Current Psychiatry

Presently, FDA-approved first-line treatments and standard adjunctive strategies (eg, lithium, thyroid supplementation, stimulants, second-generation antipsychotics) for major depressive disorder (MDD) often produce less-than-desired outcomes while carrying a potentially substantial safety and tolerability burden. The lack of clinically useful and individual-based biomarkers (eg, genetic, neurophysiological, imaging) is a major obstacle to enhancing treatment efficacy and/or decreasing associated adverse effects (AEs). While the discovery of such tools is being aggressively pursued and ultimately will facilitate a more precision-based choice of therapy, empirical strategies remain our primary approach.

In controlled trials, several nontraditional treatments used primarily as adjuncts to standard antidepressants have shown promise. These include “repurposed” (off-label) medications, herbal/nutraceuticals, anti-inflammatory/immune system therapies, device-based treatments, and other alternative approaches.

Importantly, some nontraditional treatments also demonstrate AEs (Table^1-16). With a careful consideration of the risk/benefit balance, this article reviews some of the better-studied treatment options for patients with treatment-resistant depression (TRD). In Part 1, we will examine off-label medications. In Part 2, we will review other nontraditional approaches to TRD, including herbal/nutraceuticals, anti-inflammatory/immune system therapies, device-based treatments, and other alternative approaches.

We believe this review will help clinicians who need to formulate a different approach after their patient with depression is not helped by traditional first-, second-, and third-line treatments. The potential options discussed in Part 1 of this article are categorized based on their putative mechanism of action (MOA) for depression.

Serotonergic and noradrenergic strategies

Pimavanserin is FDA-approved for treatment of Parkinson’s psychosis. Its potential MOA as an adjunctive strategy for MDD may involve 5-HT2A antagonist and inverse agonist receptor activity, as well as lesser effects at the 5-HT2Creceptor.

A 2-stage, 5-week randomized controlled trial (RCT) (CLARITY; N = 207) found adjunctive pimavanserin (34 mg/d) produced a robust antidepressant effect vs placebo in patients whose depression did not respond to selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs).¹ Furthermore, a secondary analysis of the data suggested that pimavanserin also improved sleepiness (P < .0003) and daily functioning (P < .014) at Week 5.²

Unfortunately, two 6-week, Phase III RCTs (CLARITY-2 and -3; N = 298) did not find a statistically significant difference between active treatment and placebo. This was based on change in the primary outcome measure (Hamilton Depression Rating Scale-17 score) when adjunctive pimavanserin (34 mg/d) was added to an SSRI or SNRI in patients with TRD.³ There was, however, a significant difference favoring active treatment over placebo based on the Clinical Global Impression–Severity score.

Continue to: In these trials...

In these trials, pimavanserin was generally well-tolerated. The most common AEs were dry mouth, nausea, and headache. Pimavanserin has minimal activity at norepinephrine, dopamine, histamine, or acetylcholine receptors, thus avoiding AEs associated with these receptor interactions.

Given the mixed efficacy results of existing trials, further studies are needed to clarify this agent’s overall risk/benefit in the context of TRD.

Antihypertensive medications

Emerging data suggest that some beta-adrenergic blockers, angiotensin-inhibiting agents, and calcium antagonists are associated with a decreased incidence of depression. A large 2020 study (N = 3,747,190) used population-based Danish registries (2005 to 2015) to evaluate if any of the 41 most commonly prescribed antihypertensive medications were associated with the diagnosis of depressive disorder or use of antidepressants.⁴ These researchers found that enalapril, ramipril, amlodipine, propranolol, atenolol, bisoprolol, carvedilol (P < .001), and verapamil (P < .004) were strongly associated with a decreased risk of depression.⁴

Adverse effects across these different classes of antihypertensives are well characterized, can be substantial, and commonly are related to their impact on cardiovascular function (eg, hypotension). Clinically, these agents may be potential adjuncts for patients with TRD who need antihypertensive therapy. Their use and the choice of specific agent should only be determined in consultation with the patient’s primary care physician (PCP) or appropriate specialist.

Glutamatergic strategies

Ketamine is a dissociative anesthetic and analgesic. Its MOA for treating depression appears to occur primarily through antagonist activity at the N-methyl-D-aspartate ionotropic receptor of the glutamatergic system. There is preliminary evidence that its opioid receptor actions also may contribute to its antidepressant effect.⁵

Continue to: Many published studies...

Many published studies and reviews have described ketamine’s role for treating MDD. Several studies have reported that low-dose (0.5 mg/kg) IV ketamine infusions can rapidly attenuate severe episodes of MDD as well as associated suicidality. For example, a meta-analysis of 9 RCTs (N = 368) comparing ketamine to placebo for acute treatment of unipolar and bipolar depression reported superior therapeutic effects with active treatment at 24 hours, 72 hours, and 7 days.⁶ The response and remission rates for ketamine were 52% and 21% at 24 hours; 48% and 24% at 72 hours; and 40% and 26% at 7 days, respectively.⁶

The most commonly reported AEs during the 4 hours after ketamine infusion included⁷:

• drowsiness, dizziness, poor coordination
• blurred vision, feeling strange or unreal
• hemodynamic changes (approximately 33%)
• small but significant (P < .05) increases in psychotomimetic and dissociative symptoms.

Because some individuals use ketamine recreationally, this agent also carries the risk of abuse.

Research is ongoing on strategies for long-term maintenance ketamine treatment, and the results of both short- and long-term trials will require careful scrutiny to better assess this agent’s safety and tolerability. Clinicians should first consider esketamine—the S-enantiomer of ketamine—because an intranasal formulation of this agent is FDA-approved for treating patients with TRD or MDD with suicidality when administered in a Risk Evaluation and Mitigation Strategy–certified setting.

Cholinergic strategies

Scopolamine is a potent muscarinic receptor antagonist used to prevent nausea and vomiting caused by motion sickness or medications used during surgery. Its use for MDD is based on the theory that muscarinic receptors may be hypersensitive in mood disorders.

Continue to: Several double-blind RCTs...

Several double-blind RCTs of patients with unipolar or bipolar depression that used 3 pulsed IV infusions (4.0 mcg/kg) over 15 minutes found a rapid, robust antidepressant effect with scopolamine vs placebo.^8,9 The oral formulation might also be effective, but would not have a rapid onset.

Common adverse effects of scopolamine include agitation, dry mouth, urinary retention, and cognitive clouding. Given scopolamine’s substantial AE profile, it should be considered only for patients with TRD who could also benefit from the oral formulation for the medical indications noted above, should generally be avoided in older patients, and should be prescribed in consultation with the patient’s PCP.

Botulinum toxin. This neurotoxin inhibits acetylcholine release. It is used to treat disorders characterized by abnormal muscular contraction, such as strabismus, blepharospasm, and chronic pain syndromes. Its MOA for depression may involve its paralytic effects after injection into the glabella forehead muscle (based on the facial feedback hypothesis), as well as modulation of neurotransmitters implicated in the pathophysiology of depression.

In several small trials, injectable botulinum toxin type A (BTA) (29 units) demonstrated antidepressant effects. A recent review that considered 6 trials (N = 235; 4 of the 6 studies were RCTs, 3 of which were rated as high quality) concluded that BTA may be a promising treatment for MDD.¹⁰ Limitations of this review included lack of a priori hypotheses, small sample sizes, gender bias, and difficulty in blinding.

