with brain metastasis. Clonazepam is continued to prevent benzodiazepine withdrawal. The psychiatry and palliative care teams are consulted to determine if Mr. G’s PTSD symptoms and/or opioids are contributing to his AMS and psychosis. After evaluation, the psychiatry team recommends decreasing clonazepam to 0.5 mg, twice daily, starting olanzapine, 5 mg, every 12 hours, for agitation and psychosis involving auditory and visual hallucinations as well as paranoid themes related to food contamination, and using non-pharmacologic interventions for delirium treatment (Table 2). In a prospective, randomized controlled trial of olanzapine vs haloperidol, clinical improvement in delirious states was seen in individuals who received either antipsychotic medication; however, haloperidol was associated with extrapyramidal side effects. Therefore, olanzapine is a safe alternative to haloperidol in delirious patients.²

The psychiatry consult service suspects delirium due to polypharmacy or Mr. G’s metastatic brain lesion. However, other collaborating treatment teams feel that Mr. G’s presentation was precipitated by an exacerbation of PTSD symptoms because of the observed psychotic themes, in addition to metabolic encephalopathy. Acute stress disorder can present with emotional numbing, depersonalization, reduced awareness of surroundings, or dissociative amnesia. However, Mr. G has not experienced PTSD symptoms involving mental status changes with fluctuating orientation in the past nor has he displayed persistent dissociation during outpatient psychiatric care. Therefore, it is unlikely that PTSD is the primary cause of his hospital admission.

The palliative care team recommends switching Mr. G’s pain medications to methadone, 20 mg, every 6 hours, to reduce possibility that opioids are contributing to his delirious state. Mr. G’s medical providers report that the chest radiography is suspicious for pneumonia and start him on levofloxacin, 500 mg/d.

The authors’ observations

DSM-5 criteria for delirium has 4 components:

• disturbance in attention and awareness
• change in cognition
• the disturbance develops over a short period of time
• there is evidence that the disturbance is a direct consequence of a medical condition, medication, or substance, or more than 1 cause.³

Mr. G presented with multi-factorial delirium, and as a result, all underlying contributions, including infection, polypharmacy, brain metastasis, and steroids needed to be considered. Treating delirium requires investigating the underlying cause and keeping the patient safe in the process (Figure). Mr. G was agitated at presentation; therefore, low-dosage olanzapine was initiated to address the imbalance between the cholinergic and dopaminergic systems in the CNS, which are thought to be the mechanism behind delirious presentations.

TREATMENT Delirium resolves

Mr. G slowly responds to multi-modal treatment including decreased opioids and benzodiazepines and the use of low-dosage antipsychotics. He begins to return to baseline with antibiotic administration. By hospital day 5, Mr. G is alert and oriented. He notes resolution of his auditory and visual hallucinations and denies any persistent paranoia or delusions. The medical team observes Mr. G is having difficulty swallowing with meals, and orders a speech therapy evaluation. After assessment, the team suspects that aspiration pneumonia could have precipitated Mr. G’s initial decline and recommends a mechanic diet with thin liquids to reduce the risk of future aspiration.

Mr. G is discharged home in his wife’s care with home hospice to continue end-of-life care. His medication regimen includes olanzapine, 10 mg/d, to continue until his next outpatient appointment, trazodone, 50 mg/d, for depression and PTSD symptoms, and clonazepam is decreased to 0.5 mg, at bedtime, for anxiety.

The authors’ observations

Mr. G’s case highlights the importance of fully evaluating all common underlying causes of delirium. The etiology of delirium is more likely to be missed in medically complex patients or in patients with a history of psychiatric illness. Palliative care patients have several risk factors for delirium, such as benzodiazepine or opioid treatment, dementia, and organic diseases such as brain metastasis.⁶ A recent study assessed the frequency of delirium in cancer patients admitted to an inpatient palliative unit and found that 71% of individuals had a diagnosis of delirium at admission and 26% developed delirium afterward.⁷ Despite the increased likelihood of developing delirium, more than one-half of palliative patients have delirium that is missed by their primary providers.⁸ Similarly, patients with documented psychiatric illness were approximately 2.5 times more likely to have overlooked delirium compared with patients without psychiatric illness.⁹

Risk and prevention

Patients with risk factors for delirium—which includes sedative and narcotic usage, advanced cancer, older age, prolonged hospital stays, surgical procedures, and/or cognitive impairment—should receive interventions to prevent delirium. However, if symptoms of AMS are present, providers should perform a complete workup for underlying causes of delirium. Remembering that individuals with delirium have an impaired ability to voice symptoms, such as dyspnea, dysuria, and headache, clinicians should have a high index of suspicion for delirium in patients at heightened risk.¹⁰

Perhaps most important, teams treating patients at high risk for delirium should employ preventive measures to reduce the development of delirium. Although more studies are needed to clarify the role of drug therapies for preventing delirium, there is strong evidence for several non-pharmacotherapeutic interventions including:

• frequent orientation activities
• early mobilization
• maintaining healthy sleep–wake cycles
• minimizing the use of psychoactive drugs and frequently reviewing the medication regimen
• allowing use of eyeglasses and hearing aids
• treating volume depletion.¹⁰

These preventive measures are important when treating delirium, such as minimizing Mr. G’s use of benzodiazepine and opioids—medications known to contribute to iatrogenic delirium.

A delirium diagnosis portends grave adverse outcomes. Research has shown significant associations with morbidity and mortality, financial and emotional burden, and prolonged hospitalizations. Often, symptoms of delirium persist for months and patients do not recover completely. However, studies have found that when underlying causes are treated effectively, delirium is more likely to be reversible.¹¹

The prompt diagnosis of delirium with good interdisciplinary communication can reduce the risk of these adverse outcomes.¹² Consultation-liaison psychiatrists are well positioned to facilitate the diagnoses of delirium and play a role in educating other health care providers of the importance of prevention, early symptom recognition, full workup, and effective treatment of its underlying causes.

CASE Confusion, hallucinations

Mr. G, age 57, is brought to the emergency department (ED) from a hospice care facility for worsening agitation and psychosis over 2 days. His wife, who accompanies him, describes a 2-month onset of “confusion” with occasional visual hallucinations. She says that at baseline Mr. G was alert and oriented and able to engage appropriately in conversations. The hospice facility administered emergency medications, including unknown dosages of haloperidol and chlorpromazine, the morning before transfer to the ED.

Mr. G has a history of posttraumatic stress disorder (PTSD), anxiety, and depression that has been managed for 6 years with several trials of antidepressant monotherapy, including fluoxetine, citalopram, mirtazapine, bupropion, and augmentation using aripiprazole, risperidone, topiramate, and zolpidem. At the time of this hospital presentation, his symptoms are controlled on clonazepam, 2 mg/d, and trazodone, 50 mg/d. For his pain attributed to non-small cell lung cancer (NSCLC), he receives methadone, 25 mg, 6 times a day, and hydromorphone, 8 mg, every 4 hours as needed, for breakthrough pain. Mr. G underwent a right upper lobectomy 5 years ago and neurosurgery with a right suboccipital craniectomy for right-sided cerebellar metastatic tumor measuring 2 × 1 × 0.6 cm, along with chemotherapy and radiation for metastasis in the brain 1 year ago. His last chemotherapy session was 3 months ago.

In the ED, Mr. G is sedated and oriented only to person and his wife. He is observed mumbling incoherently. Abnormal vital signs and laboratory findings are elevated pulse, 97 beats per minute; mild anemia, 13.5 g/dL hemoglobin and 40.8% hematocrit; an elevated glucose of 136 mg/dL; and small amounts of blood, trace ketones, and hyaline casts in urinalysis. Vital signs, laboratory results, and physical examination are unremarkable, with no focal or sensory neurologic deficits noted.

In addition to psychotropic and pain medication, Mr. G is taking cyclobenzaprine, 5 mg, every 6 hours as needed, for muscle spasms; docusate, 200 mg/d; enoxaparin, 100 mg/1mL, every 12 hours; folic acid, 1 mg/d; gabapentin, 600 mg, 3 times daily; lidocaine ointment, twice daily as needed, for pain; omeprazole, 80 mg/d; ondansetron, 4 mg, every 8 hours as needed, for nausea; and tamsulosin, 0.4 mg/d.

What is your differential diagnosis for Mr. G?

a) brain metastases
b) infection
c) PTSD
d) polypharmacy
e) benzodiazepine withdrawal

The authors’ observations

Altered mental status (AMS), or acute confusional state, describes an individual who fails to interact with environmental stimuli in an appropriate, anticipated manner. The disturbance usually is acute and transient.¹ Often providers struggle to obtain relevant facts about a patient’s history of illness and must use laboratory and diagnostic data to determine the underlying cause of the patient’s disorientation.

Mental status includes 2 components: arousal and awareness. Arousal refers to a person’s wakeful state and how an individual responds to his (her) surroundings. Impairment in arousal can result in variable states including lethargy, drowsiness, and even coma. Awareness, on the other hand, is an individual’s perception of his environment, including orientation to surroundings, executive functioning, and memory. Although arousal level is controlled by the reticular activating system of the brainstem, awareness of consciousness is mediated at the cortical level. Mr. G experienced increased arousal and AMS with a clear change in behavior from his baseline. With increasing frequency of hallucinations and agitated behaviors, several tests must be ordered to determine the etiology of his altered mentation (Table 1).

Which test would you order next?

a) urine drug screen (UDS)
b) chest CT with pulmonary embolism protocol
c) CT of the head
d) blood cultures
e) chest radiography

EVALUATION Awake, still confused

The ED physician orders a UDS, non-contrasted CT of the head, and chest radiography for preliminary workup investigating the cause of Mr. G’s AMS. UDS is negative for illicit substances. The non-contrasted CT of the head shows a stable, right cerebellar hemisphere lesion from a prior lung metastasis. Mr. G’s chest radiography reading describes an ill-defined opacity at the left lung base.

Mr. G is admitted to the medical service and is started on dexamethasone, 8 mg/d, for his NSCLC with brain metastasis. Clonazepam is continued to prevent benzodiazepine withdrawal. The psychiatry and palliative care teams are consulted to determine if Mr. G’s PTSD symptoms and/or opioids are contributing to his AMS and psychosis. After evaluation, the psychiatry team recommends decreasing clonazepam to 0.5 mg, twice daily, starting olanzapine, 5 mg, every 12 hours, for agitation and psychosis involving auditory and visual hallucinations as well as paranoid themes related to food contamination, and using non-pharmacologic interventions for delirium treatment (Table 2). In a prospective, randomized controlled trial of olanzapine vs haloperidol, clinical improvement in delirious states was seen in individuals who received either antipsychotic medication; however, haloperidol was associated with extrapyramidal side effects. Therefore, olanzapine is a safe alternative to haloperidol in delirious patients.²

The psychiatry consult service suspects delirium due to polypharmacy or Mr. G’s metastatic brain lesion. However, other collaborating treatment teams feel that Mr. G’s presentation was precipitated by an exacerbation of PTSD symptoms because of the observed psychotic themes, in addition to metabolic encephalopathy. Acute stress disorder can present with emotional numbing, depersonalization, reduced awareness of surroundings, or dissociative amnesia. However, Mr. G has not experienced PTSD symptoms involving mental status changes with fluctuating orientation in the past nor has he displayed persistent dissociation during outpatient psychiatric care. Therefore, it is unlikely that PTSD is the primary cause of his hospital admission.

The palliative care team recommends switching Mr. G’s pain medications to methadone, 20 mg, every 6 hours, to reduce possibility that opioids are contributing to his delirious state. Mr. G’s medical providers report that the chest radiography is suspicious for pneumonia and start him on levofloxacin, 500 mg/d.

The authors’ observations

DSM-5 criteria for delirium has 4 components:

• disturbance in attention and awareness
• change in cognition
• the disturbance develops over a short period of time
• there is evidence that the disturbance is a direct consequence of a medical condition, medication, or substance, or more than 1 cause.³

Mr. G presented with multi-factorial delirium, and as a result, all underlying contributions, including infection, polypharmacy, brain metastasis, and steroids needed to be considered. Treating delirium requires investigating the underlying cause and keeping the patient safe in the process (Figure). Mr. G was agitated at presentation; therefore, low-dosage olanzapine was initiated to address the imbalance between the cholinergic and dopaminergic systems in the CNS, which are thought to be the mechanism behind delirious presentations.

TREATMENT Delirium resolves

Mr. G slowly responds to multi-modal treatment including decreased opioids and benzodiazepines and the use of low-dosage antipsychotics. He begins to return to baseline with antibiotic administration. By hospital day 5, Mr. G is alert and oriented. He notes resolution of his auditory and visual hallucinations and denies any persistent paranoia or delusions. The medical team observes Mr. G is having difficulty swallowing with meals, and orders a speech therapy evaluation. After assessment, the team suspects that aspiration pneumonia could have precipitated Mr. G’s initial decline and recommends a mechanic diet with thin liquids to reduce the risk of future aspiration.

Mr. G is discharged home in his wife’s care with home hospice to continue end-of-life care. His medication regimen includes olanzapine, 10 mg/d, to continue until his next outpatient appointment, trazodone, 50 mg/d, for depression and PTSD symptoms, and clonazepam is decreased to 0.5 mg, at bedtime, for anxiety.

The authors’ observations

Mr. G’s case highlights the importance of fully evaluating all common underlying causes of delirium. The etiology of delirium is more likely to be missed in medically complex patients or in patients with a history of psychiatric illness. Palliative care patients have several risk factors for delirium, such as benzodiazepine or opioid treatment, dementia, and organic diseases such as brain metastasis.⁶ A recent study assessed the frequency of delirium in cancer patients admitted to an inpatient palliative unit and found that 71% of individuals had a diagnosis of delirium at admission and 26% developed delirium afterward.⁷ Despite the increased likelihood of developing delirium, more than one-half of palliative patients have delirium that is missed by their primary providers.⁸ Similarly, patients with documented psychiatric illness were approximately 2.5 times more likely to have overlooked delirium compared with patients without psychiatric illness.⁹

Risk and prevention

Patients with risk factors for delirium—which includes sedative and narcotic usage, advanced cancer, older age, prolonged hospital stays, surgical procedures, and/or cognitive impairment—should receive interventions to prevent delirium. However, if symptoms of AMS are present, providers should perform a complete workup for underlying causes of delirium. Remembering that individuals with delirium have an impaired ability to voice symptoms, such as dyspnea, dysuria, and headache, clinicians should have a high index of suspicion for delirium in patients at heightened risk.¹⁰

Perhaps most important, teams treating patients at high risk for delirium should employ preventive measures to reduce the development of delirium. Although more studies are needed to clarify the role of drug therapies for preventing delirium, there is strong evidence for several non-pharmacotherapeutic interventions including:

• frequent orientation activities
• early mobilization
• maintaining healthy sleep–wake cycles
• minimizing the use of psychoactive drugs and frequently reviewing the medication regimen
• allowing use of eyeglasses and hearing aids
• treating volume depletion.¹⁰

These preventive measures are important when treating delirium, such as minimizing Mr. G’s use of benzodiazepine and opioids—medications known to contribute to iatrogenic delirium.

A delirium diagnosis portends grave adverse outcomes. Research has shown significant associations with morbidity and mortality, financial and emotional burden, and prolonged hospitalizations. Often, symptoms of delirium persist for months and patients do not recover completely. However, studies have found that when underlying causes are treated effectively, delirium is more likely to be reversible.¹¹

The prompt diagnosis of delirium with good interdisciplinary communication can reduce the risk of these adverse outcomes.¹² Consultation-liaison psychiatrists are well positioned to facilitate the diagnoses of delirium and play a role in educating other health care providers of the importance of prevention, early symptom recognition, full workup, and effective treatment of its underlying causes.

CASE Confusion, hallucinations

Mr. G, age 57, is brought to the emergency department (ED) from a hospice care facility for worsening agitation and psychosis over 2 days. His wife, who accompanies him, describes a 2-month onset of “confusion” with occasional visual hallucinations. She says that at baseline Mr. G was alert and oriented and able to engage appropriately in conversations. The hospice facility administered emergency medications, including unknown dosages of haloperidol and chlorpromazine, the morning before transfer to the ED.

Mr. G has a history of posttraumatic stress disorder (PTSD), anxiety, and depression that has been managed for 6 years with several trials of antidepressant monotherapy, including fluoxetine, citalopram, mirtazapine, bupropion, and augmentation using aripiprazole, risperidone, topiramate, and zolpidem. At the time of this hospital presentation, his symptoms are controlled on clonazepam, 2 mg/d, and trazodone, 50 mg/d. For his pain attributed to non-small cell lung cancer (NSCLC), he receives methadone, 25 mg, 6 times a day, and hydromorphone, 8 mg, every 4 hours as needed, for breakthrough pain. Mr. G underwent a right upper lobectomy 5 years ago and neurosurgery with a right suboccipital craniectomy for right-sided cerebellar metastatic tumor measuring 2 × 1 × 0.6 cm, along with chemotherapy and radiation for metastasis in the brain 1 year ago. His last chemotherapy session was 3 months ago.

In the ED, Mr. G is sedated and oriented only to person and his wife. He is observed mumbling incoherently. Abnormal vital signs and laboratory findings are elevated pulse, 97 beats per minute; mild anemia, 13.5 g/dL hemoglobin and 40.8% hematocrit; an elevated glucose of 136 mg/dL; and small amounts of blood, trace ketones, and hyaline casts in urinalysis. Vital signs, laboratory results, and physical examination are unremarkable, with no focal or sensory neurologic deficits noted.

In addition to psychotropic and pain medication, Mr. G is taking cyclobenzaprine, 5 mg, every 6 hours as needed, for muscle spasms; docusate, 200 mg/d; enoxaparin, 100 mg/1mL, every 12 hours; folic acid, 1 mg/d; gabapentin, 600 mg, 3 times daily; lidocaine ointment, twice daily as needed, for pain; omeprazole, 80 mg/d; ondansetron, 4 mg, every 8 hours as needed, for nausea; and tamsulosin, 0.4 mg/d.

What is your differential diagnosis for Mr. G?

a) brain metastases
b) infection
c) PTSD
d) polypharmacy
e) benzodiazepine withdrawal

The authors’ observations

Altered mental status (AMS), or acute confusional state, describes an individual who fails to interact with environmental stimuli in an appropriate, anticipated manner. The disturbance usually is acute and transient.¹ Often providers struggle to obtain relevant facts about a patient’s history of illness and must use laboratory and diagnostic data to determine the underlying cause of the patient’s disorientation.

Mental status includes 2 components: arousal and awareness. Arousal refers to a person’s wakeful state and how an individual responds to his (her) surroundings. Impairment in arousal can result in variable states including lethargy, drowsiness, and even coma. Awareness, on the other hand, is an individual’s perception of his environment, including orientation to surroundings, executive functioning, and memory. Although arousal level is controlled by the reticular activating system of the brainstem, awareness of consciousness is mediated at the cortical level. Mr. G experienced increased arousal and AMS with a clear change in behavior from his baseline. With increasing frequency of hallucinations and agitated behaviors, several tests must be ordered to determine the etiology of his altered mentation (Table 1).

Which test would you order next?

a) urine drug screen (UDS)
b) chest CT with pulmonary embolism protocol
c) CT of the head
d) blood cultures
e) chest radiography

EVALUATION Awake, still confused

The ED physician orders a UDS, non-contrasted CT of the head, and chest radiography for preliminary workup investigating the cause of Mr. G’s AMS. UDS is negative for illicit substances. The non-contrasted CT of the head shows a stable, right cerebellar hemisphere lesion from a prior lung metastasis. Mr. G’s chest radiography reading describes an ill-defined opacity at the left lung base.

Mr. G is admitted to the medical service and is started on dexamethasone, 8 mg/d, for his NSCLC with brain metastasis. Clonazepam is continued to prevent benzodiazepine withdrawal. The psychiatry and palliative care teams are consulted to determine if Mr. G’s PTSD symptoms and/or opioids are contributing to his AMS and psychosis. After evaluation, the psychiatry team recommends decreasing clonazepam to 0.5 mg, twice daily, starting olanzapine, 5 mg, every 12 hours, for agitation and psychosis involving auditory and visual hallucinations as well as paranoid themes related to food contamination, and using non-pharmacologic interventions for delirium treatment (Table 2). In a prospective, randomized controlled trial of olanzapine vs haloperidol, clinical improvement in delirious states was seen in individuals who received either antipsychotic medication; however, haloperidol was associated with extrapyramidal side effects. Therefore, olanzapine is a safe alternative to haloperidol in delirious patients.²

The psychiatry consult service suspects delirium due to polypharmacy or Mr. G’s metastatic brain lesion. However, other collaborating treatment teams feel that Mr. G’s presentation was precipitated by an exacerbation of PTSD symptoms because of the observed psychotic themes, in addition to metabolic encephalopathy. Acute stress disorder can present with emotional numbing, depersonalization, reduced awareness of surroundings, or dissociative amnesia. However, Mr. G has not experienced PTSD symptoms involving mental status changes with fluctuating orientation in the past nor has he displayed persistent dissociation during outpatient psychiatric care. Therefore, it is unlikely that PTSD is the primary cause of his hospital admission.

The palliative care team recommends switching Mr. G’s pain medications to methadone, 20 mg, every 6 hours, to reduce possibility that opioids are contributing to his delirious state. Mr. G’s medical providers report that the chest radiography is suspicious for pneumonia and start him on levofloxacin, 500 mg/d.

The authors’ observations

DSM-5 criteria for delirium has 4 components:

• disturbance in attention and awareness
• change in cognition
• the disturbance develops over a short period of time
• there is evidence that the disturbance is a direct consequence of a medical condition, medication, or substance, or more than 1 cause.³

Mr. G presented with multi-factorial delirium, and as a result, all underlying contributions, including infection, polypharmacy, brain metastasis, and steroids needed to be considered. Treating delirium requires investigating the underlying cause and keeping the patient safe in the process (Figure). Mr. G was agitated at presentation; therefore, low-dosage olanzapine was initiated to address the imbalance between the cholinergic and dopaminergic systems in the CNS, which are thought to be the mechanism behind delirious presentations.

TREATMENT Delirium resolves

Mr. G slowly responds to multi-modal treatment including decreased opioids and benzodiazepines and the use of low-dosage antipsychotics. He begins to return to baseline with antibiotic administration. By hospital day 5, Mr. G is alert and oriented. He notes resolution of his auditory and visual hallucinations and denies any persistent paranoia or delusions. The medical team observes Mr. G is having difficulty swallowing with meals, and orders a speech therapy evaluation. After assessment, the team suspects that aspiration pneumonia could have precipitated Mr. G’s initial decline and recommends a mechanic diet with thin liquids to reduce the risk of future aspiration.

Mr. G is discharged home in his wife’s care with home hospice to continue end-of-life care. His medication regimen includes olanzapine, 10 mg/d, to continue until his next outpatient appointment, trazodone, 50 mg/d, for depression and PTSD symptoms, and clonazepam is decreased to 0.5 mg, at bedtime, for anxiety.

The authors’ observations

Mr. G’s case highlights the importance of fully evaluating all common underlying causes of delirium. The etiology of delirium is more likely to be missed in medically complex patients or in patients with a history of psychiatric illness. Palliative care patients have several risk factors for delirium, such as benzodiazepine or opioid treatment, dementia, and organic diseases such as brain metastasis.⁶ A recent study assessed the frequency of delirium in cancer patients admitted to an inpatient palliative unit and found that 71% of individuals had a diagnosis of delirium at admission and 26% developed delirium afterward.⁷ Despite the increased likelihood of developing delirium, more than one-half of palliative patients have delirium that is missed by their primary providers.⁸ Similarly, patients with documented psychiatric illness were approximately 2.5 times more likely to have overlooked delirium compared with patients without psychiatric illness.⁹

Risk and prevention

Patients with risk factors for delirium—which includes sedative and narcotic usage, advanced cancer, older age, prolonged hospital stays, surgical procedures, and/or cognitive impairment—should receive interventions to prevent delirium. However, if symptoms of AMS are present, providers should perform a complete workup for underlying causes of delirium. Remembering that individuals with delirium have an impaired ability to voice symptoms, such as dyspnea, dysuria, and headache, clinicians should have a high index of suspicion for delirium in patients at heightened risk.¹⁰

Perhaps most important, teams treating patients at high risk for delirium should employ preventive measures to reduce the development of delirium. Although more studies are needed to clarify the role of drug therapies for preventing delirium, there is strong evidence for several non-pharmacotherapeutic interventions including:

• frequent orientation activities
• early mobilization
• maintaining healthy sleep–wake cycles
• minimizing the use of psychoactive drugs and frequently reviewing the medication regimen
• allowing use of eyeglasses and hearing aids
• treating volume depletion.¹⁰

These preventive measures are important when treating delirium, such as minimizing Mr. G’s use of benzodiazepine and opioids—medications known to contribute to iatrogenic delirium.

A delirium diagnosis portends grave adverse outcomes. Research has shown significant associations with morbidity and mortality, financial and emotional burden, and prolonged hospitalizations. Often, symptoms of delirium persist for months and patients do not recover completely. However, studies have found that when underlying causes are treated effectively, delirium is more likely to be reversible.¹¹

The prompt diagnosis of delirium with good interdisciplinary communication can reduce the risk of these adverse outcomes.¹² Consultation-liaison psychiatrists are well positioned to facilitate the diagnoses of delirium and play a role in educating other health care providers of the importance of prevention, early symptom recognition, full workup, and effective treatment of its underlying causes.

