Ms. B, age 45, has a history of major depressive disorder (MDD) and migraines. She is admitted after presenting with anhedonia, hopelessness, and hypersomnia. These symptoms have become more severe over the last few weeks. Ms. B describes a past suicide attempt via overdose on doxylamine for which she required treatment in the intensive care unit. The only activity she enjoys is her weekly girls’ night, during which she drinks a few glasses of wine. Ms. B’s current medications are dextromethorphan/bupropion 45/105 mg twice daily and aripiprazole 5 mg/d, which she has taken for 3 months. She states she has “been on every antidepressant there is.”

When clinicians review Ms. B’s medication history, it is clear she has had adequate trials of selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), intranasal esketamine, multiple augmentation strategies, and electroconvulsive therapy (ECT). Ms. B seeks an alternative medication to improve her depressive symptoms.

Treatment-resistant depression (TRD) is commonly defined as depression that has not responded to ≥2 adequate trials of an antidepressant.¹ Some guidelines recommend monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) as second- or even third-line options for MDD,² while others recommend reserving them for patients with insufficient responses to alternative treatment modalities.^3,4 Although MAOIs and TCAs have been available since the 1950s, prescribing these medications has become less prevalent due to safety concerns, the availability of other pharmacologic options, and a lack of clinical training and comfort.^5,6 Most research notes that MAOIs are superior for treating atypical depression while TCAs are more effective for melancholic depression.^2-4 In a review of 20 studies, Thase et al⁷ found that 50% of TCA nonresponders benefited from an MAOI. In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, monotherapy with the MAOI tranylcypromine was associated with a lower remission rate than the TCA nortriptyline; many argue the dose of tranylcypromine was suboptimal, and few participants completed an adequate trial in the last level.^8,9 A more recent study by Kim et al¹⁰ found MAOIs to be “generally more effective” than TCAs for TRD, particularly in patients with fewer antidepressant trials; however, this was a small retrospective exploratory trial. A network meta-analysis found both classes to be “competitive” with SSRIs based on efficacy and tolerability, which leads to the question of whether these medications should be considered earlier in therapy.¹¹ Considering patient-specific factors and particular medication properties is an effective strategy when prescribing an MAOI or TCA.

Monoamine oxidase inhibitors

Four MAOIs are FDA-approved for treating MDD (Table 1^5,12-17): phenelzine, isocarboxazid, tranylcypromine, and selegiline. These medications irreversibly inhibit MAO, which exists as isomers A and B. MAO-A primarily metabolizes serotonin and norepinephrine, which is largely responsible for these medications’ antidepressant effects. Both isomers equally metabolize dopamine.^5,12,18 It is best to avoid using MAOIs in patients with cerebrovascular disease, hepatic disease, or pheochromocytoma. Patients with active substance use disorders (particularly sympathomimetics and hallucinogens) are at an increased risk for hypertensive crises and serotonin syndrome, respectively. The most common adverse effects are orthostatic hypotension (despite more well-known concerns regarding hypertension), alterations in sleep patterns (insomnia or hypersomnia, depending on the agent), gastrointestinal issues, and anticholinergic adverse effects such as dry mouth and constipation.^13,19-21

In one review and meta-analysis, phenelzine displayed the highest efficacy across all MAOIs.¹¹ It likely requires high doses to achieve adequate MAO inhibition.¹¹ A metabolite of phenelzine inhibits gamma-aminobutyric acid transaminase and may be helpful for patients with comorbid anxiety disorders or MDD with anxious distress.^18,21 Additional considerations include phenelzine’s propensity for orthostasis (with rapid titrations and higher doses), sedation, weight gain, sexual dysfunction, and a rare adverse effect of vitamin B6 deficiency.^{5,13,14,20-22}

Use of isocarboxazid in clinical practice is rare. Its adverse effects are similar to those of phenelzine but isocarboxazid is less studied. Tranylcypromine has a similar chemical structure to amphetamine. It can be stimulating at higher doses, potentially benefitting patients with comorbid attention-deficit/hyperactivity disorder (ADHD) or significant apathy.^13,23 Selegiline’s distinct quality is its availability as a transdermal patch, which may be useful for patients who struggle to take oral medications. At low doses (6 mg/24 h), the selegiline transdermal patch allows patients to disregard a dietary tyramine restriction because it avoids first-pass metabolism. It inhibits both MAO isomers in the brain but is only selective for MAO-B once concentrations are distributed to the liver. Higher doses require a tyramine-restricted diet because there is still some MAO-A inhibition in the gut. Selegiline is also stimulating because it is converted to amphetamine and methamphetamine.^{5,12,13,17,19,24}

Despite promising results from the use of MAOIs, physicians and patients may be reluctant to use these medications due to perceived limitations. One prominent barrier is the infamous “cheese reaction.” Tyramine, an amino acid found in certain food and beverages (Table 2^{5,13-18,25-28}), is broken down by MAO-A in the gut. When this enzyme is inhibited, higher concentrations of tyramine reach systemic circulation. Tyramine’s release of norepinephrine (which now cannot be broken down) can lead to a hypertensive crisis. Consequently, a tyramine-restricted diet is recommended for patients taking an MAOI. However, the common notion that cheese, wine, and beer must be avoided is false, because most of the dietary restrictions developed following the discovery of MAOIs are antiquated.^5,12,25-28 Patients who take an MAOI only need to slightly adjust their diet, as outlined in Table 2.^{5,13-18,25-28} A reasonable serving size of most foods and beverages containing tyramine is unlikely to elicit this “pressor” response. Of the 4 MAOIs FDA-approved for MDD, tranylcypromine appears to be the most sensitive to tyramine.²¹ Transient postdose hypertension (regardless of tyramine) may occur after taking an MAOI.²⁹ Encourage patients to monitor their blood pressure.

Continue to: Additional hurdles include...

Additional hurdles include the required washout period from serotonergic medications and interactions with sympathomimetics. MAOIs pose the highest risk of serotonin syndrome; however, this usually occurs if given concomitantly with other serotonergic agents. The standard recommendation is a 14-day washout period from SSRIs (5 weeks for fluoxetine and 3 weeks for vortioxetine), SNRIs, mirtazapine, and other antidepressants. It can be distressing for patients to be without medication during that period. Because some antidepressants have much shorter half-lives, waiting 5 half-lives (typically 5 to 7 days) for the discontinued medication to be excreted is feasible if patients are closely monitored.^{5,12,13,25,27,30} There are rare instances where a TCA may be combined with an MAOI (typically initiated within 1 to 2 days of each other), but never clomipramine or imipramine due to their potent serotonin reuptake inhibition.³¹ If switching to an alternative MAOI, waiting 7 to 14 days is recommended to allow adequate time for the inhibited enzyme to regenerate.^14-17,32 Taking medications that increase dopamine and norepinephrine (eg, stimulants or oral over-the-counter decongestants) with an MAOI is typically not recommended due to the risk of hypertensive crisis.^25,27 In severe TRD or comorbid ADHD, successful simultaneous use of methylphenidate or amphetamine—typically at low doses—with close blood pressure monitoring has been reported.³³ There have also been positive cases of the use of modafinil in combination with an MAOI; however, this should be done with caution.^34,35 Clinicians must use clinical judgment when considering a combination of medications that pose a higher risk.

Tricyclic antidepressants

TCAs work differently than MAOIs to increase monoamines. They inhibit presynaptic serotonin and norepinephrine transporters in the CNS to increase levels of these chemicals in the synaptic cleft. While all TCAs inhibit these transporters, they do so at varying levels (Table 3^36-51). Based on their chemical structure, TCAs can be categorized into secondary and tertiary amines. Tertiary amines are metabolized via demethylation into their derivatives (Table 3^36-51). Patients who have recently suffered a myocardial infarction (MI) should avoid tertiary amines. TCAs can reduce heart rate variability, which is already decreased after an MI, thus presenting the potential for cardiac arrhythmias. TCAs should also be avoided in patients with cardiac conduction abnormalities.^38-46,52 Patients with a prior baseline cardiac conduction defect, such as a bundle branch block, are at higher risk for further cardiac abnormalities. In those with a preexisting first-degree heart block, TCAs can still be used, but electrocardiogram monitoring is recommended.^52,53 TCAs have also been reported to decrease the seizure threshold.^38-46 They can be used with caution in patients who have a history of epilepsy or head trauma, or with concomitant medications that lower the seizure threshold.^38-46

Overdose risk is a concern with TCAs because ingestion of 10 to 20 mg/kg can lead to significant toxicity.⁵⁴ This is due to their blockage of voltage-gated sodium channels found in the CNS and heart, which contributes to overdose symptoms such as a widened QRS complex and seizures. Symptoms usually develop within 2 hours but may be delayed up to 6 hours.⁵⁵ Patients with a history of overdose must be carefully assessed before initiating a TCA. Prescribing a limited supply of these medications may be valuable. The use of TCAs has often been limited due to their adverse effects, most of which are associated with their respective affinities for alpha 1, muscarinic 1, and histamine 1 receptors. Inhibition of the alpha 1 receptor is associated with hypotension, muscarinic 1 with anticholinergic adverse effects, and histamine 1 with sedation and weight gain. Tertiary amines have a higher affinity for these receptors compared to secondary amines, leading to a more significant adverse effect profile.^36,50 Among TCAs, amitriptyline is the most likely to cause hypotension, whereas desipramine and nortriptyline are least likely. Amitriptyline and clomipramine are most likely to cause anticholinergic adverse effects, whereas desipramine and nortriptyline are the least likely. Amitriptyline, doxepin, and imipramine have the highest propensity for QTc prolongation.³⁶

Beyond treating MDD, TCAs have shown benefits for treating other disease states (Table 4^{38-46,49,56-61}).These differing indications may help psychiatrists determine the best TCA to prescribe for a given patient. Amitriptyline is the most studied TCA for MDD; however, nortriptyline is typically preferred due to its favorable tolerability profile.^4,62 Nortriptyline also has data supporting its use in ECT to prevent relapse.⁶³ Amitriptyline and nortriptyline have shown benefits in patients with neuro­pathic pain and for migraine prophylaxis.^56-60 Although frequently used for MDD, clomipramine is not FDA-approved for this indication, but is for obsessive-compulsive disorder.³⁹ Doxepin is FDA-approved for insomnia at lower doses and for MDD at higher doses.⁴⁰ Therefore, it may benefit patients with sleep difficulties secondary to depression. Desipramine has been used off-label to treat ADHD in children and has shown some benefits in adults.^64-66 Protriptyline, trimipramine, and amoxapine are infrequently used in clinical practice.

A unique feature of TCAs is the ability to monitor serum concentrations (Table 3^36-51).Guidelines recommend therapeutic drug monitoring (TDM) with amitriptyline, clomi­pramine, imipramine, and nortriptyline for routine use. TDM is still recommended for doxepin, desipramine, and trimipramine, but its utility is largely for treatment failure or resistance.³⁷ These plasma levels can be altered based on coadministered medications (Table 5^38-46) and should be closely monitored. Physicians should obtain a trough level after at least 5 half-lives and before the next dose is due, and use TDM as indicated to optimize dosing.

Continue to: CASE CONTINUED

CASE CONTINUED

Ms. B’s outpatient psychiatrist provides collateral information about her medical history and confirms her long-standing MDD with multiple medication trials, though she has never received an MAOI or TCA. Ms. B is adamant she does not want a medication-free period between treatments and refuses to adjust her diet, despite being educated on the few changes necessary. She has no contraindications for TCAs and may benefit from a TCA for her comorbid migraines. The care team expresses concern for TCA overdose to Ms. B and her family. Ms. B’s sister reassures the team they will have someone monitor and dispense her medications at home. They decide to discontinue her current psychiatric regimen, and Ms. B is started on nortriptyline 50 mg/d at night, with plans to titrate based on tolerability.

Related Resources

• Meyer JM. A concise guide to monoamine oxidase inhibitors. Current Psychiatry. 2017;16(12):14-16,18-23,47,A.
• Espejo GD. Treating major depressive disorder after limited response to an initial agent. Current Psychiatry. 2021;20(10):51-53. doi:10.12788/cp.0178
• American Association of Psychiatric Pharmacists (AAPP) MAOI Pharmacist Toolkit. https://aapp.org/guideline/maoi

Drug Brand Names

Amitriptyline • Elavil
Amphetamine • Adzenys, Dyanavel
Aripiprazole • Abilify
Clomipramine • Anafranil
Desipramine • Norpramin
Dextromethorphan/bupropion • Auvelity
Doxepin • Sinequan, Adapin
Esketamine • Spravato
Fluoxetine • Prozac
Imipramine • Tofranil
Isocarboxazid • Marplan
Methamphetamine • Desoxyn
Mirtazapine • Remeron
Modafinil • Provigil
Nortriptyline • Pamelor
Phenelzine • Nardil
Protriptyline • Vivactil
Selegiline • Emsam
Tranylcypromine • Parnate
Trimipramine • Surmontil
Vortioxetine • Trintellix

Ms. B, age 45, has a history of major depressive disorder (MDD) and migraines. She is admitted after presenting with anhedonia, hopelessness, and hypersomnia. These symptoms have become more severe over the last few weeks. Ms. B describes a past suicide attempt via overdose on doxylamine for which she required treatment in the intensive care unit. The only activity she enjoys is her weekly girls’ night, during which she drinks a few glasses of wine. Ms. B’s current medications are dextromethorphan/bupropion 45/105 mg twice daily and aripiprazole 5 mg/d, which she has taken for 3 months. She states she has “been on every antidepressant there is.”

When clinicians review Ms. B’s medication history, it is clear she has had adequate trials of selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), intranasal esketamine, multiple augmentation strategies, and electroconvulsive therapy (ECT). Ms. B seeks an alternative medication to improve her depressive symptoms.

Treatment-resistant depression (TRD) is commonly defined as depression that has not responded to ≥2 adequate trials of an antidepressant.¹ Some guidelines recommend monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) as second- or even third-line options for MDD,² while others recommend reserving them for patients with insufficient responses to alternative treatment modalities.^3,4 Although MAOIs and TCAs have been available since the 1950s, prescribing these medications has become less prevalent due to safety concerns, the availability of other pharmacologic options, and a lack of clinical training and comfort.^5,6 Most research notes that MAOIs are superior for treating atypical depression while TCAs are more effective for melancholic depression.^2-4 In a review of 20 studies, Thase et al⁷ found that 50% of TCA nonresponders benefited from an MAOI. In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, monotherapy with the MAOI tranylcypromine was associated with a lower remission rate than the TCA nortriptyline; many argue the dose of tranylcypromine was suboptimal, and few participants completed an adequate trial in the last level.^8,9 A more recent study by Kim et al¹⁰ found MAOIs to be “generally more effective” than TCAs for TRD, particularly in patients with fewer antidepressant trials; however, this was a small retrospective exploratory trial. A network meta-analysis found both classes to be “competitive” with SSRIs based on efficacy and tolerability, which leads to the question of whether these medications should be considered earlier in therapy.¹¹ Considering patient-specific factors and particular medication properties is an effective strategy when prescribing an MAOI or TCA.

Monoamine oxidase inhibitors

Four MAOIs are FDA-approved for treating MDD (Table 1^5,12-17): phenelzine, isocarboxazid, tranylcypromine, and selegiline. These medications irreversibly inhibit MAO, which exists as isomers A and B. MAO-A primarily metabolizes serotonin and norepinephrine, which is largely responsible for these medications’ antidepressant effects. Both isomers equally metabolize dopamine.^5,12,18 It is best to avoid using MAOIs in patients with cerebrovascular disease, hepatic disease, or pheochromocytoma. Patients with active substance use disorders (particularly sympathomimetics and hallucinogens) are at an increased risk for hypertensive crises and serotonin syndrome, respectively. The most common adverse effects are orthostatic hypotension (despite more well-known concerns regarding hypertension), alterations in sleep patterns (insomnia or hypersomnia, depending on the agent), gastrointestinal issues, and anticholinergic adverse effects such as dry mouth and constipation.^13,19-21

In one review and meta-analysis, phenelzine displayed the highest efficacy across all MAOIs.¹¹ It likely requires high doses to achieve adequate MAO inhibition.¹¹ A metabolite of phenelzine inhibits gamma-aminobutyric acid transaminase and may be helpful for patients with comorbid anxiety disorders or MDD with anxious distress.^18,21 Additional considerations include phenelzine’s propensity for orthostasis (with rapid titrations and higher doses), sedation, weight gain, sexual dysfunction, and a rare adverse effect of vitamin B6 deficiency.^{5,13,14,20-22}

Use of isocarboxazid in clinical practice is rare. Its adverse effects are similar to those of phenelzine but isocarboxazid is less studied. Tranylcypromine has a similar chemical structure to amphetamine. It can be stimulating at higher doses, potentially benefitting patients with comorbid attention-deficit/hyperactivity disorder (ADHD) or significant apathy.^13,23 Selegiline’s distinct quality is its availability as a transdermal patch, which may be useful for patients who struggle to take oral medications. At low doses (6 mg/24 h), the selegiline transdermal patch allows patients to disregard a dietary tyramine restriction because it avoids first-pass metabolism. It inhibits both MAO isomers in the brain but is only selective for MAO-B once concentrations are distributed to the liver. Higher doses require a tyramine-restricted diet because there is still some MAO-A inhibition in the gut. Selegiline is also stimulating because it is converted to amphetamine and methamphetamine.^{5,12,13,17,19,24}

Despite promising results from the use of MAOIs, physicians and patients may be reluctant to use these medications due to perceived limitations. One prominent barrier is the infamous “cheese reaction.” Tyramine, an amino acid found in certain food and beverages (Table 2^{5,13-18,25-28}), is broken down by MAO-A in the gut. When this enzyme is inhibited, higher concentrations of tyramine reach systemic circulation. Tyramine’s release of norepinephrine (which now cannot be broken down) can lead to a hypertensive crisis. Consequently, a tyramine-restricted diet is recommended for patients taking an MAOI. However, the common notion that cheese, wine, and beer must be avoided is false, because most of the dietary restrictions developed following the discovery of MAOIs are antiquated.^5,12,25-28 Patients who take an MAOI only need to slightly adjust their diet, as outlined in Table 2.^{5,13-18,25-28} A reasonable serving size of most foods and beverages containing tyramine is unlikely to elicit this “pressor” response. Of the 4 MAOIs FDA-approved for MDD, tranylcypromine appears to be the most sensitive to tyramine.²¹ Transient postdose hypertension (regardless of tyramine) may occur after taking an MAOI.²⁹ Encourage patients to monitor their blood pressure.

Continue to: Additional hurdles include...

Additional hurdles include the required washout period from serotonergic medications and interactions with sympathomimetics. MAOIs pose the highest risk of serotonin syndrome; however, this usually occurs if given concomitantly with other serotonergic agents. The standard recommendation is a 14-day washout period from SSRIs (5 weeks for fluoxetine and 3 weeks for vortioxetine), SNRIs, mirtazapine, and other antidepressants. It can be distressing for patients to be without medication during that period. Because some antidepressants have much shorter half-lives, waiting 5 half-lives (typically 5 to 7 days) for the discontinued medication to be excreted is feasible if patients are closely monitored.^{5,12,13,25,27,30} There are rare instances where a TCA may be combined with an MAOI (typically initiated within 1 to 2 days of each other), but never clomipramine or imipramine due to their potent serotonin reuptake inhibition.³¹ If switching to an alternative MAOI, waiting 7 to 14 days is recommended to allow adequate time for the inhibited enzyme to regenerate.^14-17,32 Taking medications that increase dopamine and norepinephrine (eg, stimulants or oral over-the-counter decongestants) with an MAOI is typically not recommended due to the risk of hypertensive crisis.^25,27 In severe TRD or comorbid ADHD, successful simultaneous use of methylphenidate or amphetamine—typically at low doses—with close blood pressure monitoring has been reported.³³ There have also been positive cases of the use of modafinil in combination with an MAOI; however, this should be done with caution.^34,35 Clinicians must use clinical judgment when considering a combination of medications that pose a higher risk.