In clinical trials, the most common AEs included local irritation at the injection site and transient headache. This agent’s relatively mild AE profile and possible overlap when used for some of the medical indications noted above opens its potential use as an adjunct in patients with comorbid TRD.

Continue to: Endocrine strategies

Endocrine strategies

Mifepristone (RU486). This anti-glucocorticoid receptor antagonist is used as an abortifacient. Based on the theory that hyperactivity of the hypothalamic-pituitary-adrenal axis is implicated in the pathophysiology of MDD with psychotic features (psychotic depression), this agent has been studied as a treatment for this indication.

An analysis of 5 double-blind RCTs (N = 1,460) found that 7 days of mifepristone, 1,200 mg/d, was superior to placebo (P < .004) in reducing psychotic symptoms of depression.¹¹ Plasma concentrations ≥1,600 ng/mL may be required to maximize benefit.¹¹

Overall, this agent demonstrated a good safety profile in clinical trials, with treatment-emergent AEs reported in 556 (66.7%) patients who received mifepristone vs 386 (61.6%) patients who received placebo.¹¹ Common AEs included gastrointestinal (GI) symptoms, headache, and dizziness. However, 3 deaths occurred: 2 patients who received mifepristone and 1 patient who received placebo. Given this potential for a fatal outcome, clinicians should first consider prescribing an adjunctive antipsychotic agent or electroconvulsive therapy.

Estrogens. These hormones are important for sexual and reproductive development and are used to treat various sexual/reproductive disorders, primarily in women. Their role in treating depression is based on the observation that perimenopause is accompanied by an increased risk of new and recurrent depression coincident with declining ovarian function.

Evidence supports the antidepressant efficacy of transdermal estradiol plus progesterone for perimenopausal depression, but not for postmenopausal depression.^12-14 However, estrogens carry significant risks that must be carefully considered in relationship to their potential benefits. These risks include:

• vaginal bleeding, dysmenorrhea
• fibroid enlargement
• galactorrhea
• ovarian cancer, endometrial cancer, breast cancer
• deep vein thrombosis, pulmonary embolism
• hypertension, chest pain, myocardial infarction, stroke.

Continue to: The use of estrogens...

The use of estrogens as an adjunctive therapy for women with treatment-resistant perimenopausal depression should only be undertaken when standard strategies have failed, and in consultation with an endocrine specialist who can monitor for potentially serious AEs.

Opioid medications

Buprenorphine is used to treat opioid use disorder (OUD) as well as acute and chronic pain. The opioid system is involved in the regulation of mood and may be an appropriate target for novel antidepressants. The use of buprenorphine in combination with samidorphan (a preferential mu-opioid receptor antagonist) has shown initial promise for TRD while minimizing abuse potential.

Although earlier results were mixed, a pooled analysis of 2 recent large RCTs (N = 760) of patients with MDD who had not responded to antidepressants reported greater reduction in Montgomery-Åsberg Depression Rating Scale scores from baseline for active treatment (buprenorphine/samidorphan; 2 mg/2 mg) vs placebo at multiple timepoints, including end of treatment (-1.8; P < .010).¹⁵

The most common AEs included nausea, constipation, dizziness, vomiting, somnolence, fatigue, and sedation. There was minimal evidence of abuse, dependence, or opioid withdrawal. Due to the opioid crisis in the United States, the resulting relaxation of regulations regarding prescribing buprenorphine, and the high rates of depression among patients with OUD, buprenorphine/samidorphan, which is an investigational agent that is not FDA-approved, may be particularly helpful for patients with OUD who also experience comorbid TRD.

Antioxidant agents

N-acetylcysteine (NAC) is an amino acid that can treat acetaminophen toxicity and moderate hepatic damage by increasing glutathione levels. Glutathione is also the primary antioxidant in the CNS. NAC may protect against oxidative stress, chelate heavy metals, reduce inflammation, protect against mitochondrial dysfunction, inhibit apoptosis, and enhance neurogenesis, all potential pathophysiological processes that may contribute to depression.¹⁶

Continue to: A systematic review...

A systematic review and meta-analysis of 5 RCTs (N = 574) considered patients with various depression diagnoses who were randomized to adjunctive NAC, 1,000 mg twice a day, or placebo. Over 12 to 24 weeks, there was a significantly greater improvement in mood symptoms and functionality with NAC vs placebo.¹⁶

Overall, NAC was well-tolerated. The most common AEs were GI symptoms, musculoskeletal complaints, decreased energy, and headache. While NAC has been touted as a potential adjunct therapy for several psychiatric disorders, including TRD, the evidence for benefit remains limited. Given its favorable AE profile, however, and over-the-counter availability, it remains an option for select patients. It is important to ask patients if they are already taking NAC.

Options beyond off-label medications

There are a multitude of options available for addressing TRD. Many FDA-approved medications are repurposed and prescribed off-label for other indications when the risk/benefit balance is favorable. In Part 1 of this article, we reviewed several off-label medications that have supportive controlled data for treating TRD. In Part 2, we will review other nontraditional therapies for TRD, including herbal/nutraceuticals, anti-inflammatory/immune system therapies, device-based treatments, and other alternative approaches.

Bottom Line

Off-label medications that may offer benefit for patients with treatment-resistant depression (TRD) include pimavanserin, antihypertensive agents, ketamine, scopolamine, botulinum toxin, mifepristone, estrogens, buprenorphine, and N-acetylcysteine. Although some evidence supports use of these agents as adjuncts for TRD, an individualized risk/benefit analysis is required.

Related Resource

• Joshi KG, Frierson RL. Off-label prescribing: How to limit your liability. Current Psychiatry. 2020;19(9):12,39.

Drug Brand Names

Amlodipine • Katerzia, Norvasc
Atenolol • Tenormin
Bisoprolol • Zebeta
Buprenorphine • Sublocade, Subutex
Carvedilol • Coreg
Enalapril • Vasotec
Esketamine • Spravato
Estradiol transdermal • Estraderm
Ketamine • Ketalar
Mifepristone • Mifeprex
Pimavanserin • Nuplazid
Progesterone • Prometrium
Propranolol • Inderal
Ramipril • Altace
Verapamil • Calan, Verelan

Presently, FDA-approved first-line treatments and standard adjunctive strategies (eg, lithium, thyroid supplementation, stimulants, second-generation antipsychotics) for major depressive disorder (MDD) often produce less-than-desired outcomes while carrying a potentially substantial safety and tolerability burden. The lack of clinically useful and individual-based biomarkers (eg, genetic, neurophysiological, imaging) is a major obstacle to enhancing treatment efficacy and/or decreasing associated adverse effects (AEs). While the discovery of such tools is being aggressively pursued and ultimately will facilitate a more precision-based choice of therapy, empirical strategies remain our primary approach.

In controlled trials, several nontraditional treatments used primarily as adjuncts to standard antidepressants have shown promise. These include “repurposed” (off-label) medications, herbal/nutraceuticals, anti-inflammatory/immune system therapies, device-based treatments, and other alternative approaches.

Importantly, some nontraditional treatments also demonstrate AEs (Table^1-16). With a careful consideration of the risk/benefit balance, this article reviews some of the better-studied treatment options for patients with treatment-resistant depression (TRD). In Part 1, we will examine off-label medications. In Part 2, we will review other nontraditional approaches to TRD, including herbal/nutraceuticals, anti-inflammatory/immune system therapies, device-based treatments, and other alternative approaches.