Maladaptive alcohol use has emerged as a risk for a subset of individuals who have undergone weight loss surgery (WLS); studies report they are vulnerable to consuming alcohol in greater quantities or more frequently.^1,2 Estimates of the prevalence of “high-risk” or “hazardous” alcohol use after WLS range from 4% to 28%,^3,4 while the prevalence of alcohol use meeting DSM-IV-TR⁵ criteria for alcohol use disorders (AUDs) hovers around 10%.⁶

Heavy alcohol users or patients who have active AUD at the time of WLS are at greater risk for continuation of these problems after surgery.^2,6 For patients with a long-remitted history of AUD, the evidence regarding risk for post-WLS relapse is lacking, and some evidence suggests they may have better weight loss outcomes after WLS.⁷

However, approximately two-third of cases of post-WLS alcohol problems occur in patients who have had no history of such problems before surgery.^5,8,9 Reported prevalence rates of new-onset alcohol problems range from 3% to 18%,^6,9 with the modal finding being approximately 7% to 8%. New-onset alcohol problems appear to occur at a considerable latency after surgery. One study found little risk at 1 year post-surgery, but a significant increase in AUD symptoms at 2 years.⁶ Another study identified 3 years post-surgery as a high-risk time point,⁸ and yet another reported a linear increase in the risk for developing alcohol problems for at least 10 years after WLS.¹⁰

This article describes a group treatment protocol developed specifically for patients with post-WLS substance use disorder (SUD), and explores:

• risk factors and causal mechanisms of post-WLS AUDs
• weight stigma and emotional stressors
• the role of specialized treatment
• group treatment based on the Health at Every Size® (HAES)-oriented, trauma-informed and fat acceptance framework.

Post-WLS patients with alcohol problems may be a distinct phenotype among people with substance abuse issues. For this reason, they may have a need to address their experiences and issues specific to WLS as part of their alcohol treatment.

Etiology

Risk factors. Empirical findings have identified few predictors or risk factors for post-WLS SUD. These patients are more likely to be male and of a younger age.⁶ Notably, the vast majority of individuals reporting post-WLS alcohol problems have undergone Roux-en-Y gastric bypass (RYGB), rather than other WLS procedures, such as the laparoscopic adjustable gastric band,^6,11 suggesting some physiological mechanism specific to RYGB.

Other potential predictors of postoperative alcohol problems include a pre-operative history of depression, generalized anxiety disorder, smoking, and/or recreational drug use.^3,6 Likewise, patients with depression or anxiety disorder symptoms after surgery also may be at higher risk for postoperative alcohol problems.⁴ The evidence of an association between postoperative weight outcomes and post-WLS alcohol problems is mixed.^3,12 Interestingly, patients who had no personal history of substance abuse but who have a family history may have a higher risk of new-onset alcohol problems after surgery.^9,12

Causal mechanisms. The etiology of post-WLS alcohol problems is not well understood. If anything, epidemiological data suggest that larger-bodied individuals tend to consume lower levels of alcohol and have lower rates of AUD than individuals in the general population with thinner bodies.¹³ However, an association has been found between a family history of SUD, but not a personal history, and being large.¹⁴ This suggests a shared etiological pathway between addiction and being “overweight,” of which the onset of AUD after RYGB may be a manifestation.

Human and animal studies have shown that WLS may affect alcohol use differently in specific subgroups. Studies have shown that wild-type rats greatly increase their consumption of, or operant responding for, alcohol after RYGB,¹⁵ while genetically “alcohol-preferring” rats decrease consumption of, or responding for, alcohol after RYGB.¹⁶ A human study likewise found some patients decreased alcohol use or experienced improvement of or remission of AUD symptoms after WLS.⁴ Combined with the finding that a family history of substance abuse is related to risk for post-operative AUD, these data suggest a potential genetic vulnerability or protection in some individuals.

Turning to potential psychosocial explanations, the lay media has popularized the concepts of “addiction transfer,” or “transfer addiction,”¹² with the implication that some patients, who had a preoperative history of “food addiction,” transfer that “addiction” after surgery to substances of abuse.

However, the “addiction transfer” model has a number of flaws:

• it is stigmatizing, because it assumes the patient possesses an innate, chronic, and inalterable pathology
• it relies upon the validity of the controversial construct of “food addiction,” a construct of mixed scientific evidence.¹⁷

Further, our knowledge of post-WLS SUD argues against “addiction transfer.” As noted, postoperative alcohol problems are more likely to develop years after surgery, rather than in the first few months afterward when eating is most significantly curtailed. Additionally, post-WLS alcohol problems are significantly more likely to occur after RYGB than other procedures, whereas the “addiction transfer” model would hypothesize that all WLS patients would be at equal risk for postoperative “addiction transfer,” because their eating is similarly affected after surgery.

Links to RYGB. Some clues to physiological mechanisms underlying alcohol problems after RYGB have been identified. After surgery, many RYGB patients report a quicker effect from a smaller amount of alcohol than was the case pre-surgery.¹⁸ Studies have demonstrated a number of changes in the pharmacodynamics of alcohol after RYGB not seen in other WLS procedures¹⁹:

• a much faster time to peak blood (or breath) alcohol content (BAC)
• significantly higher peak BAC
• a precipitous initial decline in perceived intoxication.^18,20

Anatomical features of RYGB may explain such changes.⁸ However, an increased response to both IV alcohol and IV morphine after RYGB^21,22 in rodents suggests that gastrointestinal tract changes are not solely responsible for changes in alcohol use. Emerging research reports that WLS has been found to cause alterations in brain reward pathways,²³ which may be an additional contributor to changes in alcohol misuse after surgery.

However, even combined, pharmacokinetic and neurobiological factors cannot entirely explain new-onset alcohol problems after WLS; if they could, one would expect to see a much higher prevalence of this complication. Some psychosocial factors are likely involved as well.

Emotional stressors. One possibility involves a mismatch between post-WLS stressors and coping skills. After WLS, these patients face a multitude of challenges inherent in adjusting to changes in lifestyle, weight, body image, and social functioning, which most individuals would find daunting. These challenges become even more acute in the absence of appropriate psychoeducation, preparation, and intervention from qualified professionals. Individuals who lack effective and adaptive coping skills and supports may have a particularly heightened vulnerability to increased alcohol use in the setting of post-surgery changes in brain reward circuits and pharmacodynamics in alcohol metabolism. For example, one patient reported that her spouse’s pressure to “do something about her weight” was a significant factor in her decision to undergo surgery, but that her spouse was blaming and unsupportive when post-WLS complications developed. The patient believed that these experiences helped fuel development of her post-RYGB alcohol abuse.

Specialized treatment

The number of patients experiencing post-WLS alcohol problems likely will continue to grow, given that the risk of onset of has been shown increase over years. Already, post-WLS patients are proportionally overrepresented among substance abuse treatment populations.²⁴ Empirically, however, we do not know yet if these patients need a different type of addiction treatment than patients who have not had WLS.

Some evidence suggests that post-WLS patients with alcohol problems may be a distinct phenotype within the general population with alcohol problems, as their presentations differ in several ways, including their demographics, alcohol use patterns, and premorbid functioning. A number of studies have found that, despite their increased pharmacodynamic sensitivity to alcohol, people with post-WLS AUDs actually consume a larger amount of alcohol on both typical and maximum drinking days than other individuals with AUDs.²⁴ Additionally, although the median age of onset for AUD is around age 20,²⁵ patients presenting with new-onset, post-WLS alcohol problems are usually in their late 30s, or even 40s or 50s. Further, many of these patients were quite high functioning before their alcohol problems, and are unlikely to identify with the cultural stereotype of a person with AUD (eg, homeless, unemployed), which may hamper or delay their own willingness to accept that they have a problem. These phenotypic differences suggest that post-WLS patients may require substance abuse treatment approaches tailored to their unique presentation. There are additional factors specific to the experiences of being larger-bodied and WLS that also may need to be addressed in specialized treatment for post-WLS addiction patients.

Weight stigma. By definition, patients who have undergone WLS have spent a significant portion of their lives inhabiting larger bodies, an experience that, in our culture, can produce adverse psychosocial effects. Compared with the general population, patients seeking WLS exhibit psychological distress equivalent to psychiatric patients.²⁶ Weight stigma or weight bias—negative judgments directed toward people in larger bodies—is pervasive and continues to increase.²⁷ Further, evidence suggests that, unlike almost all other stigmatized groups, people in larger bodies tend to internalize this stigma, holding an unfavorable attitude toward their own social group.²⁸ Weight stigma impacts the well-being of people all along the weight spectrum, affecting many domains including educational achievements and classroom experiences, job opportunities, salaries, and medical care.²⁷ Weight stigma increases the likelihood of bullying, teasing, and harassment for both adults and children.²⁷ Weight bias has been associated with any number of adverse psychosocial effects, including symptoms of depression, anxiety, and eating pathology; poor body image; and a decrease in healthy self-care behaviors.^29-33

Weight stigma makes it more difficult for people to enjoy physical activities, nourish their bodies, and manage stress, which contributes to poorer health outcomes and lower quality of life.^33,34 For example, one study showed that, regardless of actual body mass index, people experiencing weight stigma have significantly increased risk of developing an illness or dying.³⁵

Factors specific to WLS. WLS may lead to significant changes in eating habits, and some patients experience a sense of loss, particularly if eating represented one of their primary coping strategies—this may represent a heightened emotional vulnerability for developing AUD.

The fairly rapid and substantial weight loss that WLS produces can lead to sweeping changes in lifestyle, body image, and functional factors for many individuals. Patients often report profound changes, both positive and negative, in their relationships and interactions not only with people in their support network, but also with strangers.³⁶

After the first year or 2 post-WLS, it is fairly common for patients to regain some weight, sometimes in significant amounts.³⁷ This can lead to a sense of “failure.” Life stressors, including difficulties in important relationships, can further add to patients’ vulnerability. For example, one patient noticed that when she was at her thinnest after WLS, drivers were more likely to stop for her when she crossed the street, which pleased but also angered her because they hadn’t extended the same courtesy before WLS. After she regained a significant amount of weight, she began to notice drivers stopping for her less and less frequently. This took her back to her previous feelings of being ignored but now with the certainty that she would be treated better if she were thinner.

Patients also may experience ambivalence about changes in their body size. One might expect that body image would improve after weight loss, but the evidence is mixed.³⁸ Although there is some evidence that body image improves in the short term after WLS,³⁸ other research indicates that body image does not improve with weight loss.³⁹ However, the evidence is clear that the appearance of excess skin after weight loss worsens some patients’ body image.⁴⁰

To date, there has been no research examining treatment modalities for this population. Because experiences common to individuals who have had WLS could play a role in the development of AUD after surgery, it is intuitive that it would be important to address these factors when designing a treatment plan for post-WLS substance abuse.

Group treatment approach

In 2013, in response to the increase in rates of post-WLS addictions presenting to West End Clinic, an outpatient dual-diagnosis (addiction and psychiatry) service at Massachusetts General Hospital, a specialized treatment group was developed. Nine patients have enrolled since October 2013.

The Post-WLS Addictions Group (PWAG) was designed to be HAES-oriented, trauma-informed, and run within a fat acceptance framework. The HAES model prioritizes a weight-neutral approach that sees health and well-being as multifaceted. This approach directs both patient and clinician to focus on improving health behaviors and reducing internalized weight bias, while building a supportive community that buffers against external cultural weight bias.⁴¹

Trauma-informed care⁴² emphasizes the principles of safety, trustworthiness, and transparency; peer support; collaboration and mutuality; empowerment; and awareness of cultural, historical, and gender issues. In the context of PWAG, weight stigma is conceptualized as a traumatic experience.⁴³ The fat acceptance approach promotes a culture that accepts people of every size with dignity and equality in all aspects of life.⁴⁴

Self-care emphasis. The HAES model encourages patients to allow their bodies to determine what weight to settle at, and to focus on sustainable health-enhancing behaviors rather than weight loss. Patients who asked about the PWAG were told that this group would not explicitly support, or even encourage, continued pursuit of weight loss per se, but instead would assist patients with relapse prevention, mindful eating, improving self-care, and ongoing stress management. Moving away from a focus on weight loss and toward improvement of self-care skills allowed patients to focus on behaviors and outcomes over which they had more direct control and were more likely to yield immediate benefits.

All of the PWAG group members were in early recovery from an SUD, with a minimum of 4 weeks of abstinence; all had at least 1 co-occurring mental health diagnosis. A licensed independent clinical social worker (LICSW) and a physician familiar with bariatric surgery ran the sessions. The group met weekly for 1 hour. The 8 weekly sessions included both psychoeducation and discussion, with each session covering different topics (Table). The first 20 minutes of each session were devoted to an educational presentation; the remaining 40 minutes for reflection and discussion. In sessions 2 through 8, participants were asked about any recent use or cravings, and problem-solving techniques were employed as needed.

Process and observations. Participants described high levels of excitement and hopefulness about being in a group with other WLS patients who had developed SUDs. They had a particular interest in reviewing medical/anatomical information about WLS and understanding more about the potential reasons for the elevated risk for developing SUD following WLS. Discussions regarding weight stigma proved to be quite emotional; most participants reported that this material readily related to their own experiences with weight stigma, but they had never discussed these ideas before.

Participants explored the role that grief, loss, guilt, and shame had in the decision to have WLS, the development of SUDs, weight regain or medical complications from the surgery or from substance abuse, career and relationship changes, and worsened body image. Another theme that emerged was the various reasons that prompted the members have WLS that they may not have been conscious of, or willing to discuss with others, such as pressure from a spouse, fears of remaining single due to their size, and a desire to finally “fit in.”

Repeatedly, group members expressed how satisfied and emotionally validated they felt being with people with similar experiences. Most of them had felt alone. They reported a belief that “everyone else” who had WLS was doing well, and that they were the exceptions. Such beliefs and emotions increased the risk of relapse and decreased participants’ ability to develop more positive coping strategies and self-care skills.

Participants reported that feeling less alone, understanding how stigma impacts health and well-being, and focusing on the general benefits of good self-care rather than the pursuit of weight loss were particularly helpful. The HAES and fat acceptance approaches have given group members new ways to think about their bodies and decreased shame. Several group members reported that if they had learned about the HAES approach prior to having a WLS, they might have made a different decision about having surgery, or at least might have been better prepared to handle the emotional and psychological challenges after WLS.

Although evidence for post-WLS addictions is fairly robust, causal mechanisms are not well understood, and research identifying specific risk factors is lacking. Because post-WLS patients with addictions seem to represent a specific phenotype, specialized treatment might be indicated. Future research will be needed to determine optimal treatment approaches for post-WLS addictions. However, a number of aspects are likely to be important. For example, it is likely that unaddressed experiences of weight stigma contribute to challenges, including substance abuse, after WLS; therefore, clinicians involved in the care of individuals presenting with post-WLS SUD should be knowledgeable about weight stigma and how to address it. Because of the specific nature of post-WLS addictions, patients often feel alone and isolated, and seem to benefit from the specialized group setting. We note that the PWAG group leader is herself a large person who models fat acceptance and follows the HAES approach, and therefore led the group using this experience and her specialized clinical training. As with other addiction recovery treatment modalities, clinicians who have lived the experience can add a valuable component to the program design and patient experience.

Maladaptive alcohol use has emerged as a risk for a subset of individuals who have undergone weight loss surgery (WLS); studies report they are vulnerable to consuming alcohol in greater quantities or more frequently.^1,2 Estimates of the prevalence of “high-risk” or “hazardous” alcohol use after WLS range from 4% to 28%,^3,4 while the prevalence of alcohol use meeting DSM-IV-TR⁵ criteria for alcohol use disorders (AUDs) hovers around 10%.⁶

Heavy alcohol users or patients who have active AUD at the time of WLS are at greater risk for continuation of these problems after surgery.^2,6 For patients with a long-remitted history of AUD, the evidence regarding risk for post-WLS relapse is lacking, and some evidence suggests they may have better weight loss outcomes after WLS.⁷

However, approximately two-third of cases of post-WLS alcohol problems occur in patients who have had no history of such problems before surgery.^5,8,9 Reported prevalence rates of new-onset alcohol problems range from 3% to 18%,^6,9 with the modal finding being approximately 7% to 8%. New-onset alcohol problems appear to occur at a considerable latency after surgery. One study found little risk at 1 year post-surgery, but a significant increase in AUD symptoms at 2 years.⁶ Another study identified 3 years post-surgery as a high-risk time point,⁸ and yet another reported a linear increase in the risk for developing alcohol problems for at least 10 years after WLS.¹⁰

This article describes a group treatment protocol developed specifically for patients with post-WLS substance use disorder (SUD), and explores:

• risk factors and causal mechanisms of post-WLS AUDs
• weight stigma and emotional stressors
• the role of specialized treatment
• group treatment based on the Health at Every Size® (HAES)-oriented, trauma-informed and fat acceptance framework.

Post-WLS patients with alcohol problems may be a distinct phenotype among people with substance abuse issues. For this reason, they may have a need to address their experiences and issues specific to WLS as part of their alcohol treatment.

Etiology

Risk factors. Empirical findings have identified few predictors or risk factors for post-WLS SUD. These patients are more likely to be male and of a younger age.⁶ Notably, the vast majority of individuals reporting post-WLS alcohol problems have undergone Roux-en-Y gastric bypass (RYGB), rather than other WLS procedures, such as the laparoscopic adjustable gastric band,^6,11 suggesting some physiological mechanism specific to RYGB.

Other potential predictors of postoperative alcohol problems include a pre-operative history of depression, generalized anxiety disorder, smoking, and/or recreational drug use.^3,6 Likewise, patients with depression or anxiety disorder symptoms after surgery also may be at higher risk for postoperative alcohol problems.⁴ The evidence of an association between postoperative weight outcomes and post-WLS alcohol problems is mixed.^3,12 Interestingly, patients who had no personal history of substance abuse but who have a family history may have a higher risk of new-onset alcohol problems after surgery.^9,12

Causal mechanisms. The etiology of post-WLS alcohol problems is not well understood. If anything, epidemiological data suggest that larger-bodied individuals tend to consume lower levels of alcohol and have lower rates of AUD than individuals in the general population with thinner bodies.¹³ However, an association has been found between a family history of SUD, but not a personal history, and being large.¹⁴ This suggests a shared etiological pathway between addiction and being “overweight,” of which the onset of AUD after RYGB may be a manifestation.

Human and animal studies have shown that WLS may affect alcohol use differently in specific subgroups. Studies have shown that wild-type rats greatly increase their consumption of, or operant responding for, alcohol after RYGB,¹⁵ while genetically “alcohol-preferring” rats decrease consumption of, or responding for, alcohol after RYGB.¹⁶ A human study likewise found some patients decreased alcohol use or experienced improvement of or remission of AUD symptoms after WLS.⁴ Combined with the finding that a family history of substance abuse is related to risk for post-operative AUD, these data suggest a potential genetic vulnerability or protection in some individuals.

Turning to potential psychosocial explanations, the lay media has popularized the concepts of “addiction transfer,” or “transfer addiction,”¹² with the implication that some patients, who had a preoperative history of “food addiction,” transfer that “addiction” after surgery to substances of abuse.

However, the “addiction transfer” model has a number of flaws:

• it is stigmatizing, because it assumes the patient possesses an innate, chronic, and inalterable pathology
• it relies upon the validity of the controversial construct of “food addiction,” a construct of mixed scientific evidence.¹⁷

Further, our knowledge of post-WLS SUD argues against “addiction transfer.” As noted, postoperative alcohol problems are more likely to develop years after surgery, rather than in the first few months afterward when eating is most significantly curtailed. Additionally, post-WLS alcohol problems are significantly more likely to occur after RYGB than other procedures, whereas the “addiction transfer” model would hypothesize that all WLS patients would be at equal risk for postoperative “addiction transfer,” because their eating is similarly affected after surgery.

Links to RYGB. Some clues to physiological mechanisms underlying alcohol problems after RYGB have been identified. After surgery, many RYGB patients report a quicker effect from a smaller amount of alcohol than was the case pre-surgery.¹⁸ Studies have demonstrated a number of changes in the pharmacodynamics of alcohol after RYGB not seen in other WLS procedures¹⁹:

• a much faster time to peak blood (or breath) alcohol content (BAC)
• significantly higher peak BAC
• a precipitous initial decline in perceived intoxication.^18,20

Anatomical features of RYGB may explain such changes.⁸ However, an increased response to both IV alcohol and IV morphine after RYGB^21,22 in rodents suggests that gastrointestinal tract changes are not solely responsible for changes in alcohol use. Emerging research reports that WLS has been found to cause alterations in brain reward pathways,²³ which may be an additional contributor to changes in alcohol misuse after surgery.

However, even combined, pharmacokinetic and neurobiological factors cannot entirely explain new-onset alcohol problems after WLS; if they could, one would expect to see a much higher prevalence of this complication. Some psychosocial factors are likely involved as well.

Emotional stressors. One possibility involves a mismatch between post-WLS stressors and coping skills. After WLS, these patients face a multitude of challenges inherent in adjusting to changes in lifestyle, weight, body image, and social functioning, which most individuals would find daunting. These challenges become even more acute in the absence of appropriate psychoeducation, preparation, and intervention from qualified professionals. Individuals who lack effective and adaptive coping skills and supports may have a particularly heightened vulnerability to increased alcohol use in the setting of post-surgery changes in brain reward circuits and pharmacodynamics in alcohol metabolism. For example, one patient reported that her spouse’s pressure to “do something about her weight” was a significant factor in her decision to undergo surgery, but that her spouse was blaming and unsupportive when post-WLS complications developed. The patient believed that these experiences helped fuel development of her post-RYGB alcohol abuse.

Specialized treatment

The number of patients experiencing post-WLS alcohol problems likely will continue to grow, given that the risk of onset of has been shown increase over years. Already, post-WLS patients are proportionally overrepresented among substance abuse treatment populations.²⁴ Empirically, however, we do not know yet if these patients need a different type of addiction treatment than patients who have not had WLS.

Some evidence suggests that post-WLS patients with alcohol problems may be a distinct phenotype within the general population with alcohol problems, as their presentations differ in several ways, including their demographics, alcohol use patterns, and premorbid functioning. A number of studies have found that, despite their increased pharmacodynamic sensitivity to alcohol, people with post-WLS AUDs actually consume a larger amount of alcohol on both typical and maximum drinking days than other individuals with AUDs.²⁴ Additionally, although the median age of onset for AUD is around age 20,²⁵ patients presenting with new-onset, post-WLS alcohol problems are usually in their late 30s, or even 40s or 50s. Further, many of these patients were quite high functioning before their alcohol problems, and are unlikely to identify with the cultural stereotype of a person with AUD (eg, homeless, unemployed), which may hamper or delay their own willingness to accept that they have a problem. These phenotypic differences suggest that post-WLS patients may require substance abuse treatment approaches tailored to their unique presentation. There are additional factors specific to the experiences of being larger-bodied and WLS that also may need to be addressed in specialized treatment for post-WLS addiction patients.

Weight stigma. By definition, patients who have undergone WLS have spent a significant portion of their lives inhabiting larger bodies, an experience that, in our culture, can produce adverse psychosocial effects. Compared with the general population, patients seeking WLS exhibit psychological distress equivalent to psychiatric patients.²⁶ Weight stigma or weight bias—negative judgments directed toward people in larger bodies—is pervasive and continues to increase.²⁷ Further, evidence suggests that, unlike almost all other stigmatized groups, people in larger bodies tend to internalize this stigma, holding an unfavorable attitude toward their own social group.²⁸ Weight stigma impacts the well-being of people all along the weight spectrum, affecting many domains including educational achievements and classroom experiences, job opportunities, salaries, and medical care.²⁷ Weight stigma increases the likelihood of bullying, teasing, and harassment for both adults and children.²⁷ Weight bias has been associated with any number of adverse psychosocial effects, including symptoms of depression, anxiety, and eating pathology; poor body image; and a decrease in healthy self-care behaviors.^29-33

Weight stigma makes it more difficult for people to enjoy physical activities, nourish their bodies, and manage stress, which contributes to poorer health outcomes and lower quality of life.^33,34 For example, one study showed that, regardless of actual body mass index, people experiencing weight stigma have significantly increased risk of developing an illness or dying.³⁵

Factors specific to WLS. WLS may lead to significant changes in eating habits, and some patients experience a sense of loss, particularly if eating represented one of their primary coping strategies—this may represent a heightened emotional vulnerability for developing AUD.

The fairly rapid and substantial weight loss that WLS produces can lead to sweeping changes in lifestyle, body image, and functional factors for many individuals. Patients often report profound changes, both positive and negative, in their relationships and interactions not only with people in their support network, but also with strangers.³⁶

After the first year or 2 post-WLS, it is fairly common for patients to regain some weight, sometimes in significant amounts.³⁷ This can lead to a sense of “failure.” Life stressors, including difficulties in important relationships, can further add to patients’ vulnerability. For example, one patient noticed that when she was at her thinnest after WLS, drivers were more likely to stop for her when she crossed the street, which pleased but also angered her because they hadn’t extended the same courtesy before WLS. After she regained a significant amount of weight, she began to notice drivers stopping for her less and less frequently. This took her back to her previous feelings of being ignored but now with the certainty that she would be treated better if she were thinner.