Tricyclic antidepressants

TCAs work differently than MAOIs to increase monoamines. They inhibit presynaptic serotonin and norepinephrine transporters in the CNS to increase levels of these chemicals in the synaptic cleft. While all TCAs inhibit these transporters, they do so at varying levels (Table 3^36-51). Based on their chemical structure, TCAs can be categorized into secondary and tertiary amines. Tertiary amines are metabolized via demethylation into their derivatives (Table 3^36-51). Patients who have recently suffered a myocardial infarction (MI) should avoid tertiary amines. TCAs can reduce heart rate variability, which is already decreased after an MI, thus presenting the potential for cardiac arrhythmias. TCAs should also be avoided in patients with cardiac conduction abnormalities.^38-46,52 Patients with a prior baseline cardiac conduction defect, such as a bundle branch block, are at higher risk for further cardiac abnormalities. In those with a preexisting first-degree heart block, TCAs can still be used, but electrocardiogram monitoring is recommended.^52,53 TCAs have also been reported to decrease the seizure threshold.^38-46 They can be used with caution in patients who have a history of epilepsy or head trauma, or with concomitant medications that lower the seizure threshold.^38-46

Overdose risk is a concern with TCAs because ingestion of 10 to 20 mg/kg can lead to significant toxicity.⁵⁴ This is due to their blockage of voltage-gated sodium channels found in the CNS and heart, which contributes to overdose symptoms such as a widened QRS complex and seizures. Symptoms usually develop within 2 hours but may be delayed up to 6 hours.⁵⁵ Patients with a history of overdose must be carefully assessed before initiating a TCA. Prescribing a limited supply of these medications may be valuable. The use of TCAs has often been limited due to their adverse effects, most of which are associated with their respective affinities for alpha 1, muscarinic 1, and histamine 1 receptors. Inhibition of the alpha 1 receptor is associated with hypotension, muscarinic 1 with anticholinergic adverse effects, and histamine 1 with sedation and weight gain. Tertiary amines have a higher affinity for these receptors compared to secondary amines, leading to a more significant adverse effect profile.^36,50 Among TCAs, amitriptyline is the most likely to cause hypotension, whereas desipramine and nortriptyline are least likely. Amitriptyline and clomipramine are most likely to cause anticholinergic adverse effects, whereas desipramine and nortriptyline are the least likely. Amitriptyline, doxepin, and imipramine have the highest propensity for QTc prolongation.³⁶

Beyond treating MDD, TCAs have shown benefits for treating other disease states (Table 4^{38-46,49,56-61}).These differing indications may help psychiatrists determine the best TCA to prescribe for a given patient. Amitriptyline is the most studied TCA for MDD; however, nortriptyline is typically preferred due to its favorable tolerability profile.^4,62 Nortriptyline also has data supporting its use in ECT to prevent relapse.⁶³ Amitriptyline and nortriptyline have shown benefits in patients with neuro­pathic pain and for migraine prophylaxis.^56-60 Although frequently used for MDD, clomipramine is not FDA-approved for this indication, but is for obsessive-compulsive disorder.³⁹ Doxepin is FDA-approved for insomnia at lower doses and for MDD at higher doses.⁴⁰ Therefore, it may benefit patients with sleep difficulties secondary to depression. Desipramine has been used off-label to treat ADHD in children and has shown some benefits in adults.^64-66 Protriptyline, trimipramine, and amoxapine are infrequently used in clinical practice.

A unique feature of TCAs is the ability to monitor serum concentrations (Table 3^36-51).Guidelines recommend therapeutic drug monitoring (TDM) with amitriptyline, clomi­pramine, imipramine, and nortriptyline for routine use. TDM is still recommended for doxepin, desipramine, and trimipramine, but its utility is largely for treatment failure or resistance.³⁷ These plasma levels can be altered based on coadministered medications (Table 5^38-46) and should be closely monitored. Physicians should obtain a trough level after at least 5 half-lives and before the next dose is due, and use TDM as indicated to optimize dosing.

Continue to: CASE CONTINUED

CASE CONTINUED

Ms. B’s outpatient psychiatrist provides collateral information about her medical history and confirms her long-standing MDD with multiple medication trials, though she has never received an MAOI or TCA. Ms. B is adamant she does not want a medication-free period between treatments and refuses to adjust her diet, despite being educated on the few changes necessary. She has no contraindications for TCAs and may benefit from a TCA for her comorbid migraines. The care team expresses concern for TCA overdose to Ms. B and her family. Ms. B’s sister reassures the team they will have someone monitor and dispense her medications at home. They decide to discontinue her current psychiatric regimen, and Ms. B is started on nortriptyline 50 mg/d at night, with plans to titrate based on tolerability.

Related Resources

• Meyer JM. A concise guide to monoamine oxidase inhibitors. Current Psychiatry. 2017;16(12):14-16,18-23,47,A.
• Espejo GD. Treating major depressive disorder after limited response to an initial agent. Current Psychiatry. 2021;20(10):51-53. doi:10.12788/cp.0178
• American Association of Psychiatric Pharmacists (AAPP) MAOI Pharmacist Toolkit. https://aapp.org/guideline/maoi

Drug Brand Names

Amitriptyline • Elavil
Amphetamine • Adzenys, Dyanavel
Aripiprazole • Abilify
Clomipramine • Anafranil
Desipramine • Norpramin
Dextromethorphan/bupropion • Auvelity
Doxepin • Sinequan, Adapin
Esketamine • Spravato
Fluoxetine • Prozac
Imipramine • Tofranil
Isocarboxazid • Marplan
Methamphetamine • Desoxyn
Mirtazapine • Remeron
Modafinil • Provigil
Nortriptyline • Pamelor
Phenelzine • Nardil
Protriptyline • Vivactil
Selegiline • Emsam
Tranylcypromine • Parnate
Trimipramine • Surmontil
Vortioxetine • Trintellix

Ms. B, age 45, has a history of major depressive disorder (MDD) and migraines. She is admitted after presenting with anhedonia, hopelessness, and hypersomnia. These symptoms have become more severe over the last few weeks. Ms. B describes a past suicide attempt via overdose on doxylamine for which she required treatment in the intensive care unit. The only activity she enjoys is her weekly girls’ night, during which she drinks a few glasses of wine. Ms. B’s current medications are dextromethorphan/bupropion 45/105 mg twice daily and aripiprazole 5 mg/d, which she has taken for 3 months. She states she has “been on every antidepressant there is.”

When clinicians review Ms. B’s medication history, it is clear she has had adequate trials of selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), intranasal esketamine, multiple augmentation strategies, and electroconvulsive therapy (ECT). Ms. B seeks an alternative medication to improve her depressive symptoms.

Treatment-resistant depression (TRD) is commonly defined as depression that has not responded to ≥2 adequate trials of an antidepressant.¹ Some guidelines recommend monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) as second- or even third-line options for MDD,² while others recommend reserving them for patients with insufficient responses to alternative treatment modalities.^3,4 Although MAOIs and TCAs have been available since the 1950s, prescribing these medications has become less prevalent due to safety concerns, the availability of other pharmacologic options, and a lack of clinical training and comfort.^5,6 Most research notes that MAOIs are superior for treating atypical depression while TCAs are more effective for melancholic depression.^2-4 In a review of 20 studies, Thase et al⁷ found that 50% of TCA nonresponders benefited from an MAOI. In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, monotherapy with the MAOI tranylcypromine was associated with a lower remission rate than the TCA nortriptyline; many argue the dose of tranylcypromine was suboptimal, and few participants completed an adequate trial in the last level.^8,9 A more recent study by Kim et al¹⁰ found MAOIs to be “generally more effective” than TCAs for TRD, particularly in patients with fewer antidepressant trials; however, this was a small retrospective exploratory trial. A network meta-analysis found both classes to be “competitive” with SSRIs based on efficacy and tolerability, which leads to the question of whether these medications should be considered earlier in therapy.¹¹ Considering patient-specific factors and particular medication properties is an effective strategy when prescribing an MAOI or TCA.

Monoamine oxidase inhibitors

Four MAOIs are FDA-approved for treating MDD (Table 1^5,12-17): phenelzine, isocarboxazid, tranylcypromine, and selegiline. These medications irreversibly inhibit MAO, which exists as isomers A and B. MAO-A primarily metabolizes serotonin and norepinephrine, which is largely responsible for these medications’ antidepressant effects. Both isomers equally metabolize dopamine.^5,12,18 It is best to avoid using MAOIs in patients with cerebrovascular disease, hepatic disease, or pheochromocytoma. Patients with active substance use disorders (particularly sympathomimetics and hallucinogens) are at an increased risk for hypertensive crises and serotonin syndrome, respectively. The most common adverse effects are orthostatic hypotension (despite more well-known concerns regarding hypertension), alterations in sleep patterns (insomnia or hypersomnia, depending on the agent), gastrointestinal issues, and anticholinergic adverse effects such as dry mouth and constipation.^13,19-21

In one review and meta-analysis, phenelzine displayed the highest efficacy across all MAOIs.¹¹ It likely requires high doses to achieve adequate MAO inhibition.¹¹ A metabolite of phenelzine inhibits gamma-aminobutyric acid transaminase and may be helpful for patients with comorbid anxiety disorders or MDD with anxious distress.^18,21 Additional considerations include phenelzine’s propensity for orthostasis (with rapid titrations and higher doses), sedation, weight gain, sexual dysfunction, and a rare adverse effect of vitamin B6 deficiency.^{5,13,14,20-22}

Use of isocarboxazid in clinical practice is rare. Its adverse effects are similar to those of phenelzine but isocarboxazid is less studied. Tranylcypromine has a similar chemical structure to amphetamine. It can be stimulating at higher doses, potentially benefitting patients with comorbid attention-deficit/hyperactivity disorder (ADHD) or significant apathy.^13,23 Selegiline’s distinct quality is its availability as a transdermal patch, which may be useful for patients who struggle to take oral medications. At low doses (6 mg/24 h), the selegiline transdermal patch allows patients to disregard a dietary tyramine restriction because it avoids first-pass metabolism. It inhibits both MAO isomers in the brain but is only selective for MAO-B once concentrations are distributed to the liver. Higher doses require a tyramine-restricted diet because there is still some MAO-A inhibition in the gut. Selegiline is also stimulating because it is converted to amphetamine and methamphetamine.^{5,12,13,17,19,24}

Despite promising results from the use of MAOIs, physicians and patients may be reluctant to use these medications due to perceived limitations. One prominent barrier is the infamous “cheese reaction.” Tyramine, an amino acid found in certain food and beverages (Table 2^{5,13-18,25-28}), is broken down by MAO-A in the gut. When this enzyme is inhibited, higher concentrations of tyramine reach systemic circulation. Tyramine’s release of norepinephrine (which now cannot be broken down) can lead to a hypertensive crisis. Consequently, a tyramine-restricted diet is recommended for patients taking an MAOI. However, the common notion that cheese, wine, and beer must be avoided is false, because most of the dietary restrictions developed following the discovery of MAOIs are antiquated.^5,12,25-28 Patients who take an MAOI only need to slightly adjust their diet, as outlined in Table 2.^{5,13-18,25-28} A reasonable serving size of most foods and beverages containing tyramine is unlikely to elicit this “pressor” response. Of the 4 MAOIs FDA-approved for MDD, tranylcypromine appears to be the most sensitive to tyramine.²¹ Transient postdose hypertension (regardless of tyramine) may occur after taking an MAOI.²⁹ Encourage patients to monitor their blood pressure.

Continue to: Additional hurdles include...

Additional hurdles include the required washout period from serotonergic medications and interactions with sympathomimetics. MAOIs pose the highest risk of serotonin syndrome; however, this usually occurs if given concomitantly with other serotonergic agents. The standard recommendation is a 14-day washout period from SSRIs (5 weeks for fluoxetine and 3 weeks for vortioxetine), SNRIs, mirtazapine, and other antidepressants. It can be distressing for patients to be without medication during that period. Because some antidepressants have much shorter half-lives, waiting 5 half-lives (typically 5 to 7 days) for the discontinued medication to be excreted is feasible if patients are closely monitored.^{5,12,13,25,27,30} There are rare instances where a TCA may be combined with an MAOI (typically initiated within 1 to 2 days of each other), but never clomipramine or imipramine due to their potent serotonin reuptake inhibition.³¹ If switching to an alternative MAOI, waiting 7 to 14 days is recommended to allow adequate time for the inhibited enzyme to regenerate.^14-17,32 Taking medications that increase dopamine and norepinephrine (eg, stimulants or oral over-the-counter decongestants) with an MAOI is typically not recommended due to the risk of hypertensive crisis.^25,27 In severe TRD or comorbid ADHD, successful simultaneous use of methylphenidate or amphetamine—typically at low doses—with close blood pressure monitoring has been reported.³³ There have also been positive cases of the use of modafinil in combination with an MAOI; however, this should be done with caution.^34,35 Clinicians must use clinical judgment when considering a combination of medications that pose a higher risk.

Tricyclic antidepressants

TCAs work differently than MAOIs to increase monoamines. They inhibit presynaptic serotonin and norepinephrine transporters in the CNS to increase levels of these chemicals in the synaptic cleft. While all TCAs inhibit these transporters, they do so at varying levels (Table 3^36-51). Based on their chemical structure, TCAs can be categorized into secondary and tertiary amines. Tertiary amines are metabolized via demethylation into their derivatives (Table 3^36-51). Patients who have recently suffered a myocardial infarction (MI) should avoid tertiary amines. TCAs can reduce heart rate variability, which is already decreased after an MI, thus presenting the potential for cardiac arrhythmias. TCAs should also be avoided in patients with cardiac conduction abnormalities.^38-46,52 Patients with a prior baseline cardiac conduction defect, such as a bundle branch block, are at higher risk for further cardiac abnormalities. In those with a preexisting first-degree heart block, TCAs can still be used, but electrocardiogram monitoring is recommended.^52,53 TCAs have also been reported to decrease the seizure threshold.^38-46 They can be used with caution in patients who have a history of epilepsy or head trauma, or with concomitant medications that lower the seizure threshold.^38-46

Overdose risk is a concern with TCAs because ingestion of 10 to 20 mg/kg can lead to significant toxicity.⁵⁴ This is due to their blockage of voltage-gated sodium channels found in the CNS and heart, which contributes to overdose symptoms such as a widened QRS complex and seizures. Symptoms usually develop within 2 hours but may be delayed up to 6 hours.⁵⁵ Patients with a history of overdose must be carefully assessed before initiating a TCA. Prescribing a limited supply of these medications may be valuable. The use of TCAs has often been limited due to their adverse effects, most of which are associated with their respective affinities for alpha 1, muscarinic 1, and histamine 1 receptors. Inhibition of the alpha 1 receptor is associated with hypotension, muscarinic 1 with anticholinergic adverse effects, and histamine 1 with sedation and weight gain. Tertiary amines have a higher affinity for these receptors compared to secondary amines, leading to a more significant adverse effect profile.^36,50 Among TCAs, amitriptyline is the most likely to cause hypotension, whereas desipramine and nortriptyline are least likely. Amitriptyline and clomipramine are most likely to cause anticholinergic adverse effects, whereas desipramine and nortriptyline are the least likely. Amitriptyline, doxepin, and imipramine have the highest propensity for QTc prolongation.³⁶

Beyond treating MDD, TCAs have shown benefits for treating other disease states (Table 4^{38-46,49,56-61}).These differing indications may help psychiatrists determine the best TCA to prescribe for a given patient. Amitriptyline is the most studied TCA for MDD; however, nortriptyline is typically preferred due to its favorable tolerability profile.^4,62 Nortriptyline also has data supporting its use in ECT to prevent relapse.⁶³ Amitriptyline and nortriptyline have shown benefits in patients with neuro­pathic pain and for migraine prophylaxis.^56-60 Although frequently used for MDD, clomipramine is not FDA-approved for this indication, but is for obsessive-compulsive disorder.³⁹ Doxepin is FDA-approved for insomnia at lower doses and for MDD at higher doses.⁴⁰ Therefore, it may benefit patients with sleep difficulties secondary to depression. Desipramine has been used off-label to treat ADHD in children and has shown some benefits in adults.^64-66 Protriptyline, trimipramine, and amoxapine are infrequently used in clinical practice.

A unique feature of TCAs is the ability to monitor serum concentrations (Table 3^36-51).Guidelines recommend therapeutic drug monitoring (TDM) with amitriptyline, clomi­pramine, imipramine, and nortriptyline for routine use. TDM is still recommended for doxepin, desipramine, and trimipramine, but its utility is largely for treatment failure or resistance.³⁷ These plasma levels can be altered based on coadministered medications (Table 5^38-46) and should be closely monitored. Physicians should obtain a trough level after at least 5 half-lives and before the next dose is due, and use TDM as indicated to optimize dosing.

Continue to: CASE CONTINUED

CASE CONTINUED

Ms. B’s outpatient psychiatrist provides collateral information about her medical history and confirms her long-standing MDD with multiple medication trials, though she has never received an MAOI or TCA. Ms. B is adamant she does not want a medication-free period between treatments and refuses to adjust her diet, despite being educated on the few changes necessary. She has no contraindications for TCAs and may benefit from a TCA for her comorbid migraines. The care team expresses concern for TCA overdose to Ms. B and her family. Ms. B’s sister reassures the team they will have someone monitor and dispense her medications at home. They decide to discontinue her current psychiatric regimen, and Ms. B is started on nortriptyline 50 mg/d at night, with plans to titrate based on tolerability.

Related Resources

• Meyer JM. A concise guide to monoamine oxidase inhibitors. Current Psychiatry. 2017;16(12):14-16,18-23,47,A.
• Espejo GD. Treating major depressive disorder after limited response to an initial agent. Current Psychiatry. 2021;20(10):51-53. doi:10.12788/cp.0178
• American Association of Psychiatric Pharmacists (AAPP) MAOI Pharmacist Toolkit. https://aapp.org/guideline/maoi

Drug Brand Names

Amitriptyline • Elavil
Amphetamine • Adzenys, Dyanavel
Aripiprazole • Abilify
Clomipramine • Anafranil
Desipramine • Norpramin
Dextromethorphan/bupropion • Auvelity
Doxepin • Sinequan, Adapin
Esketamine • Spravato
Fluoxetine • Prozac
Imipramine • Tofranil
Isocarboxazid • Marplan
Methamphetamine • Desoxyn
Mirtazapine • Remeron
Modafinil • Provigil
Nortriptyline • Pamelor
Phenelzine • Nardil
Protriptyline • Vivactil
Selegiline • Emsam
Tranylcypromine • Parnate
Trimipramine • Surmontil
Vortioxetine • Trintellix

CASE Thoughts of harming baby

Ms. A, age 37, is G4P2, 4 months postpartum, and breastfeeding. She has major depressive disorder (MDD) with peripartum onset, posttraumatic stress disorder, and mild intellectual disability. For years she has been stable on fluoxetine 40 mg/d and prazosin 2 mg/d. Despite recent titration of her medications, at her most recent outpatient appointment Ms. A reports having a depressed mood with frequent crying, insomnia, a lack of desire to bond with her baby, and feelings of shame. She also says she has had auditory hallucinations and thoughts of harming her baby. Ms. A’s outpatient physician makes an urgent request for her to be evaluated at the psychiatric emergency department (ED).