We believe this review will help clinicians who need to formulate a different approach after their patient with depression is not helped by traditional first-, second-, and third-line treatments. The potential options discussed in Part 1 of this article are categorized based on their putative mechanism of action (MOA) for depression.

Serotonergic and noradrenergic strategies

Pimavanserin is FDA-approved for treatment of Parkinson’s psychosis. Its potential MOA as an adjunctive strategy for MDD may involve 5-HT2A antagonist and inverse agonist receptor activity, as well as lesser effects at the 5-HT2Creceptor.

A 2-stage, 5-week randomized controlled trial (RCT) (CLARITY; N = 207) found adjunctive pimavanserin (34 mg/d) produced a robust antidepressant effect vs placebo in patients whose depression did not respond to selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs).¹ Furthermore, a secondary analysis of the data suggested that pimavanserin also improved sleepiness (P < .0003) and daily functioning (P < .014) at Week 5.²

Unfortunately, two 6-week, Phase III RCTs (CLARITY-2 and -3; N = 298) did not find a statistically significant difference between active treatment and placebo. This was based on change in the primary outcome measure (Hamilton Depression Rating Scale-17 score) when adjunctive pimavanserin (34 mg/d) was added to an SSRI or SNRI in patients with TRD.³ There was, however, a significant difference favoring active treatment over placebo based on the Clinical Global Impression–Severity score.

Continue to: In these trials...

In these trials, pimavanserin was generally well-tolerated. The most common AEs were dry mouth, nausea, and headache. Pimavanserin has minimal activity at norepinephrine, dopamine, histamine, or acetylcholine receptors, thus avoiding AEs associated with these receptor interactions.

Given the mixed efficacy results of existing trials, further studies are needed to clarify this agent’s overall risk/benefit in the context of TRD.

Antihypertensive medications

Emerging data suggest that some beta-adrenergic blockers, angiotensin-inhibiting agents, and calcium antagonists are associated with a decreased incidence of depression. A large 2020 study (N = 3,747,190) used population-based Danish registries (2005 to 2015) to evaluate if any of the 41 most commonly prescribed antihypertensive medications were associated with the diagnosis of depressive disorder or use of antidepressants.⁴ These researchers found that enalapril, ramipril, amlodipine, propranolol, atenolol, bisoprolol, carvedilol (P < .001), and verapamil (P < .004) were strongly associated with a decreased risk of depression.⁴

Adverse effects across these different classes of antihypertensives are well characterized, can be substantial, and commonly are related to their impact on cardiovascular function (eg, hypotension). Clinically, these agents may be potential adjuncts for patients with TRD who need antihypertensive therapy. Their use and the choice of specific agent should only be determined in consultation with the patient’s primary care physician (PCP) or appropriate specialist.

Glutamatergic strategies

Ketamine is a dissociative anesthetic and analgesic. Its MOA for treating depression appears to occur primarily through antagonist activity at the N-methyl-D-aspartate ionotropic receptor of the glutamatergic system. There is preliminary evidence that its opioid receptor actions also may contribute to its antidepressant effect.⁵

Continue to: Many published studies...

Many published studies and reviews have described ketamine’s role for treating MDD. Several studies have reported that low-dose (0.5 mg/kg) IV ketamine infusions can rapidly attenuate severe episodes of MDD as well as associated suicidality. For example, a meta-analysis of 9 RCTs (N = 368) comparing ketamine to placebo for acute treatment of unipolar and bipolar depression reported superior therapeutic effects with active treatment at 24 hours, 72 hours, and 7 days.⁶ The response and remission rates for ketamine were 52% and 21% at 24 hours; 48% and 24% at 72 hours; and 40% and 26% at 7 days, respectively.⁶

The most commonly reported AEs during the 4 hours after ketamine infusion included⁷:

• drowsiness, dizziness, poor coordination
• blurred vision, feeling strange or unreal
• hemodynamic changes (approximately 33%)
• small but significant (P < .05) increases in psychotomimetic and dissociative symptoms.

Because some individuals use ketamine recreationally, this agent also carries the risk of abuse.

Research is ongoing on strategies for long-term maintenance ketamine treatment, and the results of both short- and long-term trials will require careful scrutiny to better assess this agent’s safety and tolerability. Clinicians should first consider esketamine—the S-enantiomer of ketamine—because an intranasal formulation of this agent is FDA-approved for treating patients with TRD or MDD with suicidality when administered in a Risk Evaluation and Mitigation Strategy–certified setting.

Cholinergic strategies

Scopolamine is a potent muscarinic receptor antagonist used to prevent nausea and vomiting caused by motion sickness or medications used during surgery. Its use for MDD is based on the theory that muscarinic receptors may be hypersensitive in mood disorders.

Continue to: Several double-blind RCTs...

Several double-blind RCTs of patients with unipolar or bipolar depression that used 3 pulsed IV infusions (4.0 mcg/kg) over 15 minutes found a rapid, robust antidepressant effect with scopolamine vs placebo.^8,9 The oral formulation might also be effective, but would not have a rapid onset.

Common adverse effects of scopolamine include agitation, dry mouth, urinary retention, and cognitive clouding. Given scopolamine’s substantial AE profile, it should be considered only for patients with TRD who could also benefit from the oral formulation for the medical indications noted above, should generally be avoided in older patients, and should be prescribed in consultation with the patient’s PCP.

Botulinum toxin. This neurotoxin inhibits acetylcholine release. It is used to treat disorders characterized by abnormal muscular contraction, such as strabismus, blepharospasm, and chronic pain syndromes. Its MOA for depression may involve its paralytic effects after injection into the glabella forehead muscle (based on the facial feedback hypothesis), as well as modulation of neurotransmitters implicated in the pathophysiology of depression.

In several small trials, injectable botulinum toxin type A (BTA) (29 units) demonstrated antidepressant effects. A recent review that considered 6 trials (N = 235; 4 of the 6 studies were RCTs, 3 of which were rated as high quality) concluded that BTA may be a promising treatment for MDD.¹⁰ Limitations of this review included lack of a priori hypotheses, small sample sizes, gender bias, and difficulty in blinding.

In clinical trials, the most common AEs included local irritation at the injection site and transient headache. This agent’s relatively mild AE profile and possible overlap when used for some of the medical indications noted above opens its potential use as an adjunct in patients with comorbid TRD.

Continue to: Endocrine strategies

Endocrine strategies

Mifepristone (RU486). This anti-glucocorticoid receptor antagonist is used as an abortifacient. Based on the theory that hyperactivity of the hypothalamic-pituitary-adrenal axis is implicated in the pathophysiology of MDD with psychotic features (psychotic depression), this agent has been studied as a treatment for this indication.

An analysis of 5 double-blind RCTs (N = 1,460) found that 7 days of mifepristone, 1,200 mg/d, was superior to placebo (P < .004) in reducing psychotic symptoms of depression.¹¹ Plasma concentrations ≥1,600 ng/mL may be required to maximize benefit.¹¹

Overall, this agent demonstrated a good safety profile in clinical trials, with treatment-emergent AEs reported in 556 (66.7%) patients who received mifepristone vs 386 (61.6%) patients who received placebo.¹¹ Common AEs included gastrointestinal (GI) symptoms, headache, and dizziness. However, 3 deaths occurred: 2 patients who received mifepristone and 1 patient who received placebo. Given this potential for a fatal outcome, clinicians should first consider prescribing an adjunctive antipsychotic agent or electroconvulsive therapy.