Patients also may experience ambivalence about changes in their body size. One might expect that body image would improve after weight loss, but the evidence is mixed.³⁸ Although there is some evidence that body image improves in the short term after WLS,³⁸ other research indicates that body image does not improve with weight loss.³⁹ However, the evidence is clear that the appearance of excess skin after weight loss worsens some patients’ body image.⁴⁰

To date, there has been no research examining treatment modalities for this population. Because experiences common to individuals who have had WLS could play a role in the development of AUD after surgery, it is intuitive that it would be important to address these factors when designing a treatment plan for post-WLS substance abuse.

Group treatment approach

In 2013, in response to the increase in rates of post-WLS addictions presenting to West End Clinic, an outpatient dual-diagnosis (addiction and psychiatry) service at Massachusetts General Hospital, a specialized treatment group was developed. Nine patients have enrolled since October 2013.

The Post-WLS Addictions Group (PWAG) was designed to be HAES-oriented, trauma-informed, and run within a fat acceptance framework. The HAES model prioritizes a weight-neutral approach that sees health and well-being as multifaceted. This approach directs both patient and clinician to focus on improving health behaviors and reducing internalized weight bias, while building a supportive community that buffers against external cultural weight bias.⁴¹

Trauma-informed care⁴² emphasizes the principles of safety, trustworthiness, and transparency; peer support; collaboration and mutuality; empowerment; and awareness of cultural, historical, and gender issues. In the context of PWAG, weight stigma is conceptualized as a traumatic experience.⁴³ The fat acceptance approach promotes a culture that accepts people of every size with dignity and equality in all aspects of life.⁴⁴

Self-care emphasis. The HAES model encourages patients to allow their bodies to determine what weight to settle at, and to focus on sustainable health-enhancing behaviors rather than weight loss. Patients who asked about the PWAG were told that this group would not explicitly support, or even encourage, continued pursuit of weight loss per se, but instead would assist patients with relapse prevention, mindful eating, improving self-care, and ongoing stress management. Moving away from a focus on weight loss and toward improvement of self-care skills allowed patients to focus on behaviors and outcomes over which they had more direct control and were more likely to yield immediate benefits.

All of the PWAG group members were in early recovery from an SUD, with a minimum of 4 weeks of abstinence; all had at least 1 co-occurring mental health diagnosis. A licensed independent clinical social worker (LICSW) and a physician familiar with bariatric surgery ran the sessions. The group met weekly for 1 hour. The 8 weekly sessions included both psychoeducation and discussion, with each session covering different topics (Table). The first 20 minutes of each session were devoted to an educational presentation; the remaining 40 minutes for reflection and discussion. In sessions 2 through 8, participants were asked about any recent use or cravings, and problem-solving techniques were employed as needed.

Process and observations. Participants described high levels of excitement and hopefulness about being in a group with other WLS patients who had developed SUDs. They had a particular interest in reviewing medical/anatomical information about WLS and understanding more about the potential reasons for the elevated risk for developing SUD following WLS. Discussions regarding weight stigma proved to be quite emotional; most participants reported that this material readily related to their own experiences with weight stigma, but they had never discussed these ideas before.

Participants explored the role that grief, loss, guilt, and shame had in the decision to have WLS, the development of SUDs, weight regain or medical complications from the surgery or from substance abuse, career and relationship changes, and worsened body image. Another theme that emerged was the various reasons that prompted the members have WLS that they may not have been conscious of, or willing to discuss with others, such as pressure from a spouse, fears of remaining single due to their size, and a desire to finally “fit in.”

Repeatedly, group members expressed how satisfied and emotionally validated they felt being with people with similar experiences. Most of them had felt alone. They reported a belief that “everyone else” who had WLS was doing well, and that they were the exceptions. Such beliefs and emotions increased the risk of relapse and decreased participants’ ability to develop more positive coping strategies and self-care skills.

Participants reported that feeling less alone, understanding how stigma impacts health and well-being, and focusing on the general benefits of good self-care rather than the pursuit of weight loss were particularly helpful. The HAES and fat acceptance approaches have given group members new ways to think about their bodies and decreased shame. Several group members reported that if they had learned about the HAES approach prior to having a WLS, they might have made a different decision about having surgery, or at least might have been better prepared to handle the emotional and psychological challenges after WLS.

Although evidence for post-WLS addictions is fairly robust, causal mechanisms are not well understood, and research identifying specific risk factors is lacking. Because post-WLS patients with addictions seem to represent a specific phenotype, specialized treatment might be indicated. Future research will be needed to determine optimal treatment approaches for post-WLS addictions. However, a number of aspects are likely to be important. For example, it is likely that unaddressed experiences of weight stigma contribute to challenges, including substance abuse, after WLS; therefore, clinicians involved in the care of individuals presenting with post-WLS SUD should be knowledgeable about weight stigma and how to address it. Because of the specific nature of post-WLS addictions, patients often feel alone and isolated, and seem to benefit from the specialized group setting. We note that the PWAG group leader is herself a large person who models fat acceptance and follows the HAES approach, and therefore led the group using this experience and her specialized clinical training. As with other addiction recovery treatment modalities, clinicians who have lived the experience can add a valuable component to the program design and patient experience.

Maladaptive alcohol use has emerged as a risk for a subset of individuals who have undergone weight loss surgery (WLS); studies report they are vulnerable to consuming alcohol in greater quantities or more frequently.^1,2 Estimates of the prevalence of “high-risk” or “hazardous” alcohol use after WLS range from 4% to 28%,^3,4 while the prevalence of alcohol use meeting DSM-IV-TR⁵ criteria for alcohol use disorders (AUDs) hovers around 10%.⁶

Heavy alcohol users or patients who have active AUD at the time of WLS are at greater risk for continuation of these problems after surgery.^2,6 For patients with a long-remitted history of AUD, the evidence regarding risk for post-WLS relapse is lacking, and some evidence suggests they may have better weight loss outcomes after WLS.⁷

However, approximately two-third of cases of post-WLS alcohol problems occur in patients who have had no history of such problems before surgery.^5,8,9 Reported prevalence rates of new-onset alcohol problems range from 3% to 18%,^6,9 with the modal finding being approximately 7% to 8%. New-onset alcohol problems appear to occur at a considerable latency after surgery. One study found little risk at 1 year post-surgery, but a significant increase in AUD symptoms at 2 years.⁶ Another study identified 3 years post-surgery as a high-risk time point,⁸ and yet another reported a linear increase in the risk for developing alcohol problems for at least 10 years after WLS.¹⁰

This article describes a group treatment protocol developed specifically for patients with post-WLS substance use disorder (SUD), and explores:

• risk factors and causal mechanisms of post-WLS AUDs
• weight stigma and emotional stressors
• the role of specialized treatment
• group treatment based on the Health at Every Size® (HAES)-oriented, trauma-informed and fat acceptance framework.

Post-WLS patients with alcohol problems may be a distinct phenotype among people with substance abuse issues. For this reason, they may have a need to address their experiences and issues specific to WLS as part of their alcohol treatment.

Etiology

Risk factors. Empirical findings have identified few predictors or risk factors for post-WLS SUD. These patients are more likely to be male and of a younger age.⁶ Notably, the vast majority of individuals reporting post-WLS alcohol problems have undergone Roux-en-Y gastric bypass (RYGB), rather than other WLS procedures, such as the laparoscopic adjustable gastric band,^6,11 suggesting some physiological mechanism specific to RYGB.

Other potential predictors of postoperative alcohol problems include a pre-operative history of depression, generalized anxiety disorder, smoking, and/or recreational drug use.^3,6 Likewise, patients with depression or anxiety disorder symptoms after surgery also may be at higher risk for postoperative alcohol problems.⁴ The evidence of an association between postoperative weight outcomes and post-WLS alcohol problems is mixed.^3,12 Interestingly, patients who had no personal history of substance abuse but who have a family history may have a higher risk of new-onset alcohol problems after surgery.^9,12

Causal mechanisms. The etiology of post-WLS alcohol problems is not well understood. If anything, epidemiological data suggest that larger-bodied individuals tend to consume lower levels of alcohol and have lower rates of AUD than individuals in the general population with thinner bodies.¹³ However, an association has been found between a family history of SUD, but not a personal history, and being large.¹⁴ This suggests a shared etiological pathway between addiction and being “overweight,” of which the onset of AUD after RYGB may be a manifestation.

Human and animal studies have shown that WLS may affect alcohol use differently in specific subgroups. Studies have shown that wild-type rats greatly increase their consumption of, or operant responding for, alcohol after RYGB,¹⁵ while genetically “alcohol-preferring” rats decrease consumption of, or responding for, alcohol after RYGB.¹⁶ A human study likewise found some patients decreased alcohol use or experienced improvement of or remission of AUD symptoms after WLS.⁴ Combined with the finding that a family history of substance abuse is related to risk for post-operative AUD, these data suggest a potential genetic vulnerability or protection in some individuals.

Turning to potential psychosocial explanations, the lay media has popularized the concepts of “addiction transfer,” or “transfer addiction,”¹² with the implication that some patients, who had a preoperative history of “food addiction,” transfer that “addiction” after surgery to substances of abuse.

However, the “addiction transfer” model has a number of flaws:

• it is stigmatizing, because it assumes the patient possesses an innate, chronic, and inalterable pathology
• it relies upon the validity of the controversial construct of “food addiction,” a construct of mixed scientific evidence.¹⁷

Further, our knowledge of post-WLS SUD argues against “addiction transfer.” As noted, postoperative alcohol problems are more likely to develop years after surgery, rather than in the first few months afterward when eating is most significantly curtailed. Additionally, post-WLS alcohol problems are significantly more likely to occur after RYGB than other procedures, whereas the “addiction transfer” model would hypothesize that all WLS patients would be at equal risk for postoperative “addiction transfer,” because their eating is similarly affected after surgery.

Links to RYGB. Some clues to physiological mechanisms underlying alcohol problems after RYGB have been identified. After surgery, many RYGB patients report a quicker effect from a smaller amount of alcohol than was the case pre-surgery.¹⁸ Studies have demonstrated a number of changes in the pharmacodynamics of alcohol after RYGB not seen in other WLS procedures¹⁹:

• a much faster time to peak blood (or breath) alcohol content (BAC)
• significantly higher peak BAC
• a precipitous initial decline in perceived intoxication.^18,20

Anatomical features of RYGB may explain such changes.⁸ However, an increased response to both IV alcohol and IV morphine after RYGB^21,22 in rodents suggests that gastrointestinal tract changes are not solely responsible for changes in alcohol use. Emerging research reports that WLS has been found to cause alterations in brain reward pathways,²³ which may be an additional contributor to changes in alcohol misuse after surgery.

However, even combined, pharmacokinetic and neurobiological factors cannot entirely explain new-onset alcohol problems after WLS; if they could, one would expect to see a much higher prevalence of this complication. Some psychosocial factors are likely involved as well.

Emotional stressors. One possibility involves a mismatch between post-WLS stressors and coping skills. After WLS, these patients face a multitude of challenges inherent in adjusting to changes in lifestyle, weight, body image, and social functioning, which most individuals would find daunting. These challenges become even more acute in the absence of appropriate psychoeducation, preparation, and intervention from qualified professionals. Individuals who lack effective and adaptive coping skills and supports may have a particularly heightened vulnerability to increased alcohol use in the setting of post-surgery changes in brain reward circuits and pharmacodynamics in alcohol metabolism. For example, one patient reported that her spouse’s pressure to “do something about her weight” was a significant factor in her decision to undergo surgery, but that her spouse was blaming and unsupportive when post-WLS complications developed. The patient believed that these experiences helped fuel development of her post-RYGB alcohol abuse.

Specialized treatment

The number of patients experiencing post-WLS alcohol problems likely will continue to grow, given that the risk of onset of has been shown increase over years. Already, post-WLS patients are proportionally overrepresented among substance abuse treatment populations.²⁴ Empirically, however, we do not know yet if these patients need a different type of addiction treatment than patients who have not had WLS.

Some evidence suggests that post-WLS patients with alcohol problems may be a distinct phenotype within the general population with alcohol problems, as their presentations differ in several ways, including their demographics, alcohol use patterns, and premorbid functioning. A number of studies have found that, despite their increased pharmacodynamic sensitivity to alcohol, people with post-WLS AUDs actually consume a larger amount of alcohol on both typical and maximum drinking days than other individuals with AUDs.²⁴ Additionally, although the median age of onset for AUD is around age 20,²⁵ patients presenting with new-onset, post-WLS alcohol problems are usually in their late 30s, or even 40s or 50s. Further, many of these patients were quite high functioning before their alcohol problems, and are unlikely to identify with the cultural stereotype of a person with AUD (eg, homeless, unemployed), which may hamper or delay their own willingness to accept that they have a problem. These phenotypic differences suggest that post-WLS patients may require substance abuse treatment approaches tailored to their unique presentation. There are additional factors specific to the experiences of being larger-bodied and WLS that also may need to be addressed in specialized treatment for post-WLS addiction patients.

Weight stigma. By definition, patients who have undergone WLS have spent a significant portion of their lives inhabiting larger bodies, an experience that, in our culture, can produce adverse psychosocial effects. Compared with the general population, patients seeking WLS exhibit psychological distress equivalent to psychiatric patients.²⁶ Weight stigma or weight bias—negative judgments directed toward people in larger bodies—is pervasive and continues to increase.²⁷ Further, evidence suggests that, unlike almost all other stigmatized groups, people in larger bodies tend to internalize this stigma, holding an unfavorable attitude toward their own social group.²⁸ Weight stigma impacts the well-being of people all along the weight spectrum, affecting many domains including educational achievements and classroom experiences, job opportunities, salaries, and medical care.²⁷ Weight stigma increases the likelihood of bullying, teasing, and harassment for both adults and children.²⁷ Weight bias has been associated with any number of adverse psychosocial effects, including symptoms of depression, anxiety, and eating pathology; poor body image; and a decrease in healthy self-care behaviors.^29-33

Weight stigma makes it more difficult for people to enjoy physical activities, nourish their bodies, and manage stress, which contributes to poorer health outcomes and lower quality of life.^33,34 For example, one study showed that, regardless of actual body mass index, people experiencing weight stigma have significantly increased risk of developing an illness or dying.³⁵

Factors specific to WLS. WLS may lead to significant changes in eating habits, and some patients experience a sense of loss, particularly if eating represented one of their primary coping strategies—this may represent a heightened emotional vulnerability for developing AUD.

The fairly rapid and substantial weight loss that WLS produces can lead to sweeping changes in lifestyle, body image, and functional factors for many individuals. Patients often report profound changes, both positive and negative, in their relationships and interactions not only with people in their support network, but also with strangers.³⁶

After the first year or 2 post-WLS, it is fairly common for patients to regain some weight, sometimes in significant amounts.³⁷ This can lead to a sense of “failure.” Life stressors, including difficulties in important relationships, can further add to patients’ vulnerability. For example, one patient noticed that when she was at her thinnest after WLS, drivers were more likely to stop for her when she crossed the street, which pleased but also angered her because they hadn’t extended the same courtesy before WLS. After she regained a significant amount of weight, she began to notice drivers stopping for her less and less frequently. This took her back to her previous feelings of being ignored but now with the certainty that she would be treated better if she were thinner.

Patients also may experience ambivalence about changes in their body size. One might expect that body image would improve after weight loss, but the evidence is mixed.³⁸ Although there is some evidence that body image improves in the short term after WLS,³⁸ other research indicates that body image does not improve with weight loss.³⁹ However, the evidence is clear that the appearance of excess skin after weight loss worsens some patients’ body image.⁴⁰

To date, there has been no research examining treatment modalities for this population. Because experiences common to individuals who have had WLS could play a role in the development of AUD after surgery, it is intuitive that it would be important to address these factors when designing a treatment plan for post-WLS substance abuse.

Group treatment approach

In 2013, in response to the increase in rates of post-WLS addictions presenting to West End Clinic, an outpatient dual-diagnosis (addiction and psychiatry) service at Massachusetts General Hospital, a specialized treatment group was developed. Nine patients have enrolled since October 2013.

The Post-WLS Addictions Group (PWAG) was designed to be HAES-oriented, trauma-informed, and run within a fat acceptance framework. The HAES model prioritizes a weight-neutral approach that sees health and well-being as multifaceted. This approach directs both patient and clinician to focus on improving health behaviors and reducing internalized weight bias, while building a supportive community that buffers against external cultural weight bias.⁴¹

Trauma-informed care⁴² emphasizes the principles of safety, trustworthiness, and transparency; peer support; collaboration and mutuality; empowerment; and awareness of cultural, historical, and gender issues. In the context of PWAG, weight stigma is conceptualized as a traumatic experience.⁴³ The fat acceptance approach promotes a culture that accepts people of every size with dignity and equality in all aspects of life.⁴⁴

Self-care emphasis. The HAES model encourages patients to allow their bodies to determine what weight to settle at, and to focus on sustainable health-enhancing behaviors rather than weight loss. Patients who asked about the PWAG were told that this group would not explicitly support, or even encourage, continued pursuit of weight loss per se, but instead would assist patients with relapse prevention, mindful eating, improving self-care, and ongoing stress management. Moving away from a focus on weight loss and toward improvement of self-care skills allowed patients to focus on behaviors and outcomes over which they had more direct control and were more likely to yield immediate benefits.

All of the PWAG group members were in early recovery from an SUD, with a minimum of 4 weeks of abstinence; all had at least 1 co-occurring mental health diagnosis. A licensed independent clinical social worker (LICSW) and a physician familiar with bariatric surgery ran the sessions. The group met weekly for 1 hour. The 8 weekly sessions included both psychoeducation and discussion, with each session covering different topics (Table). The first 20 minutes of each session were devoted to an educational presentation; the remaining 40 minutes for reflection and discussion. In sessions 2 through 8, participants were asked about any recent use or cravings, and problem-solving techniques were employed as needed.

Process and observations. Participants described high levels of excitement and hopefulness about being in a group with other WLS patients who had developed SUDs. They had a particular interest in reviewing medical/anatomical information about WLS and understanding more about the potential reasons for the elevated risk for developing SUD following WLS. Discussions regarding weight stigma proved to be quite emotional; most participants reported that this material readily related to their own experiences with weight stigma, but they had never discussed these ideas before.

Participants explored the role that grief, loss, guilt, and shame had in the decision to have WLS, the development of SUDs, weight regain or medical complications from the surgery or from substance abuse, career and relationship changes, and worsened body image. Another theme that emerged was the various reasons that prompted the members have WLS that they may not have been conscious of, or willing to discuss with others, such as pressure from a spouse, fears of remaining single due to their size, and a desire to finally “fit in.”

Repeatedly, group members expressed how satisfied and emotionally validated they felt being with people with similar experiences. Most of them had felt alone. They reported a belief that “everyone else” who had WLS was doing well, and that they were the exceptions. Such beliefs and emotions increased the risk of relapse and decreased participants’ ability to develop more positive coping strategies and self-care skills.

Participants reported that feeling less alone, understanding how stigma impacts health and well-being, and focusing on the general benefits of good self-care rather than the pursuit of weight loss were particularly helpful. The HAES and fat acceptance approaches have given group members new ways to think about their bodies and decreased shame. Several group members reported that if they had learned about the HAES approach prior to having a WLS, they might have made a different decision about having surgery, or at least might have been better prepared to handle the emotional and psychological challenges after WLS.

Although evidence for post-WLS addictions is fairly robust, causal mechanisms are not well understood, and research identifying specific risk factors is lacking. Because post-WLS patients with addictions seem to represent a specific phenotype, specialized treatment might be indicated. Future research will be needed to determine optimal treatment approaches for post-WLS addictions. However, a number of aspects are likely to be important. For example, it is likely that unaddressed experiences of weight stigma contribute to challenges, including substance abuse, after WLS; therefore, clinicians involved in the care of individuals presenting with post-WLS SUD should be knowledgeable about weight stigma and how to address it. Because of the specific nature of post-WLS addictions, patients often feel alone and isolated, and seem to benefit from the specialized group setting. We note that the PWAG group leader is herself a large person who models fat acceptance and follows the HAES approach, and therefore led the group using this experience and her specialized clinical training. As with other addiction recovery treatment modalities, clinicians who have lived the experience can add a valuable component to the program design and patient experience.

Sexually transmitted infections (STIs) continue to be a significant public health problem with potentially serious complications.¹ The incidence of new STIs, including viral STIs, in the United States is estimated at 19 million cases per year.²Chlamydia trachomatis remains the most common bacterial STI with an estimated annual incidence of 2.8 million cases in the United States and 50 million worldwide. Second in prevalence is gonococcal infection. Herpes simplex virus is one of the most common viral STIs, but the incidence of human papillomavirus virus (HPV), which is associated with cervical cancer, has steadily increased worldwide.³ Young persons age 15 to 24 are at the highest risk of acquiring new STIs with almost 50% of new cases reported among this age group.⁴

STIs can have serious complications and sequelae. For example, 20% to 40% of women who have chlamydia infections and 10% to 20% of women who have gonococcal infections develop pelvic inflammatory disease (PID),² which increases the risk for ectopic pregnancy, infertility, and chronic pelvic pain.

Patients with mental illness are at high risk of acquiring STIs. In the United States, the prevalence of HIV among patients with psychiatric illness is 10 to 20 times higher than in the general population.^4,5 Factors contributing to increased vulnerability to STIs among psychiatric patients include:

• impaired autonomy
• increased impulsivity
• increased susceptibility to coerced sex.⁶
  

Furthermore, a higher incidence of poverty, placement in risky environments, and overall poor health and medical care also contribute to the high prevalence of STIs and their complications in this population (Table 1). Because of risk factors specific to psychiatric illness, standard STI prevention interventions are not always successful and novel and innovative behavioral approaches are necessary.⁷

Case Abdominal pain and fever

Ms. K, age 25, has a history of bipolar disorder treated with lithium and presents to the community psychiatrist with lower abdominal pain. She recently recovered from a manic episode and has started to reintegrate with the community mental health team. She refuses to see her primary care physician and is adamant that she wishes to see her psychiatrist, who is the only doctor she has rapport with.

Ms. K reports lower abdominal pain for 3 or 4 days and fever for 1 day. The pain is dull in character. She denies diarrhea, vomiting, or urinary symptoms, but on further questioning describes new-onset, foul-smelling vaginal discharge without vaginal bleeding. Her menstrual cycle usually is regular, but her last menstrual period occurred 2 months ago. Her medical history includes an appendectomy at age 10 and she is a current cigarette smoker. Chart notes taken during her manic episode describe high-risk behavior, including having unprotected sexual intercourse with several partners. On examination, she is febrile and tachycardic with a tender lower abdomen.

Diagnosing STIs

To diagnose an STI, first a clinician must consider its likelihood. Taking a thorough sexual history allows assessment of the need for further investigation and provides an opportunity to discuss risk reduction. In accordance with recent guidelines,⁸ all health care providers are encouraged to consider the sexual history a routine aspect of the clinical encounter. The Centers for Disease Control and Prevention’s (CDC’s) “Five Ps” approach (Table 2) is an excellent tool for guiding investigation and counseling.⁹

The Figure provides health care providers with an algorithm to guide testing for STIs among psychiatric patients. Note that chlamydia, gonorrhea, syphilis, chancroid, viral hepatitis, and HIV must be reported to state public health agencies and the CDC.

Modern laboratory techniques make diagnosing STIs easier. Analysis of urine or serum reduces the need for invasive sampling. If swabs are required for diagnosis, patient self-collection of urethral, vulvovaginal, rectal, or pharyngeal specimens is as accurate as clinician collected samples and is better tolerated.⁸ Because of variation in diagnostic assays, we recommend contacting the laboratory before sending non-standard samples to ensure accurate collection and analysis.

Guidelines for preventing and screening for STIs

There are no prevention guidelines for STIs specific to the psychiatric population, although there is a clear need for focused intervention in this vulnerable patient group.¹⁰ Rates of STI screening generally are low in the psychiatric setting,¹¹ which results in a considerable burden of disease. All psychiatric patients should be encouraged to engage with STI screening programs that are in line with national guidelines. In the inpatient psychiatric or medical environment, clinicians have a responsibility to ensure that STI screening is considered for each patient.

Patients with mental illness should be assumed to be sexually active, even if they do not volunteer this information to clinicians. Employ a low threshold for recommending safer sex practices including condom use. Encourage women to develop a relationship with a family practitioner, internist, or gynecologist. Advise men who have sex with men (MSM) to visit a doctor regularly for screening of HIV and rectal, anal, and oral STIs as behavior and symptoms dictate.

HPV. Routine HPV screening is not recommended; however, 2 vaccines are available to prevent oncogenic HPV (types 16 and 18). All females age 13 to 26 should receive 3 doses of HPV vaccine over a 6-month period. The quadrivalent vaccine (Gardasil) also protects against HPV types 6 and 11, which cause 90% of genital warts and is preferred when available. Males age 9 to 26 also can receive the vaccine, although ideally it should be administered before sexual activity begins.¹⁵ Women still should attend routine cervical cancer screening even if they have the vaccine because 30% of cervical cancers are not caused by HPV 16/18. However, this means that 70% of cervical cancers are associated with HPV 16/18, making screening and the vaccine an important public health initiative. There also is a link between HPV and oral cancers.

Treating STIs among mentally ill individuals

Treatment of STIs among mentally ill individuals is important to prevent medical complications and to reduce transmission. Here are a few additional questions to keep in mind when treating a patient with psychiatric illness:

Does the patient have a primary psychiatric disorder, or is the patient’s current psychiatric presentation a result of the infection?
Some STIs can manifest with psychiatric symptoms—for example, neurosyphilis and HIV-associated neurocognitive disorders—and pose a diagnostic challenge. Obtaining a longitudinal history of the patient’s mental health, age of onset, and family history can help clarify the cause.