HISTORY Depression and possible auditory hallucinations

Ms. A developed MDD following the birth of her first child, for which her care team initiated fluoxetine at 20 mg/d and titrated it to 40 mg/d,which was effective. At that time, her outpatient physician documented potential psychotic features, including vague descriptions of derogatory auditory hallucinations. However, it was unclear if these auditory hallucinations were more representative of a distressing inner monologue without the quality of an external voice. The team determined that Ms. A was not at acute risk for harm to herself or her baby and was appropriate for outpatient care. Because the nature of these possible auditory hallucinations was mild, nondistressing, and nonthreatening, the treatment team did not initiate an antipsychotic and Ms. A was not hospitalized. She has no history of hypomanic/manic episodes and has never met criteria for a psychotic disorder.

EVALUATION Distressing thoughts and discontinued medications

During the evaluation by psychiatric emergency services, Ms. A reports that 2 weeks after giving birth she experienced a worsening of her depressive symptoms. She says she began hearing voices telling her to harm herself and her baby and describes frequent distressing thoughts, such as stabbing her baby with a knife and running over her baby with a car. Ms. A says she repeatedly wakes up at night to check on her baby’s breathing, overfeeds her baby due to a fear of inadequate nutrition, and notes intermittent feelings of confusion. Afraid of being alone with her infant, Ms. A asks her partner and mother to move in with her. Additionally, she says 2 weeks ago she discontinued all her medications at the suggestion of her partner, who recommended herbal supplements. Ms. A’s initial routine laboratory results are unremarkable and her urine drug screen is negative for all substances.

[polldaddy:13041928]

The authors’ observations

Approximately 85% of birthing parents experience some form of postpartum mood disturbance; 10% to 15% develop more significant symptoms of anxiety or depression.³ The etiology of postpartum illness is multifactorial, and includes psychiatric personal/family history, insomnia, acute and chronic psychosocial stressors, and rapid hormone fluctuations.¹ As a result, the postpartum period represents a vulnerable time for birthing parents, particularly those with previously established psychiatric illness.

Ms. A’s initial presentation was concerning for a possible diagnosis of postpartum psychosis vs obsessive-compulsive disorder (OCD) with postpartum onset; other differential diagnoses included MDD with peripartum onset and psychotic features (Table^1-6). Ms. A’s subjective clinical history was significant for critical pertinent findings of both OCD with postpartum onset (ie, egodystonic intrusive thoughts, checking behaviors, feelings of shame, and seeking reassurance) and postpartum psychosis (ie, command auditory hallucinations and waxing/waning confusion), which added to diagnostic complexity.

Although postpartum psychosis is rare (1 to 2 cases per 1,000 women),⁵ it is considered a psychiatric emergency because it has significant potential for infanticide, morbidity, and mortality. Most symptoms develop within the first 2 weeks of the postpartum period.² There are many risk factors for the development of postpartum psychosis; however, in first-time pregnancies, a previous diagnosis of BD I is the single most important risk factor.¹ Approximately 20% to 30% of women with BD experience postpartum psychosis.⁴

For many patients (approximately 56.7%, according to 1 meta-analysis⁷), postpartum psychosis denotes an episode of BD, representing a more severe form of illness with increased risk of recurrence. Most manic or mixed mood episodes reoccur within the first year removed from the perinatal period. In contrast, for some patients (approximately 43.5% according to the same meta-analysis), the episode denotes “isolated postpartum psychosis.”⁷ Isolated postpartum psychosis is a psychotic episode that occurs only in the postpartum period with no recurrence of psychosis or recurrence of psychosis exclusive to postpartum periods. If treated, this type of postpartum psychosis has a more favorable prognosis than postpartum psychosis in a patient with BD.⁷ As such, a BD diagnosis should not be established at the onset of a patient’s first postpartum psychosis presentation. Regardless of type, all presentations of postpartum psychosis are considered a psychiatry emergency.

Continue to: The prevalence of OCD...

The prevalence of OCD with postpartum onset varies. One study estimated it occurs in 2.43% of cases.⁴ However, the true prevalence is likely underreported due to feelings of guilt or shame associated with intrusive thoughts, and fear of stigmatization and separation from the baby. Approximately 70.6% of women experiencing OCD with postpartum onset have a comorbid depressive disorder.⁴

Ms. A’s presentation to the psychiatric ED carried with it diagnostic complexity and uncertainty. Her initial presentation was concerning for elements of both postpartum psychosis and OCD with postpartum onset. After her evaluation in the psychiatric ED, there remained a lack of clear and convincing evidence for a diagnosis of OCD with postpartum onset, which eliminated the possibility of discharging Ms. A with robust safety planning and reinitiation of a selective serotonin reuptake inhibitor.

Additionally, because auditory hallucinations are atypical in OCD, the treatment team remained concerned for a diagnosis of postpartum psychosis, which would warrant hospitalization. With assistance from the institution’s reproductive psychiatrists, the treatment team discussed the importance of inpatient hospitalization for risk mitigation, close observation, and thorough evaluation for greater diagnostic clarity and certainty.

TREATMENT Involuntary hospitalization

The treatment team counsels Ms. A and her partner on her differential diagnoses, including the elevated acute risk of harm to herself and her baby if she has postpartum psychosis, as well as the need for continued observation and evaluation. When alone with a clinician, Ms. A says she understands and agrees to voluntary hospitalization. However, following a subsequent risk-benefit discussion with her partner, they both grew increasingly concerned about her separation from the baby and reinitiating her medications. Amid these concerns, the treatment team notices that Ms. A attempts to minimize her symptoms. Ms. A changes her mind and no longer consents to hospitalization. She is placed on a psychiatric hold for involuntary hospitalization on the psychiatric inpatient unit.

On the inpatient unit, the inpatient clinicians and a reproductive psychiatrist continue to evaluate Ms. A. Though her diagnosis remains unclear, Ms. A agrees to start a trial of quetiapine 100 mg/d titrated to 150 mg/d to manage her potential postpartum psychosis, depressed mood, insomnia (off-label), anxiety (off-label), and OCD (off-label). Lithium is deferred because Ms. A is breastfeeding.

[polldaddy:13041932]

Continue to: The authors' observations

Due to an elevated acute risk of suicide and infanticide, postpartum psychosis represents a psychiatric emergency and often requires hospitalization. The Figure outlines steps in evaluating a patient with concerns for postpartum psychosis in a psychiatric emergency service setting. Due to the waxing and waning nature of symptoms, patients may appear psychiatrically stable at any time but remain at an overall elevated acute risk of harm to self and/or their baby.

If a patient is being considered for discharge based on yes answers to all questions in Step 2 of the Figure, the emergency psychiatric clinician must initiate appropriate psychotropic medications and complete robust safety planning with the patient and a trusted adult who will provide direct supervision. Safety planning may include (but is not limited to) strict return precautions, education on concerning symptoms and behaviors, psychotropic education and agreement of compliance, and detailed instructions on outpatient follow-up within 1 week. Ideally—and as was the case for Ms. A—a reproductive psychiatrist should be consulted in the emergency setting for shared decision-making on admission vs discharge, medication management, and outpatient follow-up considerations.

Because postpartum psychosis carries significant risks and hospitalization generally results in separating the patient from their baby, initiating psychotropics should not be delayed. Clinicians must consider the patient’s psychiatric history, allergies, and breastfeeding status.

Based on current evidence, first-line treatment for postpartum psychosis includes a mood stabilizer, an antipsychotic, and possibly a benzodiazepine.⁶ Thus, an appropriate initial treatment regimen would be a benzodiazepine (particularly lorazepam due to its relatively shorter half-life) and an antipsychotic (eg, haloperidol, olanzapine, or quetiapine) for acute psychosis, plus lithium for mood stabilization.^1,5

If the postpartum psychosis represents an episode of BD, use of a long-term mood stabilizer may be required. In contrast, for isolated postpartum psychosis, clinicians may consider initiating psychotropics only in the immediate postpartum period, with an eventual slow taper. In future pregnancies, psychotropics may be reintroduced postpartum, which will avoid peripartum fetal exposure.⁸ If the patient is breastfeeding, lithium may be deferred in an acute care setting. For patients with evidence of catatonia, severe suicidality, refusal of oral intake with compromised nutrition, severe agitation, or treatment resistance, electro­convulsive therapy remains a safe and effective treatment option.⁶ Additionally, the safety of continued breastfeeding in acute psychosis must be considered, with the potential for recommending discontinuation, which would decrease sleep disruptions at night and increase the ability of others to feed the baby. Comprehensive care requires nonpharmacologic interventions, including psychoeducation for the patient and their family, individual psychotherapy, and expansion of psychosocial supports.

Continue to: Patients who have experienced...

Patients who have experienced an episode of postpartum psychosis are predisposed to another episode in future pregnancies.¹ Current research recommends prophylaxis of recurrence with lithium monotherapy.^1,2,5,6 Similar to other psychotropics in reproductive psychiatry, maintenance therapy on lithium requires a thorough “risk vs risk” discussion with the patient. The risk of lithium use while pregnant and/or breastfeeding must be weighed against the risks associated with postpartum psychosis (ie, infanticide, suicide, poor peripartum care, or poor infant bonding).

OUTCOME Improved mood

After 7 days of inpatient treatment with quetiapine, Ms. A demonstrates improvement in the targeted depressive symptoms (including improved motivation/energy and insomnia, decreased feelings of guilt, and denial of ongoing suicidal ideation). Additionally, the thoughts of harming her baby are less frequent, and command auditory hallucinations resolve. Upon discharge, Ms. A and her partner meet with inpatient clinicians for continued counseling, safety planning, and plans for outpatient follow-up with the institution’s reproductive psychiatrist.

The authors’ observations

Many aspects of Ms. A’s initial presentation in the psychiatric ED were challenging. Given the presence of symptoms of both psychosis and OCD, a diagnosis was difficult to ascertain in the emergency setting. Since command auditory hallucinations are atypical in patients with postpartum OCD, the treatment team maintained high suspicion for postpartum psychosis, which represented an emergency requiring inpatient care.

Hospitalization separated Ms. A from her baby, for whom she was the primary caregiver. Additional considerations for inpatient admission and psychotropic initiation were necessary, because Ms. A was breastfeeding. Although Ms. A’s partner was able to provide full-time childcare, the patient ultimately did not agree to hospitalization and required an emergency hold for involuntary admission, which was an additional barrier to care. Furthermore, her partner held unfavorable beliefs regarding psychotropic medications and Ms. A’s need for hospital admission, which required ongoing patient and partner education in the emergency, inpatient, and outpatient settings. Moreover, if Ms. A’s symptoms were ultimately attributable to postpartum OCD, the patient’s involuntary hospitalization might have increased the risk of stigmatization of mental illness and treatment with psychotropics.

Bottom Line

The peripartum period is a vulnerable time for patients, particularly those with previously diagnosed psychiatric illnesses. Postpartum psychosis is the most severe form of postpartum psychiatric illness and often represents an episode of bipolar disorder. Due to an elevated acute risk of suicide and infanticide, postpartum psychosis is a psychiatric emergency and warrants inpatient hospitalization for immediate intervention.

Related Resources

• Sharma V. Does your patient have postpartum OCD? Current Psychiatry. 2019;18(5):9-10.
• Hatters Friedman S, Prakash C, Nagel-Yang S. Postpartum psychosis: protecting mother and infant. Current Psychiatry. 2019;18(4):12-21.

Drug Brand Names

Fluoxetine • Prozac
Haloperidol • Haldol
Lithium • Eskalith, Lithobid
Lorazepam • Ativan
Olanzapine • Zyprexa
Prazosin • Minipress
Quetiapine • Seroquel
Sertraline • Zoloft
Valproic acid • Depakene

CASE Thoughts of harming baby

Ms. A, age 37, is G4P2, 4 months postpartum, and breastfeeding. She has major depressive disorder (MDD) with peripartum onset, posttraumatic stress disorder, and mild intellectual disability. For years she has been stable on fluoxetine 40 mg/d and prazosin 2 mg/d. Despite recent titration of her medications, at her most recent outpatient appointment Ms. A reports having a depressed mood with frequent crying, insomnia, a lack of desire to bond with her baby, and feelings of shame. She also says she has had auditory hallucinations and thoughts of harming her baby. Ms. A’s outpatient physician makes an urgent request for her to be evaluated at the psychiatric emergency department (ED).

HISTORY Depression and possible auditory hallucinations

Ms. A developed MDD following the birth of her first child, for which her care team initiated fluoxetine at 20 mg/d and titrated it to 40 mg/d,which was effective. At that time, her outpatient physician documented potential psychotic features, including vague descriptions of derogatory auditory hallucinations. However, it was unclear if these auditory hallucinations were more representative of a distressing inner monologue without the quality of an external voice. The team determined that Ms. A was not at acute risk for harm to herself or her baby and was appropriate for outpatient care. Because the nature of these possible auditory hallucinations was mild, nondistressing, and nonthreatening, the treatment team did not initiate an antipsychotic and Ms. A was not hospitalized. She has no history of hypomanic/manic episodes and has never met criteria for a psychotic disorder.

EVALUATION Distressing thoughts and discontinued medications

During the evaluation by psychiatric emergency services, Ms. A reports that 2 weeks after giving birth she experienced a worsening of her depressive symptoms. She says she began hearing voices telling her to harm herself and her baby and describes frequent distressing thoughts, such as stabbing her baby with a knife and running over her baby with a car. Ms. A says she repeatedly wakes up at night to check on her baby’s breathing, overfeeds her baby due to a fear of inadequate nutrition, and notes intermittent feelings of confusion. Afraid of being alone with her infant, Ms. A asks her partner and mother to move in with her. Additionally, she says 2 weeks ago she discontinued all her medications at the suggestion of her partner, who recommended herbal supplements. Ms. A’s initial routine laboratory results are unremarkable and her urine drug screen is negative for all substances.

[polldaddy:13041928]

The authors’ observations

Approximately 85% of birthing parents experience some form of postpartum mood disturbance; 10% to 15% develop more significant symptoms of anxiety or depression.³ The etiology of postpartum illness is multifactorial, and includes psychiatric personal/family history, insomnia, acute and chronic psychosocial stressors, and rapid hormone fluctuations.¹ As a result, the postpartum period represents a vulnerable time for birthing parents, particularly those with previously established psychiatric illness.

Ms. A’s initial presentation was concerning for a possible diagnosis of postpartum psychosis vs obsessive-compulsive disorder (OCD) with postpartum onset; other differential diagnoses included MDD with peripartum onset and psychotic features (Table^1-6). Ms. A’s subjective clinical history was significant for critical pertinent findings of both OCD with postpartum onset (ie, egodystonic intrusive thoughts, checking behaviors, feelings of shame, and seeking reassurance) and postpartum psychosis (ie, command auditory hallucinations and waxing/waning confusion), which added to diagnostic complexity.

Although postpartum psychosis is rare (1 to 2 cases per 1,000 women),⁵ it is considered a psychiatric emergency because it has significant potential for infanticide, morbidity, and mortality. Most symptoms develop within the first 2 weeks of the postpartum period.² There are many risk factors for the development of postpartum psychosis; however, in first-time pregnancies, a previous diagnosis of BD I is the single most important risk factor.¹ Approximately 20% to 30% of women with BD experience postpartum psychosis.⁴

For many patients (approximately 56.7%, according to 1 meta-analysis⁷), postpartum psychosis denotes an episode of BD, representing a more severe form of illness with increased risk of recurrence. Most manic or mixed mood episodes reoccur within the first year removed from the perinatal period. In contrast, for some patients (approximately 43.5% according to the same meta-analysis), the episode denotes “isolated postpartum psychosis.”⁷ Isolated postpartum psychosis is a psychotic episode that occurs only in the postpartum period with no recurrence of psychosis or recurrence of psychosis exclusive to postpartum periods. If treated, this type of postpartum psychosis has a more favorable prognosis than postpartum psychosis in a patient with BD.⁷ As such, a BD diagnosis should not be established at the onset of a patient’s first postpartum psychosis presentation. Regardless of type, all presentations of postpartum psychosis are considered a psychiatry emergency.

Continue to: The prevalence of OCD...

The prevalence of OCD with postpartum onset varies. One study estimated it occurs in 2.43% of cases.⁴ However, the true prevalence is likely underreported due to feelings of guilt or shame associated with intrusive thoughts, and fear of stigmatization and separation from the baby. Approximately 70.6% of women experiencing OCD with postpartum onset have a comorbid depressive disorder.⁴

Ms. A’s presentation to the psychiatric ED carried with it diagnostic complexity and uncertainty. Her initial presentation was concerning for elements of both postpartum psychosis and OCD with postpartum onset. After her evaluation in the psychiatric ED, there remained a lack of clear and convincing evidence for a diagnosis of OCD with postpartum onset, which eliminated the possibility of discharging Ms. A with robust safety planning and reinitiation of a selective serotonin reuptake inhibitor.

Additionally, because auditory hallucinations are atypical in OCD, the treatment team remained concerned for a diagnosis of postpartum psychosis, which would warrant hospitalization. With assistance from the institution’s reproductive psychiatrists, the treatment team discussed the importance of inpatient hospitalization for risk mitigation, close observation, and thorough evaluation for greater diagnostic clarity and certainty.

TREATMENT Involuntary hospitalization

The treatment team counsels Ms. A and her partner on her differential diagnoses, including the elevated acute risk of harm to herself and her baby if she has postpartum psychosis, as well as the need for continued observation and evaluation. When alone with a clinician, Ms. A says she understands and agrees to voluntary hospitalization. However, following a subsequent risk-benefit discussion with her partner, they both grew increasingly concerned about her separation from the baby and reinitiating her medications. Amid these concerns, the treatment team notices that Ms. A attempts to minimize her symptoms. Ms. A changes her mind and no longer consents to hospitalization. She is placed on a psychiatric hold for involuntary hospitalization on the psychiatric inpatient unit.

On the inpatient unit, the inpatient clinicians and a reproductive psychiatrist continue to evaluate Ms. A. Though her diagnosis remains unclear, Ms. A agrees to start a trial of quetiapine 100 mg/d titrated to 150 mg/d to manage her potential postpartum psychosis, depressed mood, insomnia (off-label), anxiety (off-label), and OCD (off-label). Lithium is deferred because Ms. A is breastfeeding.

[polldaddy:13041932]

Continue to: The authors' observations

Due to an elevated acute risk of suicide and infanticide, postpartum psychosis represents a psychiatric emergency and often requires hospitalization. The Figure outlines steps in evaluating a patient with concerns for postpartum psychosis in a psychiatric emergency service setting. Due to the waxing and waning nature of symptoms, patients may appear psychiatrically stable at any time but remain at an overall elevated acute risk of harm to self and/or their baby.

If a patient is being considered for discharge based on yes answers to all questions in Step 2 of the Figure, the emergency psychiatric clinician must initiate appropriate psychotropic medications and complete robust safety planning with the patient and a trusted adult who will provide direct supervision. Safety planning may include (but is not limited to) strict return precautions, education on concerning symptoms and behaviors, psychotropic education and agreement of compliance, and detailed instructions on outpatient follow-up within 1 week. Ideally—and as was the case for Ms. A—a reproductive psychiatrist should be consulted in the emergency setting for shared decision-making on admission vs discharge, medication management, and outpatient follow-up considerations.