Estrogens. These hormones are important for sexual and reproductive development and are used to treat various sexual/reproductive disorders, primarily in women. Their role in treating depression is based on the observation that perimenopause is accompanied by an increased risk of new and recurrent depression coincident with declining ovarian function.

Evidence supports the antidepressant efficacy of transdermal estradiol plus progesterone for perimenopausal depression, but not for postmenopausal depression.^12-14 However, estrogens carry significant risks that must be carefully considered in relationship to their potential benefits. These risks include:

• vaginal bleeding, dysmenorrhea
• fibroid enlargement
• galactorrhea
• ovarian cancer, endometrial cancer, breast cancer
• deep vein thrombosis, pulmonary embolism
• hypertension, chest pain, myocardial infarction, stroke.

Continue to: The use of estrogens...

The use of estrogens as an adjunctive therapy for women with treatment-resistant perimenopausal depression should only be undertaken when standard strategies have failed, and in consultation with an endocrine specialist who can monitor for potentially serious AEs.

Opioid medications

Buprenorphine is used to treat opioid use disorder (OUD) as well as acute and chronic pain. The opioid system is involved in the regulation of mood and may be an appropriate target for novel antidepressants. The use of buprenorphine in combination with samidorphan (a preferential mu-opioid receptor antagonist) has shown initial promise for TRD while minimizing abuse potential.

Although earlier results were mixed, a pooled analysis of 2 recent large RCTs (N = 760) of patients with MDD who had not responded to antidepressants reported greater reduction in Montgomery-Åsberg Depression Rating Scale scores from baseline for active treatment (buprenorphine/samidorphan; 2 mg/2 mg) vs placebo at multiple timepoints, including end of treatment (-1.8; P < .010).¹⁵

The most common AEs included nausea, constipation, dizziness, vomiting, somnolence, fatigue, and sedation. There was minimal evidence of abuse, dependence, or opioid withdrawal. Due to the opioid crisis in the United States, the resulting relaxation of regulations regarding prescribing buprenorphine, and the high rates of depression among patients with OUD, buprenorphine/samidorphan, which is an investigational agent that is not FDA-approved, may be particularly helpful for patients with OUD who also experience comorbid TRD.

Antioxidant agents

N-acetylcysteine (NAC) is an amino acid that can treat acetaminophen toxicity and moderate hepatic damage by increasing glutathione levels. Glutathione is also the primary antioxidant in the CNS. NAC may protect against oxidative stress, chelate heavy metals, reduce inflammation, protect against mitochondrial dysfunction, inhibit apoptosis, and enhance neurogenesis, all potential pathophysiological processes that may contribute to depression.¹⁶

Continue to: A systematic review...

A systematic review and meta-analysis of 5 RCTs (N = 574) considered patients with various depression diagnoses who were randomized to adjunctive NAC, 1,000 mg twice a day, or placebo. Over 12 to 24 weeks, there was a significantly greater improvement in mood symptoms and functionality with NAC vs placebo.¹⁶

Overall, NAC was well-tolerated. The most common AEs were GI symptoms, musculoskeletal complaints, decreased energy, and headache. While NAC has been touted as a potential adjunct therapy for several psychiatric disorders, including TRD, the evidence for benefit remains limited. Given its favorable AE profile, however, and over-the-counter availability, it remains an option for select patients. It is important to ask patients if they are already taking NAC.

Options beyond off-label medications

There are a multitude of options available for addressing TRD. Many FDA-approved medications are repurposed and prescribed off-label for other indications when the risk/benefit balance is favorable. In Part 1 of this article, we reviewed several off-label medications that have supportive controlled data for treating TRD. In Part 2, we will review other nontraditional therapies for TRD, including herbal/nutraceuticals, anti-inflammatory/immune system therapies, device-based treatments, and other alternative approaches.

Bottom Line

Off-label medications that may offer benefit for patients with treatment-resistant depression (TRD) include pimavanserin, antihypertensive agents, ketamine, scopolamine, botulinum toxin, mifepristone, estrogens, buprenorphine, and N-acetylcysteine. Although some evidence supports use of these agents as adjuncts for TRD, an individualized risk/benefit analysis is required.

Related Resource

• Joshi KG, Frierson RL. Off-label prescribing: How to limit your liability. Current Psychiatry. 2020;19(9):12,39.

Drug Brand Names

Amlodipine • Katerzia, Norvasc
Atenolol • Tenormin
Bisoprolol • Zebeta
Buprenorphine • Sublocade, Subutex
Carvedilol • Coreg
Enalapril • Vasotec
Esketamine • Spravato
Estradiol transdermal • Estraderm
Ketamine • Ketalar
Mifepristone • Mifeprex
Pimavanserin • Nuplazid
Progesterone • Prometrium
Propranolol • Inderal
Ramipril • Altace
Verapamil • Calan, Verelan

Presently, FDA-approved first-line treatments and standard adjunctive strategies (eg, lithium, thyroid supplementation, stimulants, second-generation antipsychotics) for major depressive disorder (MDD) often produce less-than-desired outcomes while carrying a potentially substantial safety and tolerability burden. The lack of clinically useful and individual-based biomarkers (eg, genetic, neurophysiological, imaging) is a major obstacle to enhancing treatment efficacy and/or decreasing associated adverse effects (AEs). While the discovery of such tools is being aggressively pursued and ultimately will facilitate a more precision-based choice of therapy, empirical strategies remain our primary approach.

In controlled trials, several nontraditional treatments used primarily as adjuncts to standard antidepressants have shown promise. These include “repurposed” (off-label) medications, herbal/nutraceuticals, anti-inflammatory/immune system therapies, device-based treatments, and other alternative approaches.

Importantly, some nontraditional treatments also demonstrate AEs (Table^1-16). With a careful consideration of the risk/benefit balance, this article reviews some of the better-studied treatment options for patients with treatment-resistant depression (TRD). In Part 1, we will examine off-label medications. In Part 2, we will review other nontraditional approaches to TRD, including herbal/nutraceuticals, anti-inflammatory/immune system therapies, device-based treatments, and other alternative approaches.

We believe this review will help clinicians who need to formulate a different approach after their patient with depression is not helped by traditional first-, second-, and third-line treatments. The potential options discussed in Part 1 of this article are categorized based on their putative mechanism of action (MOA) for depression.

Serotonergic and noradrenergic strategies

Pimavanserin is FDA-approved for treatment of Parkinson’s psychosis. Its potential MOA as an adjunctive strategy for MDD may involve 5-HT2A antagonist and inverse agonist receptor activity, as well as lesser effects at the 5-HT2Creceptor.

A 2-stage, 5-week randomized controlled trial (RCT) (CLARITY; N = 207) found adjunctive pimavanserin (34 mg/d) produced a robust antidepressant effect vs placebo in patients whose depression did not respond to selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs).¹ Furthermore, a secondary analysis of the data suggested that pimavanserin also improved sleepiness (P < .0003) and daily functioning (P < .014) at Week 5.²

Unfortunately, two 6-week, Phase III RCTs (CLARITY-2 and -3; N = 298) did not find a statistically significant difference between active treatment and placebo. This was based on change in the primary outcome measure (Hamilton Depression Rating Scale-17 score) when adjunctive pimavanserin (34 mg/d) was added to an SSRI or SNRI in patients with TRD.³ There was, however, a significant difference favoring active treatment over placebo based on the Clinical Global Impression–Severity score.