Are there any psychiatric adverse effects of STI treatment?

Most drugs used for treating common STIs are not known to cause psychiatric adverse effects (See the American Psychiatric Association¹⁶ and Sockalingham et al¹⁷ for a thorough discussion of HIV and hepatitis C treatment). The exception is fluoroquinolones, which could be prescribed for PID if cephalosporin therapy is not feasible. CNS effects of fluoroquinolones include insomnia, restlessness, confusion, and, in rare cases, mania and psychosis.

What are possible medication interactions to keep in mind when treating a psychiatric patient?
Nonsteroidal anti-inflammatory drugs (NSAIDs), other than sulindac, could increase serum lithium levels. Although NSAIDs are not contraindicated in patients taking lithium, other pain relievers, such as acetaminophen, may be preferred as a first-line choice.

Carbamazepine could lower serum levels of doxycycline.¹⁸
Azithromycin and other macrolides, as well as fluoroquinolones, could have QTc prolonging effects and has been associated with torsades de pointes.¹⁹ Several psychiatric medications, in particular, atypical antipsychotics, also could prolong the QTc interval. This could be a consideration in patients with underlying long QT intervals at baseline or a family history of sudden cardiac death.

Psychiatric patients might refuse or not adhere to their medication. Refusals could be the result of grandiose delusions (“I don’t need treatment”) or paranoia (“The doctor is trying to poison me”). Consider 1-time doses of antibiotics that can be given in the clinic for uncomplicated infections when adherence is an issue. Because psychiatric patients are at higher risk for acquiring STIs, education and counseling—especially substance abuse counseling—are vital as both primary and secondary prevention strategies. Treatment of STIs should be accompanied by referrals to the social work team or a therapist when appropriate.

Finally, as with any proposed treatment, it is important to consider whether the patient has capacity to consent to or refuse treatment. To assess for capacity, a patient must be able to:

• communicate a choice
• understand the relevant information
• appreciate the medical consequences of the decision
• demonstrate the ability to reason about treatment choices.²⁰

Case continued

In the emergency department, Ms. K’s vital signs are: temperature 39.5°C; pulse 110 beats per minute; blood pressure 96/67 mm Hg; and breathing 20 respirations per minute. She complains of nausea and has 2 episodes of emesis. She allows clinicians to perform a complete physical examination, including pelvic exam. Her cervix is inflamed, and she is noted to have adnexal and cervical motion tenderness.

Labs and imaging confirm a diagnosis of PID due to gonorrhea and she is admitted to the hospital for IV antibiotics. She continues to experience nausea and vomiting, but also complains of dizziness and diarrhea. Her speech is slurred and a coarse tremor is noticed in her hands. Renal function tests show slight impairment, probably due to dehydration. A pregnancy test is negative.

Lithium is held. Her nausea, vomiting, and diarrhea resolve quickly, and Ms. K asks to leave. When she is told that she is not ready for discharge, Ms. K becomes upset and rips out her IV yelling, “I don’t need treatment from you guys!” A psychiatry consult is called to assess for her capacity to refuse treatment. The team determines that she has capacity, but she becomes agreeable to remaining in the hospital after a phone conversation with her community mental health team.

Ms. K improves with antibiotic treatment. HIV and syphilis serology tests are negative. Before discharge, both the community psychiatrist and her primary care physicians are informed her lithium was held during hospitalization and restarted before discharge. Ms. K also is educated about the signs and symptoms of lithium toxicity, as well as common STIs.

Clinical considerations

• Physicians should have a low threshold of suspicion for PID in a sexually active young woman who presents with abdominal pain and shuffling gait, which is a natural attempt to reduce cervical irritation and is associated with PID.
• Ask about sexual history and symptoms of STIs.
• Rule out STIs in men presenting with urinary tract infections.
• If chlamydia is diagnosed, treatment for gonorrhea also is essential, and vice versa.
• Always think about HIV and hepatatis B and C in a patient with a STI.
• Treatment with single-dose medications can be effective.
• Risk of STIs is higher during episodes of mania or psychosis.
• Consider hospitalization if medically indicated or if you suspect non-adherence to therapy. It is important to remember that all kinds of systemic infections—including PID—can result in dehydration and alter renal metabolism leading to lithium accumulation.
• Mentally ill patients might require placement under involuntary commitment if they are found to be a danger to themselves or others. It is important to liaise with both the community psychiatry team and primary care physician both during hospitalization and before discharge to ensure a smooth transition.

Sexually transmitted infections (STIs) continue to be a significant public health problem with potentially serious complications.¹ The incidence of new STIs, including viral STIs, in the United States is estimated at 19 million cases per year.²Chlamydia trachomatis remains the most common bacterial STI with an estimated annual incidence of 2.8 million cases in the United States and 50 million worldwide. Second in prevalence is gonococcal infection. Herpes simplex virus is one of the most common viral STIs, but the incidence of human papillomavirus virus (HPV), which is associated with cervical cancer, has steadily increased worldwide.³ Young persons age 15 to 24 are at the highest risk of acquiring new STIs with almost 50% of new cases reported among this age group.⁴

STIs can have serious complications and sequelae. For example, 20% to 40% of women who have chlamydia infections and 10% to 20% of women who have gonococcal infections develop pelvic inflammatory disease (PID),² which increases the risk for ectopic pregnancy, infertility, and chronic pelvic pain.

Patients with mental illness are at high risk of acquiring STIs. In the United States, the prevalence of HIV among patients with psychiatric illness is 10 to 20 times higher than in the general population.^4,5 Factors contributing to increased vulnerability to STIs among psychiatric patients include:

• impaired autonomy
• increased impulsivity
• increased susceptibility to coerced sex.⁶
  

Furthermore, a higher incidence of poverty, placement in risky environments, and overall poor health and medical care also contribute to the high prevalence of STIs and their complications in this population (Table 1). Because of risk factors specific to psychiatric illness, standard STI prevention interventions are not always successful and novel and innovative behavioral approaches are necessary.⁷

Case Abdominal pain and fever

Ms. K, age 25, has a history of bipolar disorder treated with lithium and presents to the community psychiatrist with lower abdominal pain. She recently recovered from a manic episode and has started to reintegrate with the community mental health team. She refuses to see her primary care physician and is adamant that she wishes to see her psychiatrist, who is the only doctor she has rapport with.

Ms. K reports lower abdominal pain for 3 or 4 days and fever for 1 day. The pain is dull in character. She denies diarrhea, vomiting, or urinary symptoms, but on further questioning describes new-onset, foul-smelling vaginal discharge without vaginal bleeding. Her menstrual cycle usually is regular, but her last menstrual period occurred 2 months ago. Her medical history includes an appendectomy at age 10 and she is a current cigarette smoker. Chart notes taken during her manic episode describe high-risk behavior, including having unprotected sexual intercourse with several partners. On examination, she is febrile and tachycardic with a tender lower abdomen.

Diagnosing STIs

To diagnose an STI, first a clinician must consider its likelihood. Taking a thorough sexual history allows assessment of the need for further investigation and provides an opportunity to discuss risk reduction. In accordance with recent guidelines,⁸ all health care providers are encouraged to consider the sexual history a routine aspect of the clinical encounter. The Centers for Disease Control and Prevention’s (CDC’s) “Five Ps” approach (Table 2) is an excellent tool for guiding investigation and counseling.⁹

The Figure provides health care providers with an algorithm to guide testing for STIs among psychiatric patients. Note that chlamydia, gonorrhea, syphilis, chancroid, viral hepatitis, and HIV must be reported to state public health agencies and the CDC.

Modern laboratory techniques make diagnosing STIs easier. Analysis of urine or serum reduces the need for invasive sampling. If swabs are required for diagnosis, patient self-collection of urethral, vulvovaginal, rectal, or pharyngeal specimens is as accurate as clinician collected samples and is better tolerated.⁸ Because of variation in diagnostic assays, we recommend contacting the laboratory before sending non-standard samples to ensure accurate collection and analysis.

Guidelines for preventing and screening for STIs

There are no prevention guidelines for STIs specific to the psychiatric population, although there is a clear need for focused intervention in this vulnerable patient group.¹⁰ Rates of STI screening generally are low in the psychiatric setting,¹¹ which results in a considerable burden of disease. All psychiatric patients should be encouraged to engage with STI screening programs that are in line with national guidelines. In the inpatient psychiatric or medical environment, clinicians have a responsibility to ensure that STI screening is considered for each patient.

Patients with mental illness should be assumed to be sexually active, even if they do not volunteer this information to clinicians. Employ a low threshold for recommending safer sex practices including condom use. Encourage women to develop a relationship with a family practitioner, internist, or gynecologist. Advise men who have sex with men (MSM) to visit a doctor regularly for screening of HIV and rectal, anal, and oral STIs as behavior and symptoms dictate.

HPV. Routine HPV screening is not recommended; however, 2 vaccines are available to prevent oncogenic HPV (types 16 and 18). All females age 13 to 26 should receive 3 doses of HPV vaccine over a 6-month period. The quadrivalent vaccine (Gardasil) also protects against HPV types 6 and 11, which cause 90% of genital warts and is preferred when available. Males age 9 to 26 also can receive the vaccine, although ideally it should be administered before sexual activity begins.¹⁵ Women still should attend routine cervical cancer screening even if they have the vaccine because 30% of cervical cancers are not caused by HPV 16/18. However, this means that 70% of cervical cancers are associated with HPV 16/18, making screening and the vaccine an important public health initiative. There also is a link between HPV and oral cancers.

Treating STIs among mentally ill individuals

Treatment of STIs among mentally ill individuals is important to prevent medical complications and to reduce transmission. Here are a few additional questions to keep in mind when treating a patient with psychiatric illness:

Does the patient have a primary psychiatric disorder, or is the patient’s current psychiatric presentation a result of the infection?
Some STIs can manifest with psychiatric symptoms—for example, neurosyphilis and HIV-associated neurocognitive disorders—and pose a diagnostic challenge. Obtaining a longitudinal history of the patient’s mental health, age of onset, and family history can help clarify the cause.

Are there any psychiatric adverse effects of STI treatment?

Most drugs used for treating common STIs are not known to cause psychiatric adverse effects (See the American Psychiatric Association¹⁶ and Sockalingham et al¹⁷ for a thorough discussion of HIV and hepatitis C treatment). The exception is fluoroquinolones, which could be prescribed for PID if cephalosporin therapy is not feasible. CNS effects of fluoroquinolones include insomnia, restlessness, confusion, and, in rare cases, mania and psychosis.

What are possible medication interactions to keep in mind when treating a psychiatric patient?
Nonsteroidal anti-inflammatory drugs (NSAIDs), other than sulindac, could increase serum lithium levels. Although NSAIDs are not contraindicated in patients taking lithium, other pain relievers, such as acetaminophen, may be preferred as a first-line choice.

Carbamazepine could lower serum levels of doxycycline.¹⁸
Azithromycin and other macrolides, as well as fluoroquinolones, could have QTc prolonging effects and has been associated with torsades de pointes.¹⁹ Several psychiatric medications, in particular, atypical antipsychotics, also could prolong the QTc interval. This could be a consideration in patients with underlying long QT intervals at baseline or a family history of sudden cardiac death.

Psychiatric patients might refuse or not adhere to their medication. Refusals could be the result of grandiose delusions (“I don’t need treatment”) or paranoia (“The doctor is trying to poison me”). Consider 1-time doses of antibiotics that can be given in the clinic for uncomplicated infections when adherence is an issue. Because psychiatric patients are at higher risk for acquiring STIs, education and counseling—especially substance abuse counseling—are vital as both primary and secondary prevention strategies. Treatment of STIs should be accompanied by referrals to the social work team or a therapist when appropriate.

Finally, as with any proposed treatment, it is important to consider whether the patient has capacity to consent to or refuse treatment. To assess for capacity, a patient must be able to:

• communicate a choice
• understand the relevant information
• appreciate the medical consequences of the decision
• demonstrate the ability to reason about treatment choices.²⁰

Case continued

In the emergency department, Ms. K’s vital signs are: temperature 39.5°C; pulse 110 beats per minute; blood pressure 96/67 mm Hg; and breathing 20 respirations per minute. She complains of nausea and has 2 episodes of emesis. She allows clinicians to perform a complete physical examination, including pelvic exam. Her cervix is inflamed, and she is noted to have adnexal and cervical motion tenderness.

Labs and imaging confirm a diagnosis of PID due to gonorrhea and she is admitted to the hospital for IV antibiotics. She continues to experience nausea and vomiting, but also complains of dizziness and diarrhea. Her speech is slurred and a coarse tremor is noticed in her hands. Renal function tests show slight impairment, probably due to dehydration. A pregnancy test is negative.

Lithium is held. Her nausea, vomiting, and diarrhea resolve quickly, and Ms. K asks to leave. When she is told that she is not ready for discharge, Ms. K becomes upset and rips out her IV yelling, “I don’t need treatment from you guys!” A psychiatry consult is called to assess for her capacity to refuse treatment. The team determines that she has capacity, but she becomes agreeable to remaining in the hospital after a phone conversation with her community mental health team.

Ms. K improves with antibiotic treatment. HIV and syphilis serology tests are negative. Before discharge, both the community psychiatrist and her primary care physicians are informed her lithium was held during hospitalization and restarted before discharge. Ms. K also is educated about the signs and symptoms of lithium toxicity, as well as common STIs.

Clinical considerations

• Physicians should have a low threshold of suspicion for PID in a sexually active young woman who presents with abdominal pain and shuffling gait, which is a natural attempt to reduce cervical irritation and is associated with PID.
• Ask about sexual history and symptoms of STIs.
• Rule out STIs in men presenting with urinary tract infections.
• If chlamydia is diagnosed, treatment for gonorrhea also is essential, and vice versa.
• Always think about HIV and hepatatis B and C in a patient with a STI.
• Treatment with single-dose medications can be effective.
• Risk of STIs is higher during episodes of mania or psychosis.
• Consider hospitalization if medically indicated or if you suspect non-adherence to therapy. It is important to remember that all kinds of systemic infections—including PID—can result in dehydration and alter renal metabolism leading to lithium accumulation.
• Mentally ill patients might require placement under involuntary commitment if they are found to be a danger to themselves or others. It is important to liaise with both the community psychiatry team and primary care physician both during hospitalization and before discharge to ensure a smooth transition.

Sexually transmitted infections (STIs) continue to be a significant public health problem with potentially serious complications.¹ The incidence of new STIs, including viral STIs, in the United States is estimated at 19 million cases per year.²Chlamydia trachomatis remains the most common bacterial STI with an estimated annual incidence of 2.8 million cases in the United States and 50 million worldwide. Second in prevalence is gonococcal infection. Herpes simplex virus is one of the most common viral STIs, but the incidence of human papillomavirus virus (HPV), which is associated with cervical cancer, has steadily increased worldwide.³ Young persons age 15 to 24 are at the highest risk of acquiring new STIs with almost 50% of new cases reported among this age group.⁴

STIs can have serious complications and sequelae. For example, 20% to 40% of women who have chlamydia infections and 10% to 20% of women who have gonococcal infections develop pelvic inflammatory disease (PID),² which increases the risk for ectopic pregnancy, infertility, and chronic pelvic pain.

Patients with mental illness are at high risk of acquiring STIs. In the United States, the prevalence of HIV among patients with psychiatric illness is 10 to 20 times higher than in the general population.^4,5 Factors contributing to increased vulnerability to STIs among psychiatric patients include:

• impaired autonomy
• increased impulsivity
• increased susceptibility to coerced sex.⁶
  

Furthermore, a higher incidence of poverty, placement in risky environments, and overall poor health and medical care also contribute to the high prevalence of STIs and their complications in this population (Table 1). Because of risk factors specific to psychiatric illness, standard STI prevention interventions are not always successful and novel and innovative behavioral approaches are necessary.⁷

Case Abdominal pain and fever

Ms. K, age 25, has a history of bipolar disorder treated with lithium and presents to the community psychiatrist with lower abdominal pain. She recently recovered from a manic episode and has started to reintegrate with the community mental health team. She refuses to see her primary care physician and is adamant that she wishes to see her psychiatrist, who is the only doctor she has rapport with.

Ms. K reports lower abdominal pain for 3 or 4 days and fever for 1 day. The pain is dull in character. She denies diarrhea, vomiting, or urinary symptoms, but on further questioning describes new-onset, foul-smelling vaginal discharge without vaginal bleeding. Her menstrual cycle usually is regular, but her last menstrual period occurred 2 months ago. Her medical history includes an appendectomy at age 10 and she is a current cigarette smoker. Chart notes taken during her manic episode describe high-risk behavior, including having unprotected sexual intercourse with several partners. On examination, she is febrile and tachycardic with a tender lower abdomen.

Diagnosing STIs

To diagnose an STI, first a clinician must consider its likelihood. Taking a thorough sexual history allows assessment of the need for further investigation and provides an opportunity to discuss risk reduction. In accordance with recent guidelines,⁸ all health care providers are encouraged to consider the sexual history a routine aspect of the clinical encounter. The Centers for Disease Control and Prevention’s (CDC’s) “Five Ps” approach (Table 2) is an excellent tool for guiding investigation and counseling.⁹

The Figure provides health care providers with an algorithm to guide testing for STIs among psychiatric patients. Note that chlamydia, gonorrhea, syphilis, chancroid, viral hepatitis, and HIV must be reported to state public health agencies and the CDC.

Modern laboratory techniques make diagnosing STIs easier. Analysis of urine or serum reduces the need for invasive sampling. If swabs are required for diagnosis, patient self-collection of urethral, vulvovaginal, rectal, or pharyngeal specimens is as accurate as clinician collected samples and is better tolerated.⁸ Because of variation in diagnostic assays, we recommend contacting the laboratory before sending non-standard samples to ensure accurate collection and analysis.

Guidelines for preventing and screening for STIs

There are no prevention guidelines for STIs specific to the psychiatric population, although there is a clear need for focused intervention in this vulnerable patient group.¹⁰ Rates of STI screening generally are low in the psychiatric setting,¹¹ which results in a considerable burden of disease. All psychiatric patients should be encouraged to engage with STI screening programs that are in line with national guidelines. In the inpatient psychiatric or medical environment, clinicians have a responsibility to ensure that STI screening is considered for each patient.

Patients with mental illness should be assumed to be sexually active, even if they do not volunteer this information to clinicians. Employ a low threshold for recommending safer sex practices including condom use. Encourage women to develop a relationship with a family practitioner, internist, or gynecologist. Advise men who have sex with men (MSM) to visit a doctor regularly for screening of HIV and rectal, anal, and oral STIs as behavior and symptoms dictate.

HPV. Routine HPV screening is not recommended; however, 2 vaccines are available to prevent oncogenic HPV (types 16 and 18). All females age 13 to 26 should receive 3 doses of HPV vaccine over a 6-month period. The quadrivalent vaccine (Gardasil) also protects against HPV types 6 and 11, which cause 90% of genital warts and is preferred when available. Males age 9 to 26 also can receive the vaccine, although ideally it should be administered before sexual activity begins.¹⁵ Women still should attend routine cervical cancer screening even if they have the vaccine because 30% of cervical cancers are not caused by HPV 16/18. However, this means that 70% of cervical cancers are associated with HPV 16/18, making screening and the vaccine an important public health initiative. There also is a link between HPV and oral cancers.

Treating STIs among mentally ill individuals

Treatment of STIs among mentally ill individuals is important to prevent medical complications and to reduce transmission. Here are a few additional questions to keep in mind when treating a patient with psychiatric illness:

Does the patient have a primary psychiatric disorder, or is the patient’s current psychiatric presentation a result of the infection?
Some STIs can manifest with psychiatric symptoms—for example, neurosyphilis and HIV-associated neurocognitive disorders—and pose a diagnostic challenge. Obtaining a longitudinal history of the patient’s mental health, age of onset, and family history can help clarify the cause.

Are there any psychiatric adverse effects of STI treatment?

Most drugs used for treating common STIs are not known to cause psychiatric adverse effects (See the American Psychiatric Association¹⁶ and Sockalingham et al¹⁷ for a thorough discussion of HIV and hepatitis C treatment). The exception is fluoroquinolones, which could be prescribed for PID if cephalosporin therapy is not feasible. CNS effects of fluoroquinolones include insomnia, restlessness, confusion, and, in rare cases, mania and psychosis.

What are possible medication interactions to keep in mind when treating a psychiatric patient?
Nonsteroidal anti-inflammatory drugs (NSAIDs), other than sulindac, could increase serum lithium levels. Although NSAIDs are not contraindicated in patients taking lithium, other pain relievers, such as acetaminophen, may be preferred as a first-line choice.

Carbamazepine could lower serum levels of doxycycline.¹⁸
Azithromycin and other macrolides, as well as fluoroquinolones, could have QTc prolonging effects and has been associated with torsades de pointes.¹⁹ Several psychiatric medications, in particular, atypical antipsychotics, also could prolong the QTc interval. This could be a consideration in patients with underlying long QT intervals at baseline or a family history of sudden cardiac death.

Psychiatric patients might refuse or not adhere to their medication. Refusals could be the result of grandiose delusions (“I don’t need treatment”) or paranoia (“The doctor is trying to poison me”). Consider 1-time doses of antibiotics that can be given in the clinic for uncomplicated infections when adherence is an issue. Because psychiatric patients are at higher risk for acquiring STIs, education and counseling—especially substance abuse counseling—are vital as both primary and secondary prevention strategies. Treatment of STIs should be accompanied by referrals to the social work team or a therapist when appropriate.

Finally, as with any proposed treatment, it is important to consider whether the patient has capacity to consent to or refuse treatment. To assess for capacity, a patient must be able to:

• communicate a choice
• understand the relevant information
• appreciate the medical consequences of the decision
• demonstrate the ability to reason about treatment choices.²⁰

Case continued

In the emergency department, Ms. K’s vital signs are: temperature 39.5°C; pulse 110 beats per minute; blood pressure 96/67 mm Hg; and breathing 20 respirations per minute. She complains of nausea and has 2 episodes of emesis. She allows clinicians to perform a complete physical examination, including pelvic exam. Her cervix is inflamed, and she is noted to have adnexal and cervical motion tenderness.

Labs and imaging confirm a diagnosis of PID due to gonorrhea and she is admitted to the hospital for IV antibiotics. She continues to experience nausea and vomiting, but also complains of dizziness and diarrhea. Her speech is slurred and a coarse tremor is noticed in her hands. Renal function tests show slight impairment, probably due to dehydration. A pregnancy test is negative.

Lithium is held. Her nausea, vomiting, and diarrhea resolve quickly, and Ms. K asks to leave. When she is told that she is not ready for discharge, Ms. K becomes upset and rips out her IV yelling, “I don’t need treatment from you guys!” A psychiatry consult is called to assess for her capacity to refuse treatment. The team determines that she has capacity, but she becomes agreeable to remaining in the hospital after a phone conversation with her community mental health team.

Ms. K improves with antibiotic treatment. HIV and syphilis serology tests are negative. Before discharge, both the community psychiatrist and her primary care physicians are informed her lithium was held during hospitalization and restarted before discharge. Ms. K also is educated about the signs and symptoms of lithium toxicity, as well as common STIs.

Clinical considerations

• Physicians should have a low threshold of suspicion for PID in a sexually active young woman who presents with abdominal pain and shuffling gait, which is a natural attempt to reduce cervical irritation and is associated with PID.
• Ask about sexual history and symptoms of STIs.
• Rule out STIs in men presenting with urinary tract infections.
• If chlamydia is diagnosed, treatment for gonorrhea also is essential, and vice versa.
• Always think about HIV and hepatatis B and C in a patient with a STI.
• Treatment with single-dose medications can be effective.
• Risk of STIs is higher during episodes of mania or psychosis.
• Consider hospitalization if medically indicated or if you suspect non-adherence to therapy. It is important to remember that all kinds of systemic infections—including PID—can result in dehydration and alter renal metabolism leading to lithium accumulation.
• Mentally ill patients might require placement under involuntary commitment if they are found to be a danger to themselves or others. It is important to liaise with both the community psychiatry team and primary care physician both during hospitalization and before discharge to ensure a smooth transition.

Snake venom is deadly but is being used to treat some cancers,¹ because it produces contortrostatin, a protein that “paralyzes” cancer cells and prevents them from migrating. Venoms from spiders are being investigated as a treatment to slow the progression of muscular dystrophy by preventing muscle cells from deteriorating. Venom from tarantulas can relieve chronic pain, and those from centipedes help rodents tolerate thermal, chemical, or acid pain. Scorpion venom can cause cancer cells to glow under a flashlight, enabling surgeons to locate and remove them. Anemones toxin could be used to treat autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, and lupus.

Vaccines are an excellent example of how deadly pathogens can be transformed into life-saving therapies. Billions of people have been protected from polio, smallpox, tetanus, diphtheria, measles, mumps, rubella, influenza, pneumococcus, hepatitis A and B, rabies, shingles, typhoid, meningitis, or cholera. Turning killers into saviors is one of the most remarkable miracles of medical research.²

The mind-boggling transformation of mind-altering drugs

In psychiatry, psychedelic drugs have been repurposed into useful therapies for mental illness. As recently as a decade ago, psychiatric practitioners—physicians and nurse practitioners—regarded hallucinogens as dangerous, “must-avoid” drugs of abuse that could trigger or exacerbate serious psychiatric disorders. Then, thanks to ongoing research, the psychedelic “caterpillars” transformed into therapeutic “butterflies,” and the despised drugs of abuse became welcome adjuncts for treating some stubborn psychopathologies. Such paradoxical developments are emblematic of how one can always find a silver lining.