Because postpartum psychosis carries significant risks and hospitalization generally results in separating the patient from their baby, initiating psychotropics should not be delayed. Clinicians must consider the patient’s psychiatric history, allergies, and breastfeeding status.

Based on current evidence, first-line treatment for postpartum psychosis includes a mood stabilizer, an antipsychotic, and possibly a benzodiazepine.⁶ Thus, an appropriate initial treatment regimen would be a benzodiazepine (particularly lorazepam due to its relatively shorter half-life) and an antipsychotic (eg, haloperidol, olanzapine, or quetiapine) for acute psychosis, plus lithium for mood stabilization.^1,5

If the postpartum psychosis represents an episode of BD, use of a long-term mood stabilizer may be required. In contrast, for isolated postpartum psychosis, clinicians may consider initiating psychotropics only in the immediate postpartum period, with an eventual slow taper. In future pregnancies, psychotropics may be reintroduced postpartum, which will avoid peripartum fetal exposure.⁸ If the patient is breastfeeding, lithium may be deferred in an acute care setting. For patients with evidence of catatonia, severe suicidality, refusal of oral intake with compromised nutrition, severe agitation, or treatment resistance, electro­convulsive therapy remains a safe and effective treatment option.⁶ Additionally, the safety of continued breastfeeding in acute psychosis must be considered, with the potential for recommending discontinuation, which would decrease sleep disruptions at night and increase the ability of others to feed the baby. Comprehensive care requires nonpharmacologic interventions, including psychoeducation for the patient and their family, individual psychotherapy, and expansion of psychosocial supports.

Continue to: Patients who have experienced...

Patients who have experienced an episode of postpartum psychosis are predisposed to another episode in future pregnancies.¹ Current research recommends prophylaxis of recurrence with lithium monotherapy.^1,2,5,6 Similar to other psychotropics in reproductive psychiatry, maintenance therapy on lithium requires a thorough “risk vs risk” discussion with the patient. The risk of lithium use while pregnant and/or breastfeeding must be weighed against the risks associated with postpartum psychosis (ie, infanticide, suicide, poor peripartum care, or poor infant bonding).

OUTCOME Improved mood

After 7 days of inpatient treatment with quetiapine, Ms. A demonstrates improvement in the targeted depressive symptoms (including improved motivation/energy and insomnia, decreased feelings of guilt, and denial of ongoing suicidal ideation). Additionally, the thoughts of harming her baby are less frequent, and command auditory hallucinations resolve. Upon discharge, Ms. A and her partner meet with inpatient clinicians for continued counseling, safety planning, and plans for outpatient follow-up with the institution’s reproductive psychiatrist.

The authors’ observations

Many aspects of Ms. A’s initial presentation in the psychiatric ED were challenging. Given the presence of symptoms of both psychosis and OCD, a diagnosis was difficult to ascertain in the emergency setting. Since command auditory hallucinations are atypical in patients with postpartum OCD, the treatment team maintained high suspicion for postpartum psychosis, which represented an emergency requiring inpatient care.

Hospitalization separated Ms. A from her baby, for whom she was the primary caregiver. Additional considerations for inpatient admission and psychotropic initiation were necessary, because Ms. A was breastfeeding. Although Ms. A’s partner was able to provide full-time childcare, the patient ultimately did not agree to hospitalization and required an emergency hold for involuntary admission, which was an additional barrier to care. Furthermore, her partner held unfavorable beliefs regarding psychotropic medications and Ms. A’s need for hospital admission, which required ongoing patient and partner education in the emergency, inpatient, and outpatient settings. Moreover, if Ms. A’s symptoms were ultimately attributable to postpartum OCD, the patient’s involuntary hospitalization might have increased the risk of stigmatization of mental illness and treatment with psychotropics.

Bottom Line

The peripartum period is a vulnerable time for patients, particularly those with previously diagnosed psychiatric illnesses. Postpartum psychosis is the most severe form of postpartum psychiatric illness and often represents an episode of bipolar disorder. Due to an elevated acute risk of suicide and infanticide, postpartum psychosis is a psychiatric emergency and warrants inpatient hospitalization for immediate intervention.

Related Resources

• Sharma V. Does your patient have postpartum OCD? Current Psychiatry. 2019;18(5):9-10.
• Hatters Friedman S, Prakash C, Nagel-Yang S. Postpartum psychosis: protecting mother and infant. Current Psychiatry. 2019;18(4):12-21.

Drug Brand Names

Fluoxetine • Prozac
Haloperidol • Haldol
Lithium • Eskalith, Lithobid
Lorazepam • Ativan
Olanzapine • Zyprexa
Prazosin • Minipress
Quetiapine • Seroquel
Sertraline • Zoloft
Valproic acid • Depakene

CASE Thoughts of harming baby

Ms. A, age 37, is G4P2, 4 months postpartum, and breastfeeding. She has major depressive disorder (MDD) with peripartum onset, posttraumatic stress disorder, and mild intellectual disability. For years she has been stable on fluoxetine 40 mg/d and prazosin 2 mg/d. Despite recent titration of her medications, at her most recent outpatient appointment Ms. A reports having a depressed mood with frequent crying, insomnia, a lack of desire to bond with her baby, and feelings of shame. She also says she has had auditory hallucinations and thoughts of harming her baby. Ms. A’s outpatient physician makes an urgent request for her to be evaluated at the psychiatric emergency department (ED).

HISTORY Depression and possible auditory hallucinations

Ms. A developed MDD following the birth of her first child, for which her care team initiated fluoxetine at 20 mg/d and titrated it to 40 mg/d,which was effective. At that time, her outpatient physician documented potential psychotic features, including vague descriptions of derogatory auditory hallucinations. However, it was unclear if these auditory hallucinations were more representative of a distressing inner monologue without the quality of an external voice. The team determined that Ms. A was not at acute risk for harm to herself or her baby and was appropriate for outpatient care. Because the nature of these possible auditory hallucinations was mild, nondistressing, and nonthreatening, the treatment team did not initiate an antipsychotic and Ms. A was not hospitalized. She has no history of hypomanic/manic episodes and has never met criteria for a psychotic disorder.

EVALUATION Distressing thoughts and discontinued medications

During the evaluation by psychiatric emergency services, Ms. A reports that 2 weeks after giving birth she experienced a worsening of her depressive symptoms. She says she began hearing voices telling her to harm herself and her baby and describes frequent distressing thoughts, such as stabbing her baby with a knife and running over her baby with a car. Ms. A says she repeatedly wakes up at night to check on her baby’s breathing, overfeeds her baby due to a fear of inadequate nutrition, and notes intermittent feelings of confusion. Afraid of being alone with her infant, Ms. A asks her partner and mother to move in with her. Additionally, she says 2 weeks ago she discontinued all her medications at the suggestion of her partner, who recommended herbal supplements. Ms. A’s initial routine laboratory results are unremarkable and her urine drug screen is negative for all substances.

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The authors’ observations

Approximately 85% of birthing parents experience some form of postpartum mood disturbance; 10% to 15% develop more significant symptoms of anxiety or depression.³ The etiology of postpartum illness is multifactorial, and includes psychiatric personal/family history, insomnia, acute and chronic psychosocial stressors, and rapid hormone fluctuations.¹ As a result, the postpartum period represents a vulnerable time for birthing parents, particularly those with previously established psychiatric illness.

Ms. A’s initial presentation was concerning for a possible diagnosis of postpartum psychosis vs obsessive-compulsive disorder (OCD) with postpartum onset; other differential diagnoses included MDD with peripartum onset and psychotic features (Table^1-6). Ms. A’s subjective clinical history was significant for critical pertinent findings of both OCD with postpartum onset (ie, egodystonic intrusive thoughts, checking behaviors, feelings of shame, and seeking reassurance) and postpartum psychosis (ie, command auditory hallucinations and waxing/waning confusion), which added to diagnostic complexity.

Although postpartum psychosis is rare (1 to 2 cases per 1,000 women),⁵ it is considered a psychiatric emergency because it has significant potential for infanticide, morbidity, and mortality. Most symptoms develop within the first 2 weeks of the postpartum period.² There are many risk factors for the development of postpartum psychosis; however, in first-time pregnancies, a previous diagnosis of BD I is the single most important risk factor.¹ Approximately 20% to 30% of women with BD experience postpartum psychosis.⁴

For many patients (approximately 56.7%, according to 1 meta-analysis⁷), postpartum psychosis denotes an episode of BD, representing a more severe form of illness with increased risk of recurrence. Most manic or mixed mood episodes reoccur within the first year removed from the perinatal period. In contrast, for some patients (approximately 43.5% according to the same meta-analysis), the episode denotes “isolated postpartum psychosis.”⁷ Isolated postpartum psychosis is a psychotic episode that occurs only in the postpartum period with no recurrence of psychosis or recurrence of psychosis exclusive to postpartum periods. If treated, this type of postpartum psychosis has a more favorable prognosis than postpartum psychosis in a patient with BD.⁷ As such, a BD diagnosis should not be established at the onset of a patient’s first postpartum psychosis presentation. Regardless of type, all presentations of postpartum psychosis are considered a psychiatry emergency.

Continue to: The prevalence of OCD...

The prevalence of OCD with postpartum onset varies. One study estimated it occurs in 2.43% of cases.⁴ However, the true prevalence is likely underreported due to feelings of guilt or shame associated with intrusive thoughts, and fear of stigmatization and separation from the baby. Approximately 70.6% of women experiencing OCD with postpartum onset have a comorbid depressive disorder.⁴

Ms. A’s presentation to the psychiatric ED carried with it diagnostic complexity and uncertainty. Her initial presentation was concerning for elements of both postpartum psychosis and OCD with postpartum onset. After her evaluation in the psychiatric ED, there remained a lack of clear and convincing evidence for a diagnosis of OCD with postpartum onset, which eliminated the possibility of discharging Ms. A with robust safety planning and reinitiation of a selective serotonin reuptake inhibitor.

Additionally, because auditory hallucinations are atypical in OCD, the treatment team remained concerned for a diagnosis of postpartum psychosis, which would warrant hospitalization. With assistance from the institution’s reproductive psychiatrists, the treatment team discussed the importance of inpatient hospitalization for risk mitigation, close observation, and thorough evaluation for greater diagnostic clarity and certainty.

TREATMENT Involuntary hospitalization

The treatment team counsels Ms. A and her partner on her differential diagnoses, including the elevated acute risk of harm to herself and her baby if she has postpartum psychosis, as well as the need for continued observation and evaluation. When alone with a clinician, Ms. A says she understands and agrees to voluntary hospitalization. However, following a subsequent risk-benefit discussion with her partner, they both grew increasingly concerned about her separation from the baby and reinitiating her medications. Amid these concerns, the treatment team notices that Ms. A attempts to minimize her symptoms. Ms. A changes her mind and no longer consents to hospitalization. She is placed on a psychiatric hold for involuntary hospitalization on the psychiatric inpatient unit.

On the inpatient unit, the inpatient clinicians and a reproductive psychiatrist continue to evaluate Ms. A. Though her diagnosis remains unclear, Ms. A agrees to start a trial of quetiapine 100 mg/d titrated to 150 mg/d to manage her potential postpartum psychosis, depressed mood, insomnia (off-label), anxiety (off-label), and OCD (off-label). Lithium is deferred because Ms. A is breastfeeding.

[polldaddy:13041932]

Continue to: The authors' observations

Due to an elevated acute risk of suicide and infanticide, postpartum psychosis represents a psychiatric emergency and often requires hospitalization. The Figure outlines steps in evaluating a patient with concerns for postpartum psychosis in a psychiatric emergency service setting. Due to the waxing and waning nature of symptoms, patients may appear psychiatrically stable at any time but remain at an overall elevated acute risk of harm to self and/or their baby.

If a patient is being considered for discharge based on yes answers to all questions in Step 2 of the Figure, the emergency psychiatric clinician must initiate appropriate psychotropic medications and complete robust safety planning with the patient and a trusted adult who will provide direct supervision. Safety planning may include (but is not limited to) strict return precautions, education on concerning symptoms and behaviors, psychotropic education and agreement of compliance, and detailed instructions on outpatient follow-up within 1 week. Ideally—and as was the case for Ms. A—a reproductive psychiatrist should be consulted in the emergency setting for shared decision-making on admission vs discharge, medication management, and outpatient follow-up considerations.

Because postpartum psychosis carries significant risks and hospitalization generally results in separating the patient from their baby, initiating psychotropics should not be delayed. Clinicians must consider the patient’s psychiatric history, allergies, and breastfeeding status.

Based on current evidence, first-line treatment for postpartum psychosis includes a mood stabilizer, an antipsychotic, and possibly a benzodiazepine.⁶ Thus, an appropriate initial treatment regimen would be a benzodiazepine (particularly lorazepam due to its relatively shorter half-life) and an antipsychotic (eg, haloperidol, olanzapine, or quetiapine) for acute psychosis, plus lithium for mood stabilization.^1,5

If the postpartum psychosis represents an episode of BD, use of a long-term mood stabilizer may be required. In contrast, for isolated postpartum psychosis, clinicians may consider initiating psychotropics only in the immediate postpartum period, with an eventual slow taper. In future pregnancies, psychotropics may be reintroduced postpartum, which will avoid peripartum fetal exposure.⁸ If the patient is breastfeeding, lithium may be deferred in an acute care setting. For patients with evidence of catatonia, severe suicidality, refusal of oral intake with compromised nutrition, severe agitation, or treatment resistance, electro­convulsive therapy remains a safe and effective treatment option.⁶ Additionally, the safety of continued breastfeeding in acute psychosis must be considered, with the potential for recommending discontinuation, which would decrease sleep disruptions at night and increase the ability of others to feed the baby. Comprehensive care requires nonpharmacologic interventions, including psychoeducation for the patient and their family, individual psychotherapy, and expansion of psychosocial supports.

Continue to: Patients who have experienced...

Patients who have experienced an episode of postpartum psychosis are predisposed to another episode in future pregnancies.¹ Current research recommends prophylaxis of recurrence with lithium monotherapy.^1,2,5,6 Similar to other psychotropics in reproductive psychiatry, maintenance therapy on lithium requires a thorough “risk vs risk” discussion with the patient. The risk of lithium use while pregnant and/or breastfeeding must be weighed against the risks associated with postpartum psychosis (ie, infanticide, suicide, poor peripartum care, or poor infant bonding).

OUTCOME Improved mood

After 7 days of inpatient treatment with quetiapine, Ms. A demonstrates improvement in the targeted depressive symptoms (including improved motivation/energy and insomnia, decreased feelings of guilt, and denial of ongoing suicidal ideation). Additionally, the thoughts of harming her baby are less frequent, and command auditory hallucinations resolve. Upon discharge, Ms. A and her partner meet with inpatient clinicians for continued counseling, safety planning, and plans for outpatient follow-up with the institution’s reproductive psychiatrist.

The authors’ observations

Many aspects of Ms. A’s initial presentation in the psychiatric ED were challenging. Given the presence of symptoms of both psychosis and OCD, a diagnosis was difficult to ascertain in the emergency setting. Since command auditory hallucinations are atypical in patients with postpartum OCD, the treatment team maintained high suspicion for postpartum psychosis, which represented an emergency requiring inpatient care.

Hospitalization separated Ms. A from her baby, for whom she was the primary caregiver. Additional considerations for inpatient admission and psychotropic initiation were necessary, because Ms. A was breastfeeding. Although Ms. A’s partner was able to provide full-time childcare, the patient ultimately did not agree to hospitalization and required an emergency hold for involuntary admission, which was an additional barrier to care. Furthermore, her partner held unfavorable beliefs regarding psychotropic medications and Ms. A’s need for hospital admission, which required ongoing patient and partner education in the emergency, inpatient, and outpatient settings. Moreover, if Ms. A’s symptoms were ultimately attributable to postpartum OCD, the patient’s involuntary hospitalization might have increased the risk of stigmatization of mental illness and treatment with psychotropics.

Bottom Line

The peripartum period is a vulnerable time for patients, particularly those with previously diagnosed psychiatric illnesses. Postpartum psychosis is the most severe form of postpartum psychiatric illness and often represents an episode of bipolar disorder. Due to an elevated acute risk of suicide and infanticide, postpartum psychosis is a psychiatric emergency and warrants inpatient hospitalization for immediate intervention.

Related Resources

• Sharma V. Does your patient have postpartum OCD? Current Psychiatry. 2019;18(5):9-10.
• Hatters Friedman S, Prakash C, Nagel-Yang S. Postpartum psychosis: protecting mother and infant. Current Psychiatry. 2019;18(4):12-21.

Drug Brand Names

Fluoxetine • Prozac
Haloperidol • Haldol
Lithium • Eskalith, Lithobid
Lorazepam • Ativan
Olanzapine • Zyprexa
Prazosin • Minipress
Quetiapine • Seroquel
Sertraline • Zoloft
Valproic acid • Depakene

With the diagnosis of attention-deficit/hyperactivity disorder (ADHD) on the rise¹ and a surge in prescriptions to treat the disorder leading to stimulant shortages,² ensuring that patients are appropriately evaluated for ADHD is more critical than ever. ADHD is a clinical diagnosis that can be established by clinical interview, although the results of neuropsychological testing and collateral information from family members are helpful. Assessing adults for ADHD can be challenging when they appear to want to convince the clinician that they have the disorder. In this article, I provide tips to help you accurately diagnose ADHD in adult patients.

Use an ADHD symptom scale

An ADHD symptom checklist, such as the Adult ADHD Self-Report Scale, is an effective tool to establish the presence of ADHD symptoms. A patient can complete this self-assessment tool before their visit, and you can use the results as a springboard to ask them about ADHD symptoms. It is important to elicit specific examples of the ADHD symptoms the patient reports, and to understand how these symptoms affect their functioning and quality of life.

Review the prescription drug monitoring program

Review your state’s prescription drug monitoring program to explore the patient’s prior and current prescriptions of stimulants and other controlled substances. Discern if, when, and by whom a patient was previously treated for ADHD, and rule out the rare possibility that the patient has obtained multiple prescriptions for controlled substances from multiple clinicians, which suggests the patient may have a substance use disorder.

Begin the assessment at your initial contact with the patient

How patients present on an initial screening call or how they compose emails can reveal clues about their level of organization and overall executive functioning. The way patients complete intake forms (eg, using a concise vs a meandering writing style) as well as their punctuality when presenting to appointments can also be telling.

Conduct a mental status examination

Patients can have difficulty focusing and completing tasks for reasons other than having ADHD. A mental status examination can sometimes provide objective clues that an individual has ADHD. A digressive thought process, visible physical restlessness, and instances of a patient interrupting the evaluator are suggestive of ADHD, although all these symptoms can be present in other conditions (eg, mania). However, signs of ADHD in the mental status examination do not confirm an ADHD diagnosis, nor does their absence rule it out.

Maintain an appropriate diagnostic threshold

Per DSM-5, an ADHD diagnosis requires that the symptoms cause a significant impairment in functioning.³ It is up to the clinician to determine if this threshold is met. It is imperative to thoughtfully consider this because stimulants are first-line treatment for ADHD and are commonly misused. Psychiatrists are usually motivated to please their patients in order to maintain them as patients and develop a positive therapeutic relationship, which improves outcomes.⁴ However, it is important to demonstrate integrity, provide an accurate diagnosis, and not be unduly swayed by a patient’s wish to receive an ADHD diagnosis. If you sense that a prospective patient is hoping they will receive an ADHD diagnosis and be prescribed a stimulant, it may be prudent to emphasize that the patient will be assessed for multiple mental health conditions, including ADHD, and that treatment will depend on the outcome of the evaluation.