Continue to: In these trials...

In these trials, pimavanserin was generally well-tolerated. The most common AEs were dry mouth, nausea, and headache. Pimavanserin has minimal activity at norepinephrine, dopamine, histamine, or acetylcholine receptors, thus avoiding AEs associated with these receptor interactions.

Given the mixed efficacy results of existing trials, further studies are needed to clarify this agent’s overall risk/benefit in the context of TRD.

Antihypertensive medications

Emerging data suggest that some beta-adrenergic blockers, angiotensin-inhibiting agents, and calcium antagonists are associated with a decreased incidence of depression. A large 2020 study (N = 3,747,190) used population-based Danish registries (2005 to 2015) to evaluate if any of the 41 most commonly prescribed antihypertensive medications were associated with the diagnosis of depressive disorder or use of antidepressants.⁴ These researchers found that enalapril, ramipril, amlodipine, propranolol, atenolol, bisoprolol, carvedilol (P < .001), and verapamil (P < .004) were strongly associated with a decreased risk of depression.⁴

Adverse effects across these different classes of antihypertensives are well characterized, can be substantial, and commonly are related to their impact on cardiovascular function (eg, hypotension). Clinically, these agents may be potential adjuncts for patients with TRD who need antihypertensive therapy. Their use and the choice of specific agent should only be determined in consultation with the patient’s primary care physician (PCP) or appropriate specialist.

Glutamatergic strategies

Ketamine is a dissociative anesthetic and analgesic. Its MOA for treating depression appears to occur primarily through antagonist activity at the N-methyl-D-aspartate ionotropic receptor of the glutamatergic system. There is preliminary evidence that its opioid receptor actions also may contribute to its antidepressant effect.⁵

Continue to: Many published studies...

Many published studies and reviews have described ketamine’s role for treating MDD. Several studies have reported that low-dose (0.5 mg/kg) IV ketamine infusions can rapidly attenuate severe episodes of MDD as well as associated suicidality. For example, a meta-analysis of 9 RCTs (N = 368) comparing ketamine to placebo for acute treatment of unipolar and bipolar depression reported superior therapeutic effects with active treatment at 24 hours, 72 hours, and 7 days.⁶ The response and remission rates for ketamine were 52% and 21% at 24 hours; 48% and 24% at 72 hours; and 40% and 26% at 7 days, respectively.⁶

The most commonly reported AEs during the 4 hours after ketamine infusion included⁷:

• drowsiness, dizziness, poor coordination
• blurred vision, feeling strange or unreal
• hemodynamic changes (approximately 33%)
• small but significant (P < .05) increases in psychotomimetic and dissociative symptoms.

Because some individuals use ketamine recreationally, this agent also carries the risk of abuse.

Research is ongoing on strategies for long-term maintenance ketamine treatment, and the results of both short- and long-term trials will require careful scrutiny to better assess this agent’s safety and tolerability. Clinicians should first consider esketamine—the S-enantiomer of ketamine—because an intranasal formulation of this agent is FDA-approved for treating patients with TRD or MDD with suicidality when administered in a Risk Evaluation and Mitigation Strategy–certified setting.

Cholinergic strategies

Scopolamine is a potent muscarinic receptor antagonist used to prevent nausea and vomiting caused by motion sickness or medications used during surgery. Its use for MDD is based on the theory that muscarinic receptors may be hypersensitive in mood disorders.

Continue to: Several double-blind RCTs...

Several double-blind RCTs of patients with unipolar or bipolar depression that used 3 pulsed IV infusions (4.0 mcg/kg) over 15 minutes found a rapid, robust antidepressant effect with scopolamine vs placebo.^8,9 The oral formulation might also be effective, but would not have a rapid onset.

Common adverse effects of scopolamine include agitation, dry mouth, urinary retention, and cognitive clouding. Given scopolamine’s substantial AE profile, it should be considered only for patients with TRD who could also benefit from the oral formulation for the medical indications noted above, should generally be avoided in older patients, and should be prescribed in consultation with the patient’s PCP.

Botulinum toxin. This neurotoxin inhibits acetylcholine release. It is used to treat disorders characterized by abnormal muscular contraction, such as strabismus, blepharospasm, and chronic pain syndromes. Its MOA for depression may involve its paralytic effects after injection into the glabella forehead muscle (based on the facial feedback hypothesis), as well as modulation of neurotransmitters implicated in the pathophysiology of depression.

In several small trials, injectable botulinum toxin type A (BTA) (29 units) demonstrated antidepressant effects. A recent review that considered 6 trials (N = 235; 4 of the 6 studies were RCTs, 3 of which were rated as high quality) concluded that BTA may be a promising treatment for MDD.¹⁰ Limitations of this review included lack of a priori hypotheses, small sample sizes, gender bias, and difficulty in blinding.

In clinical trials, the most common AEs included local irritation at the injection site and transient headache. This agent’s relatively mild AE profile and possible overlap when used for some of the medical indications noted above opens its potential use as an adjunct in patients with comorbid TRD.

Continue to: Endocrine strategies

Endocrine strategies

Mifepristone (RU486). This anti-glucocorticoid receptor antagonist is used as an abortifacient. Based on the theory that hyperactivity of the hypothalamic-pituitary-adrenal axis is implicated in the pathophysiology of MDD with psychotic features (psychotic depression), this agent has been studied as a treatment for this indication.

An analysis of 5 double-blind RCTs (N = 1,460) found that 7 days of mifepristone, 1,200 mg/d, was superior to placebo (P < .004) in reducing psychotic symptoms of depression.¹¹ Plasma concentrations ≥1,600 ng/mL may be required to maximize benefit.¹¹

Overall, this agent demonstrated a good safety profile in clinical trials, with treatment-emergent AEs reported in 556 (66.7%) patients who received mifepristone vs 386 (61.6%) patients who received placebo.¹¹ Common AEs included gastrointestinal (GI) symptoms, headache, and dizziness. However, 3 deaths occurred: 2 patients who received mifepristone and 1 patient who received placebo. Given this potential for a fatal outcome, clinicians should first consider prescribing an adjunctive antipsychotic agent or electroconvulsive therapy.

Estrogens. These hormones are important for sexual and reproductive development and are used to treat various sexual/reproductive disorders, primarily in women. Their role in treating depression is based on the observation that perimenopause is accompanied by an increased risk of new and recurrent depression coincident with declining ovarian function.

Evidence supports the antidepressant efficacy of transdermal estradiol plus progesterone for perimenopausal depression, but not for postmenopausal depression.^12-14 However, estrogens carry significant risks that must be carefully considered in relationship to their potential benefits. These risks include:

• vaginal bleeding, dysmenorrhea
• fibroid enlargement
• galactorrhea
• ovarian cancer, endometrial cancer, breast cancer
• deep vein thrombosis, pulmonary embolism
• hypertension, chest pain, myocardial infarction, stroke.

Continue to: The use of estrogens...

The use of estrogens as an adjunctive therapy for women with treatment-resistant perimenopausal depression should only be undertaken when standard strategies have failed, and in consultation with an endocrine specialist who can monitor for potentially serious AEs.