Consider the following transformations of various psychedelics and hallucinogens—also called “entheogens”—into novel pharmacotherapies. Note that in most cases, the application of these mind-altering drugs into useful medications is still a work in progress.

Lysergic acid diethylamide (LSD) was used extensively for treating mood disorders in the pre-antidepressant era, before it was prohibited in the late 1960s. A review of 19 studies—many uncontrolled—concluded that approximately 80% of patients improved, according to the treating physicians.³ However, research on LSD was halted for several decades after it became illegal, and resumed in 2010. Neuropsychiatrists and neuroscience researchers are now employing advanced techniques, such as neuroimaging, molecular pharmacology, and connectomics, to study its therapeutic effects.⁴ LSD is not only being used for treatment-resistant depression but also anxiety, alcoholism, autism, and even schizophrenia. However, despite its potential uses for treating alcoholism and anxiety, enhancing creativity, or caring for terminally ill patients, using LSD requires expertise, caution, and adherence to ethical standards.⁵

In healthy individuals, the effects of LSD include visual hallucinations, audiovisual synesthesia, depersonalization and derealization, and a sense of well-being, happiness, closeness to others, and trust.

Biologic effects include increased heart rate and blood pressure, elevated temperature, dilated pupils, and increased serum cortisol, prolactin, oxytocin, and epinephrine. All effects subside within 3 days.⁶

Psilocybin

Psilocybin, a component of some mushrooms that is known for its use during rituals in some cultures, has been discovered to have antidepressant, anxiolytic, and anti-addictive effects.⁷ Recent controlled studies at Johns Hopkins University reported that a single dose of psilocybin can relieve anxiety or depression for up to 6 months, which, if replicated, could lead to a remarkable paradigm shift in treating mood and anxiety disorders, especially if patients do not respond to standard antidepressants.³ Other emerging uses of both psilocybin and LSD are in treating addictions⁸ where psychiatry is desperately looking for innovative new therapies.

Ecstasy

MDMA (3,4-methylenedioxymethamphetamine), also known as ecstasy, is widely regarded as a harmful party drug that produces euphoria, but not hallucinations. However, it has emerged as a useful treatment for posttraumatic stress disorder (PTSD). In one study of female sexual abuse victims, 80% of the patients who received MDMA with psychotherapy no longer met diagnostic criteria for PTSD after 2 months.⁹ Other studies showed no effects. Despite persistent skepticisms by many, the Multidisciplinary Association for Psychedelics Studies organization is investing millions of dollars into studying MDMA for PTSD in several countries.^9,10 One hurdle is that it is difficult to conduct truly blind studies with psychedelic drugs because of their profound effects. MDMA releases cortisol, oxytocin—which are known to facilitate psychotherapy—and testosterone, but the debate about the risk–benefit ratio will continue.¹¹ MDMA also is being studied for treating social anxiety in adults with autism.¹²

Ketamine

Ketamine is a weaker cousin of the potent psychotogenic phencyclidine (approximately one-fiftieth the potency) and is a well-known drug of abuse that causes dissociation and hallucinations. It is used as an anesthetic in veterinary medicine and in children undergoing surgical procedures. Until recently, its only use in psychiatry has been as an anesthetic during electroconvulsive therapy. However, over the past few years, IV ketamine has been in the spotlight as a breakthrough, rapid-onset antidepressant and anti-suicidal agent in several controlled studies.¹³ This drug is revolutionizing the management of treatment-resistant depression and suicidal ideation and generating new insights into the neurobiology of depression.

Cannabis

Last, but certainly not least, is marijuana, which is more widely used than all the other psychedelics combined, and is currently at the center of a national debate about its legalization. Although the director of the National Institute on Drug Abuse highlighted the many risk of marijuana,¹⁴ studies have pointed to the myriad medical uses of Cannabis.^15,16 An editorial in Nature Medicine recently urged that regulators reconsider the tight constraints on marijuana research.¹⁷ Some of the medical applications of marijuana include:

• psychiatry (anxiety, PTSD)
• neurology (severe epilepsy, tremors in Parkinson’s disease, traumatic brain injury, pain of multiple sclerosis, muscle spasms, and progression of Alzheimer’s disease)
• oncology (nausea and pain of chemotherapy, reduction of metastasis)
• ophthalmology (decrease of intraocular pressure in glaucoma)
• autoimmune disorders (rheumatoid arthritis, Crohn’s disease, lupus).

However, as a schizophrenia researcher, I am wary about marijuana’s high risk of triggering psychosis in young adults with a family history of schizophrenia spectrum disorders.¹⁸

The above are examples of how psychiatry is finally recognizing the therapeutic value inherent in traditionally “evil” street drugs that we euphemistically refer to as “recreational drugs.” Even methamphetamine, the universally condemned and clearly harmful drug, was recently reported to be neuroprotective at low dosages!¹⁹ Could our field have suffered from a blind eye to the benefits of these hallucinogens and ignored the possibility that some persons with addiction who use these “recreational drugs” may have been self-medicating to alleviate their un-diagnosed psychiatric disorder? We need to reconceptualize the pejorative term “mind-altering drug” because of its implicitly negative connotation. After all, alteration may indicate a favorable, not just a deleterious, outcome.

Snake venom is deadly but is being used to treat some cancers,¹ because it produces contortrostatin, a protein that “paralyzes” cancer cells and prevents them from migrating. Venoms from spiders are being investigated as a treatment to slow the progression of muscular dystrophy by preventing muscle cells from deteriorating. Venom from tarantulas can relieve chronic pain, and those from centipedes help rodents tolerate thermal, chemical, or acid pain. Scorpion venom can cause cancer cells to glow under a flashlight, enabling surgeons to locate and remove them. Anemones toxin could be used to treat autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, and lupus.

Vaccines are an excellent example of how deadly pathogens can be transformed into life-saving therapies. Billions of people have been protected from polio, smallpox, tetanus, diphtheria, measles, mumps, rubella, influenza, pneumococcus, hepatitis A and B, rabies, shingles, typhoid, meningitis, or cholera. Turning killers into saviors is one of the most remarkable miracles of medical research.²

The mind-boggling transformation of mind-altering drugs

In psychiatry, psychedelic drugs have been repurposed into useful therapies for mental illness. As recently as a decade ago, psychiatric practitioners—physicians and nurse practitioners—regarded hallucinogens as dangerous, “must-avoid” drugs of abuse that could trigger or exacerbate serious psychiatric disorders. Then, thanks to ongoing research, the psychedelic “caterpillars” transformed into therapeutic “butterflies,” and the despised drugs of abuse became welcome adjuncts for treating some stubborn psychopathologies. Such paradoxical developments are emblematic of how one can always find a silver lining.

Consider the following transformations of various psychedelics and hallucinogens—also called “entheogens”—into novel pharmacotherapies. Note that in most cases, the application of these mind-altering drugs into useful medications is still a work in progress.

Lysergic acid diethylamide (LSD) was used extensively for treating mood disorders in the pre-antidepressant era, before it was prohibited in the late 1960s. A review of 19 studies—many uncontrolled—concluded that approximately 80% of patients improved, according to the treating physicians.³ However, research on LSD was halted for several decades after it became illegal, and resumed in 2010. Neuropsychiatrists and neuroscience researchers are now employing advanced techniques, such as neuroimaging, molecular pharmacology, and connectomics, to study its therapeutic effects.⁴ LSD is not only being used for treatment-resistant depression but also anxiety, alcoholism, autism, and even schizophrenia. However, despite its potential uses for treating alcoholism and anxiety, enhancing creativity, or caring for terminally ill patients, using LSD requires expertise, caution, and adherence to ethical standards.⁵

In healthy individuals, the effects of LSD include visual hallucinations, audiovisual synesthesia, depersonalization and derealization, and a sense of well-being, happiness, closeness to others, and trust.

Biologic effects include increased heart rate and blood pressure, elevated temperature, dilated pupils, and increased serum cortisol, prolactin, oxytocin, and epinephrine. All effects subside within 3 days.⁶

Psilocybin

Psilocybin, a component of some mushrooms that is known for its use during rituals in some cultures, has been discovered to have antidepressant, anxiolytic, and anti-addictive effects.⁷ Recent controlled studies at Johns Hopkins University reported that a single dose of psilocybin can relieve anxiety or depression for up to 6 months, which, if replicated, could lead to a remarkable paradigm shift in treating mood and anxiety disorders, especially if patients do not respond to standard antidepressants.³ Other emerging uses of both psilocybin and LSD are in treating addictions⁸ where psychiatry is desperately looking for innovative new therapies.

Ecstasy

MDMA (3,4-methylenedioxymethamphetamine), also known as ecstasy, is widely regarded as a harmful party drug that produces euphoria, but not hallucinations. However, it has emerged as a useful treatment for posttraumatic stress disorder (PTSD). In one study of female sexual abuse victims, 80% of the patients who received MDMA with psychotherapy no longer met diagnostic criteria for PTSD after 2 months.⁹ Other studies showed no effects. Despite persistent skepticisms by many, the Multidisciplinary Association for Psychedelics Studies organization is investing millions of dollars into studying MDMA for PTSD in several countries.^9,10 One hurdle is that it is difficult to conduct truly blind studies with psychedelic drugs because of their profound effects. MDMA releases cortisol, oxytocin—which are known to facilitate psychotherapy—and testosterone, but the debate about the risk–benefit ratio will continue.¹¹ MDMA also is being studied for treating social anxiety in adults with autism.¹²

Ketamine

Ketamine is a weaker cousin of the potent psychotogenic phencyclidine (approximately one-fiftieth the potency) and is a well-known drug of abuse that causes dissociation and hallucinations. It is used as an anesthetic in veterinary medicine and in children undergoing surgical procedures. Until recently, its only use in psychiatry has been as an anesthetic during electroconvulsive therapy. However, over the past few years, IV ketamine has been in the spotlight as a breakthrough, rapid-onset antidepressant and anti-suicidal agent in several controlled studies.¹³ This drug is revolutionizing the management of treatment-resistant depression and suicidal ideation and generating new insights into the neurobiology of depression.

Cannabis

Last, but certainly not least, is marijuana, which is more widely used than all the other psychedelics combined, and is currently at the center of a national debate about its legalization. Although the director of the National Institute on Drug Abuse highlighted the many risk of marijuana,¹⁴ studies have pointed to the myriad medical uses of Cannabis.^15,16 An editorial in Nature Medicine recently urged that regulators reconsider the tight constraints on marijuana research.¹⁷ Some of the medical applications of marijuana include:

• psychiatry (anxiety, PTSD)
• neurology (severe epilepsy, tremors in Parkinson’s disease, traumatic brain injury, pain of multiple sclerosis, muscle spasms, and progression of Alzheimer’s disease)
• oncology (nausea and pain of chemotherapy, reduction of metastasis)
• ophthalmology (decrease of intraocular pressure in glaucoma)
• autoimmune disorders (rheumatoid arthritis, Crohn’s disease, lupus).

However, as a schizophrenia researcher, I am wary about marijuana’s high risk of triggering psychosis in young adults with a family history of schizophrenia spectrum disorders.¹⁸

The above are examples of how psychiatry is finally recognizing the therapeutic value inherent in traditionally “evil” street drugs that we euphemistically refer to as “recreational drugs.” Even methamphetamine, the universally condemned and clearly harmful drug, was recently reported to be neuroprotective at low dosages!¹⁹ Could our field have suffered from a blind eye to the benefits of these hallucinogens and ignored the possibility that some persons with addiction who use these “recreational drugs” may have been self-medicating to alleviate their un-diagnosed psychiatric disorder? We need to reconceptualize the pejorative term “mind-altering drug” because of its implicitly negative connotation. After all, alteration may indicate a favorable, not just a deleterious, outcome.

Snake venom is deadly but is being used to treat some cancers,¹ because it produces contortrostatin, a protein that “paralyzes” cancer cells and prevents them from migrating. Venoms from spiders are being investigated as a treatment to slow the progression of muscular dystrophy by preventing muscle cells from deteriorating. Venom from tarantulas can relieve chronic pain, and those from centipedes help rodents tolerate thermal, chemical, or acid pain. Scorpion venom can cause cancer cells to glow under a flashlight, enabling surgeons to locate and remove them. Anemones toxin could be used to treat autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, and lupus.

Vaccines are an excellent example of how deadly pathogens can be transformed into life-saving therapies. Billions of people have been protected from polio, smallpox, tetanus, diphtheria, measles, mumps, rubella, influenza, pneumococcus, hepatitis A and B, rabies, shingles, typhoid, meningitis, or cholera. Turning killers into saviors is one of the most remarkable miracles of medical research.²

The mind-boggling transformation of mind-altering drugs

In psychiatry, psychedelic drugs have been repurposed into useful therapies for mental illness. As recently as a decade ago, psychiatric practitioners—physicians and nurse practitioners—regarded hallucinogens as dangerous, “must-avoid” drugs of abuse that could trigger or exacerbate serious psychiatric disorders. Then, thanks to ongoing research, the psychedelic “caterpillars” transformed into therapeutic “butterflies,” and the despised drugs of abuse became welcome adjuncts for treating some stubborn psychopathologies. Such paradoxical developments are emblematic of how one can always find a silver lining.

Consider the following transformations of various psychedelics and hallucinogens—also called “entheogens”—into novel pharmacotherapies. Note that in most cases, the application of these mind-altering drugs into useful medications is still a work in progress.

Lysergic acid diethylamide (LSD) was used extensively for treating mood disorders in the pre-antidepressant era, before it was prohibited in the late 1960s. A review of 19 studies—many uncontrolled—concluded that approximately 80% of patients improved, according to the treating physicians.³ However, research on LSD was halted for several decades after it became illegal, and resumed in 2010. Neuropsychiatrists and neuroscience researchers are now employing advanced techniques, such as neuroimaging, molecular pharmacology, and connectomics, to study its therapeutic effects.⁴ LSD is not only being used for treatment-resistant depression but also anxiety, alcoholism, autism, and even schizophrenia. However, despite its potential uses for treating alcoholism and anxiety, enhancing creativity, or caring for terminally ill patients, using LSD requires expertise, caution, and adherence to ethical standards.⁵

In healthy individuals, the effects of LSD include visual hallucinations, audiovisual synesthesia, depersonalization and derealization, and a sense of well-being, happiness, closeness to others, and trust.

Biologic effects include increased heart rate and blood pressure, elevated temperature, dilated pupils, and increased serum cortisol, prolactin, oxytocin, and epinephrine. All effects subside within 3 days.⁶

Psilocybin

Psilocybin, a component of some mushrooms that is known for its use during rituals in some cultures, has been discovered to have antidepressant, anxiolytic, and anti-addictive effects.⁷ Recent controlled studies at Johns Hopkins University reported that a single dose of psilocybin can relieve anxiety or depression for up to 6 months, which, if replicated, could lead to a remarkable paradigm shift in treating mood and anxiety disorders, especially if patients do not respond to standard antidepressants.³ Other emerging uses of both psilocybin and LSD are in treating addictions⁸ where psychiatry is desperately looking for innovative new therapies.

Ecstasy

MDMA (3,4-methylenedioxymethamphetamine), also known as ecstasy, is widely regarded as a harmful party drug that produces euphoria, but not hallucinations. However, it has emerged as a useful treatment for posttraumatic stress disorder (PTSD). In one study of female sexual abuse victims, 80% of the patients who received MDMA with psychotherapy no longer met diagnostic criteria for PTSD after 2 months.⁹ Other studies showed no effects. Despite persistent skepticisms by many, the Multidisciplinary Association for Psychedelics Studies organization is investing millions of dollars into studying MDMA for PTSD in several countries.^9,10 One hurdle is that it is difficult to conduct truly blind studies with psychedelic drugs because of their profound effects. MDMA releases cortisol, oxytocin—which are known to facilitate psychotherapy—and testosterone, but the debate about the risk–benefit ratio will continue.¹¹ MDMA also is being studied for treating social anxiety in adults with autism.¹²

Ketamine

Ketamine is a weaker cousin of the potent psychotogenic phencyclidine (approximately one-fiftieth the potency) and is a well-known drug of abuse that causes dissociation and hallucinations. It is used as an anesthetic in veterinary medicine and in children undergoing surgical procedures. Until recently, its only use in psychiatry has been as an anesthetic during electroconvulsive therapy. However, over the past few years, IV ketamine has been in the spotlight as a breakthrough, rapid-onset antidepressant and anti-suicidal agent in several controlled studies.¹³ This drug is revolutionizing the management of treatment-resistant depression and suicidal ideation and generating new insights into the neurobiology of depression.

Cannabis

Last, but certainly not least, is marijuana, which is more widely used than all the other psychedelics combined, and is currently at the center of a national debate about its legalization. Although the director of the National Institute on Drug Abuse highlighted the many risk of marijuana,¹⁴ studies have pointed to the myriad medical uses of Cannabis.^15,16 An editorial in Nature Medicine recently urged that regulators reconsider the tight constraints on marijuana research.¹⁷ Some of the medical applications of marijuana include:

• psychiatry (anxiety, PTSD)
• neurology (severe epilepsy, tremors in Parkinson’s disease, traumatic brain injury, pain of multiple sclerosis, muscle spasms, and progression of Alzheimer’s disease)
• oncology (nausea and pain of chemotherapy, reduction of metastasis)
• ophthalmology (decrease of intraocular pressure in glaucoma)
• autoimmune disorders (rheumatoid arthritis, Crohn’s disease, lupus).

However, as a schizophrenia researcher, I am wary about marijuana’s high risk of triggering psychosis in young adults with a family history of schizophrenia spectrum disorders.¹⁸

The above are examples of how psychiatry is finally recognizing the therapeutic value inherent in traditionally “evil” street drugs that we euphemistically refer to as “recreational drugs.” Even methamphetamine, the universally condemned and clearly harmful drug, was recently reported to be neuroprotective at low dosages!¹⁹ Could our field have suffered from a blind eye to the benefits of these hallucinogens and ignored the possibility that some persons with addiction who use these “recreational drugs” may have been self-medicating to alleviate their un-diagnosed psychiatric disorder? We need to reconceptualize the pejorative term “mind-altering drug” because of its implicitly negative connotation. After all, alteration may indicate a favorable, not just a deleterious, outcome.

Ms. C, age 44, has a history of hypertension, chronic shoulder pain associated with a motor vehicle accident almost 2 decades ago, and major depressive disorder (MDD). Her medication regimen includes losartan, 100 mg/d; atenolol, 25 mg/d; gabapentin, 100 mg, 3 times a day; sertraline, 100 mg/d; and naproxen, 500 mg, twice a day as needed for pain. She does not take opioids for pain control because she had a poor response when used in the past. Ms. C denies muscle pain or tenderness but describes pain in nonspecific areas of her arm, shoulder, neck, and chest. Ms. C reports poor quality of sleep and early morning awakenings, which she attributes to her unmanaged pain. Her last appointment with a psychiatrist was “many, many months ago.”

A reciprocal relationship exists between depression and pain. A 2-year, population-based, prospective, observational study of 3,654 patients showed that pain at baseline was an independent predictor of depression and a depression diagnosis was a predictor of developing pain within 2 years.¹ Patients with MDD might complain of physical symptoms, such as constipation, generalized aches, frequent headache, and fatigue, many of which overlap with chronic pain disorders. Therefore, a thorough symptom assessment and history is vital for an accurate diagnosis. To decrease polypharmacy and pill burden, optimal treatment should employ agents that treat both conditions.

Using antidepressants to treat pain disorders

Several antidepressants have been studied for managing pain disorders including:

• fibromyalgia
• diabetic neuropathy
• neuropathic pain
• postherpetic neuralgia
• migraine prophylaxis
• chronic musculoskeletal pain.

Antidepressants that treat both depression and chronic neuropathic pain include tricyclic antidepressants (TCAs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) (Table).^2-12 Notably, most antidepressants studied for pain management are used off-label; duloxetine is the only medication with an FDA indication for MDD and pain disorders.

TCAs used to treat comorbid depression and pain conditions include amitriptyline, nortriptyline, imipramine, and desipramine.¹⁴ TCAs are cost-effective medications for managing neuropathy and headache; however, the dosages used for pain tend to be lower than those typically used for depression.

TCAs are not commonly prescribed for depression because of their side-effect profile and poor tolerability. TCAs are contraindicated in patients with cardiac conduction abnormalities, epilepsy, and narrow-angle glaucoma. Common adverse effects include dry mouth, sweating, dizziness, orthostatic hypotension, sedation, weight gain, urinary retention, and constipation. These adverse effects limit their use and have organizations, such as the American Geriatric Society, to caution against their use in geriatric patients.

SNRIs that have been studied for pain disorders include venlafaxine, duloxetine, and milnacipran.² Of note, milnacipran is not FDA-approved for MDD, but its L-enantiomer, levomilnacipran, is. Unlike duloxetine and venlafaxine, both milnacipran and levomilnacipran are not available as a generic formulation, therefore they have a higher patient cost. The SNRI dosages used for pain management tend to be similar to those used for MDD, indicating that the target dosage may be effective for both depressive and pain symptoms.

Selective serotonin reuptake inhibitors (SSRIs). Compared with data available supporting the use of TCAs and SNRIs for pain management, the data for SSRI are sparse. Studies have evaluated fluoxetine, paroxetine, and citalopram for pain, with the most promising data supporting fluoxetine.² Fluoxetine, 10 to 80 mg/d, has been evaluated in randomized, placebo-controlled trials for pain conditions, including fibromyalgia (n = 3), painful diabetic neuropathy (n = 1), and facial pain (n = 1). Fluoxetine was more effective than placebo at controlling pain in 2 fibromyalgia studies (dosage range, 10 to 80 mg/d) and 1 facial pain study (dosage, 20 mg/d).²

CASE CONTINUED

When evaluating potential treatment options, it is noted that Ms. C is prescribed sertraline, 200 mg/d, but has been taking a lower dosage. Ms. C states that she has been taking sertraline, 100 mg every morning, for months, and noticed some minor initial improvements in mood, but still has days when she don’t feel like doing anything. She fills out a depression rating scale classifying her current depression as moderately severe. Today she rates her pain as 7 out of 10. Suboptimal control of her depression may require a dosage increase; however, perhaps a change in therapy is warranted. It may be prudent to switch Ms. C to an SNRI, such as duloxetine, an agent that can address her depression and provide additional benefits of pain control.

Switching from a SSRI to duloxetine has been shown to be effective when targeting pain symptoms in patients with comorbid MDD. In addition, improvements in pain scores have been seen after a switch to duloxetine in patients with depression with nonresponse or partial response to a SSRI.¹⁵

Studies support the decision to change Ms. C’s medication from sertraline to duloxetine, despite an inadequate therapeutic trial of the SSRI.

Conversely, the use of pain medications to treat depression also has been studied. The most notable data supports the use of ketamine, an anesthetic. IV ketamine is well documented for treating pain and, in recent years, has been evaluated for MDD in several small studies. Results show that IV ketamine, 0.5 mg/kg, produced a rapid response in depressed patients.¹⁶ For pain conditions studies support the use of ketamine as an IV push, continuous infusion, intermittent infusion, as well as oral administration, for many conditions, including acute and postoperative pain, chronic regional pain, and neuropathic pain. However, there is little evidence evaluating ketamine’s effect on both pain scores and depression symptoms in patients such as Ms. C.

Ms. C, age 44, has a history of hypertension, chronic shoulder pain associated with a motor vehicle accident almost 2 decades ago, and major depressive disorder (MDD). Her medication regimen includes losartan, 100 mg/d; atenolol, 25 mg/d; gabapentin, 100 mg, 3 times a day; sertraline, 100 mg/d; and naproxen, 500 mg, twice a day as needed for pain. She does not take opioids for pain control because she had a poor response when used in the past. Ms. C denies muscle pain or tenderness but describes pain in nonspecific areas of her arm, shoulder, neck, and chest. Ms. C reports poor quality of sleep and early morning awakenings, which she attributes to her unmanaged pain. Her last appointment with a psychiatrist was “many, many months ago.”

A reciprocal relationship exists between depression and pain. A 2-year, population-based, prospective, observational study of 3,654 patients showed that pain at baseline was an independent predictor of depression and a depression diagnosis was a predictor of developing pain within 2 years.¹ Patients with MDD might complain of physical symptoms, such as constipation, generalized aches, frequent headache, and fatigue, many of which overlap with chronic pain disorders. Therefore, a thorough symptom assessment and history is vital for an accurate diagnosis. To decrease polypharmacy and pill burden, optimal treatment should employ agents that treat both conditions.

Using antidepressants to treat pain disorders

Several antidepressants have been studied for managing pain disorders including:

• fibromyalgia
• diabetic neuropathy
• neuropathic pain
• postherpetic neuralgia
• migraine prophylaxis
• chronic musculoskeletal pain.

Antidepressants that treat both depression and chronic neuropathic pain include tricyclic antidepressants (TCAs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) (Table).^2-12 Notably, most antidepressants studied for pain management are used off-label; duloxetine is the only medication with an FDA indication for MDD and pain disorders.