With the diagnosis of attention-deficit/hyperactivity disorder (ADHD) on the rise¹ and a surge in prescriptions to treat the disorder leading to stimulant shortages,² ensuring that patients are appropriately evaluated for ADHD is more critical than ever. ADHD is a clinical diagnosis that can be established by clinical interview, although the results of neuropsychological testing and collateral information from family members are helpful. Assessing adults for ADHD can be challenging when they appear to want to convince the clinician that they have the disorder. In this article, I provide tips to help you accurately diagnose ADHD in adult patients.

Use an ADHD symptom scale

An ADHD symptom checklist, such as the Adult ADHD Self-Report Scale, is an effective tool to establish the presence of ADHD symptoms. A patient can complete this self-assessment tool before their visit, and you can use the results as a springboard to ask them about ADHD symptoms. It is important to elicit specific examples of the ADHD symptoms the patient reports, and to understand how these symptoms affect their functioning and quality of life.

Review the prescription drug monitoring program

Review your state’s prescription drug monitoring program to explore the patient’s prior and current prescriptions of stimulants and other controlled substances. Discern if, when, and by whom a patient was previously treated for ADHD, and rule out the rare possibility that the patient has obtained multiple prescriptions for controlled substances from multiple clinicians, which suggests the patient may have a substance use disorder.

Begin the assessment at your initial contact with the patient

How patients present on an initial screening call or how they compose emails can reveal clues about their level of organization and overall executive functioning. The way patients complete intake forms (eg, using a concise vs a meandering writing style) as well as their punctuality when presenting to appointments can also be telling.

Conduct a mental status examination

Patients can have difficulty focusing and completing tasks for reasons other than having ADHD. A mental status examination can sometimes provide objective clues that an individual has ADHD. A digressive thought process, visible physical restlessness, and instances of a patient interrupting the evaluator are suggestive of ADHD, although all these symptoms can be present in other conditions (eg, mania). However, signs of ADHD in the mental status examination do not confirm an ADHD diagnosis, nor does their absence rule it out.

Maintain an appropriate diagnostic threshold

Per DSM-5, an ADHD diagnosis requires that the symptoms cause a significant impairment in functioning.³ It is up to the clinician to determine if this threshold is met. It is imperative to thoughtfully consider this because stimulants are first-line treatment for ADHD and are commonly misused. Psychiatrists are usually motivated to please their patients in order to maintain them as patients and develop a positive therapeutic relationship, which improves outcomes.⁴ However, it is important to demonstrate integrity, provide an accurate diagnosis, and not be unduly swayed by a patient’s wish to receive an ADHD diagnosis. If you sense that a prospective patient is hoping they will receive an ADHD diagnosis and be prescribed a stimulant, it may be prudent to emphasize that the patient will be assessed for multiple mental health conditions, including ADHD, and that treatment will depend on the outcome of the evaluation.

With the diagnosis of attention-deficit/hyperactivity disorder (ADHD) on the rise¹ and a surge in prescriptions to treat the disorder leading to stimulant shortages,² ensuring that patients are appropriately evaluated for ADHD is more critical than ever. ADHD is a clinical diagnosis that can be established by clinical interview, although the results of neuropsychological testing and collateral information from family members are helpful. Assessing adults for ADHD can be challenging when they appear to want to convince the clinician that they have the disorder. In this article, I provide tips to help you accurately diagnose ADHD in adult patients.

Use an ADHD symptom scale

An ADHD symptom checklist, such as the Adult ADHD Self-Report Scale, is an effective tool to establish the presence of ADHD symptoms. A patient can complete this self-assessment tool before their visit, and you can use the results as a springboard to ask them about ADHD symptoms. It is important to elicit specific examples of the ADHD symptoms the patient reports, and to understand how these symptoms affect their functioning and quality of life.

Review the prescription drug monitoring program

Review your state’s prescription drug monitoring program to explore the patient’s prior and current prescriptions of stimulants and other controlled substances. Discern if, when, and by whom a patient was previously treated for ADHD, and rule out the rare possibility that the patient has obtained multiple prescriptions for controlled substances from multiple clinicians, which suggests the patient may have a substance use disorder.

Begin the assessment at your initial contact with the patient

How patients present on an initial screening call or how they compose emails can reveal clues about their level of organization and overall executive functioning. The way patients complete intake forms (eg, using a concise vs a meandering writing style) as well as their punctuality when presenting to appointments can also be telling.

Conduct a mental status examination

Patients can have difficulty focusing and completing tasks for reasons other than having ADHD. A mental status examination can sometimes provide objective clues that an individual has ADHD. A digressive thought process, visible physical restlessness, and instances of a patient interrupting the evaluator are suggestive of ADHD, although all these symptoms can be present in other conditions (eg, mania). However, signs of ADHD in the mental status examination do not confirm an ADHD diagnosis, nor does their absence rule it out.

Maintain an appropriate diagnostic threshold

Per DSM-5, an ADHD diagnosis requires that the symptoms cause a significant impairment in functioning.³ It is up to the clinician to determine if this threshold is met. It is imperative to thoughtfully consider this because stimulants are first-line treatment for ADHD and are commonly misused. Psychiatrists are usually motivated to please their patients in order to maintain them as patients and develop a positive therapeutic relationship, which improves outcomes.⁴ However, it is important to demonstrate integrity, provide an accurate diagnosis, and not be unduly swayed by a patient’s wish to receive an ADHD diagnosis. If you sense that a prospective patient is hoping they will receive an ADHD diagnosis and be prescribed a stimulant, it may be prudent to emphasize that the patient will be assessed for multiple mental health conditions, including ADHD, and that treatment will depend on the outcome of the evaluation.

Childbirth-related posttraumatic stress disorder (CB-PTSD) is a form of PTSD that can develop related to trauma surrounding the events of giving birth. It affects approximately 5% of women after any birth, which is similar to the rate of PTSD after experiencing a natural disaster.¹ Up to 17% of women may have posttraumatic symptoms in the postpartum period.¹ Despite the high prevalence of CB-PTSD, many psychiatric clinicians have not incorporated screening for and management of CB-PTSD into their practice.

This is partly because childbirth has been conceptualized as a “stressful but positive life event.”² Historically, childbirth was not recognized as a traumatic event; for example, in DSM-III-R, the criteria for trauma in PTSD required an event outside the range of usual human experience, and childbirth was implicitly excluded as being too common to be traumatic. In the past decade, this clinical phenomenon has been more formally recognized and studied.²

CB-PTSD presents with symptoms similar to those of other forms of PTSD, with some nuances, as outlined in Table 1.³ Avoidance can be the predominant symptom; this can affect mothers’ engagement in postnatal care and is a major risk factor for postpartum depression.³

Many risk factors in the peripartum period can impact the development of CB-PTSD (Table 2³). The most significant risk factor is whether the patient views the delivery of their baby as a subjectively negative experience, regardless of the presence or lack of peripartum complications.¹ However, parents of infants who require treatment in a neonatal intensive care unit and women who require emergency medical treatment following delivery are at higher risk.

Screening and treatment

Ideally, every woman should be screened for CB-PTSD by their psychiatrist or obstetrician during a postpartum visit at least 1 month after delivery. In particular, high-risk populations and women with subjectively negative birth experiences should be screened, as well as women with postpartum depression that may have been precipitated or perpetuated by a traumatic experience. The City Birth Trauma Scale is a free 31-item self-report scale that can be used for such screening. It addresses both general and birth-related symptoms and is validated in multiple languages.⁴

Selective serotonin reuptake inhibitors and prazosin may be helpful for symptomatic treatment of CB-PTSD. Ongoing research studying the efficacy of cognitive-behavioral therapy and eye movement desensitization and reprocessing for CB-PTSD has yielded promising results but is limited in its generalizability.

Many women who develop CB-PTSD choose to get pregnant again. Psychiatrists can apply the principles of trauma-informed care and collaborate with obstetric and pediatric physicians to reduce the risk of retraumatization. It is critical to identify at-risk women and educate and prepare them for their next delivery experience. By focusing on communication, informed consent, and emotional support, we can do our best to prevent the recurrence of CB-PTSD.

Childbirth-related posttraumatic stress disorder (CB-PTSD) is a form of PTSD that can develop related to trauma surrounding the events of giving birth. It affects approximately 5% of women after any birth, which is similar to the rate of PTSD after experiencing a natural disaster.¹ Up to 17% of women may have posttraumatic symptoms in the postpartum period.¹ Despite the high prevalence of CB-PTSD, many psychiatric clinicians have not incorporated screening for and management of CB-PTSD into their practice.

This is partly because childbirth has been conceptualized as a “stressful but positive life event.”² Historically, childbirth was not recognized as a traumatic event; for example, in DSM-III-R, the criteria for trauma in PTSD required an event outside the range of usual human experience, and childbirth was implicitly excluded as being too common to be traumatic. In the past decade, this clinical phenomenon has been more formally recognized and studied.²

CB-PTSD presents with symptoms similar to those of other forms of PTSD, with some nuances, as outlined in Table 1.³ Avoidance can be the predominant symptom; this can affect mothers’ engagement in postnatal care and is a major risk factor for postpartum depression.³

Many risk factors in the peripartum period can impact the development of CB-PTSD (Table 2³). The most significant risk factor is whether the patient views the delivery of their baby as a subjectively negative experience, regardless of the presence or lack of peripartum complications.¹ However, parents of infants who require treatment in a neonatal intensive care unit and women who require emergency medical treatment following delivery are at higher risk.

Screening and treatment

Ideally, every woman should be screened for CB-PTSD by their psychiatrist or obstetrician during a postpartum visit at least 1 month after delivery. In particular, high-risk populations and women with subjectively negative birth experiences should be screened, as well as women with postpartum depression that may have been precipitated or perpetuated by a traumatic experience. The City Birth Trauma Scale is a free 31-item self-report scale that can be used for such screening. It addresses both general and birth-related symptoms and is validated in multiple languages.⁴

Selective serotonin reuptake inhibitors and prazosin may be helpful for symptomatic treatment of CB-PTSD. Ongoing research studying the efficacy of cognitive-behavioral therapy and eye movement desensitization and reprocessing for CB-PTSD has yielded promising results but is limited in its generalizability.

Many women who develop CB-PTSD choose to get pregnant again. Psychiatrists can apply the principles of trauma-informed care and collaborate with obstetric and pediatric physicians to reduce the risk of retraumatization. It is critical to identify at-risk women and educate and prepare them for their next delivery experience. By focusing on communication, informed consent, and emotional support, we can do our best to prevent the recurrence of CB-PTSD.

Childbirth-related posttraumatic stress disorder (CB-PTSD) is a form of PTSD that can develop related to trauma surrounding the events of giving birth. It affects approximately 5% of women after any birth, which is similar to the rate of PTSD after experiencing a natural disaster.¹ Up to 17% of women may have posttraumatic symptoms in the postpartum period.¹ Despite the high prevalence of CB-PTSD, many psychiatric clinicians have not incorporated screening for and management of CB-PTSD into their practice.

This is partly because childbirth has been conceptualized as a “stressful but positive life event.”² Historically, childbirth was not recognized as a traumatic event; for example, in DSM-III-R, the criteria for trauma in PTSD required an event outside the range of usual human experience, and childbirth was implicitly excluded as being too common to be traumatic. In the past decade, this clinical phenomenon has been more formally recognized and studied.²

CB-PTSD presents with symptoms similar to those of other forms of PTSD, with some nuances, as outlined in Table 1.³ Avoidance can be the predominant symptom; this can affect mothers’ engagement in postnatal care and is a major risk factor for postpartum depression.³

Many risk factors in the peripartum period can impact the development of CB-PTSD (Table 2³). The most significant risk factor is whether the patient views the delivery of their baby as a subjectively negative experience, regardless of the presence or lack of peripartum complications.¹ However, parents of infants who require treatment in a neonatal intensive care unit and women who require emergency medical treatment following delivery are at higher risk.

Screening and treatment

Ideally, every woman should be screened for CB-PTSD by their psychiatrist or obstetrician during a postpartum visit at least 1 month after delivery. In particular, high-risk populations and women with subjectively negative birth experiences should be screened, as well as women with postpartum depression that may have been precipitated or perpetuated by a traumatic experience. The City Birth Trauma Scale is a free 31-item self-report scale that can be used for such screening. It addresses both general and birth-related symptoms and is validated in multiple languages.⁴

Selective serotonin reuptake inhibitors and prazosin may be helpful for symptomatic treatment of CB-PTSD. Ongoing research studying the efficacy of cognitive-behavioral therapy and eye movement desensitization and reprocessing for CB-PTSD has yielded promising results but is limited in its generalizability.

Many women who develop CB-PTSD choose to get pregnant again. Psychiatrists can apply the principles of trauma-informed care and collaborate with obstetric and pediatric physicians to reduce the risk of retraumatization. It is critical to identify at-risk women and educate and prepare them for their next delivery experience. By focusing on communication, informed consent, and emotional support, we can do our best to prevent the recurrence of CB-PTSD.

Perinatal psychiatry focuses on the evaluation, diagnosis, and treatment of mental health disorders during the preconception, pregnancy, and postpartum periods. Mood disorders, anxiety disorders, and posttraumatic stress disorder are the most common mental health conditions that arise during the perinatal period.¹ Mediating factors include hormone fluctuations, sleep deprivation, trauma exposure, financial stress, having a history of psychiatric illness, and factors related to newborn care.

During the perinatal period, a comprehensive psychiatric interview is crucial. Effective screening and identification of maternal mental health conditions necessitate more than merely checking off boxes on a questionnaire. It requires compassionate, informed, and individualized conversations between physicians and their patients.

In addition to asking about pertinent positive and negative psychiatric symptoms, the following screening questions could be asked during a structured interview to identify perinatal issues during pregnancy and the postpartum period.

During pregnancy

• How do you feel about your pregnancy?
• Was this pregnancy planned or unplanned, desired or not?
• Was fertility treatment needed or used?
• Did you think about stopping the pregnancy? If so, was your decision influenced by laws that restrict abortion in your state?
• Do you feel connected to the fetus?
• Do you have a room or crib at home for the baby? A car seat? Clothing? Baby supplies?
• Are you planning on breastfeeding?
• Do you have thoughts on future desired fertility and/or contraception?
• Who is your support system at home?
• How is your relationship with the baby’s father?
• How is the baby’s father’s mental well-being?
• Have you been subject to any abuse, intimate partner violence, or neglect?
• Are your other children being taken care of properly? What is the plan for them during delivery days at the hospital?

During the postpartum period

• Was your baby born prematurely?
• Did you have a vaginal or cesarean delivery?
• Did you encounter any delivery complications?
• Did you see the baby after the delivery?
• Do you feel connected to or able to bond with the baby?
• Do you have access to maternity leave from work?
• Have you had scary or upsetting thoughts about hurting your baby?
• Do you have any concerns about your treatment plan, such as medication use?
• In case of an emergency, are you aware of perinatal psychiatry resources in your area or the national maternal mental health hotline (833-852-6262)?

The American College of Obstetricians and Gynecologists clinical practice guidelines recommend that clinicians conduct depression and anxiety screening at least once during the perinatal period by using a standardized, validated tool.² Psychiatry residents should receive adequate guidance and education about perinatal psychiatric evaluation, risk assessment, and treatment counseling. Early detection of mental health symptoms allows for early referral, close surveillance during episodes of vulnerability, and better access to mental health care during the perinatal period.

Perinatal psychiatry focuses on the evaluation, diagnosis, and treatment of mental health disorders during the preconception, pregnancy, and postpartum periods. Mood disorders, anxiety disorders, and posttraumatic stress disorder are the most common mental health conditions that arise during the perinatal period.¹ Mediating factors include hormone fluctuations, sleep deprivation, trauma exposure, financial stress, having a history of psychiatric illness, and factors related to newborn care.

During the perinatal period, a comprehensive psychiatric interview is crucial. Effective screening and identification of maternal mental health conditions necessitate more than merely checking off boxes on a questionnaire. It requires compassionate, informed, and individualized conversations between physicians and their patients.

In addition to asking about pertinent positive and negative psychiatric symptoms, the following screening questions could be asked during a structured interview to identify perinatal issues during pregnancy and the postpartum period.

During pregnancy

• How do you feel about your pregnancy?
• Was this pregnancy planned or unplanned, desired or not?
• Was fertility treatment needed or used?
• Did you think about stopping the pregnancy? If so, was your decision influenced by laws that restrict abortion in your state?
• Do you feel connected to the fetus?
• Do you have a room or crib at home for the baby? A car seat? Clothing? Baby supplies?
• Are you planning on breastfeeding?
• Do you have thoughts on future desired fertility and/or contraception?
• Who is your support system at home?
• How is your relationship with the baby’s father?
• How is the baby’s father’s mental well-being?
• Have you been subject to any abuse, intimate partner violence, or neglect?
• Are your other children being taken care of properly? What is the plan for them during delivery days at the hospital?

During the postpartum period

• Was your baby born prematurely?
• Did you have a vaginal or cesarean delivery?
• Did you encounter any delivery complications?
• Did you see the baby after the delivery?
• Do you feel connected to or able to bond with the baby?
• Do you have access to maternity leave from work?
• Have you had scary or upsetting thoughts about hurting your baby?
• Do you have any concerns about your treatment plan, such as medication use?
• In case of an emergency, are you aware of perinatal psychiatry resources in your area or the national maternal mental health hotline (833-852-6262)?

The American College of Obstetricians and Gynecologists clinical practice guidelines recommend that clinicians conduct depression and anxiety screening at least once during the perinatal period by using a standardized, validated tool.² Psychiatry residents should receive adequate guidance and education about perinatal psychiatric evaluation, risk assessment, and treatment counseling. Early detection of mental health symptoms allows for early referral, close surveillance during episodes of vulnerability, and better access to mental health care during the perinatal period.

Perinatal psychiatry focuses on the evaluation, diagnosis, and treatment of mental health disorders during the preconception, pregnancy, and postpartum periods. Mood disorders, anxiety disorders, and posttraumatic stress disorder are the most common mental health conditions that arise during the perinatal period.¹ Mediating factors include hormone fluctuations, sleep deprivation, trauma exposure, financial stress, having a history of psychiatric illness, and factors related to newborn care.

During the perinatal period, a comprehensive psychiatric interview is crucial. Effective screening and identification of maternal mental health conditions necessitate more than merely checking off boxes on a questionnaire. It requires compassionate, informed, and individualized conversations between physicians and their patients.

In addition to asking about pertinent positive and negative psychiatric symptoms, the following screening questions could be asked during a structured interview to identify perinatal issues during pregnancy and the postpartum period.

During pregnancy

• How do you feel about your pregnancy?
• Was this pregnancy planned or unplanned, desired or not?
• Was fertility treatment needed or used?
• Did you think about stopping the pregnancy? If so, was your decision influenced by laws that restrict abortion in your state?
• Do you feel connected to the fetus?
• Do you have a room or crib at home for the baby? A car seat? Clothing? Baby supplies?
• Are you planning on breastfeeding?
• Do you have thoughts on future desired fertility and/or contraception?
• Who is your support system at home?
• How is your relationship with the baby’s father?
• How is the baby’s father’s mental well-being?
• Have you been subject to any abuse, intimate partner violence, or neglect?
• Are your other children being taken care of properly? What is the plan for them during delivery days at the hospital?