Opioid medications

Buprenorphine is used to treat opioid use disorder (OUD) as well as acute and chronic pain. The opioid system is involved in the regulation of mood and may be an appropriate target for novel antidepressants. The use of buprenorphine in combination with samidorphan (a preferential mu-opioid receptor antagonist) has shown initial promise for TRD while minimizing abuse potential.

Although earlier results were mixed, a pooled analysis of 2 recent large RCTs (N = 760) of patients with MDD who had not responded to antidepressants reported greater reduction in Montgomery-Åsberg Depression Rating Scale scores from baseline for active treatment (buprenorphine/samidorphan; 2 mg/2 mg) vs placebo at multiple timepoints, including end of treatment (-1.8; P < .010).¹⁵

The most common AEs included nausea, constipation, dizziness, vomiting, somnolence, fatigue, and sedation. There was minimal evidence of abuse, dependence, or opioid withdrawal. Due to the opioid crisis in the United States, the resulting relaxation of regulations regarding prescribing buprenorphine, and the high rates of depression among patients with OUD, buprenorphine/samidorphan, which is an investigational agent that is not FDA-approved, may be particularly helpful for patients with OUD who also experience comorbid TRD.

Antioxidant agents

N-acetylcysteine (NAC) is an amino acid that can treat acetaminophen toxicity and moderate hepatic damage by increasing glutathione levels. Glutathione is also the primary antioxidant in the CNS. NAC may protect against oxidative stress, chelate heavy metals, reduce inflammation, protect against mitochondrial dysfunction, inhibit apoptosis, and enhance neurogenesis, all potential pathophysiological processes that may contribute to depression.¹⁶

Continue to: A systematic review...

A systematic review and meta-analysis of 5 RCTs (N = 574) considered patients with various depression diagnoses who were randomized to adjunctive NAC, 1,000 mg twice a day, or placebo. Over 12 to 24 weeks, there was a significantly greater improvement in mood symptoms and functionality with NAC vs placebo.¹⁶

Overall, NAC was well-tolerated. The most common AEs were GI symptoms, musculoskeletal complaints, decreased energy, and headache. While NAC has been touted as a potential adjunct therapy for several psychiatric disorders, including TRD, the evidence for benefit remains limited. Given its favorable AE profile, however, and over-the-counter availability, it remains an option for select patients. It is important to ask patients if they are already taking NAC.

Options beyond off-label medications

There are a multitude of options available for addressing TRD. Many FDA-approved medications are repurposed and prescribed off-label for other indications when the risk/benefit balance is favorable. In Part 1 of this article, we reviewed several off-label medications that have supportive controlled data for treating TRD. In Part 2, we will review other nontraditional therapies for TRD, including herbal/nutraceuticals, anti-inflammatory/immune system therapies, device-based treatments, and other alternative approaches.

Bottom Line

Off-label medications that may offer benefit for patients with treatment-resistant depression (TRD) include pimavanserin, antihypertensive agents, ketamine, scopolamine, botulinum toxin, mifepristone, estrogens, buprenorphine, and N-acetylcysteine. Although some evidence supports use of these agents as adjuncts for TRD, an individualized risk/benefit analysis is required.

Related Resource

• Joshi KG, Frierson RL. Off-label prescribing: How to limit your liability. Current Psychiatry. 2020;19(9):12,39.

Drug Brand Names

Amlodipine • Katerzia, Norvasc
Atenolol • Tenormin
Bisoprolol • Zebeta
Buprenorphine • Sublocade, Subutex
Carvedilol • Coreg
Enalapril • Vasotec
Esketamine • Spravato
Estradiol transdermal • Estraderm
Ketamine • Ketalar
Mifepristone • Mifeprex
Pimavanserin • Nuplazid
Progesterone • Prometrium
Propranolol • Inderal
Ramipril • Altace
Verapamil • Calan, Verelan

Mrs. W, age 35, presents to your clinic seeking treatment for anxiety and depression. She has no psychiatric history but reports feeling sad, overwhelmed, and stressed. Mrs. W has been married for 10 years, has 2 young children, and is currently pregnant. She recently discovered that her husband has been having an affair. Mrs. W tells you that she feels her marriage is unsalvageable and would like to ask her husband for a divorce, but worries that he will “put up a fight” and demand full custody of their children. When you ask why, she states that her husband is “pretty narcissistic” and tends to become combative when criticized or threatened, such as a recent discussion they had about his affair that ended with him concluding that if she were “sexier and more confident” he would not have cheated on her.

As Mrs. W is talking, you recall a conversation you recently overheard at a continuing medical education event. Two clinicians were discussing how their records had been subpoenaed in a child custody case, even though the patient’s mental health was not contested. You realize that Mrs. W’s situation may also fit under this exception to confidentiality or privilege. You wonder if you should have disclosed this possibility to her at the outset of your session and wonder what you should say now, because she is clearly in distress and in need of psychiatric treatment. On the other hand, you want her to be fully informed of the potential repercussions if she continues with treatment.

Confidentiality and privilege allow our patients to disclose sensitive details in a safe space. The psychiatrist’s duty is to keep the patient’s information confidential, except in limited circumstances. The patient’s privilege is their right to prevent someone in a special confidential relationship from testifying against them or releasing their private records. In certain instances, a patient may waive or be forced to waive privilege, and a psychiatrist may be compelled to testify or release treatment records to a court. This article reviews exceptions to confidentiality and privilege, focusing specifically on a little-known exception to privilege that arises in divorce and child custody cases. We discuss relevant legislation and provide recommendations for psychiatrists to better understand how to discuss these legal realities with patients who are or may go through a divorce or child custody case.

Understanding confidentiality and privilege

Confidentiality and privilege are related but distinct concepts. Confidentiality relates to the overall trusting relationship created between 2 parties, such as a physician and their patient, and the duty on the part of the trusted individual to keep information private. Privilege refers to a person’s specific legal right to prevent someone in that confidential, trusting relationship from testifying against them in court or releasing confidential records. Privilege is owned by the patient and must be asserted or waived by the patient in legal proceedings. The concepts of confidentiality and privilege are crucial in creating an open, candid therapeutic environment. Many courts, including the US Supreme Court,¹ have recognized the importance of confidentiality and privilege in establishing a positive therapeutic relationship between a psychotherapist and a patient. Without confidentiality and privilege, patients would be less likely to share sensitive yet clinically important information.

Commonly encountered exceptions to confidentiality (Table 1²) and privilege (Table 2) exist in medical practice. Psychiatrists should discuss these exceptions with patients at the outset of clinical treatment. A little-known exception to privilege that may compel a psychiatrist to disclose confidential records can occur in child custody proceedings. In certain states, the mere filing of a child custody claim constitutes an exception to physician-patient privilege. In these states, the parent filing for divorce and custody may automatically waive privilege and thus compel disclosure of psychiatric records, even if their mental health is not in question. The following recent Ohio Supreme Court case illustrates this exception.