TCAs used to treat comorbid depression and pain conditions include amitriptyline, nortriptyline, imipramine, and desipramine.¹⁴ TCAs are cost-effective medications for managing neuropathy and headache; however, the dosages used for pain tend to be lower than those typically used for depression.

TCAs are not commonly prescribed for depression because of their side-effect profile and poor tolerability. TCAs are contraindicated in patients with cardiac conduction abnormalities, epilepsy, and narrow-angle glaucoma. Common adverse effects include dry mouth, sweating, dizziness, orthostatic hypotension, sedation, weight gain, urinary retention, and constipation. These adverse effects limit their use and have organizations, such as the American Geriatric Society, to caution against their use in geriatric patients.

SNRIs that have been studied for pain disorders include venlafaxine, duloxetine, and milnacipran.² Of note, milnacipran is not FDA-approved for MDD, but its L-enantiomer, levomilnacipran, is. Unlike duloxetine and venlafaxine, both milnacipran and levomilnacipran are not available as a generic formulation, therefore they have a higher patient cost. The SNRI dosages used for pain management tend to be similar to those used for MDD, indicating that the target dosage may be effective for both depressive and pain symptoms.

Selective serotonin reuptake inhibitors (SSRIs). Compared with data available supporting the use of TCAs and SNRIs for pain management, the data for SSRI are sparse. Studies have evaluated fluoxetine, paroxetine, and citalopram for pain, with the most promising data supporting fluoxetine.² Fluoxetine, 10 to 80 mg/d, has been evaluated in randomized, placebo-controlled trials for pain conditions, including fibromyalgia (n = 3), painful diabetic neuropathy (n = 1), and facial pain (n = 1). Fluoxetine was more effective than placebo at controlling pain in 2 fibromyalgia studies (dosage range, 10 to 80 mg/d) and 1 facial pain study (dosage, 20 mg/d).²

CASE CONTINUED

When evaluating potential treatment options, it is noted that Ms. C is prescribed sertraline, 200 mg/d, but has been taking a lower dosage. Ms. C states that she has been taking sertraline, 100 mg every morning, for months, and noticed some minor initial improvements in mood, but still has days when she don’t feel like doing anything. She fills out a depression rating scale classifying her current depression as moderately severe. Today she rates her pain as 7 out of 10. Suboptimal control of her depression may require a dosage increase; however, perhaps a change in therapy is warranted. It may be prudent to switch Ms. C to an SNRI, such as duloxetine, an agent that can address her depression and provide additional benefits of pain control.

Switching from a SSRI to duloxetine has been shown to be effective when targeting pain symptoms in patients with comorbid MDD. In addition, improvements in pain scores have been seen after a switch to duloxetine in patients with depression with nonresponse or partial response to a SSRI.¹⁵

Studies support the decision to change Ms. C’s medication from sertraline to duloxetine, despite an inadequate therapeutic trial of the SSRI.

Conversely, the use of pain medications to treat depression also has been studied. The most notable data supports the use of ketamine, an anesthetic. IV ketamine is well documented for treating pain and, in recent years, has been evaluated for MDD in several small studies. Results show that IV ketamine, 0.5 mg/kg, produced a rapid response in depressed patients.¹⁶ For pain conditions studies support the use of ketamine as an IV push, continuous infusion, intermittent infusion, as well as oral administration, for many conditions, including acute and postoperative pain, chronic regional pain, and neuropathic pain. However, there is little evidence evaluating ketamine’s effect on both pain scores and depression symptoms in patients such as Ms. C.

Ms. C, age 44, has a history of hypertension, chronic shoulder pain associated with a motor vehicle accident almost 2 decades ago, and major depressive disorder (MDD). Her medication regimen includes losartan, 100 mg/d; atenolol, 25 mg/d; gabapentin, 100 mg, 3 times a day; sertraline, 100 mg/d; and naproxen, 500 mg, twice a day as needed for pain. She does not take opioids for pain control because she had a poor response when used in the past. Ms. C denies muscle pain or tenderness but describes pain in nonspecific areas of her arm, shoulder, neck, and chest. Ms. C reports poor quality of sleep and early morning awakenings, which she attributes to her unmanaged pain. Her last appointment with a psychiatrist was “many, many months ago.”

A reciprocal relationship exists between depression and pain. A 2-year, population-based, prospective, observational study of 3,654 patients showed that pain at baseline was an independent predictor of depression and a depression diagnosis was a predictor of developing pain within 2 years.¹ Patients with MDD might complain of physical symptoms, such as constipation, generalized aches, frequent headache, and fatigue, many of which overlap with chronic pain disorders. Therefore, a thorough symptom assessment and history is vital for an accurate diagnosis. To decrease polypharmacy and pill burden, optimal treatment should employ agents that treat both conditions.

Using antidepressants to treat pain disorders

Several antidepressants have been studied for managing pain disorders including:

• fibromyalgia
• diabetic neuropathy
• neuropathic pain
• postherpetic neuralgia
• migraine prophylaxis
• chronic musculoskeletal pain.

Antidepressants that treat both depression and chronic neuropathic pain include tricyclic antidepressants (TCAs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) (Table).^2-12 Notably, most antidepressants studied for pain management are used off-label; duloxetine is the only medication with an FDA indication for MDD and pain disorders.

TCAs used to treat comorbid depression and pain conditions include amitriptyline, nortriptyline, imipramine, and desipramine.¹⁴ TCAs are cost-effective medications for managing neuropathy and headache; however, the dosages used for pain tend to be lower than those typically used for depression.

TCAs are not commonly prescribed for depression because of their side-effect profile and poor tolerability. TCAs are contraindicated in patients with cardiac conduction abnormalities, epilepsy, and narrow-angle glaucoma. Common adverse effects include dry mouth, sweating, dizziness, orthostatic hypotension, sedation, weight gain, urinary retention, and constipation. These adverse effects limit their use and have organizations, such as the American Geriatric Society, to caution against their use in geriatric patients.

SNRIs that have been studied for pain disorders include venlafaxine, duloxetine, and milnacipran.² Of note, milnacipran is not FDA-approved for MDD, but its L-enantiomer, levomilnacipran, is. Unlike duloxetine and venlafaxine, both milnacipran and levomilnacipran are not available as a generic formulation, therefore they have a higher patient cost. The SNRI dosages used for pain management tend to be similar to those used for MDD, indicating that the target dosage may be effective for both depressive and pain symptoms.

Selective serotonin reuptake inhibitors (SSRIs). Compared with data available supporting the use of TCAs and SNRIs for pain management, the data for SSRI are sparse. Studies have evaluated fluoxetine, paroxetine, and citalopram for pain, with the most promising data supporting fluoxetine.² Fluoxetine, 10 to 80 mg/d, has been evaluated in randomized, placebo-controlled trials for pain conditions, including fibromyalgia (n = 3), painful diabetic neuropathy (n = 1), and facial pain (n = 1). Fluoxetine was more effective than placebo at controlling pain in 2 fibromyalgia studies (dosage range, 10 to 80 mg/d) and 1 facial pain study (dosage, 20 mg/d).²

CASE CONTINUED

When evaluating potential treatment options, it is noted that Ms. C is prescribed sertraline, 200 mg/d, but has been taking a lower dosage. Ms. C states that she has been taking sertraline, 100 mg every morning, for months, and noticed some minor initial improvements in mood, but still has days when she don’t feel like doing anything. She fills out a depression rating scale classifying her current depression as moderately severe. Today she rates her pain as 7 out of 10. Suboptimal control of her depression may require a dosage increase; however, perhaps a change in therapy is warranted. It may be prudent to switch Ms. C to an SNRI, such as duloxetine, an agent that can address her depression and provide additional benefits of pain control.

Switching from a SSRI to duloxetine has been shown to be effective when targeting pain symptoms in patients with comorbid MDD. In addition, improvements in pain scores have been seen after a switch to duloxetine in patients with depression with nonresponse or partial response to a SSRI.¹⁵

Studies support the decision to change Ms. C’s medication from sertraline to duloxetine, despite an inadequate therapeutic trial of the SSRI.

Conversely, the use of pain medications to treat depression also has been studied. The most notable data supports the use of ketamine, an anesthetic. IV ketamine is well documented for treating pain and, in recent years, has been evaluated for MDD in several small studies. Results show that IV ketamine, 0.5 mg/kg, produced a rapid response in depressed patients.¹⁶ For pain conditions studies support the use of ketamine as an IV push, continuous infusion, intermittent infusion, as well as oral administration, for many conditions, including acute and postoperative pain, chronic regional pain, and neuropathic pain. However, there is little evidence evaluating ketamine’s effect on both pain scores and depression symptoms in patients such as Ms. C.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) have been a welcome addition to the armamentarium for treating depressive disorders, neuropathic pain, and anxiety disorders. Despite the more favorable side-effect profile compared with tricyclic antidepressants and monoamine oxidase inhibitors, these serotonergic agents have been associated with bleeding disorders, purpura, thrombocytopenia, and, in extreme cases, death.^1-4

We describe a case of purpura associated with different classes of antidepressants, including the non-serotonergic agent bupropion, as well as a family history of similar adverse effects to antidepressants.

CASE Purpura resolves when drug is stopped

Ms. R, age 70, presents with major depressive disorder and fibromyalgia and is receiving duloxetine, 20 mg/d, which is gradually increased to 60 mg. She also has a history of chronic obstructive pulmonary disease (COPD), for which she is taking albuterol and a steroid inhaler. Ms. R responds well to treatment; however, she develops blue–purple purpura on her arms each measuring 1 to 2 inches. Laboratory test results including platelet count and prothrombin time/international normalized ratio are within normal ranges. Duloxetine is stopped, and purpura resolves in 1 to 2 weeks. To avoid serotonergic antidepressants, Ms. R receives bupropion XL, 150 mg; however, similar purpura develops, then resolves when the medication is discontinued. She is lost to follow up for approximately 6 months, but returns requesting a rechallenge with duloxetine for her depression, which has worsened. Duloxetine is restarted with similar results and is then discontinued. Because she has developed neuropathy, Ms. R is started on nortriptyline, 25 mg/d, increased to 50 mg/d, but purpura develops again, which resolves when medication is discontinued. Ms. R’s daughter reports she also developed a similar reaction with several antidepressants, which resolved with medication discontinuation.

Bleeding risk with antidepressants

The role of serotonin reuptake inhibitors (SRIs) in inducing bleeding has emerged as a safety concern,^5,6 which have been documented in case reports.^7-11 Mechanisms of action that have been thought to affect platelet aggregation include:

• depletion of serotonin in platelets
• increase in capillary fragility
• modification of platelet plug formation
• responsiveness of peptide-induced activation of platelets through stimulation of the thrombin receptor.^7,8,12,13

The severity of bleeding varies with patient-related factors, such as a history of gastritis, peptic ulcer disease, and heavy bleeding during menses; use of gastrotoxic drugs, particularly nonsteroidal anti-inflammatory drugs (NSAIDs), also have been shown to increase this risk.^14,15 For patients taking SRIs and gastrotoxic drugs (eg, NSAIDs), use of acid-suppressing agents have been shown to limit the risk of bleeding.¹⁶

Studies evaluating relative bleeding risks among classes of antidepressants have not shown increased risk with tricyclic antidepressants compared with SSRIs.¹⁷ Adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) are signaling molecules in the vascular system and are important in the thromboregulatory system. Studies in rats reported significant inhibition of ATP, ADP, and AMP hydrolysis with chronic treatment with fluoxetine and nortriptyline, and suggested that both medications changed the nucleotide catabolism, which means that homeostasis of the vascular system can be altered by antidepressant treatments.¹⁸ This is one possible pathway in the role these medications play in the etiology of dysregulation of the thromboregulatory system.

We did not anticipate that our patient would develop similar purpura with bupropion because the bleeding risk associated with antidepressants has been attributed to the effect of serotonin on platelets. Studies observing the effect of SSRIs, SNRIs, and bupropion on platelets and bleeding have not shown significant risk with bupropion.¹⁹ Bleeding associated with bupropion is atypical and needs to be further studied. Although this medication is centrally selective in its action on dopamine receptors, it might have possible peripheral effect on other neurotransmitters, including serotonin.

Ms. R had no personal or family history of purpura or a bleeding disorder. Significant improvement in her physical signs after discontinuing medications and recurrence of pupura with rechallenge indicate that this reaction was triggered by 3 different classes of antidepressants. Family history of similar reaction further suggests a genetic predisposition to platelet dysfunction to antidepressant treatment in a select group of patients.

Limitations include the possibility of senile purpura, which cannot be ruled out despite strong indications that antidepressants were the cause. The possibility of drug interactions needs be considered as well. Ms. R was taking albuterol and a steroid inhaler for her COPD at the time of the initial medication trials, which did not interact with duloxetine or bupropion. During the trials with duloxetine and then nortriptyline, she was taking acetaminophen/hydrocodone in addition to her inhalers, and no significant interactions with the antidepressants were identified. Interactions with unreported or over-the-counter medications or supplements are a possibility.

Before prescribing an antidepressant, we suggest taking a careful history including a family history of bleeding disorders and adverse effects of antidepressants, especially in patients who have risk factors (eg, concomitant use of gastrotoxic medications). Use of gastric acid-suppressing medications could be considered if antidepressants are used. Further investigations into the incidence, risk factors, mechanism of action, and treatment of this adverse effect are indicated.

Drug Brand Names
Acetaminophen/hydrocodone • Lorcet, Norco, Vicodin
Albuterol • Proventil
Bupropion • Wellbutrin
Duloxetine • Cymbalta
Nortriptyline • Pamelor, Aventyl

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) have been a welcome addition to the armamentarium for treating depressive disorders, neuropathic pain, and anxiety disorders. Despite the more favorable side-effect profile compared with tricyclic antidepressants and monoamine oxidase inhibitors, these serotonergic agents have been associated with bleeding disorders, purpura, thrombocytopenia, and, in extreme cases, death.^1-4

We describe a case of purpura associated with different classes of antidepressants, including the non-serotonergic agent bupropion, as well as a family history of similar adverse effects to antidepressants.

CASE Purpura resolves when drug is stopped

Ms. R, age 70, presents with major depressive disorder and fibromyalgia and is receiving duloxetine, 20 mg/d, which is gradually increased to 60 mg. She also has a history of chronic obstructive pulmonary disease (COPD), for which she is taking albuterol and a steroid inhaler. Ms. R responds well to treatment; however, she develops blue–purple purpura on her arms each measuring 1 to 2 inches. Laboratory test results including platelet count and prothrombin time/international normalized ratio are within normal ranges. Duloxetine is stopped, and purpura resolves in 1 to 2 weeks. To avoid serotonergic antidepressants, Ms. R receives bupropion XL, 150 mg; however, similar purpura develops, then resolves when the medication is discontinued. She is lost to follow up for approximately 6 months, but returns requesting a rechallenge with duloxetine for her depression, which has worsened. Duloxetine is restarted with similar results and is then discontinued. Because she has developed neuropathy, Ms. R is started on nortriptyline, 25 mg/d, increased to 50 mg/d, but purpura develops again, which resolves when medication is discontinued. Ms. R’s daughter reports she also developed a similar reaction with several antidepressants, which resolved with medication discontinuation.

Bleeding risk with antidepressants

The role of serotonin reuptake inhibitors (SRIs) in inducing bleeding has emerged as a safety concern,^5,6 which have been documented in case reports.^7-11 Mechanisms of action that have been thought to affect platelet aggregation include:

• depletion of serotonin in platelets
• increase in capillary fragility
• modification of platelet plug formation
• responsiveness of peptide-induced activation of platelets through stimulation of the thrombin receptor.^7,8,12,13

The severity of bleeding varies with patient-related factors, such as a history of gastritis, peptic ulcer disease, and heavy bleeding during menses; use of gastrotoxic drugs, particularly nonsteroidal anti-inflammatory drugs (NSAIDs), also have been shown to increase this risk.^14,15 For patients taking SRIs and gastrotoxic drugs (eg, NSAIDs), use of acid-suppressing agents have been shown to limit the risk of bleeding.¹⁶

Studies evaluating relative bleeding risks among classes of antidepressants have not shown increased risk with tricyclic antidepressants compared with SSRIs.¹⁷ Adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) are signaling molecules in the vascular system and are important in the thromboregulatory system. Studies in rats reported significant inhibition of ATP, ADP, and AMP hydrolysis with chronic treatment with fluoxetine and nortriptyline, and suggested that both medications changed the nucleotide catabolism, which means that homeostasis of the vascular system can be altered by antidepressant treatments.¹⁸ This is one possible pathway in the role these medications play in the etiology of dysregulation of the thromboregulatory system.

We did not anticipate that our patient would develop similar purpura with bupropion because the bleeding risk associated with antidepressants has been attributed to the effect of serotonin on platelets. Studies observing the effect of SSRIs, SNRIs, and bupropion on platelets and bleeding have not shown significant risk with bupropion.¹⁹ Bleeding associated with bupropion is atypical and needs to be further studied. Although this medication is centrally selective in its action on dopamine receptors, it might have possible peripheral effect on other neurotransmitters, including serotonin.

Ms. R had no personal or family history of purpura or a bleeding disorder. Significant improvement in her physical signs after discontinuing medications and recurrence of pupura with rechallenge indicate that this reaction was triggered by 3 different classes of antidepressants. Family history of similar reaction further suggests a genetic predisposition to platelet dysfunction to antidepressant treatment in a select group of patients.

Limitations include the possibility of senile purpura, which cannot be ruled out despite strong indications that antidepressants were the cause. The possibility of drug interactions needs be considered as well. Ms. R was taking albuterol and a steroid inhaler for her COPD at the time of the initial medication trials, which did not interact with duloxetine or bupropion. During the trials with duloxetine and then nortriptyline, she was taking acetaminophen/hydrocodone in addition to her inhalers, and no significant interactions with the antidepressants were identified. Interactions with unreported or over-the-counter medications or supplements are a possibility.

Before prescribing an antidepressant, we suggest taking a careful history including a family history of bleeding disorders and adverse effects of antidepressants, especially in patients who have risk factors (eg, concomitant use of gastrotoxic medications). Use of gastric acid-suppressing medications could be considered if antidepressants are used. Further investigations into the incidence, risk factors, mechanism of action, and treatment of this adverse effect are indicated.

Drug Brand Names
Acetaminophen/hydrocodone • Lorcet, Norco, Vicodin
Albuterol • Proventil
Bupropion • Wellbutrin
Duloxetine • Cymbalta
Nortriptyline • Pamelor, Aventyl

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) have been a welcome addition to the armamentarium for treating depressive disorders, neuropathic pain, and anxiety disorders. Despite the more favorable side-effect profile compared with tricyclic antidepressants and monoamine oxidase inhibitors, these serotonergic agents have been associated with bleeding disorders, purpura, thrombocytopenia, and, in extreme cases, death.^1-4

We describe a case of purpura associated with different classes of antidepressants, including the non-serotonergic agent bupropion, as well as a family history of similar adverse effects to antidepressants.

CASE Purpura resolves when drug is stopped

Ms. R, age 70, presents with major depressive disorder and fibromyalgia and is receiving duloxetine, 20 mg/d, which is gradually increased to 60 mg. She also has a history of chronic obstructive pulmonary disease (COPD), for which she is taking albuterol and a steroid inhaler. Ms. R responds well to treatment; however, she develops blue–purple purpura on her arms each measuring 1 to 2 inches. Laboratory test results including platelet count and prothrombin time/international normalized ratio are within normal ranges. Duloxetine is stopped, and purpura resolves in 1 to 2 weeks. To avoid serotonergic antidepressants, Ms. R receives bupropion XL, 150 mg; however, similar purpura develops, then resolves when the medication is discontinued. She is lost to follow up for approximately 6 months, but returns requesting a rechallenge with duloxetine for her depression, which has worsened. Duloxetine is restarted with similar results and is then discontinued. Because she has developed neuropathy, Ms. R is started on nortriptyline, 25 mg/d, increased to 50 mg/d, but purpura develops again, which resolves when medication is discontinued. Ms. R’s daughter reports she also developed a similar reaction with several antidepressants, which resolved with medication discontinuation.

Bleeding risk with antidepressants

The role of serotonin reuptake inhibitors (SRIs) in inducing bleeding has emerged as a safety concern,^5,6 which have been documented in case reports.^7-11 Mechanisms of action that have been thought to affect platelet aggregation include:

• depletion of serotonin in platelets
• increase in capillary fragility
• modification of platelet plug formation
• responsiveness of peptide-induced activation of platelets through stimulation of the thrombin receptor.^7,8,12,13

The severity of bleeding varies with patient-related factors, such as a history of gastritis, peptic ulcer disease, and heavy bleeding during menses; use of gastrotoxic drugs, particularly nonsteroidal anti-inflammatory drugs (NSAIDs), also have been shown to increase this risk.^14,15 For patients taking SRIs and gastrotoxic drugs (eg, NSAIDs), use of acid-suppressing agents have been shown to limit the risk of bleeding.¹⁶

Studies evaluating relative bleeding risks among classes of antidepressants have not shown increased risk with tricyclic antidepressants compared with SSRIs.¹⁷ Adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) are signaling molecules in the vascular system and are important in the thromboregulatory system. Studies in rats reported significant inhibition of ATP, ADP, and AMP hydrolysis with chronic treatment with fluoxetine and nortriptyline, and suggested that both medications changed the nucleotide catabolism, which means that homeostasis of the vascular system can be altered by antidepressant treatments.¹⁸ This is one possible pathway in the role these medications play in the etiology of dysregulation of the thromboregulatory system.

We did not anticipate that our patient would develop similar purpura with bupropion because the bleeding risk associated with antidepressants has been attributed to the effect of serotonin on platelets. Studies observing the effect of SSRIs, SNRIs, and bupropion on platelets and bleeding have not shown significant risk with bupropion.¹⁹ Bleeding associated with bupropion is atypical and needs to be further studied. Although this medication is centrally selective in its action on dopamine receptors, it might have possible peripheral effect on other neurotransmitters, including serotonin.

Ms. R had no personal or family history of purpura or a bleeding disorder. Significant improvement in her physical signs after discontinuing medications and recurrence of pupura with rechallenge indicate that this reaction was triggered by 3 different classes of antidepressants. Family history of similar reaction further suggests a genetic predisposition to platelet dysfunction to antidepressant treatment in a select group of patients.

Limitations include the possibility of senile purpura, which cannot be ruled out despite strong indications that antidepressants were the cause. The possibility of drug interactions needs be considered as well. Ms. R was taking albuterol and a steroid inhaler for her COPD at the time of the initial medication trials, which did not interact with duloxetine or bupropion. During the trials with duloxetine and then nortriptyline, she was taking acetaminophen/hydrocodone in addition to her inhalers, and no significant interactions with the antidepressants were identified. Interactions with unreported or over-the-counter medications or supplements are a possibility.

Before prescribing an antidepressant, we suggest taking a careful history including a family history of bleeding disorders and adverse effects of antidepressants, especially in patients who have risk factors (eg, concomitant use of gastrotoxic medications). Use of gastric acid-suppressing medications could be considered if antidepressants are used. Further investigations into the incidence, risk factors, mechanism of action, and treatment of this adverse effect are indicated.

Drug Brand Names
Acetaminophen/hydrocodone • Lorcet, Norco, Vicodin
Albuterol • Proventil
Bupropion • Wellbutrin
Duloxetine • Cymbalta
Nortriptyline • Pamelor, Aventyl

Once thought to only be associated with depression, self-criticism is a transdiagnostic risk factor for diverse forms of psychopathology.^1,2 However, research has shown that self-compassion is a robust resilience factor when faced with feelings of personal inadequacy.^3,4

Self-critical individuals experience feelings of unworthiness, inferiority, failure, and guilt. They engage in constant and harsh self-scrutiny and evaluation, and fear being disapproved and criticized and losing the approval and acceptance of others.⁵ Self-compassion involves treating oneself with care and concern when confronted with personal inadequacies, mistakes, failures, and painful life situations.^6,7Although self-criticism is the aspect of perfectionism most associated with maladjustment,⁸ one can be harshly self-critical without being a perfectionist. Most studies of self-criticism have not measured shame; however, this self-conscious emotion has been implicated in diverse forms of psychopathology.⁹ In contrast to guilt, which results from acknowledging bad behavior, shame results from seeing oneself as a bad or inadequate person.

Although self-criticism is destructive across clinical disorders and interpersonal relationships, self-compassion is associated with healthy relationships, emotional well-being, and better treatment outcomes.

Recent research shows how clinicians can teach their patients how to be less self-critical and more self-compassionate. Neff^6,7 proposes that self-compassion involves treating yourself with care and concern when being confronted with personal inadequacies, mistakes, failures, and painful life situations. It consists of 3 interacting components, each of which has a positive and negative pole:

• self-kindness vs self-judgment
• a sense of common humanity vs isolation
• mindfulness vs over-identification.

Self-kindness refers to being caring and understanding with oneself rather than harshly judgmental. Instead of attacking and berating oneself for personal shortcomings, the self is offered warmth and unconditional acceptance.

Humanity involves recognizing that humans are imperfect, that all people fail, make mistakes, and have serious life challenges. By remembering that imperfection is part of life, we feel less isolated when we are in pain.

Mindfulness in the context of self-compassion involves being aware of one’s painful experiences in a balanced way that neither ignores and avoids nor exaggerates painful thoughts and emotions.