During the postpartum period

• Was your baby born prematurely?
• Did you have a vaginal or cesarean delivery?
• Did you encounter any delivery complications?
• Did you see the baby after the delivery?
• Do you feel connected to or able to bond with the baby?
• Do you have access to maternity leave from work?
• Have you had scary or upsetting thoughts about hurting your baby?
• Do you have any concerns about your treatment plan, such as medication use?
• In case of an emergency, are you aware of perinatal psychiatry resources in your area or the national maternal mental health hotline (833-852-6262)?

The American College of Obstetricians and Gynecologists clinical practice guidelines recommend that clinicians conduct depression and anxiety screening at least once during the perinatal period by using a standardized, validated tool.² Psychiatry residents should receive adequate guidance and education about perinatal psychiatric evaluation, risk assessment, and treatment counseling. Early detection of mental health symptoms allows for early referral, close surveillance during episodes of vulnerability, and better access to mental health care during the perinatal period.

My colleagues and I entered the realm of outpatient psychiatry during residency at a logistically and dynamically interesting time. At the beginning of our third year in training (July 2022), almost all of the outpatients we were treating were still being seen virtually. For much of the year, they remained that way. However, with the reinstatement of the Ryan Haight Act in May 2023, I began to meet patients in person for the first time—the same patients whom I had known only virtually for the first 10 months of our therapeutic relationship. I observed vast changes in the dynamic of the room; many of these patients opened up more in their first in-person session than they had all year over Zoom.

Once in-person sessions resumed, patients who during virtual visits had assured me for almost a year that their home situation was optimized had a plethora of new things to share about their seemingly straightforward living situations. Relationships that appeared stable had more layers to reveal once the half of the relationship I was treating was now comfortably seated within the walls of my office. Problems that had previously seemed biologically based suddenly had complex sociocultural elements that were divulged for the first time. Some patients felt freer to be unrestricted in their affect, in contrast to the logistical (and metaphorical) buttoned-up virtual environment. Emotions ranged from cathartic (“It’s so great to see you in person!”) to bemused (“You’re taller/shorter, older/younger than I thought!”). The screen was gone, and the tangibility of it all breathed a different air into the room.

Virtual vs in-person: Crabs on a beach

The virtual treatment space could be envisioned as crabs in shells scattered on a beach, in which 2 crabs situated in their own shells, not necessarily adjacent to each other, could communicate. This certainly had benefits, such as the convenience of not having to move to another shell, as well as the brief but telling opportunity to gaze into their home shell environment. However, sometimes there would be disadvantages, such as interference with the connection due to static in the sand; at other times, there was the potential for other crabs to overhear and inadvertently learn of each other’s presence, thus affecting the openness of the communication. In this analogy, perhaps the equivalent of an in-person meeting would be 1 crab meandering over and the 2 crabs cohabiting a conch for the first time—it’s spacious (enough), all-enveloping, and within the harkened privacy of a shared sacred space.

A unique training experience

My co-residents and I are uniquely positioned to observe this novel phenomenon due to the timing of having entered our outpatient psychiatry training during the COVID-19 pandemic. Previous generations of residents—as well as practicing psychiatrists who had initially met their patients in person and were forced to switch to virtual sessions during the pandemic—had certain perspectives and challenges of their own, but they had a known dynamic of in-person interactions at baseline. Accordingly, residents who practiced peak- and mid-pandemic and graduated without being required to treat patients face-to-face (the classes of 2022 and 2023) might have spent entire therapeutic relationships having never met their patients in person. My class (2024) was situated in this time- and situation-bound frame in which we started virtually, and by requirements of the law, later met our patients in person. Being not only an observer but an active participant in a treatment dyad within the context of this phenomenon taught me astutely about transference, countertransference, and the holding environment. Training in psychodynamic psychotherapy has taught me about the act of listening deeply and qualities of therapeutic communication. Having the opportunity to enact these principles in such a dichotomy of treatment settings has been invaluable in my education, in getting to know different facets of my patients, and in understanding the nuances of the human experience.

My colleagues and I entered the realm of outpatient psychiatry during residency at a logistically and dynamically interesting time. At the beginning of our third year in training (July 2022), almost all of the outpatients we were treating were still being seen virtually. For much of the year, they remained that way. However, with the reinstatement of the Ryan Haight Act in May 2023, I began to meet patients in person for the first time—the same patients whom I had known only virtually for the first 10 months of our therapeutic relationship. I observed vast changes in the dynamic of the room; many of these patients opened up more in their first in-person session than they had all year over Zoom.

Once in-person sessions resumed, patients who during virtual visits had assured me for almost a year that their home situation was optimized had a plethora of new things to share about their seemingly straightforward living situations. Relationships that appeared stable had more layers to reveal once the half of the relationship I was treating was now comfortably seated within the walls of my office. Problems that had previously seemed biologically based suddenly had complex sociocultural elements that were divulged for the first time. Some patients felt freer to be unrestricted in their affect, in contrast to the logistical (and metaphorical) buttoned-up virtual environment. Emotions ranged from cathartic (“It’s so great to see you in person!”) to bemused (“You’re taller/shorter, older/younger than I thought!”). The screen was gone, and the tangibility of it all breathed a different air into the room.

Virtual vs in-person: Crabs on a beach

The virtual treatment space could be envisioned as crabs in shells scattered on a beach, in which 2 crabs situated in their own shells, not necessarily adjacent to each other, could communicate. This certainly had benefits, such as the convenience of not having to move to another shell, as well as the brief but telling opportunity to gaze into their home shell environment. However, sometimes there would be disadvantages, such as interference with the connection due to static in the sand; at other times, there was the potential for other crabs to overhear and inadvertently learn of each other’s presence, thus affecting the openness of the communication. In this analogy, perhaps the equivalent of an in-person meeting would be 1 crab meandering over and the 2 crabs cohabiting a conch for the first time—it’s spacious (enough), all-enveloping, and within the harkened privacy of a shared sacred space.

A unique training experience

My co-residents and I are uniquely positioned to observe this novel phenomenon due to the timing of having entered our outpatient psychiatry training during the COVID-19 pandemic. Previous generations of residents—as well as practicing psychiatrists who had initially met their patients in person and were forced to switch to virtual sessions during the pandemic—had certain perspectives and challenges of their own, but they had a known dynamic of in-person interactions at baseline. Accordingly, residents who practiced peak- and mid-pandemic and graduated without being required to treat patients face-to-face (the classes of 2022 and 2023) might have spent entire therapeutic relationships having never met their patients in person. My class (2024) was situated in this time- and situation-bound frame in which we started virtually, and by requirements of the law, later met our patients in person. Being not only an observer but an active participant in a treatment dyad within the context of this phenomenon taught me astutely about transference, countertransference, and the holding environment. Training in psychodynamic psychotherapy has taught me about the act of listening deeply and qualities of therapeutic communication. Having the opportunity to enact these principles in such a dichotomy of treatment settings has been invaluable in my education, in getting to know different facets of my patients, and in understanding the nuances of the human experience.

My colleagues and I entered the realm of outpatient psychiatry during residency at a logistically and dynamically interesting time. At the beginning of our third year in training (July 2022), almost all of the outpatients we were treating were still being seen virtually. For much of the year, they remained that way. However, with the reinstatement of the Ryan Haight Act in May 2023, I began to meet patients in person for the first time—the same patients whom I had known only virtually for the first 10 months of our therapeutic relationship. I observed vast changes in the dynamic of the room; many of these patients opened up more in their first in-person session than they had all year over Zoom.

Once in-person sessions resumed, patients who during virtual visits had assured me for almost a year that their home situation was optimized had a plethora of new things to share about their seemingly straightforward living situations. Relationships that appeared stable had more layers to reveal once the half of the relationship I was treating was now comfortably seated within the walls of my office. Problems that had previously seemed biologically based suddenly had complex sociocultural elements that were divulged for the first time. Some patients felt freer to be unrestricted in their affect, in contrast to the logistical (and metaphorical) buttoned-up virtual environment. Emotions ranged from cathartic (“It’s so great to see you in person!”) to bemused (“You’re taller/shorter, older/younger than I thought!”). The screen was gone, and the tangibility of it all breathed a different air into the room.

Virtual vs in-person: Crabs on a beach

The virtual treatment space could be envisioned as crabs in shells scattered on a beach, in which 2 crabs situated in their own shells, not necessarily adjacent to each other, could communicate. This certainly had benefits, such as the convenience of not having to move to another shell, as well as the brief but telling opportunity to gaze into their home shell environment. However, sometimes there would be disadvantages, such as interference with the connection due to static in the sand; at other times, there was the potential for other crabs to overhear and inadvertently learn of each other’s presence, thus affecting the openness of the communication. In this analogy, perhaps the equivalent of an in-person meeting would be 1 crab meandering over and the 2 crabs cohabiting a conch for the first time—it’s spacious (enough), all-enveloping, and within the harkened privacy of a shared sacred space.

A unique training experience

My co-residents and I are uniquely positioned to observe this novel phenomenon due to the timing of having entered our outpatient psychiatry training during the COVID-19 pandemic. Previous generations of residents—as well as practicing psychiatrists who had initially met their patients in person and were forced to switch to virtual sessions during the pandemic—had certain perspectives and challenges of their own, but they had a known dynamic of in-person interactions at baseline. Accordingly, residents who practiced peak- and mid-pandemic and graduated without being required to treat patients face-to-face (the classes of 2022 and 2023) might have spent entire therapeutic relationships having never met their patients in person. My class (2024) was situated in this time- and situation-bound frame in which we started virtually, and by requirements of the law, later met our patients in person. Being not only an observer but an active participant in a treatment dyad within the context of this phenomenon taught me astutely about transference, countertransference, and the holding environment. Training in psychodynamic psychotherapy has taught me about the act of listening deeply and qualities of therapeutic communication. Having the opportunity to enact these principles in such a dichotomy of treatment settings has been invaluable in my education, in getting to know different facets of my patients, and in understanding the nuances of the human experience.

As a 2020 graduate, my medical school experience was largely untouched by the coronavirus. However, when I transitioned to residency, the world was 4 months into the COVID-19 pandemic, and I was required to wear an N95 mask. Just as I started calling myself Dr. Petteruti, I stopped seeing my patients’ entire face, and they stopped seeing mine. In this article, I share my reflections on wearing a mask during residency.

Even after 3 years of daily practice, I have found that wearing a mask brings an acute awareness of my face. As a community physician, the spheres of personal and public life intersect as I treat patients. Learning to navigate this is an important and shared experience across many community-based residency programs. However, during the first few years of residency, I have been able to shop at a local grocery store or eat at a nearby restaurant without any concerns of being recognized by a patient. Until recently, my patients had never seen my face. That has now changed.

For a new intern, a mask can be a savior. It can hide most of what is on your face from your patient. It is remarkable how the brain fills in the gaps of the visage and, by extension, aspects of the person. Many times, I was thankful to have my morning yawn or facial expression covered during provoking conversations with patients. Furthermore, masks gave me an opportunity to examine my own reactions, emotions, affect, and countertransference of each interaction on my own time.

The mask mandate also protected some features that illustrated my youth. For the patient, a mask can add a dry, clinical distance to the physician, often emitting a professional interpretation to the encounter. For the physician, the mask serves as a concrete barrier to the otherwise effortless acts of observation. Early in my career, I had to set reminders to have patients who were taking antipsychotic medications remove their masks to assess for tardive dyskinesia. Sometimes this surprised the patient, who was hesitant to expose themselves physically and psychologically. Alternatively, mask wearing has proved to be an additional data point on some patients, such as those with disorganized behavior. If the mask is located on the patient’s head, chin, or eyes, or is otherwise inappropriately placed, this provides the clinician with supplemental information.

After spending most of my third year of residency in an outpatient office diligently learning how to build a sturdy therapeutic patient alliance, the mask mandate was lifted. Patients’ transference began to change right before my newly bared face. People often relate age to wisdom and experience, so my lack of age—and thus, possible perceived lack of knowledge—became glaringly apparent. During our initial encounters without masks, patients I had known for most of the year began discussing their symptoms and treatments with more hesitancy. My established patients suddenly had a noticeable change in the intensity of their eye contact. Some even asked if I had cut my hair or what had changed about my appearance since our previous visit. This change in affect and behavior offers a unique experience for the resident; renovating the patient-doctor relationship based on the physician’s appearance.

As psychiatrists, we would generally assume mask wearing has an undesirable effect on the therapeutic alliance and increases skewed inferences in our evaluations. This held true for my experience in residency. In psychotherapy, we work to help patients remove their own metaphorical “masks” of defense and security in self-exploration. However, as young physicians, rather than creating barriers between us and our patients, the mask mandate seemed to have created a sense of credibility in our practice and trustworthiness in our decisions.

Some questions remain. As clinicians, what are we missing when we can only see our patient’s eyes and forehead? How will the COVID-19 pandemic affect my training and career as a psychiatrist? These may remain unanswered for my generation of trainees for some time, as society will look back and contemplate this period for decades. Though we entered our career in uncertain times, with an increased risk of morbidity and death and high demand for proper personal protective equipment, we were and still are thankful for our masks and for the limited infection exposure afforded by the nature of our specialty.

As a 2020 graduate, my medical school experience was largely untouched by the coronavirus. However, when I transitioned to residency, the world was 4 months into the COVID-19 pandemic, and I was required to wear an N95 mask. Just as I started calling myself Dr. Petteruti, I stopped seeing my patients’ entire face, and they stopped seeing mine. In this article, I share my reflections on wearing a mask during residency.

Even after 3 years of daily practice, I have found that wearing a mask brings an acute awareness of my face. As a community physician, the spheres of personal and public life intersect as I treat patients. Learning to navigate this is an important and shared experience across many community-based residency programs. However, during the first few years of residency, I have been able to shop at a local grocery store or eat at a nearby restaurant without any concerns of being recognized by a patient. Until recently, my patients had never seen my face. That has now changed.

For a new intern, a mask can be a savior. It can hide most of what is on your face from your patient. It is remarkable how the brain fills in the gaps of the visage and, by extension, aspects of the person. Many times, I was thankful to have my morning yawn or facial expression covered during provoking conversations with patients. Furthermore, masks gave me an opportunity to examine my own reactions, emotions, affect, and countertransference of each interaction on my own time.

The mask mandate also protected some features that illustrated my youth. For the patient, a mask can add a dry, clinical distance to the physician, often emitting a professional interpretation to the encounter. For the physician, the mask serves as a concrete barrier to the otherwise effortless acts of observation. Early in my career, I had to set reminders to have patients who were taking antipsychotic medications remove their masks to assess for tardive dyskinesia. Sometimes this surprised the patient, who was hesitant to expose themselves physically and psychologically. Alternatively, mask wearing has proved to be an additional data point on some patients, such as those with disorganized behavior. If the mask is located on the patient’s head, chin, or eyes, or is otherwise inappropriately placed, this provides the clinician with supplemental information.

After spending most of my third year of residency in an outpatient office diligently learning how to build a sturdy therapeutic patient alliance, the mask mandate was lifted. Patients’ transference began to change right before my newly bared face. People often relate age to wisdom and experience, so my lack of age—and thus, possible perceived lack of knowledge—became glaringly apparent. During our initial encounters without masks, patients I had known for most of the year began discussing their symptoms and treatments with more hesitancy. My established patients suddenly had a noticeable change in the intensity of their eye contact. Some even asked if I had cut my hair or what had changed about my appearance since our previous visit. This change in affect and behavior offers a unique experience for the resident; renovating the patient-doctor relationship based on the physician’s appearance.

As psychiatrists, we would generally assume mask wearing has an undesirable effect on the therapeutic alliance and increases skewed inferences in our evaluations. This held true for my experience in residency. In psychotherapy, we work to help patients remove their own metaphorical “masks” of defense and security in self-exploration. However, as young physicians, rather than creating barriers between us and our patients, the mask mandate seemed to have created a sense of credibility in our practice and trustworthiness in our decisions.

Some questions remain. As clinicians, what are we missing when we can only see our patient’s eyes and forehead? How will the COVID-19 pandemic affect my training and career as a psychiatrist? These may remain unanswered for my generation of trainees for some time, as society will look back and contemplate this period for decades. Though we entered our career in uncertain times, with an increased risk of morbidity and death and high demand for proper personal protective equipment, we were and still are thankful for our masks and for the limited infection exposure afforded by the nature of our specialty.

As a 2020 graduate, my medical school experience was largely untouched by the coronavirus. However, when I transitioned to residency, the world was 4 months into the COVID-19 pandemic, and I was required to wear an N95 mask. Just as I started calling myself Dr. Petteruti, I stopped seeing my patients’ entire face, and they stopped seeing mine. In this article, I share my reflections on wearing a mask during residency.

Even after 3 years of daily practice, I have found that wearing a mask brings an acute awareness of my face. As a community physician, the spheres of personal and public life intersect as I treat patients. Learning to navigate this is an important and shared experience across many community-based residency programs. However, during the first few years of residency, I have been able to shop at a local grocery store or eat at a nearby restaurant without any concerns of being recognized by a patient. Until recently, my patients had never seen my face. That has now changed.

For a new intern, a mask can be a savior. It can hide most of what is on your face from your patient. It is remarkable how the brain fills in the gaps of the visage and, by extension, aspects of the person. Many times, I was thankful to have my morning yawn or facial expression covered during provoking conversations with patients. Furthermore, masks gave me an opportunity to examine my own reactions, emotions, affect, and countertransference of each interaction on my own time.

The mask mandate also protected some features that illustrated my youth. For the patient, a mask can add a dry, clinical distance to the physician, often emitting a professional interpretation to the encounter. For the physician, the mask serves as a concrete barrier to the otherwise effortless acts of observation. Early in my career, I had to set reminders to have patients who were taking antipsychotic medications remove their masks to assess for tardive dyskinesia. Sometimes this surprised the patient, who was hesitant to expose themselves physically and psychologically. Alternatively, mask wearing has proved to be an additional data point on some patients, such as those with disorganized behavior. If the mask is located on the patient’s head, chin, or eyes, or is otherwise inappropriately placed, this provides the clinician with supplemental information.

After spending most of my third year of residency in an outpatient office diligently learning how to build a sturdy therapeutic patient alliance, the mask mandate was lifted. Patients’ transference began to change right before my newly bared face. People often relate age to wisdom and experience, so my lack of age—and thus, possible perceived lack of knowledge—became glaringly apparent. During our initial encounters without masks, patients I had known for most of the year began discussing their symptoms and treatments with more hesitancy. My established patients suddenly had a noticeable change in the intensity of their eye contact. Some even asked if I had cut my hair or what had changed about my appearance since our previous visit. This change in affect and behavior offers a unique experience for the resident; renovating the patient-doctor relationship based on the physician’s appearance.

As psychiatrists, we would generally assume mask wearing has an undesirable effect on the therapeutic alliance and increases skewed inferences in our evaluations. This held true for my experience in residency. In psychotherapy, we work to help patients remove their own metaphorical “masks” of defense and security in self-exploration. However, as young physicians, rather than creating barriers between us and our patients, the mask mandate seemed to have created a sense of credibility in our practice and trustworthiness in our decisions.

Some questions remain. As clinicians, what are we missing when we can only see our patient’s eyes and forehead? How will the COVID-19 pandemic affect my training and career as a psychiatrist? These may remain unanswered for my generation of trainees for some time, as society will look back and contemplate this period for decades. Though we entered our career in uncertain times, with an increased risk of morbidity and death and high demand for proper personal protective equipment, we were and still are thankful for our masks and for the limited infection exposure afforded by the nature of our specialty.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style.