Friedenberg v Friedenberg (2020)

Friedenberg v Friedenberg³ addressed the issue of privilege and release of mental health treatment records in custody disputes. Belinda Torres Friedenberg and Keith Friedenberg were married with 4 minor children. Mrs. Friedenberg filed for divorce in 2016, requesting custody of the children and spousal support. In response, Mr. Friedenberg also filed a complaint seeking custody. Mr. Friedenberg subpoenaed mental health treatment records for Mrs. Friedenberg, who responded by filing a request to prevent the release of these records given physician-patient privilege. Mr. Friedenberg argued that Mrs. Friedenberg had placed her physical and mental health at issue when she filed for divorce and custody. At no point did Mr. Friedenberg allege that Mrs. Friedenberg’s mental health made her an unfit parent. The court agreed with Mr. Friedenberg and compelled disclosure of Mrs. Friedenberg’s psychiatric records, stating it is “hard to imagine a scenario where the mental health records of a parent would not be relevant to issues around custody and the best interests of the children.” The judge reviewed Mrs. Friedenberg’s psychiatric records privately and released records deemed relevant to the custody proceedings. On appeal, the Ohio Supreme Court agreed with this approach, holding that a parent’s mental fitness is always an issue in child custody cases, even if not asserted by either party. The court further held that unnecessary disclosure of sensitive information was prevented by the judge’s private review of records before deciding which records to release to the opposing spouse.

Waiver of physician-patient privilege

Waiver of physician-patient privilege in custody and divorce proceedings varies by state (Table 3^3-6). The Friedenberg decision highlights the most restrictive approach, where the mere filing of a divorce and child custody request automatically waives privilege. Some states, such as Indiana,⁴ follow a similar scheme to Ohio. Other states are silent on this issue or explicitly prohibit a waiver of privilege, asserting that custody disputes alone do not trigger disclosure without additional justifications, such as aberrant parental behaviors or other historical information concerning for abuse, neglect, or lack of parental fitness, or if a parent places their mental health at issue.⁷

Continue to: Once privilege is waived...

Once privilege is waived, the next step is to determine who should examine psychiatric records, deem relevance, and disclose sensitive information to the court and the opposing party. A judge may make this determination, as in the Friedenberg case. Alternatively, an independent psychiatric examiner may be appointed by the court to examine one or both parties; to obtain collateral information, including psychiatric records; and to submit a report to the court with medicolegal opinions regarding parental fitness. For example, in Maryland,⁶ the mere filing of a custody suit does not waive privilege. If a parent’s mental health is questioned, the judge may order an independent psychiatric examination to determine the parent’s fitness, thus balancing the best interests of the child with the parent’s right to physician-patient privilege.

The problem with automatic waivers

The foundation of the physician-patient relationship is trust and confidentiality. While this holds true for every specialty, perhaps it is even more important in psychiatry, where our patients routinely disclose sensitive, personal information in hopes of healing. Patients may not be aware of exceptions to confidentiality, or only be aware of the most well-known exceptions, such as the clinician’s duty to report abuse, or to warn a third party about risk of harm by a patient. Furthermore, clinicians and patients alike may not be aware of less-common exceptions to privilege, such as those that may occur in custody proceedings. This is critically important in light of the high number of patients who are or may be seeking divorce and custody of their children.

As psychiatric clinicians, it is highly likely that we will see patients going through divorce and custody proceedings. In 2018, there were 2.24 marriages for every divorce,⁸ and in 2014, 27% of all American children were living with a custodial parent, with the other parent living elsewhere.⁹ Divorce can be a profoundly stressful time; thus, it would be expected that many individuals going through divorce would seek psychiatric treatment and support.

Our concern is that the Friedenberg approach, which results in automatic disclosure of sensitive mental health information when a party files for divorce and custody, could deter patients from seeking psychiatric treatment, especially those anticipating divorce. Importantly, because women are nearly twice as likely as men to experience depression and anxiety¹⁰ and are more likely to seek treatment, this approach could disproportionately impact them.¹¹ In general, an automatic waiver policy may create an additional obstacle for individuals who are already reticent to seek treatment.

How to handle these situations

As a psychiatrist, you should be familiar with your state’s laws regarding exceptions to patient-physician privilege, and should discuss exceptions at the outset of treatment. However, you will need to weigh the potential negative impacts of this information on the therapeutic relationship, including possible early termination. Furthermore, this information may impact a patient’s willingness to disclose all relevant information to mental health treatment if there is concern for later court disclosure. How should you balance these concerns? First, encourage patients to ask questions and raise concerns about confidentiality and privilege.¹² In addition, you may direct the patient to other resources, such as a family law attorney, if they have questions about how certain information may be used in a legal proceeding.

Continue to: Second, you should be...

Second, you should be transparent regarding documentation of psychiatric visits. While documentation must meet ethical, legal, and billing requirements, you should take care to include only relevant information needed to make a diagnosis and provide indicated treatment while maintaining a neutral tone and avoiding medical jargon.¹³ For instance, we frequently use the term “denied” in medical documentation, as in “Mr. X denied cough, sore throat, fever or chills.” However, in psychiatric notes, if a patient “denied alcohol use,” the colloquial interpretation of this word could imply a tone of distrust toward the patient. A more sensitive way to document this might be: “When screened, reported no alcohol use.” If a patient divulges information and then asks you to omit this from their chart, but you do not feel comfortable doing so, explain what and why you must include the information in the chart.¹⁴

Third, if you receive a subpoena or other document requesting privileged information, first contact the patient and inform them of the request, and then seek legal consultation through your employer or malpractice insurer.¹⁵ Not all subpoenas are valid and enforceable, so it is important for an attorney to examine the subpoena; in addition, the patient’s attorney may choose to challenge the subpoena and limit the disclosure of privileged information.

Finally, inform legislatures and courts about the potential harm of automatic waivers in custody proceedings. A judge’s examination of the psychiatric records, as in Friedenberg, is not an adequate safeguard. A judge is not a trained mental health professional and may deem “relevant” information to be nearly everything: a history of abuse, remote drug or alcohol use, disclosure of a past crime, or financial troubles. We advocate for courts to follow the Maryland model, where a spouse does not automatically waive privilege if filing for divorce or custody. If mental health becomes an issue in a case, then the court may seek an independent psychiatric examination. The independent examiner will have access to patient records but will be in a better position to determine which details are relevant in determining diagnosis and parental fitness, and to render an opinion to the court.

CASE CONTINUED

You inform Mrs. W about a possible exception to privilege in divorce and custody cases. She decides to first talk with a family law attorney before proceeding with treatment. You defer your diagnosis and wait to see if she wants to proceed with treatment. Unfortunately, she does not return to your office.

Bottom Line

Some states limit the confidentiality and privilege of parents who are in psychiatric treatment and also involved in divorce and child custody cases. Psychiatrists should be mindful of these exceptions, and discuss them with patients at the onset of treatment.

Related Resources

• Legal Information Institute. Child custody: an overview. www.law.cornell.edu/wex/child_custody
• Melton GB, Petrila J, Poythress NG, et al. Child custody in divorce. In: Melton GB, Petrila J, Poythress NG, et al. Psychological evaluations for the courts. Guilford Press; 2018:530-533.

Mrs. W, age 35, presents to your clinic seeking treatment for anxiety and depression. She has no psychiatric history but reports feeling sad, overwhelmed, and stressed. Mrs. W has been married for 10 years, has 2 young children, and is currently pregnant. She recently discovered that her husband has been having an affair. Mrs. W tells you that she feels her marriage is unsalvageable and would like to ask her husband for a divorce, but worries that he will “put up a fight” and demand full custody of their children. When you ask why, she states that her husband is “pretty narcissistic” and tends to become combative when criticized or threatened, such as a recent discussion they had about his affair that ended with him concluding that if she were “sexier and more confident” he would not have cheated on her.