Self-compassion is more than the absence of self-judgment, although a defining feature of self-compassion is the lack of self-judgment, and self-judgment overlaps with self-criticism. Rather, self-compassion provides several access points for reducing self-criticism. For example, being kind and understanding when confronting personal inadequacies (eg, “it’s okay not to be perfect”) can counter harsh self-talk (eg, “I’m not defective”). Mindfulness of emotional pain (eg, “this is hard”) can facilitate a kind and warm response (eg, “what can I do to take care of myself right now?”) and therefore lessen self-blame (eg, “blaming myself is just causing me more suffering”). Similarly, remembering that failure is part of the human experience (eg, “it’s normal to mess up sometimes”) can lessen egocentric feelings of isolation (eg, “it’s not just me”) and over-identification (eg, “it’s not the end of the world”), resulting in lessened self-criticism (eg, “maybe it’s not just because I’m a bad person”).

Depression

Several studies have found that self-criticism predicts depression. In 3 epidemiological studies, “feeling worthless” was among the top 2 symptoms predicting a depression diagnosis and later depressive episodes.¹⁰ Self-criticism in fourth-year medical students predicted depression 2 years later, and—in males—10 years later in their medical careers better than a history of depression.¹¹ Self-critical perfectionism also is associated with suicidal ideation and lethality of suicide attempts.¹²

Self-criticism has been shown to predict depressive relapse and residual self-devaluative symptoms in recovered depressed patients.¹³ In one study, currently depressed and remitted depressed patients had higher self-criticism and lower self-compassion compared with healthy controls. Both factors were more strongly associated with depression status than higher perfectionistic beliefs and cognitions, rumination, and maladaptive emotional regulation.¹⁴

Self-criticism and response to treatment. In the National Institute of Mental Health Treatment of Depression Collaborative Research Program,¹⁵ self-critical perfectionism predicted a poorer outcome across all 4 treatments (cognitive-behavioral therapy [CBT], interpersonal psychotherapy [IPT], pharmacotherapy plus clinical management, and placebo plus clinical management). Subsequent studies found that self-criticism predicted poorer response to CBT¹⁶ and IPT.¹⁷ The authors suggest that self-criticism could interfere with treatment because self-critical patients might have difficulty developing a strong therapeutic alliance.^18,19

Anxiety disorders

Self-criticism is common across psychiatric disorders. In a study of 5,877 respondents in the National Comorbidity Survey (NCS), self-criticism was associated with social phobia, findings that were significant after controlling for current emotional distress, neuroticism, and lifetime history of mood, anxiety, and substance use disorders.²⁰ Further, in a CBT treatment study, baseline self-criticism was associated with severity of social phobia and changes in self-criticism predicted treatment outcome.²¹ Self-criticism might be an important core psychological process in the development, maintenance, and course of social phobia. Patients with social anxiety disorder have less self-compassion than healthy controls and greater fear of negative evaluation.

In the NCS, self-criticism was associated with posttraumatic stress disorder (PTSD) even after controlling for lifetime history of affective and anxiety disorders.²⁰ Self-criticism predicted greater severity of combat-related PTSD in hospitalized male veterans,²² and those with PTSD had higher scores on self-criticism scales than those with major depressive disorder.²³ In a study of Holocaust survivors, those with PTSD scored higher on self-criticism than survivors without PTSD.²⁴ Self-criticism also distinguished between female victims of domestic violence with and without PTSD.²⁵

Self-compassion could be a protective factor for posttraumatic stress.²⁶ Combat veterans with higher levels of self-compassion showed lower levels of psychopathology, better functioning in daily life, and fewer symptoms of posttraumatic stress.²⁷ In fact, self-compassion has been found to be a stronger predictor of PTSD than level of combat exposure.²⁸

In an early study, self-criticism scores were higher in patients with panic disorder than in healthy controls, but lower than in patients with depression.²⁹ In a study of a mixed sample of anxiety disorder patients, symptoms of generalized anxiety disorder were associated with shame proneness.³⁰ Consistent with these results, Hoge et al³¹ found that self-compassion was lower in generalized anxiety disorder patients compared with healthy controls with elevated stress. Low self-compassion has been associated with severity of obsessive-compulsive disorder.³²

Eating disorders

Self-criticism is correlated with eating disorder severity.³³ In a study of patients with binge eating disorder, Dunkley and Grilo³⁴ found that self-criticism was associated with the over-evaluation of shape and weight independently of self-esteem and depression. Self-criticism also is associated with body dissatisfaction, independent of self-esteem and depression. Dunkley et al³⁵ found that self-criticism, but not global self-esteem, in patients with binge eating disorder mediated the relationship between childhood abuse and body dissatisfaction and depression. Numerous studies have shown that shame is associated with more severe eating disorder pathology.³³

Self-compassion seems to buffer against body image concerns. It is associated with less body dissatisfaction, body preoccupation, and weight worries,³⁶ greater body appreciation³⁷ and less disordered eating.^37-39 Early decreases in shame during eating disorder treatment was associated with more rapid reduction in eating disorder symptoms.⁴⁰

Interpersonal relationships

Several studies have shown that self-criticism has negative effects on interpersonal relationships throughout life.^5,41,42

• Self-criticism at age 12 predicted less involvement in high school activities and, at age 31, personal and social maladjustment.⁴³
• High school students with high self-criticism reported more interpersonal problems.⁴⁴
• Self-criticism was associated with loneliness, depression, and lack of intimacy with opposite sex friends or partners during the transition to college.⁴⁵
• In a study of college roommates,⁴⁶ self-criticism was associated with increased likelihood of rejection.
• Whiffen and Aube⁴⁷ found that self-criticism was associated with marital dissatisfaction and depression.
• Self-critical mothers with postpartum depression were less satisfied with social support and were more vulnerable to depression.⁴⁸

Self-compassion appears to enhance interpersonal relationships. In a study of heterosexual couples,⁴⁹ self-compassionate individuals were described by their partners as being more emotionally connected, as well as accepting and supporting autonomy, while being less detached, controlling, and verbally or physically aggressive than those lacking self-compassion. Because self-compassionate people give themselves care and support, they seem to have more emotional resources available to give to others.

See the Box examining the evidence on the role of self-compassion in borderline personality disorder and non-suicidal self-injury.

Achieving goals

Powers et al⁵⁰ suggest that self-critics approach goals based on motivation to avoid failure and disapproval, rather than on intrinsic interest and personal meaning. In studies of college students pursuing academic, social, or weight loss goals, self-criticism was associated with less progress to that goal. Self-criticism was associated with rumination and procrastination, which the authors suggest might have focused the self-critic on potential failure, negative evaluation from others, and loss of self-esteem. Additional studies showed the deleterious effects of self-criticism on college students’ progress on obtaining academic or music performance goals and on community residents’ weight loss goals.⁵¹

Not surprisingly, self-compassion is associated with successful goal pursuit and resilience when goals are not met⁵² and less procrastination and academic worry.⁵³ Self-compassion also is associated with intrinsic motivation, goals based on mastery rather than performance, and less fear of academic failure.⁵⁴

How self-criticism and self-compassion develop

Studies have explored the impact of early relationships with parents and development of self-criticism. Parental overcontrol and restrictiveness and lack of warmth consistently have been identified as parenting styles associated with development of self-criticism in children.⁵⁵ One study found that self-criticism fully mediated the relationship between childhood verbal abuse from parents and depression and anxiety in adulthood.⁵⁶ Reports from parents on their current parenting styles are consistent with these studies.⁵⁷ Amitay et al⁵⁷ states that “[s]elf-critics’ negative childhood experiences thus seem to contribute to a pattern of entering, creating, or manipulating subsequent interpersonal environments in ways that perpetuate their negative self-image and increase vulnerability to depression.” Not surprisingly, self-criticism is associated with a fearful avoidant attachment style.⁵⁸ Review of the developmental origins of self-criticism confirms these factors and presents findings that peer relationships also are important factors in the development of self-criticism.^59,60

Early positive relationships with caregivers are associated with self-compassion. Recollections of maternal support are correlated with self-compassion and secure attachment styles in adolescents and adults.⁶¹ Pepping et al⁶² found that retrospective reports of parental rejection, overprotection, and low parental warmth was associated with low self-compassion.

Benefits of self-compassion

A growing body of research suggests that self-compassion is strongly linked to mental health. Greater self-compassion consistently has been associated with lower levels of depression and anxiety,³ with a large effect size.⁴ Of course, central to self-compassion is the lack of self-criticism, but self-compassion still protects against anxiety and depression when controlling for self-criticism and negative affect.^6,63 Self-compassion is a strong predictor of symptom severity and quality of life among individuals with anxious distress.⁶⁴

The benefits of self-compassion stem partly from a greater ability to cope with negative emotions.^6,63,65 Self-compassionate people are less likely to ruminate on their negative thoughts and emotions or suppress them,^6,66 which helps to explain why self-compassion is a negative predictor of depression.⁶⁷

Self-compassion also enhances positive mind states. A number of studies have found links between self-compassion and positive psychological qualities, such as happiness, optimism, wisdom, curiosity, and exploration, and personal initiative.^63,65,68,69 By embracing one’s suffering with compassion, negative states are ameliorated when positive emotions of kindness, connectedness, and mindful presence are generated.

Misconceptions about self-compassion

A common misconception is that abandoning self-criticism in favor of self-compassion will undermine motivation⁷⁰; however, research indicates the opposite. Although self-compassion is negatively associated with maladaptive perfectionism, it is not correlated with self-adopted performance standards.⁶ Self-compassionate people have less fear of failure⁵⁴ and, when they do fail, they are more likely to try again.⁷¹ Breines and Chen⁷² found in a series of experimental studies that engendering feelings of self-compassion for personal weaknesses, failures, and past transgressions resulted in more motivation to change, to try harder to learn, and to avoid repeating past mistakes.

Another common misunderstanding is that self-compassion is a weakness. In fact, research suggests that self-compassion is a powerful way to cope with life challenges.⁷³

Although some fear that self-compassion leads to self-indulgence, there is evidence that self-compassion promotes health-related behaviors. Self-compassionate individuals are more likely to seek medical treatment when needed,⁷⁴ exercise for intrinsic reasons,⁷⁵ and drink less alcohol.⁷⁶ Inducing self-compassion has been found to help people stick to their diets⁷⁷ and quit smoking.⁷⁸

Self-compassion interventions

Individuals can develop self-compassion. Shapira and Mongrain⁷⁹ found that adults who wrote a compassionate letter to themselves once a day for a week about the distressing events they were experiencing showed significant reductions in depression up to 3 months and significant increases in happiness up to 6 months compared with a control group who wrote about early memories. Albertson et al⁸⁰ found that, compared with a wait-list control group, 3 weeks of self-compassion meditation training improved body dissatisfaction, body shame, and body appreciation among women with body image concerns. Similarly, Smeets et al⁸¹ found that 3 weeks of self-compassion training for female college students led to significantly greater increases in mindfulness, optimism, and self-efficacy, as well as greater decreases in rumination compared with a time management control group.

The Box^6,70,82-86 describes rating scales that can measure self-compassion and self-criticism.

Mindful self-compassion (MSC), developed by Neff and Germer,⁸⁷ is an 8-week group intervention designed to teach people how to be more self-compassionate through meditation and informal practices in daily life. Results of a randomized controlled trial found that, compared with a wait-list control group, participants using MSC reported significantly greater increases in self-compassion, compassion for others, mindfulness, and life satisfaction, and greater decreases in depression, anxiety, stress, and emotional avoidance, with large effect sizes indicated. These results were maintained up to 1 year.

Compassion-focused therapy (CFT) is designed to enhance self-compassion in clinical populations.⁸⁸ The approach uses a number of imagery and experiential exercises to enhance patients’ abilities to extend feelings of reassurance, safeness, and understanding toward themselves. CFT has shown promise in treating a diverse group of clinical disorders such as depression and shame,^8,89 social anxiety and shame,⁹⁰ eating disorders,⁹¹ psychosis,⁹² and patients with acquired brain injury.⁹³ A group-based CFT intervention with a heterogeneous group of community mental health patients led to significant reductions in depression, anxiety, stress, and self-criticism.⁹⁴ See Leaviss and Utley⁹⁵ for a review of the benefits of CFT.

Fears of developing self-compassion

It is important to note that some people can access self-compassion more easily than others. Highly self-critical patients could feel anxious when learning to be compassionate to themselves, a phenomenon known as “fear of compassion”⁹⁶ or “backdraft.”⁹⁷ Backdraft occurs when a firefighter opens a door with a hot fire behind it. Oxygen rushes in, causing a burst of flame. Similarly, when the door of the heart is opened with compassion, intense pain could be released. Unconditional love reveals the conditions under which we were unloved in the past. Some individuals, especially those with a history of childhood abuse or neglect, are fearful of compassion because it activates grief associated with feelings of wanting, but not receiving, affection and care from significant others in childhood.

Clinicians should be aware that anxiety could arise and should help patients learn how to go slowly and stabilize themselves if overwhelming emotions occur as a part of self-compassion practice. Both CFT and MSC have processes to deal with fear of compassion in their protocols,^98,99 with the focus on explaining to individuals that although such fears may occur, they are a normal and necessary part of the healing process. Individuals also are taught to focus on the breath, feeling the sensations in the soles of their feet, or other mindfulness practices to ground and stabilize attention when overwhelming feelings arise.

Clinical interventions

Self-compassion interventions that I (R.W.) find most helpful, in the order I administer them, are:

• exploring perceived advantages and disadvantages of self-criticism
• presenting self-compassion as a way to get the perceived advantages of self-criticism without the disadvantages
• discussing what it means to be compassionate for someone else who is suffering, and then asking what it would be like if they treated themselves with the same compassion
• exploring patients’ misconceptions and fears of self-compassion
• directing patients to the self-compassion Web site to get an understanding of what self-compassion is and how it differs from self-esteem
• taking an example of a recent situation in which the patient was self-critical and exploring how a self-compassionate response would differ.

Asking what they would say to a friend often is an effective way to get at this. In a later therapy session, self-compassionate imagery is a useful way to get the patient to experience self-compassion on an emotional level. See Neff¹⁰⁰ and Gilbert⁹⁸ for other techniques to enhance self-compassion.

Once thought to only be associated with depression, self-criticism is a transdiagnostic risk factor for diverse forms of psychopathology.^1,2 However, research has shown that self-compassion is a robust resilience factor when faced with feelings of personal inadequacy.^3,4

Self-critical individuals experience feelings of unworthiness, inferiority, failure, and guilt. They engage in constant and harsh self-scrutiny and evaluation, and fear being disapproved and criticized and losing the approval and acceptance of others.⁵ Self-compassion involves treating oneself with care and concern when confronted with personal inadequacies, mistakes, failures, and painful life situations.^6,7Although self-criticism is the aspect of perfectionism most associated with maladjustment,⁸ one can be harshly self-critical without being a perfectionist. Most studies of self-criticism have not measured shame; however, this self-conscious emotion has been implicated in diverse forms of psychopathology.⁹ In contrast to guilt, which results from acknowledging bad behavior, shame results from seeing oneself as a bad or inadequate person.

Although self-criticism is destructive across clinical disorders and interpersonal relationships, self-compassion is associated with healthy relationships, emotional well-being, and better treatment outcomes.

Recent research shows how clinicians can teach their patients how to be less self-critical and more self-compassionate. Neff^6,7 proposes that self-compassion involves treating yourself with care and concern when being confronted with personal inadequacies, mistakes, failures, and painful life situations. It consists of 3 interacting components, each of which has a positive and negative pole:

• self-kindness vs self-judgment
• a sense of common humanity vs isolation
• mindfulness vs over-identification.

Self-kindness refers to being caring and understanding with oneself rather than harshly judgmental. Instead of attacking and berating oneself for personal shortcomings, the self is offered warmth and unconditional acceptance.

Humanity involves recognizing that humans are imperfect, that all people fail, make mistakes, and have serious life challenges. By remembering that imperfection is part of life, we feel less isolated when we are in pain.

Mindfulness in the context of self-compassion involves being aware of one’s painful experiences in a balanced way that neither ignores and avoids nor exaggerates painful thoughts and emotions.

Self-compassion is more than the absence of self-judgment, although a defining feature of self-compassion is the lack of self-judgment, and self-judgment overlaps with self-criticism. Rather, self-compassion provides several access points for reducing self-criticism. For example, being kind and understanding when confronting personal inadequacies (eg, “it’s okay not to be perfect”) can counter harsh self-talk (eg, “I’m not defective”). Mindfulness of emotional pain (eg, “this is hard”) can facilitate a kind and warm response (eg, “what can I do to take care of myself right now?”) and therefore lessen self-blame (eg, “blaming myself is just causing me more suffering”). Similarly, remembering that failure is part of the human experience (eg, “it’s normal to mess up sometimes”) can lessen egocentric feelings of isolation (eg, “it’s not just me”) and over-identification (eg, “it’s not the end of the world”), resulting in lessened self-criticism (eg, “maybe it’s not just because I’m a bad person”).

Depression

Several studies have found that self-criticism predicts depression. In 3 epidemiological studies, “feeling worthless” was among the top 2 symptoms predicting a depression diagnosis and later depressive episodes.¹⁰ Self-criticism in fourth-year medical students predicted depression 2 years later, and—in males—10 years later in their medical careers better than a history of depression.¹¹ Self-critical perfectionism also is associated with suicidal ideation and lethality of suicide attempts.¹²

Self-criticism has been shown to predict depressive relapse and residual self-devaluative symptoms in recovered depressed patients.¹³ In one study, currently depressed and remitted depressed patients had higher self-criticism and lower self-compassion compared with healthy controls. Both factors were more strongly associated with depression status than higher perfectionistic beliefs and cognitions, rumination, and maladaptive emotional regulation.¹⁴

Self-criticism and response to treatment. In the National Institute of Mental Health Treatment of Depression Collaborative Research Program,¹⁵ self-critical perfectionism predicted a poorer outcome across all 4 treatments (cognitive-behavioral therapy [CBT], interpersonal psychotherapy [IPT], pharmacotherapy plus clinical management, and placebo plus clinical management). Subsequent studies found that self-criticism predicted poorer response to CBT¹⁶ and IPT.¹⁷ The authors suggest that self-criticism could interfere with treatment because self-critical patients might have difficulty developing a strong therapeutic alliance.^18,19

Anxiety disorders

Self-criticism is common across psychiatric disorders. In a study of 5,877 respondents in the National Comorbidity Survey (NCS), self-criticism was associated with social phobia, findings that were significant after controlling for current emotional distress, neuroticism, and lifetime history of mood, anxiety, and substance use disorders.²⁰ Further, in a CBT treatment study, baseline self-criticism was associated with severity of social phobia and changes in self-criticism predicted treatment outcome.²¹ Self-criticism might be an important core psychological process in the development, maintenance, and course of social phobia. Patients with social anxiety disorder have less self-compassion than healthy controls and greater fear of negative evaluation.

In the NCS, self-criticism was associated with posttraumatic stress disorder (PTSD) even after controlling for lifetime history of affective and anxiety disorders.²⁰ Self-criticism predicted greater severity of combat-related PTSD in hospitalized male veterans,²² and those with PTSD had higher scores on self-criticism scales than those with major depressive disorder.²³ In a study of Holocaust survivors, those with PTSD scored higher on self-criticism than survivors without PTSD.²⁴ Self-criticism also distinguished between female victims of domestic violence with and without PTSD.²⁵

Self-compassion could be a protective factor for posttraumatic stress.²⁶ Combat veterans with higher levels of self-compassion showed lower levels of psychopathology, better functioning in daily life, and fewer symptoms of posttraumatic stress.²⁷ In fact, self-compassion has been found to be a stronger predictor of PTSD than level of combat exposure.²⁸

In an early study, self-criticism scores were higher in patients with panic disorder than in healthy controls, but lower than in patients with depression.²⁹ In a study of a mixed sample of anxiety disorder patients, symptoms of generalized anxiety disorder were associated with shame proneness.³⁰ Consistent with these results, Hoge et al³¹ found that self-compassion was lower in generalized anxiety disorder patients compared with healthy controls with elevated stress. Low self-compassion has been associated with severity of obsessive-compulsive disorder.³²

Eating disorders

Self-criticism is correlated with eating disorder severity.³³ In a study of patients with binge eating disorder, Dunkley and Grilo³⁴ found that self-criticism was associated with the over-evaluation of shape and weight independently of self-esteem and depression. Self-criticism also is associated with body dissatisfaction, independent of self-esteem and depression. Dunkley et al³⁵ found that self-criticism, but not global self-esteem, in patients with binge eating disorder mediated the relationship between childhood abuse and body dissatisfaction and depression. Numerous studies have shown that shame is associated with more severe eating disorder pathology.³³

Self-compassion seems to buffer against body image concerns. It is associated with less body dissatisfaction, body preoccupation, and weight worries,³⁶ greater body appreciation³⁷ and less disordered eating.^37-39 Early decreases in shame during eating disorder treatment was associated with more rapid reduction in eating disorder symptoms.⁴⁰

Interpersonal relationships

Several studies have shown that self-criticism has negative effects on interpersonal relationships throughout life.^5,41,42

• Self-criticism at age 12 predicted less involvement in high school activities and, at age 31, personal and social maladjustment.⁴³
• High school students with high self-criticism reported more interpersonal problems.⁴⁴
• Self-criticism was associated with loneliness, depression, and lack of intimacy with opposite sex friends or partners during the transition to college.⁴⁵
• In a study of college roommates,⁴⁶ self-criticism was associated with increased likelihood of rejection.
• Whiffen and Aube⁴⁷ found that self-criticism was associated with marital dissatisfaction and depression.
• Self-critical mothers with postpartum depression were less satisfied with social support and were more vulnerable to depression.⁴⁸

Self-compassion appears to enhance interpersonal relationships. In a study of heterosexual couples,⁴⁹ self-compassionate individuals were described by their partners as being more emotionally connected, as well as accepting and supporting autonomy, while being less detached, controlling, and verbally or physically aggressive than those lacking self-compassion. Because self-compassionate people give themselves care and support, they seem to have more emotional resources available to give to others.

See the Box examining the evidence on the role of self-compassion in borderline personality disorder and non-suicidal self-injury.

Achieving goals

Powers et al⁵⁰ suggest that self-critics approach goals based on motivation to avoid failure and disapproval, rather than on intrinsic interest and personal meaning. In studies of college students pursuing academic, social, or weight loss goals, self-criticism was associated with less progress to that goal. Self-criticism was associated with rumination and procrastination, which the authors suggest might have focused the self-critic on potential failure, negative evaluation from others, and loss of self-esteem. Additional studies showed the deleterious effects of self-criticism on college students’ progress on obtaining academic or music performance goals and on community residents’ weight loss goals.⁵¹

Not surprisingly, self-compassion is associated with successful goal pursuit and resilience when goals are not met⁵² and less procrastination and academic worry.⁵³ Self-compassion also is associated with intrinsic motivation, goals based on mastery rather than performance, and less fear of academic failure.⁵⁴

How self-criticism and self-compassion develop

Studies have explored the impact of early relationships with parents and development of self-criticism. Parental overcontrol and restrictiveness and lack of warmth consistently have been identified as parenting styles associated with development of self-criticism in children.⁵⁵ One study found that self-criticism fully mediated the relationship between childhood verbal abuse from parents and depression and anxiety in adulthood.⁵⁶ Reports from parents on their current parenting styles are consistent with these studies.⁵⁷ Amitay et al⁵⁷ states that “[s]elf-critics’ negative childhood experiences thus seem to contribute to a pattern of entering, creating, or manipulating subsequent interpersonal environments in ways that perpetuate their negative self-image and increase vulnerability to depression.” Not surprisingly, self-criticism is associated with a fearful avoidant attachment style.⁵⁸ Review of the developmental origins of self-criticism confirms these factors and presents findings that peer relationships also are important factors in the development of self-criticism.^59,60

Early positive relationships with caregivers are associated with self-compassion. Recollections of maternal support are correlated with self-compassion and secure attachment styles in adolescents and adults.⁶¹ Pepping et al⁶² found that retrospective reports of parental rejection, overprotection, and low parental warmth was associated with low self-compassion.

Benefits of self-compassion

A growing body of research suggests that self-compassion is strongly linked to mental health. Greater self-compassion consistently has been associated with lower levels of depression and anxiety,³ with a large effect size.⁴ Of course, central to self-compassion is the lack of self-criticism, but self-compassion still protects against anxiety and depression when controlling for self-criticism and negative affect.^6,63 Self-compassion is a strong predictor of symptom severity and quality of life among individuals with anxious distress.⁶⁴

The benefits of self-compassion stem partly from a greater ability to cope with negative emotions.^6,63,65 Self-compassionate people are less likely to ruminate on their negative thoughts and emotions or suppress them,^6,66 which helps to explain why self-compassion is a negative predictor of depression.⁶⁷

Self-compassion also enhances positive mind states. A number of studies have found links between self-compassion and positive psychological qualities, such as happiness, optimism, wisdom, curiosity, and exploration, and personal initiative.^63,65,68,69 By embracing one’s suffering with compassion, negative states are ameliorated when positive emotions of kindness, connectedness, and mindful presence are generated.

Misconceptions about self-compassion

A common misconception is that abandoning self-criticism in favor of self-compassion will undermine motivation⁷⁰; however, research indicates the opposite. Although self-compassion is negatively associated with maladaptive perfectionism, it is not correlated with self-adopted performance standards.⁶ Self-compassionate people have less fear of failure⁵⁴ and, when they do fail, they are more likely to try again.⁷¹ Breines and Chen⁷² found in a series of experimental studies that engendering feelings of self-compassion for personal weaknesses, failures, and past transgressions resulted in more motivation to change, to try harder to learn, and to avoid repeating past mistakes.