The second-generation antipsychotic quetiapine is commonly used to treat several psychiatric disorders, including bipolar disorder (BD) and insomnia. In this case report, we discuss a patient with a history of unipolar depression and initial signs of mania who experienced an exacerbation of manic symptoms following administration of low-dose quetiapine. This case underscores the need for careful monitoring of patients receiving quetiapine, especially at lower doses, and the potential limitations of its efficacy in controlling manic symptoms.

Depressed with racing thoughts

Mr. X, age 58, is an Army veteran who lives with his wife of 29 years and works as a contractor. He has a history of depression and a suicide attempt 10 years ago by self-inflicted gunshot wound to the head, which left him with a bullet lodged in his sinus cavity and residual dysarthria after tongue surgery. After the suicide attempt, Mr. X was medically hospitalized, but not psychiatrically hospitalized. Shortly after, he self-discontinued all psychotropic medications and follow-up.

Mr. X has no other medical history and takes no other medications or supplements. His family history includes a mother with schizoaffective disorder, 1 brother with BD, and another brother with developmental delay.

Mr. X remained euthymic until his brother died. Soon after, he began to experience low mood, heightened anxiety, racing thoughts, tearfulness, and mild insomnia. He was prescribed quetiapine 25 mg/d at bedtime and instructed to titrate up to 50 mg/d.

Ten days later, Mr. X was brought to the hospital by his wife, who reported that after starting quetiapine, her husband began to act erratically. He had disorganized and racing thoughts, loose associations, labile affect, hyperactivity/restlessness, and was not sleeping. In the morning before presenting to the hospital, Mr. X had gone to work, laid down on the floor, began mumbling to himself, and would not respond to coworkers. Upon evaluation, Mr. X was noted to have pressured speech, disorganized speech, delusions, anxiety, and hallucinations. A CT scan of his head was normal, and a complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, B12, folate, and hemoglobin A1c were within normal limits. Mr. X’s vitamin D level was low at 22 ng/mL, and a syphilis screen was negative.

Mr. X was admitted to the hospital for his safety. The treatment team discontinued quetiapine and started risperidone 3 mg twice a day for psychotic symptoms and mood stabilization. At the time of discharge 7 days later, Mr. X was no longer experiencing any hallucinations or delusions, his thought process was linear and goal-directed, his mood was stable, and his insomnia had improved. Based on the temporal relationship between the initiation of quetiapine and the onset of Mr. X’s manic symptoms, along with an absence of organic causes, the treatment team suspected Mr. X had experienced a worsening of manic symptoms induced by quetiapine. Before starting quetiapine, he had presented with an initial manic symptom of racing thoughts.

At his next outpatient appointment, Mr. X exhibited significant akathisia. The treatment team initiated propranolol 20 mg twice a day but Mr. X did not experience much improvement. Risperidone was reduced to 1 mg twice a day and Mr. X was started on clonazepam 0.5 mg twice a day. The akathisia resolved. The treatment team decided to discontinue all medications and observe Mr. X for any recurrence of symptoms. One year after his manic episode. Mr. X remained euthymic. He was able to resume full-time work and began psychotherapy to process the grief over the loss of his brother.

Quetiapine’s unique profile

This case sheds light on the potential limitations of quetiapine, especially at lower doses, for managing manic symptoms. Quetiapine exhibits antidepressant effects, even at doses as low as 50 mg/d.¹ At higher doses, quetiapine acts as an antagonist at serotonin (5-HT1A and 5-HT2A), dopamine (D1 and D2), histamine H1, and adrenergic receptors.² At doses <300 mg/d, there is an absence of dopamine receptor blockade and a higher affinity for 5-HT2A receptors, which could explain why higher doses are generally necessary for treating mania and psychotic symptoms.^3-5 High 5-HT2A antagonism may disinhibit the dopaminergic system and paradoxically increase dopaminergic activity, which could be the mechanism responsible for lack of control of manic symptoms with low doses of quetiapine.² Another possible explanation is that the metabolite of quetiapine, N-desalkylquetiapine, acts as a norepine­phrine reuptake blocker and partial 5-HT1Aantagonist, which acts as an antidepressant, and antidepressants are known to induce mania in vulnerable patients.⁴

The antimanic property of most antipsychotics (except possibly clozapine) is attributed to their D2 antagonistic potency. Because quetiapine is among the weaker D2 antagonists, its inability to prevent the progression of mania, especially at 50 mg/d, is not unexpected. Mr. X’s subsequent need for a stronger D2 antagonist—risperidone—at a significant dose further supports this observation. A common misconception is that quetiapine’s sedating effects make it effective for treating mania, but that is not the case. Clinicians should be cautious when prescribing quetiapine, especially at lower doses, to patients who exhibit signs of mania. Given the potential risk, clinicians should consider alternative treatments before resorting to low-dose quetiapine for insomnia. Regular monitoring for manic symptoms is crucial for all patients receiving quetiapine. If patients present with signs of mania or hypomania, a therapeutic dose range of 600 to 800 mg/d is recommended.⁶

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style.

The second-generation antipsychotic quetiapine is commonly used to treat several psychiatric disorders, including bipolar disorder (BD) and insomnia. In this case report, we discuss a patient with a history of unipolar depression and initial signs of mania who experienced an exacerbation of manic symptoms following administration of low-dose quetiapine. This case underscores the need for careful monitoring of patients receiving quetiapine, especially at lower doses, and the potential limitations of its efficacy in controlling manic symptoms.

Depressed with racing thoughts

Mr. X, age 58, is an Army veteran who lives with his wife of 29 years and works as a contractor. He has a history of depression and a suicide attempt 10 years ago by self-inflicted gunshot wound to the head, which left him with a bullet lodged in his sinus cavity and residual dysarthria after tongue surgery. After the suicide attempt, Mr. X was medically hospitalized, but not psychiatrically hospitalized. Shortly after, he self-discontinued all psychotropic medications and follow-up.

Mr. X has no other medical history and takes no other medications or supplements. His family history includes a mother with schizoaffective disorder, 1 brother with BD, and another brother with developmental delay.

Mr. X remained euthymic until his brother died. Soon after, he began to experience low mood, heightened anxiety, racing thoughts, tearfulness, and mild insomnia. He was prescribed quetiapine 25 mg/d at bedtime and instructed to titrate up to 50 mg/d.

Ten days later, Mr. X was brought to the hospital by his wife, who reported that after starting quetiapine, her husband began to act erratically. He had disorganized and racing thoughts, loose associations, labile affect, hyperactivity/restlessness, and was not sleeping. In the morning before presenting to the hospital, Mr. X had gone to work, laid down on the floor, began mumbling to himself, and would not respond to coworkers. Upon evaluation, Mr. X was noted to have pressured speech, disorganized speech, delusions, anxiety, and hallucinations. A CT scan of his head was normal, and a complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, B12, folate, and hemoglobin A1c were within normal limits. Mr. X’s vitamin D level was low at 22 ng/mL, and a syphilis screen was negative.

Mr. X was admitted to the hospital for his safety. The treatment team discontinued quetiapine and started risperidone 3 mg twice a day for psychotic symptoms and mood stabilization. At the time of discharge 7 days later, Mr. X was no longer experiencing any hallucinations or delusions, his thought process was linear and goal-directed, his mood was stable, and his insomnia had improved. Based on the temporal relationship between the initiation of quetiapine and the onset of Mr. X’s manic symptoms, along with an absence of organic causes, the treatment team suspected Mr. X had experienced a worsening of manic symptoms induced by quetiapine. Before starting quetiapine, he had presented with an initial manic symptom of racing thoughts.

At his next outpatient appointment, Mr. X exhibited significant akathisia. The treatment team initiated propranolol 20 mg twice a day but Mr. X did not experience much improvement. Risperidone was reduced to 1 mg twice a day and Mr. X was started on clonazepam 0.5 mg twice a day. The akathisia resolved. The treatment team decided to discontinue all medications and observe Mr. X for any recurrence of symptoms. One year after his manic episode. Mr. X remained euthymic. He was able to resume full-time work and began psychotherapy to process the grief over the loss of his brother.

Quetiapine’s unique profile

This case sheds light on the potential limitations of quetiapine, especially at lower doses, for managing manic symptoms. Quetiapine exhibits antidepressant effects, even at doses as low as 50 mg/d.¹ At higher doses, quetiapine acts as an antagonist at serotonin (5-HT1A and 5-HT2A), dopamine (D1 and D2), histamine H1, and adrenergic receptors.² At doses <300 mg/d, there is an absence of dopamine receptor blockade and a higher affinity for 5-HT2A receptors, which could explain why higher doses are generally necessary for treating mania and psychotic symptoms.^3-5 High 5-HT2A antagonism may disinhibit the dopaminergic system and paradoxically increase dopaminergic activity, which could be the mechanism responsible for lack of control of manic symptoms with low doses of quetiapine.² Another possible explanation is that the metabolite of quetiapine, N-desalkylquetiapine, acts as a norepine­phrine reuptake blocker and partial 5-HT1Aantagonist, which acts as an antidepressant, and antidepressants are known to induce mania in vulnerable patients.⁴

The antimanic property of most antipsychotics (except possibly clozapine) is attributed to their D2 antagonistic potency. Because quetiapine is among the weaker D2 antagonists, its inability to prevent the progression of mania, especially at 50 mg/d, is not unexpected. Mr. X’s subsequent need for a stronger D2 antagonist—risperidone—at a significant dose further supports this observation. A common misconception is that quetiapine’s sedating effects make it effective for treating mania, but that is not the case. Clinicians should be cautious when prescribing quetiapine, especially at lower doses, to patients who exhibit signs of mania. Given the potential risk, clinicians should consider alternative treatments before resorting to low-dose quetiapine for insomnia. Regular monitoring for manic symptoms is crucial for all patients receiving quetiapine. If patients present with signs of mania or hypomania, a therapeutic dose range of 600 to 800 mg/d is recommended.⁶

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style.

The second-generation antipsychotic quetiapine is commonly used to treat several psychiatric disorders, including bipolar disorder (BD) and insomnia. In this case report, we discuss a patient with a history of unipolar depression and initial signs of mania who experienced an exacerbation of manic symptoms following administration of low-dose quetiapine. This case underscores the need for careful monitoring of patients receiving quetiapine, especially at lower doses, and the potential limitations of its efficacy in controlling manic symptoms.

Depressed with racing thoughts

Mr. X, age 58, is an Army veteran who lives with his wife of 29 years and works as a contractor. He has a history of depression and a suicide attempt 10 years ago by self-inflicted gunshot wound to the head, which left him with a bullet lodged in his sinus cavity and residual dysarthria after tongue surgery. After the suicide attempt, Mr. X was medically hospitalized, but not psychiatrically hospitalized. Shortly after, he self-discontinued all psychotropic medications and follow-up.

Mr. X has no other medical history and takes no other medications or supplements. His family history includes a mother with schizoaffective disorder, 1 brother with BD, and another brother with developmental delay.

Mr. X remained euthymic until his brother died. Soon after, he began to experience low mood, heightened anxiety, racing thoughts, tearfulness, and mild insomnia. He was prescribed quetiapine 25 mg/d at bedtime and instructed to titrate up to 50 mg/d.

Ten days later, Mr. X was brought to the hospital by his wife, who reported that after starting quetiapine, her husband began to act erratically. He had disorganized and racing thoughts, loose associations, labile affect, hyperactivity/restlessness, and was not sleeping. In the morning before presenting to the hospital, Mr. X had gone to work, laid down on the floor, began mumbling to himself, and would not respond to coworkers. Upon evaluation, Mr. X was noted to have pressured speech, disorganized speech, delusions, anxiety, and hallucinations. A CT scan of his head was normal, and a complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, B12, folate, and hemoglobin A1c were within normal limits. Mr. X’s vitamin D level was low at 22 ng/mL, and a syphilis screen was negative.

Mr. X was admitted to the hospital for his safety. The treatment team discontinued quetiapine and started risperidone 3 mg twice a day for psychotic symptoms and mood stabilization. At the time of discharge 7 days later, Mr. X was no longer experiencing any hallucinations or delusions, his thought process was linear and goal-directed, his mood was stable, and his insomnia had improved. Based on the temporal relationship between the initiation of quetiapine and the onset of Mr. X’s manic symptoms, along with an absence of organic causes, the treatment team suspected Mr. X had experienced a worsening of manic symptoms induced by quetiapine. Before starting quetiapine, he had presented with an initial manic symptom of racing thoughts.

At his next outpatient appointment, Mr. X exhibited significant akathisia. The treatment team initiated propranolol 20 mg twice a day but Mr. X did not experience much improvement. Risperidone was reduced to 1 mg twice a day and Mr. X was started on clonazepam 0.5 mg twice a day. The akathisia resolved. The treatment team decided to discontinue all medications and observe Mr. X for any recurrence of symptoms. One year after his manic episode. Mr. X remained euthymic. He was able to resume full-time work and began psychotherapy to process the grief over the loss of his brother.

Quetiapine’s unique profile

This case sheds light on the potential limitations of quetiapine, especially at lower doses, for managing manic symptoms. Quetiapine exhibits antidepressant effects, even at doses as low as 50 mg/d.¹ At higher doses, quetiapine acts as an antagonist at serotonin (5-HT1A and 5-HT2A), dopamine (D1 and D2), histamine H1, and adrenergic receptors.² At doses <300 mg/d, there is an absence of dopamine receptor blockade and a higher affinity for 5-HT2A receptors, which could explain why higher doses are generally necessary for treating mania and psychotic symptoms.^3-5 High 5-HT2A antagonism may disinhibit the dopaminergic system and paradoxically increase dopaminergic activity, which could be the mechanism responsible for lack of control of manic symptoms with low doses of quetiapine.² Another possible explanation is that the metabolite of quetiapine, N-desalkylquetiapine, acts as a norepine­phrine reuptake blocker and partial 5-HT1Aantagonist, which acts as an antidepressant, and antidepressants are known to induce mania in vulnerable patients.⁴

The antimanic property of most antipsychotics (except possibly clozapine) is attributed to their D2 antagonistic potency. Because quetiapine is among the weaker D2 antagonists, its inability to prevent the progression of mania, especially at 50 mg/d, is not unexpected. Mr. X’s subsequent need for a stronger D2 antagonist—risperidone—at a significant dose further supports this observation. A common misconception is that quetiapine’s sedating effects make it effective for treating mania, but that is not the case. Clinicians should be cautious when prescribing quetiapine, especially at lower doses, to patients who exhibit signs of mania. Given the potential risk, clinicians should consider alternative treatments before resorting to low-dose quetiapine for insomnia. Regular monitoring for manic symptoms is crucial for all patients receiving quetiapine. If patients present with signs of mania or hypomania, a therapeutic dose range of 600 to 800 mg/d is recommended.⁶

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry . All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style.

Working closely with individuals with substance use disorders (SUDs), we’ve observed a worrisome trend of patients leaving the hospital against medical advice (AMA). This issue is not only prevalent in psychiatric settings, but also in emergency departments, medical and surgical floors, and even intensive care units.¹

Compared to individuals without such disorders, individuals with SUDs—particularly those with opioid use disorders—are up to 3 times more likely to leave the hospital AMA.^1,2 Leaving AMA can lead to multiple complications, including an increased risk of readmission, suboptimal treatment outcomes, and an increased use of health care resources.^1-3

It is critical to understand why patients elect to leave a hospital AMA. In a qualitative study, Simon et al¹ found that individuals with SUDs often leave AMA due to uncontrolled withdrawal symptoms and pain, perceived stigma and discrimination, and dissatisfaction with care. Predictors of patients leaving the hospital AMA include the severity of their drug dependence and previous negative treatment experiences.⁴ A systematic review found housing instability and a lack of social support influence an individual’s decision to leave AMA.⁵

Recommendations for managing patients who leave AMA

Enhancing your understanding of withdrawal symptoms may allow you to offer patients more effective symptom control, possibly with methadone or buprenorphine.² Injectable opioid agonist treatment may also help to retain a patient in care. In a case report, a 47-year-old man with a severe opioid use disorder who had left the hospital AMA due to uncontrolled opioid withdrawal was readmitted, treated with IV hydromorphone, and enrolled in ongoing community injectable opioid agonist treatment.⁶

Clinicians must address the stigma and discrimination patients with SUDs often face in health care institutions. Additional training for clinicians to improve their understanding of these disorders and foster a more compassionate and nonjudgmental approach to care may be beneficial.

Like most medicolegal conflicts, leaving AMA is often a clinical and interpersonal problem disguised as a legal one. When assessing these patients’ decision-making capacity, we often find they are angry and dissatisfied with the care they have (or have not) received. The most useful intervention may be to restore communication between the patient and their treatment team.

Even after a patient leaves AMA, the treatment team may experience countertransference issues, such as heightened emotional reactions or biases, that could compromise their clinical judgment. Addressing these dynamics may require team debriefings, supervision, or further training in managing transference and countertransference, particularly since patients who leave AMA may return for subsequent care.⁷

Integrated care models, which feature close collaboration between clinicians from different specialties, can help ensure that a patient’s diverse health needs are met and reduce the likelihood of them leaving AMA. Integrated care models may be particularly effective for patients with co-occurring conditions such as HIV and SUDs.⁸

Implementing these recommendations can be challenging. Barriers to addressing AMA departures span several domains, including patient-specific barriers (eg, stigma and discrimination), clinical barriers (eg, lack of resources and training for clinicians), institutional hurdles (eg, systemic inefficiencies), and broader social barriers (eg, housing instability and inadequate social support). Overcoming these barriers requires a multifaceted approach involving clinicians, policymakers, and the community that considers medical, psychological, and social factors.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry . All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style.

Working closely with individuals with substance use disorders (SUDs), we’ve observed a worrisome trend of patients leaving the hospital against medical advice (AMA). This issue is not only prevalent in psychiatric settings, but also in emergency departments, medical and surgical floors, and even intensive care units.¹

Compared to individuals without such disorders, individuals with SUDs—particularly those with opioid use disorders—are up to 3 times more likely to leave the hospital AMA.^1,2 Leaving AMA can lead to multiple complications, including an increased risk of readmission, suboptimal treatment outcomes, and an increased use of health care resources.^1-3

It is critical to understand why patients elect to leave a hospital AMA. In a qualitative study, Simon et al¹ found that individuals with SUDs often leave AMA due to uncontrolled withdrawal symptoms and pain, perceived stigma and discrimination, and dissatisfaction with care. Predictors of patients leaving the hospital AMA include the severity of their drug dependence and previous negative treatment experiences.⁴ A systematic review found housing instability and a lack of social support influence an individual’s decision to leave AMA.⁵

Recommendations for managing patients who leave AMA

Enhancing your understanding of withdrawal symptoms may allow you to offer patients more effective symptom control, possibly with methadone or buprenorphine.² Injectable opioid agonist treatment may also help to retain a patient in care. In a case report, a 47-year-old man with a severe opioid use disorder who had left the hospital AMA due to uncontrolled opioid withdrawal was readmitted, treated with IV hydromorphone, and enrolled in ongoing community injectable opioid agonist treatment.⁶

Clinicians must address the stigma and discrimination patients with SUDs often face in health care institutions. Additional training for clinicians to improve their understanding of these disorders and foster a more compassionate and nonjudgmental approach to care may be beneficial.

Like most medicolegal conflicts, leaving AMA is often a clinical and interpersonal problem disguised as a legal one. When assessing these patients’ decision-making capacity, we often find they are angry and dissatisfied with the care they have (or have not) received. The most useful intervention may be to restore communication between the patient and their treatment team.

Even after a patient leaves AMA, the treatment team may experience countertransference issues, such as heightened emotional reactions or biases, that could compromise their clinical judgment. Addressing these dynamics may require team debriefings, supervision, or further training in managing transference and countertransference, particularly since patients who leave AMA may return for subsequent care.⁷

Integrated care models, which feature close collaboration between clinicians from different specialties, can help ensure that a patient’s diverse health needs are met and reduce the likelihood of them leaving AMA. Integrated care models may be particularly effective for patients with co-occurring conditions such as HIV and SUDs.⁸

Implementing these recommendations can be challenging. Barriers to addressing AMA departures span several domains, including patient-specific barriers (eg, stigma and discrimination), clinical barriers (eg, lack of resources and training for clinicians), institutional hurdles (eg, systemic inefficiencies), and broader social barriers (eg, housing instability and inadequate social support). Overcoming these barriers requires a multifaceted approach involving clinicians, policymakers, and the community that considers medical, psychological, and social factors.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry . All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style.

Working closely with individuals with substance use disorders (SUDs), we’ve observed a worrisome trend of patients leaving the hospital against medical advice (AMA). This issue is not only prevalent in psychiatric settings, but also in emergency departments, medical and surgical floors, and even intensive care units.¹

Compared to individuals without such disorders, individuals with SUDs—particularly those with opioid use disorders—are up to 3 times more likely to leave the hospital AMA.^1,2 Leaving AMA can lead to multiple complications, including an increased risk of readmission, suboptimal treatment outcomes, and an increased use of health care resources.^1-3

It is critical to understand why patients elect to leave a hospital AMA. In a qualitative study, Simon et al¹ found that individuals with SUDs often leave AMA due to uncontrolled withdrawal symptoms and pain, perceived stigma and discrimination, and dissatisfaction with care. Predictors of patients leaving the hospital AMA include the severity of their drug dependence and previous negative treatment experiences.⁴ A systematic review found housing instability and a lack of social support influence an individual’s decision to leave AMA.⁵

Recommendations for managing patients who leave AMA

Enhancing your understanding of withdrawal symptoms may allow you to offer patients more effective symptom control, possibly with methadone or buprenorphine.² Injectable opioid agonist treatment may also help to retain a patient in care. In a case report, a 47-year-old man with a severe opioid use disorder who had left the hospital AMA due to uncontrolled opioid withdrawal was readmitted, treated with IV hydromorphone, and enrolled in ongoing community injectable opioid agonist treatment.⁶

Clinicians must address the stigma and discrimination patients with SUDs often face in health care institutions. Additional training for clinicians to improve their understanding of these disorders and foster a more compassionate and nonjudgmental approach to care may be beneficial.

Like most medicolegal conflicts, leaving AMA is often a clinical and interpersonal problem disguised as a legal one. When assessing these patients’ decision-making capacity, we often find they are angry and dissatisfied with the care they have (or have not) received. The most useful intervention may be to restore communication between the patient and their treatment team.

Even after a patient leaves AMA, the treatment team may experience countertransference issues, such as heightened emotional reactions or biases, that could compromise their clinical judgment. Addressing these dynamics may require team debriefings, supervision, or further training in managing transference and countertransference, particularly since patients who leave AMA may return for subsequent care.⁷

Integrated care models, which feature close collaboration between clinicians from different specialties, can help ensure that a patient’s diverse health needs are met and reduce the likelihood of them leaving AMA. Integrated care models may be particularly effective for patients with co-occurring conditions such as HIV and SUDs.⁸

Implementing these recommendations can be challenging. Barriers to addressing AMA departures span several domains, including patient-specific barriers (eg, stigma and discrimination), clinical barriers (eg, lack of resources and training for clinicians), institutional hurdles (eg, systemic inefficiencies), and broader social barriers (eg, housing instability and inadequate social support). Overcoming these barriers requires a multifaceted approach involving clinicians, policymakers, and the community that considers medical, psychological, and social factors.

In 2021, when Eric Esrailian, MD, MPH, was awarded the Benemerenti Medal from Pope Francis for his humanitarian work, he recognized other people worldwide who save lives daily – but without recognition. They’re motivated for “the right reasons. To be clear, I do not deserve this honor. It is honestly overwhelming and humbling,” he said in 2021 when news of the award reached him in Los Angeles where he holds the Lincy Foundation Chair in Clinical Gastroenterology at the University of California, Los Angeles. He also serves as chief of the Vatche and Tamar Manoukian Division of Digestive Diseases, and director of the Melvin and Bren Simon Digestive Diseases Center.

Courtesy Dr. Eric Esrailian

Dr. Esrailian, the son of Armenian immigrants, says that humanitarian work has been ingrained in him since childhood. His great-grandparents were Armenian genocide survivors and their struggles have never left him. He’s devoted his life not only to medicine, but to documenting the history of the Armenian genocide and leading, or supporting, efforts to resolve humanitarian crises in Armenia and around the world. Earlier this year, he, with Kim Kardashian and singer/actor Cher, published op-eds that addressed a humanitarian crisis building as a result of Azerbaijan’s blockade of the Lachin corridor – which is the only road that links Armenia to the ethnic Armenian–populated sections of Nagorno-Karabakh. In September, Armenia and Azerbaijan reached a tentative agreement to end the blockade, but more needs to be done, he says. Tragedies continue to unfold, and he is redoubling his efforts to bring more attention to this humanitarian crisis, he said.

Because storytelling is an important part of raising awareness, in 2016 Dr. Esrailian and partners produced two films about stories of perseverance, endurance, and the inextinguishable fire of the human spirit. The first film was “The Promise,” a historical war drama set in the Ottoman Empire and released in 2016. In 2017, he and partners released “Intent to Destroy: Death, Denial, & Depiction,” a documentary about the Armenian genocide. The documentary received an Emmy nomination for Outstanding Historical Documentary. And, in 2020, he produced “Francesco,” a film about Pope Francis that documented his pilgrimage to Armenia in 2016.

“The Promise” had such an impact on viewers that in 2017 Dr. Esrailian and the UCLA School of Law created The Promise Institute for Human Rights as a center of human rights education, research, and advocacy. In 2019, Dr. Esrailian and UCLA followed up with The Promise Armenian Institute as a place for academic research and teaching of Armenian studies, language, and culture. “The impact from building these two institutes has been transformational, and they will be part of UCLA forever,” he said.

His philanthropic efforts connecting health, human rights, education, and the arts has had an impact worldwide. One person can make a difference, Dr. Esrailian said: “I’ve learned along the way that an individual can have more of an impact than ever imagined, but you have to dream big and never give up.”

In this interview, he tells us more about his work.
 

Q: Not many doctors wear hats in medicine and filmmaking. Describe your journey as a filmmaker.

Dr. Esrailian: I’ve always been interested in storytelling. I was an English minor at Berkeley. My late mentor, Kirk Kerkorian, a legendary philanthropist, businessman, and entrepreneur, pushed me to take storytelling and do something that would potentially help secure Armenian Genocide recognition by the United States. Because of genocide denialists and geopolitical pressure, he felt the United States government was reluctant to recognize the Armenian Genocide. He thought having some visual materials for educational and outreach efforts would be transformational, and as it turns out, they were.

If you talk to any advocacy organization that tried for years to get Armenian Genocide recognition, they’d say that both films, “The Promise” (a feature film) and “Intent to Destroy” (a documentary), and the social impact media campaign we launched around them, were influential in moving the needle with legislators in the United States who, 3 years after “The Promise” was released, recognized the genocide. This was followed by the Library of Congress in 2020 and President Biden’s executive branch in 2021.
 

Q: What has been your most rewarding accomplishment?

Dr. Esrailian: Giving a voice to people who don’t have a voice is something that I’m proud of. Sometimes, it’s questionable what impact it may have because we still see atrocities committed all over the world. In September, Azerbaijan completed an ethnic cleansing campaign of Armenians from a region called Artsakh, officially the Republic of Nagorno-Karabakh.

Despite having so many relationships with powerful people in government and in high-profile media, and despite our documentaries, op-eds, and interactions with influential leaders on a regular basis, it always feels like it’s not enough. Obviously, the perpetrators are still able to abuse human rights and conduct these campaigns. Nevertheless, I don’t think we should be deterred. Allowing human rights violations to occur with impunity only emboldens perpetrators even more. It takes a long time to bring people to justice through international courts, but it does happen – eventually. That’s something I’m going to continue to work on.
 

Q: What should be the role of physicians in supporting human rights?

Dr. Esrailian: Physicians and health care providers play an important role in human rights. If you look back throughout history, whether it’s the International Committee of the Red Cross, or Doctors Without Borders, or other organizations, physicians and health care professionals are often on the front lines, helping people. Unfortunately, physicians have also been part of human rights violations, like the Holocaust or other genocides. But I do think that in this day and age, with the reputation that physicians have, we can be policy advocates and upstanders in addition to taking care of patients. Telling our stories to the world is important so that people know what’s actually happening on the ground.

Lightning round

Do you prefer texting or talking?  
Talking

How many cups of coffee do you drink each day?
Two

What was the last movie you watched?
Mission Impossible

If you weren’t a gastroenterologist, what would you be?  
Entrepreneur

Who inspires you?  
My family

In 2021, when Eric Esrailian, MD, MPH, was awarded the Benemerenti Medal from Pope Francis for his humanitarian work, he recognized other people worldwide who save lives daily – but without recognition. They’re motivated for “the right reasons. To be clear, I do not deserve this honor. It is honestly overwhelming and humbling,” he said in 2021 when news of the award reached him in Los Angeles where he holds the Lincy Foundation Chair in Clinical Gastroenterology at the University of California, Los Angeles. He also serves as chief of the Vatche and Tamar Manoukian Division of Digestive Diseases, and director of the Melvin and Bren Simon Digestive Diseases Center.

Courtesy Dr. Eric Esrailian

Dr. Esrailian, the son of Armenian immigrants, says that humanitarian work has been ingrained in him since childhood. His great-grandparents were Armenian genocide survivors and their struggles have never left him. He’s devoted his life not only to medicine, but to documenting the history of the Armenian genocide and leading, or supporting, efforts to resolve humanitarian crises in Armenia and around the world. Earlier this year, he, with Kim Kardashian and singer/actor Cher, published op-eds that addressed a humanitarian crisis building as a result of Azerbaijan’s blockade of the Lachin corridor – which is the only road that links Armenia to the ethnic Armenian–populated sections of Nagorno-Karabakh. In September, Armenia and Azerbaijan reached a tentative agreement to end the blockade, but more needs to be done, he says. Tragedies continue to unfold, and he is redoubling his efforts to bring more attention to this humanitarian crisis, he said.

Because storytelling is an important part of raising awareness, in 2016 Dr. Esrailian and partners produced two films about stories of perseverance, endurance, and the inextinguishable fire of the human spirit. The first film was “The Promise,” a historical war drama set in the Ottoman Empire and released in 2016. In 2017, he and partners released “Intent to Destroy: Death, Denial, & Depiction,” a documentary about the Armenian genocide. The documentary received an Emmy nomination for Outstanding Historical Documentary. And, in 2020, he produced “Francesco,” a film about Pope Francis that documented his pilgrimage to Armenia in 2016.

“The Promise” had such an impact on viewers that in 2017 Dr. Esrailian and the UCLA School of Law created The Promise Institute for Human Rights as a center of human rights education, research, and advocacy. In 2019, Dr. Esrailian and UCLA followed up with The Promise Armenian Institute as a place for academic research and teaching of Armenian studies, language, and culture. “The impact from building these two institutes has been transformational, and they will be part of UCLA forever,” he said.

His philanthropic efforts connecting health, human rights, education, and the arts has had an impact worldwide. One person can make a difference, Dr. Esrailian said: “I’ve learned along the way that an individual can have more of an impact than ever imagined, but you have to dream big and never give up.”

In this interview, he tells us more about his work.
 

Q: Not many doctors wear hats in medicine and filmmaking. Describe your journey as a filmmaker.

Dr. Esrailian: I’ve always been interested in storytelling. I was an English minor at Berkeley. My late mentor, Kirk Kerkorian, a legendary philanthropist, businessman, and entrepreneur, pushed me to take storytelling and do something that would potentially help secure Armenian Genocide recognition by the United States. Because of genocide denialists and geopolitical pressure, he felt the United States government was reluctant to recognize the Armenian Genocide. He thought having some visual materials for educational and outreach efforts would be transformational, and as it turns out, they were.

If you talk to any advocacy organization that tried for years to get Armenian Genocide recognition, they’d say that both films, “The Promise” (a feature film) and “Intent to Destroy” (a documentary), and the social impact media campaign we launched around them, were influential in moving the needle with legislators in the United States who, 3 years after “The Promise” was released, recognized the genocide. This was followed by the Library of Congress in 2020 and President Biden’s executive branch in 2021.
 

Q: What has been your most rewarding accomplishment?

Dr. Esrailian: Giving a voice to people who don’t have a voice is something that I’m proud of. Sometimes, it’s questionable what impact it may have because we still see atrocities committed all over the world. In September, Azerbaijan completed an ethnic cleansing campaign of Armenians from a region called Artsakh, officially the Republic of Nagorno-Karabakh.

Despite having so many relationships with powerful people in government and in high-profile media, and despite our documentaries, op-eds, and interactions with influential leaders on a regular basis, it always feels like it’s not enough. Obviously, the perpetrators are still able to abuse human rights and conduct these campaigns. Nevertheless, I don’t think we should be deterred. Allowing human rights violations to occur with impunity only emboldens perpetrators even more. It takes a long time to bring people to justice through international courts, but it does happen – eventually. That’s something I’m going to continue to work on.
 

Q: What should be the role of physicians in supporting human rights?

Dr. Esrailian: Physicians and health care providers play an important role in human rights. If you look back throughout history, whether it’s the International Committee of the Red Cross, or Doctors Without Borders, or other organizations, physicians and health care professionals are often on the front lines, helping people. Unfortunately, physicians have also been part of human rights violations, like the Holocaust or other genocides. But I do think that in this day and age, with the reputation that physicians have, we can be policy advocates and upstanders in addition to taking care of patients. Telling our stories to the world is important so that people know what’s actually happening on the ground.

Lightning round

Do you prefer texting or talking?  
Talking

How many cups of coffee do you drink each day?
Two

What was the last movie you watched?
Mission Impossible

If you weren’t a gastroenterologist, what would you be?  
Entrepreneur

Who inspires you?  
My family

In 2021, when Eric Esrailian, MD, MPH, was awarded the Benemerenti Medal from Pope Francis for his humanitarian work, he recognized other people worldwide who save lives daily – but without recognition. They’re motivated for “the right reasons. To be clear, I do not deserve this honor. It is honestly overwhelming and humbling,” he said in 2021 when news of the award reached him in Los Angeles where he holds the Lincy Foundation Chair in Clinical Gastroenterology at the University of California, Los Angeles. He also serves as chief of the Vatche and Tamar Manoukian Division of Digestive Diseases, and director of the Melvin and Bren Simon Digestive Diseases Center.

Courtesy Dr. Eric Esrailian

Dr. Esrailian, the son of Armenian immigrants, says that humanitarian work has been ingrained in him since childhood. His great-grandparents were Armenian genocide survivors and their struggles have never left him. He’s devoted his life not only to medicine, but to documenting the history of the Armenian genocide and leading, or supporting, efforts to resolve humanitarian crises in Armenia and around the world. Earlier this year, he, with Kim Kardashian and singer/actor Cher, published op-eds that addressed a humanitarian crisis building as a result of Azerbaijan’s blockade of the Lachin corridor – which is the only road that links Armenia to the ethnic Armenian–populated sections of Nagorno-Karabakh. In September, Armenia and Azerbaijan reached a tentative agreement to end the blockade, but more needs to be done, he says. Tragedies continue to unfold, and he is redoubling his efforts to bring more attention to this humanitarian crisis, he said.

Because storytelling is an important part of raising awareness, in 2016 Dr. Esrailian and partners produced two films about stories of perseverance, endurance, and the inextinguishable fire of the human spirit. The first film was “The Promise,” a historical war drama set in the Ottoman Empire and released in 2016. In 2017, he and partners released “Intent to Destroy: Death, Denial, & Depiction,” a documentary about the Armenian genocide. The documentary received an Emmy nomination for Outstanding Historical Documentary. And, in 2020, he produced “Francesco,” a film about Pope Francis that documented his pilgrimage to Armenia in 2016.

“The Promise” had such an impact on viewers that in 2017 Dr. Esrailian and the UCLA School of Law created The Promise Institute for Human Rights as a center of human rights education, research, and advocacy. In 2019, Dr. Esrailian and UCLA followed up with The Promise Armenian Institute as a place for academic research and teaching of Armenian studies, language, and culture. “The impact from building these two institutes has been transformational, and they will be part of UCLA forever,” he said.

His philanthropic efforts connecting health, human rights, education, and the arts has had an impact worldwide. One person can make a difference, Dr. Esrailian said: “I’ve learned along the way that an individual can have more of an impact than ever imagined, but you have to dream big and never give up.”

In this interview, he tells us more about his work.
 

Q: Not many doctors wear hats in medicine and filmmaking. Describe your journey as a filmmaker.

Dr. Esrailian: I’ve always been interested in storytelling. I was an English minor at Berkeley. My late mentor, Kirk Kerkorian, a legendary philanthropist, businessman, and entrepreneur, pushed me to take storytelling and do something that would potentially help secure Armenian Genocide recognition by the United States. Because of genocide denialists and geopolitical pressure, he felt the United States government was reluctant to recognize the Armenian Genocide. He thought having some visual materials for educational and outreach efforts would be transformational, and as it turns out, they were.

If you talk to any advocacy organization that tried for years to get Armenian Genocide recognition, they’d say that both films, “The Promise” (a feature film) and “Intent to Destroy” (a documentary), and the social impact media campaign we launched around them, were influential in moving the needle with legislators in the United States who, 3 years after “The Promise” was released, recognized the genocide. This was followed by the Library of Congress in 2020 and President Biden’s executive branch in 2021.
 

Q: What has been your most rewarding accomplishment?

Dr. Esrailian: Giving a voice to people who don’t have a voice is something that I’m proud of. Sometimes, it’s questionable what impact it may have because we still see atrocities committed all over the world. In September, Azerbaijan completed an ethnic cleansing campaign of Armenians from a region called Artsakh, officially the Republic of Nagorno-Karabakh.

Despite having so many relationships with powerful people in government and in high-profile media, and despite our documentaries, op-eds, and interactions with influential leaders on a regular basis, it always feels like it’s not enough. Obviously, the perpetrators are still able to abuse human rights and conduct these campaigns. Nevertheless, I don’t think we should be deterred. Allowing human rights violations to occur with impunity only emboldens perpetrators even more. It takes a long time to bring people to justice through international courts, but it does happen – eventually. That’s something I’m going to continue to work on.
 

Q: What should be the role of physicians in supporting human rights?

Dr. Esrailian: Physicians and health care providers play an important role in human rights. If you look back throughout history, whether it’s the International Committee of the Red Cross, or Doctors Without Borders, or other organizations, physicians and health care professionals are often on the front lines, helping people. Unfortunately, physicians have also been part of human rights violations, like the Holocaust or other genocides. But I do think that in this day and age, with the reputation that physicians have, we can be policy advocates and upstanders in addition to taking care of patients. Telling our stories to the world is important so that people know what’s actually happening on the ground.

Lightning round

Do you prefer texting or talking?  
Talking

How many cups of coffee do you drink each day?
Two

What was the last movie you watched?
Mission Impossible

If you weren’t a gastroenterologist, what would you be?  
Entrepreneur

Who inspires you?  
My family