Another common misunderstanding is that self-compassion is a weakness. In fact, research suggests that self-compassion is a powerful way to cope with life challenges.⁷³

Although some fear that self-compassion leads to self-indulgence, there is evidence that self-compassion promotes health-related behaviors. Self-compassionate individuals are more likely to seek medical treatment when needed,⁷⁴ exercise for intrinsic reasons,⁷⁵ and drink less alcohol.⁷⁶ Inducing self-compassion has been found to help people stick to their diets⁷⁷ and quit smoking.⁷⁸

Self-compassion interventions

Individuals can develop self-compassion. Shapira and Mongrain⁷⁹ found that adults who wrote a compassionate letter to themselves once a day for a week about the distressing events they were experiencing showed significant reductions in depression up to 3 months and significant increases in happiness up to 6 months compared with a control group who wrote about early memories. Albertson et al⁸⁰ found that, compared with a wait-list control group, 3 weeks of self-compassion meditation training improved body dissatisfaction, body shame, and body appreciation among women with body image concerns. Similarly, Smeets et al⁸¹ found that 3 weeks of self-compassion training for female college students led to significantly greater increases in mindfulness, optimism, and self-efficacy, as well as greater decreases in rumination compared with a time management control group.

The Box^6,70,82-86 describes rating scales that can measure self-compassion and self-criticism.

Mindful self-compassion (MSC), developed by Neff and Germer,⁸⁷ is an 8-week group intervention designed to teach people how to be more self-compassionate through meditation and informal practices in daily life. Results of a randomized controlled trial found that, compared with a wait-list control group, participants using MSC reported significantly greater increases in self-compassion, compassion for others, mindfulness, and life satisfaction, and greater decreases in depression, anxiety, stress, and emotional avoidance, with large effect sizes indicated. These results were maintained up to 1 year.

Compassion-focused therapy (CFT) is designed to enhance self-compassion in clinical populations.⁸⁸ The approach uses a number of imagery and experiential exercises to enhance patients’ abilities to extend feelings of reassurance, safeness, and understanding toward themselves. CFT has shown promise in treating a diverse group of clinical disorders such as depression and shame,^8,89 social anxiety and shame,⁹⁰ eating disorders,⁹¹ psychosis,⁹² and patients with acquired brain injury.⁹³ A group-based CFT intervention with a heterogeneous group of community mental health patients led to significant reductions in depression, anxiety, stress, and self-criticism.⁹⁴ See Leaviss and Utley⁹⁵ for a review of the benefits of CFT.

Fears of developing self-compassion

It is important to note that some people can access self-compassion more easily than others. Highly self-critical patients could feel anxious when learning to be compassionate to themselves, a phenomenon known as “fear of compassion”⁹⁶ or “backdraft.”⁹⁷ Backdraft occurs when a firefighter opens a door with a hot fire behind it. Oxygen rushes in, causing a burst of flame. Similarly, when the door of the heart is opened with compassion, intense pain could be released. Unconditional love reveals the conditions under which we were unloved in the past. Some individuals, especially those with a history of childhood abuse or neglect, are fearful of compassion because it activates grief associated with feelings of wanting, but not receiving, affection and care from significant others in childhood.

Clinicians should be aware that anxiety could arise and should help patients learn how to go slowly and stabilize themselves if overwhelming emotions occur as a part of self-compassion practice. Both CFT and MSC have processes to deal with fear of compassion in their protocols,^98,99 with the focus on explaining to individuals that although such fears may occur, they are a normal and necessary part of the healing process. Individuals also are taught to focus on the breath, feeling the sensations in the soles of their feet, or other mindfulness practices to ground and stabilize attention when overwhelming feelings arise.

Clinical interventions

Self-compassion interventions that I (R.W.) find most helpful, in the order I administer them, are:

• exploring perceived advantages and disadvantages of self-criticism
• presenting self-compassion as a way to get the perceived advantages of self-criticism without the disadvantages
• discussing what it means to be compassionate for someone else who is suffering, and then asking what it would be like if they treated themselves with the same compassion
• exploring patients’ misconceptions and fears of self-compassion
• directing patients to the self-compassion Web site to get an understanding of what self-compassion is and how it differs from self-esteem
• taking an example of a recent situation in which the patient was self-critical and exploring how a self-compassionate response would differ.

Asking what they would say to a friend often is an effective way to get at this. In a later therapy session, self-compassionate imagery is a useful way to get the patient to experience self-compassion on an emotional level. See Neff¹⁰⁰ and Gilbert⁹⁸ for other techniques to enhance self-compassion.

Once thought to only be associated with depression, self-criticism is a transdiagnostic risk factor for diverse forms of psychopathology.^1,2 However, research has shown that self-compassion is a robust resilience factor when faced with feelings of personal inadequacy.^3,4

Self-critical individuals experience feelings of unworthiness, inferiority, failure, and guilt. They engage in constant and harsh self-scrutiny and evaluation, and fear being disapproved and criticized and losing the approval and acceptance of others.⁵ Self-compassion involves treating oneself with care and concern when confronted with personal inadequacies, mistakes, failures, and painful life situations.^6,7Although self-criticism is the aspect of perfectionism most associated with maladjustment,⁸ one can be harshly self-critical without being a perfectionist. Most studies of self-criticism have not measured shame; however, this self-conscious emotion has been implicated in diverse forms of psychopathology.⁹ In contrast to guilt, which results from acknowledging bad behavior, shame results from seeing oneself as a bad or inadequate person.

Although self-criticism is destructive across clinical disorders and interpersonal relationships, self-compassion is associated with healthy relationships, emotional well-being, and better treatment outcomes.

Recent research shows how clinicians can teach their patients how to be less self-critical and more self-compassionate. Neff^6,7 proposes that self-compassion involves treating yourself with care and concern when being confronted with personal inadequacies, mistakes, failures, and painful life situations. It consists of 3 interacting components, each of which has a positive and negative pole:

• self-kindness vs self-judgment
• a sense of common humanity vs isolation
• mindfulness vs over-identification.

Self-kindness refers to being caring and understanding with oneself rather than harshly judgmental. Instead of attacking and berating oneself for personal shortcomings, the self is offered warmth and unconditional acceptance.

Humanity involves recognizing that humans are imperfect, that all people fail, make mistakes, and have serious life challenges. By remembering that imperfection is part of life, we feel less isolated when we are in pain.

Mindfulness in the context of self-compassion involves being aware of one’s painful experiences in a balanced way that neither ignores and avoids nor exaggerates painful thoughts and emotions.

Self-compassion is more than the absence of self-judgment, although a defining feature of self-compassion is the lack of self-judgment, and self-judgment overlaps with self-criticism. Rather, self-compassion provides several access points for reducing self-criticism. For example, being kind and understanding when confronting personal inadequacies (eg, “it’s okay not to be perfect”) can counter harsh self-talk (eg, “I’m not defective”). Mindfulness of emotional pain (eg, “this is hard”) can facilitate a kind and warm response (eg, “what can I do to take care of myself right now?”) and therefore lessen self-blame (eg, “blaming myself is just causing me more suffering”). Similarly, remembering that failure is part of the human experience (eg, “it’s normal to mess up sometimes”) can lessen egocentric feelings of isolation (eg, “it’s not just me”) and over-identification (eg, “it’s not the end of the world”), resulting in lessened self-criticism (eg, “maybe it’s not just because I’m a bad person”).

Depression

Several studies have found that self-criticism predicts depression. In 3 epidemiological studies, “feeling worthless” was among the top 2 symptoms predicting a depression diagnosis and later depressive episodes.¹⁰ Self-criticism in fourth-year medical students predicted depression 2 years later, and—in males—10 years later in their medical careers better than a history of depression.¹¹ Self-critical perfectionism also is associated with suicidal ideation and lethality of suicide attempts.¹²

Self-criticism has been shown to predict depressive relapse and residual self-devaluative symptoms in recovered depressed patients.¹³ In one study, currently depressed and remitted depressed patients had higher self-criticism and lower self-compassion compared with healthy controls. Both factors were more strongly associated with depression status than higher perfectionistic beliefs and cognitions, rumination, and maladaptive emotional regulation.¹⁴

Self-criticism and response to treatment. In the National Institute of Mental Health Treatment of Depression Collaborative Research Program,¹⁵ self-critical perfectionism predicted a poorer outcome across all 4 treatments (cognitive-behavioral therapy [CBT], interpersonal psychotherapy [IPT], pharmacotherapy plus clinical management, and placebo plus clinical management). Subsequent studies found that self-criticism predicted poorer response to CBT¹⁶ and IPT.¹⁷ The authors suggest that self-criticism could interfere with treatment because self-critical patients might have difficulty developing a strong therapeutic alliance.^18,19

Anxiety disorders

Self-criticism is common across psychiatric disorders. In a study of 5,877 respondents in the National Comorbidity Survey (NCS), self-criticism was associated with social phobia, findings that were significant after controlling for current emotional distress, neuroticism, and lifetime history of mood, anxiety, and substance use disorders.²⁰ Further, in a CBT treatment study, baseline self-criticism was associated with severity of social phobia and changes in self-criticism predicted treatment outcome.²¹ Self-criticism might be an important core psychological process in the development, maintenance, and course of social phobia. Patients with social anxiety disorder have less self-compassion than healthy controls and greater fear of negative evaluation.

In the NCS, self-criticism was associated with posttraumatic stress disorder (PTSD) even after controlling for lifetime history of affective and anxiety disorders.²⁰ Self-criticism predicted greater severity of combat-related PTSD in hospitalized male veterans,²² and those with PTSD had higher scores on self-criticism scales than those with major depressive disorder.²³ In a study of Holocaust survivors, those with PTSD scored higher on self-criticism than survivors without PTSD.²⁴ Self-criticism also distinguished between female victims of domestic violence with and without PTSD.²⁵

Self-compassion could be a protective factor for posttraumatic stress.²⁶ Combat veterans with higher levels of self-compassion showed lower levels of psychopathology, better functioning in daily life, and fewer symptoms of posttraumatic stress.²⁷ In fact, self-compassion has been found to be a stronger predictor of PTSD than level of combat exposure.²⁸

In an early study, self-criticism scores were higher in patients with panic disorder than in healthy controls, but lower than in patients with depression.²⁹ In a study of a mixed sample of anxiety disorder patients, symptoms of generalized anxiety disorder were associated with shame proneness.³⁰ Consistent with these results, Hoge et al³¹ found that self-compassion was lower in generalized anxiety disorder patients compared with healthy controls with elevated stress. Low self-compassion has been associated with severity of obsessive-compulsive disorder.³²

Eating disorders

Self-criticism is correlated with eating disorder severity.³³ In a study of patients with binge eating disorder, Dunkley and Grilo³⁴ found that self-criticism was associated with the over-evaluation of shape and weight independently of self-esteem and depression. Self-criticism also is associated with body dissatisfaction, independent of self-esteem and depression. Dunkley et al³⁵ found that self-criticism, but not global self-esteem, in patients with binge eating disorder mediated the relationship between childhood abuse and body dissatisfaction and depression. Numerous studies have shown that shame is associated with more severe eating disorder pathology.³³

Self-compassion seems to buffer against body image concerns. It is associated with less body dissatisfaction, body preoccupation, and weight worries,³⁶ greater body appreciation³⁷ and less disordered eating.^37-39 Early decreases in shame during eating disorder treatment was associated with more rapid reduction in eating disorder symptoms.⁴⁰

Interpersonal relationships

Several studies have shown that self-criticism has negative effects on interpersonal relationships throughout life.^5,41,42

• Self-criticism at age 12 predicted less involvement in high school activities and, at age 31, personal and social maladjustment.⁴³
• High school students with high self-criticism reported more interpersonal problems.⁴⁴
• Self-criticism was associated with loneliness, depression, and lack of intimacy with opposite sex friends or partners during the transition to college.⁴⁵
• In a study of college roommates,⁴⁶ self-criticism was associated with increased likelihood of rejection.
• Whiffen and Aube⁴⁷ found that self-criticism was associated with marital dissatisfaction and depression.
• Self-critical mothers with postpartum depression were less satisfied with social support and were more vulnerable to depression.⁴⁸

Self-compassion appears to enhance interpersonal relationships. In a study of heterosexual couples,⁴⁹ self-compassionate individuals were described by their partners as being more emotionally connected, as well as accepting and supporting autonomy, while being less detached, controlling, and verbally or physically aggressive than those lacking self-compassion. Because self-compassionate people give themselves care and support, they seem to have more emotional resources available to give to others.

See the Box examining the evidence on the role of self-compassion in borderline personality disorder and non-suicidal self-injury.

Achieving goals

Powers et al⁵⁰ suggest that self-critics approach goals based on motivation to avoid failure and disapproval, rather than on intrinsic interest and personal meaning. In studies of college students pursuing academic, social, or weight loss goals, self-criticism was associated with less progress to that goal. Self-criticism was associated with rumination and procrastination, which the authors suggest might have focused the self-critic on potential failure, negative evaluation from others, and loss of self-esteem. Additional studies showed the deleterious effects of self-criticism on college students’ progress on obtaining academic or music performance goals and on community residents’ weight loss goals.⁵¹

Not surprisingly, self-compassion is associated with successful goal pursuit and resilience when goals are not met⁵² and less procrastination and academic worry.⁵³ Self-compassion also is associated with intrinsic motivation, goals based on mastery rather than performance, and less fear of academic failure.⁵⁴

How self-criticism and self-compassion develop

Studies have explored the impact of early relationships with parents and development of self-criticism. Parental overcontrol and restrictiveness and lack of warmth consistently have been identified as parenting styles associated with development of self-criticism in children.⁵⁵ One study found that self-criticism fully mediated the relationship between childhood verbal abuse from parents and depression and anxiety in adulthood.⁵⁶ Reports from parents on their current parenting styles are consistent with these studies.⁵⁷ Amitay et al⁵⁷ states that “[s]elf-critics’ negative childhood experiences thus seem to contribute to a pattern of entering, creating, or manipulating subsequent interpersonal environments in ways that perpetuate their negative self-image and increase vulnerability to depression.” Not surprisingly, self-criticism is associated with a fearful avoidant attachment style.⁵⁸ Review of the developmental origins of self-criticism confirms these factors and presents findings that peer relationships also are important factors in the development of self-criticism.^59,60

Early positive relationships with caregivers are associated with self-compassion. Recollections of maternal support are correlated with self-compassion and secure attachment styles in adolescents and adults.⁶¹ Pepping et al⁶² found that retrospective reports of parental rejection, overprotection, and low parental warmth was associated with low self-compassion.

Benefits of self-compassion

A growing body of research suggests that self-compassion is strongly linked to mental health. Greater self-compassion consistently has been associated with lower levels of depression and anxiety,³ with a large effect size.⁴ Of course, central to self-compassion is the lack of self-criticism, but self-compassion still protects against anxiety and depression when controlling for self-criticism and negative affect.^6,63 Self-compassion is a strong predictor of symptom severity and quality of life among individuals with anxious distress.⁶⁴

The benefits of self-compassion stem partly from a greater ability to cope with negative emotions.^6,63,65 Self-compassionate people are less likely to ruminate on their negative thoughts and emotions or suppress them,^6,66 which helps to explain why self-compassion is a negative predictor of depression.⁶⁷

Self-compassion also enhances positive mind states. A number of studies have found links between self-compassion and positive psychological qualities, such as happiness, optimism, wisdom, curiosity, and exploration, and personal initiative.^63,65,68,69 By embracing one’s suffering with compassion, negative states are ameliorated when positive emotions of kindness, connectedness, and mindful presence are generated.

Misconceptions about self-compassion

A common misconception is that abandoning self-criticism in favor of self-compassion will undermine motivation⁷⁰; however, research indicates the opposite. Although self-compassion is negatively associated with maladaptive perfectionism, it is not correlated with self-adopted performance standards.⁶ Self-compassionate people have less fear of failure⁵⁴ and, when they do fail, they are more likely to try again.⁷¹ Breines and Chen⁷² found in a series of experimental studies that engendering feelings of self-compassion for personal weaknesses, failures, and past transgressions resulted in more motivation to change, to try harder to learn, and to avoid repeating past mistakes.

Another common misunderstanding is that self-compassion is a weakness. In fact, research suggests that self-compassion is a powerful way to cope with life challenges.⁷³

Although some fear that self-compassion leads to self-indulgence, there is evidence that self-compassion promotes health-related behaviors. Self-compassionate individuals are more likely to seek medical treatment when needed,⁷⁴ exercise for intrinsic reasons,⁷⁵ and drink less alcohol.⁷⁶ Inducing self-compassion has been found to help people stick to their diets⁷⁷ and quit smoking.⁷⁸

Self-compassion interventions

Individuals can develop self-compassion. Shapira and Mongrain⁷⁹ found that adults who wrote a compassionate letter to themselves once a day for a week about the distressing events they were experiencing showed significant reductions in depression up to 3 months and significant increases in happiness up to 6 months compared with a control group who wrote about early memories. Albertson et al⁸⁰ found that, compared with a wait-list control group, 3 weeks of self-compassion meditation training improved body dissatisfaction, body shame, and body appreciation among women with body image concerns. Similarly, Smeets et al⁸¹ found that 3 weeks of self-compassion training for female college students led to significantly greater increases in mindfulness, optimism, and self-efficacy, as well as greater decreases in rumination compared with a time management control group.

The Box^6,70,82-86 describes rating scales that can measure self-compassion and self-criticism.

Mindful self-compassion (MSC), developed by Neff and Germer,⁸⁷ is an 8-week group intervention designed to teach people how to be more self-compassionate through meditation and informal practices in daily life. Results of a randomized controlled trial found that, compared with a wait-list control group, participants using MSC reported significantly greater increases in self-compassion, compassion for others, mindfulness, and life satisfaction, and greater decreases in depression, anxiety, stress, and emotional avoidance, with large effect sizes indicated. These results were maintained up to 1 year.

Compassion-focused therapy (CFT) is designed to enhance self-compassion in clinical populations.⁸⁸ The approach uses a number of imagery and experiential exercises to enhance patients’ abilities to extend feelings of reassurance, safeness, and understanding toward themselves. CFT has shown promise in treating a diverse group of clinical disorders such as depression and shame,^8,89 social anxiety and shame,⁹⁰ eating disorders,⁹¹ psychosis,⁹² and patients with acquired brain injury.⁹³ A group-based CFT intervention with a heterogeneous group of community mental health patients led to significant reductions in depression, anxiety, stress, and self-criticism.⁹⁴ See Leaviss and Utley⁹⁵ for a review of the benefits of CFT.

Fears of developing self-compassion

It is important to note that some people can access self-compassion more easily than others. Highly self-critical patients could feel anxious when learning to be compassionate to themselves, a phenomenon known as “fear of compassion”⁹⁶ or “backdraft.”⁹⁷ Backdraft occurs when a firefighter opens a door with a hot fire behind it. Oxygen rushes in, causing a burst of flame. Similarly, when the door of the heart is opened with compassion, intense pain could be released. Unconditional love reveals the conditions under which we were unloved in the past. Some individuals, especially those with a history of childhood abuse or neglect, are fearful of compassion because it activates grief associated with feelings of wanting, but not receiving, affection and care from significant others in childhood.

Clinicians should be aware that anxiety could arise and should help patients learn how to go slowly and stabilize themselves if overwhelming emotions occur as a part of self-compassion practice. Both CFT and MSC have processes to deal with fear of compassion in their protocols,^98,99 with the focus on explaining to individuals that although such fears may occur, they are a normal and necessary part of the healing process. Individuals also are taught to focus on the breath, feeling the sensations in the soles of their feet, or other mindfulness practices to ground and stabilize attention when overwhelming feelings arise.

Clinical interventions

Self-compassion interventions that I (R.W.) find most helpful, in the order I administer them, are:

• exploring perceived advantages and disadvantages of self-criticism
• presenting self-compassion as a way to get the perceived advantages of self-criticism without the disadvantages
• discussing what it means to be compassionate for someone else who is suffering, and then asking what it would be like if they treated themselves with the same compassion
• exploring patients’ misconceptions and fears of self-compassion
• directing patients to the self-compassion Web site to get an understanding of what self-compassion is and how it differs from self-esteem
• taking an example of a recent situation in which the patient was self-critical and exploring how a self-compassionate response would differ.

Asking what they would say to a friend often is an effective way to get at this. In a later therapy session, self-compassionate imagery is a useful way to get the patient to experience self-compassion on an emotional level. See Neff¹⁰⁰ and Gilbert⁹⁸ for other techniques to enhance self-compassion.

Alcohol withdrawal is an uncomfortable and potentially life-threatening condition that must be treated before patients can achieve sobriety. Benzodiazepines remain the first-line treatment for alcohol withdrawal; however, these agents could:

• exacerbate agitation
• interact adversely with other medications, particularly opioids
• be unsafe for outpatients at risk of drinking again.
  

Off-label use of anticonvulsants could reduce these risks. In our emergency department, we routinely use these agents as monotherapy for patients discharging to outpatient detoxification or as adjunctive treatment for patients who require admission for severe withdrawal (Table^1,2).

Gabapentin is safe for patients with liver disease and has few drug–drug interactions.¹ Dosages of at least 1,200 mg/d seems to be comparable to lorazepam for alcohol withdrawal and could help prevent relapse after the withdrawal period.¹ Many patients report that gabapentin helps them sleep. Gabapentin could cause gastrointestinal upset or slight dizziness; patients with severe renal disease might require dosage adjustments.

Carbamazepine. In a randomized double-blind trial, carbamazepine was superior to lorazepam in preventing rebound withdrawal symptoms and reducing post-treatment drinking, although both agents were effective in decreasing withdrawal symptoms.² Avoid this agent in patients with serum liver enzymes 3 times higher than normal values, renal disease, neuropathy, thrombocytopenia, or leukopenia. Drug–drug interactions typically are not of concern unless a patient takes carbamazepine for several weeks.

Divalproex with as-needed benzodiazepines reduces the duration of withdrawal and risk of medical complications.³ Avoid using divalproex in patients with thrombocytopenia, leukopenia, or severe liver disease.

Alcohol withdrawal is an uncomfortable and potentially life-threatening condition that must be treated before patients can achieve sobriety. Benzodiazepines remain the first-line treatment for alcohol withdrawal; however, these agents could:

• exacerbate agitation
• interact adversely with other medications, particularly opioids
• be unsafe for outpatients at risk of drinking again.
  

Off-label use of anticonvulsants could reduce these risks. In our emergency department, we routinely use these agents as monotherapy for patients discharging to outpatient detoxification or as adjunctive treatment for patients who require admission for severe withdrawal (Table^1,2).

Gabapentin is safe for patients with liver disease and has few drug–drug interactions.¹ Dosages of at least 1,200 mg/d seems to be comparable to lorazepam for alcohol withdrawal and could help prevent relapse after the withdrawal period.¹ Many patients report that gabapentin helps them sleep. Gabapentin could cause gastrointestinal upset or slight dizziness; patients with severe renal disease might require dosage adjustments.

Carbamazepine. In a randomized double-blind trial, carbamazepine was superior to lorazepam in preventing rebound withdrawal symptoms and reducing post-treatment drinking, although both agents were effective in decreasing withdrawal symptoms.² Avoid this agent in patients with serum liver enzymes 3 times higher than normal values, renal disease, neuropathy, thrombocytopenia, or leukopenia. Drug–drug interactions typically are not of concern unless a patient takes carbamazepine for several weeks.

Divalproex with as-needed benzodiazepines reduces the duration of withdrawal and risk of medical complications.³ Avoid using divalproex in patients with thrombocytopenia, leukopenia, or severe liver disease.

Alcohol withdrawal is an uncomfortable and potentially life-threatening condition that must be treated before patients can achieve sobriety. Benzodiazepines remain the first-line treatment for alcohol withdrawal; however, these agents could:

• exacerbate agitation
• interact adversely with other medications, particularly opioids
• be unsafe for outpatients at risk of drinking again.
  

Off-label use of anticonvulsants could reduce these risks. In our emergency department, we routinely use these agents as monotherapy for patients discharging to outpatient detoxification or as adjunctive treatment for patients who require admission for severe withdrawal (Table^1,2).

Gabapentin is safe for patients with liver disease and has few drug–drug interactions.¹ Dosages of at least 1,200 mg/d seems to be comparable to lorazepam for alcohol withdrawal and could help prevent relapse after the withdrawal period.¹ Many patients report that gabapentin helps them sleep. Gabapentin could cause gastrointestinal upset or slight dizziness; patients with severe renal disease might require dosage adjustments.

Carbamazepine. In a randomized double-blind trial, carbamazepine was superior to lorazepam in preventing rebound withdrawal symptoms and reducing post-treatment drinking, although both agents were effective in decreasing withdrawal symptoms.² Avoid this agent in patients with serum liver enzymes 3 times higher than normal values, renal disease, neuropathy, thrombocytopenia, or leukopenia. Drug–drug interactions typically are not of concern unless a patient takes carbamazepine for several weeks.

Divalproex with as-needed benzodiazepines reduces the duration of withdrawal and risk of medical complications.³ Avoid using divalproex in patients with thrombocytopenia, leukopenia, or severe liver disease.