As Mrs. W is talking, you recall a conversation you recently overheard at a continuing medical education event. Two clinicians were discussing how their records had been subpoenaed in a child custody case, even though the patient’s mental health was not contested. You realize that Mrs. W’s situation may also fit under this exception to confidentiality or privilege. You wonder if you should have disclosed this possibility to her at the outset of your session and wonder what you should say now, because she is clearly in distress and in need of psychiatric treatment. On the other hand, you want her to be fully informed of the potential repercussions if she continues with treatment.

Confidentiality and privilege allow our patients to disclose sensitive details in a safe space. The psychiatrist’s duty is to keep the patient’s information confidential, except in limited circumstances. The patient’s privilege is their right to prevent someone in a special confidential relationship from testifying against them or releasing their private records. In certain instances, a patient may waive or be forced to waive privilege, and a psychiatrist may be compelled to testify or release treatment records to a court. This article reviews exceptions to confidentiality and privilege, focusing specifically on a little-known exception to privilege that arises in divorce and child custody cases. We discuss relevant legislation and provide recommendations for psychiatrists to better understand how to discuss these legal realities with patients who are or may go through a divorce or child custody case.

Understanding confidentiality and privilege

Confidentiality and privilege are related but distinct concepts. Confidentiality relates to the overall trusting relationship created between 2 parties, such as a physician and their patient, and the duty on the part of the trusted individual to keep information private. Privilege refers to a person’s specific legal right to prevent someone in that confidential, trusting relationship from testifying against them in court or releasing confidential records. Privilege is owned by the patient and must be asserted or waived by the patient in legal proceedings. The concepts of confidentiality and privilege are crucial in creating an open, candid therapeutic environment. Many courts, including the US Supreme Court,¹ have recognized the importance of confidentiality and privilege in establishing a positive therapeutic relationship between a psychotherapist and a patient. Without confidentiality and privilege, patients would be less likely to share sensitive yet clinically important information.

Commonly encountered exceptions to confidentiality (Table 1²) and privilege (Table 2) exist in medical practice. Psychiatrists should discuss these exceptions with patients at the outset of clinical treatment. A little-known exception to privilege that may compel a psychiatrist to disclose confidential records can occur in child custody proceedings. In certain states, the mere filing of a child custody claim constitutes an exception to physician-patient privilege. In these states, the parent filing for divorce and custody may automatically waive privilege and thus compel disclosure of psychiatric records, even if their mental health is not in question. The following recent Ohio Supreme Court case illustrates this exception.

Friedenberg v Friedenberg (2020)

Friedenberg v Friedenberg³ addressed the issue of privilege and release of mental health treatment records in custody disputes. Belinda Torres Friedenberg and Keith Friedenberg were married with 4 minor children. Mrs. Friedenberg filed for divorce in 2016, requesting custody of the children and spousal support. In response, Mr. Friedenberg also filed a complaint seeking custody. Mr. Friedenberg subpoenaed mental health treatment records for Mrs. Friedenberg, who responded by filing a request to prevent the release of these records given physician-patient privilege. Mr. Friedenberg argued that Mrs. Friedenberg had placed her physical and mental health at issue when she filed for divorce and custody. At no point did Mr. Friedenberg allege that Mrs. Friedenberg’s mental health made her an unfit parent. The court agreed with Mr. Friedenberg and compelled disclosure of Mrs. Friedenberg’s psychiatric records, stating it is “hard to imagine a scenario where the mental health records of a parent would not be relevant to issues around custody and the best interests of the children.” The judge reviewed Mrs. Friedenberg’s psychiatric records privately and released records deemed relevant to the custody proceedings. On appeal, the Ohio Supreme Court agreed with this approach, holding that a parent’s mental fitness is always an issue in child custody cases, even if not asserted by either party. The court further held that unnecessary disclosure of sensitive information was prevented by the judge’s private review of records before deciding which records to release to the opposing spouse.

Waiver of physician-patient privilege

Waiver of physician-patient privilege in custody and divorce proceedings varies by state (Table 3^3-6). The Friedenberg decision highlights the most restrictive approach, where the mere filing of a divorce and child custody request automatically waives privilege. Some states, such as Indiana,⁴ follow a similar scheme to Ohio. Other states are silent on this issue or explicitly prohibit a waiver of privilege, asserting that custody disputes alone do not trigger disclosure without additional justifications, such as aberrant parental behaviors or other historical information concerning for abuse, neglect, or lack of parental fitness, or if a parent places their mental health at issue.⁷

Continue to: Once privilege is waived...

Once privilege is waived, the next step is to determine who should examine psychiatric records, deem relevance, and disclose sensitive information to the court and the opposing party. A judge may make this determination, as in the Friedenberg case. Alternatively, an independent psychiatric examiner may be appointed by the court to examine one or both parties; to obtain collateral information, including psychiatric records; and to submit a report to the court with medicolegal opinions regarding parental fitness. For example, in Maryland,⁶ the mere filing of a custody suit does not waive privilege. If a parent’s mental health is questioned, the judge may order an independent psychiatric examination to determine the parent’s fitness, thus balancing the best interests of the child with the parent’s right to physician-patient privilege.

The problem with automatic waivers

The foundation of the physician-patient relationship is trust and confidentiality. While this holds true for every specialty, perhaps it is even more important in psychiatry, where our patients routinely disclose sensitive, personal information in hopes of healing. Patients may not be aware of exceptions to confidentiality, or only be aware of the most well-known exceptions, such as the clinician’s duty to report abuse, or to warn a third party about risk of harm by a patient. Furthermore, clinicians and patients alike may not be aware of less-common exceptions to privilege, such as those that may occur in custody proceedings. This is critically important in light of the high number of patients who are or may be seeking divorce and custody of their children.

As psychiatric clinicians, it is highly likely that we will see patients going through divorce and custody proceedings. In 2018, there were 2.24 marriages for every divorce,⁸ and in 2014, 27% of all American children were living with a custodial parent, with the other parent living elsewhere.⁹ Divorce can be a profoundly stressful time; thus, it would be expected that many individuals going through divorce would seek psychiatric treatment and support.

Our concern is that the Friedenberg approach, which results in automatic disclosure of sensitive mental health information when a party files for divorce and custody, could deter patients from seeking psychiatric treatment, especially those anticipating divorce. Importantly, because women are nearly twice as likely as men to experience depression and anxiety¹⁰ and are more likely to seek treatment, this approach could disproportionately impact them.¹¹ In general, an automatic waiver policy may create an additional obstacle for individuals who are already reticent to seek treatment.

How to handle these situations

As a psychiatrist, you should be familiar with your state’s laws regarding exceptions to patient-physician privilege, and should discuss exceptions at the outset of treatment. However, you will need to weigh the potential negative impacts of this information on the therapeutic relationship, including possible early termination. Furthermore, this information may impact a patient’s willingness to disclose all relevant information to mental health treatment if there is concern for later court disclosure. How should you balance these concerns? First, encourage patients to ask questions and raise concerns about confidentiality and privilege.¹² In addition, you may direct the patient to other resources, such as a family law attorney, if they have questions about how certain information may be used in a legal proceeding.

Continue to: Second, you should be...

Second, you should be transparent regarding documentation of psychiatric visits. While documentation must meet ethical, legal, and billing requirements, you should take care to include only relevant information needed to make a diagnosis and provide indicated treatment while maintaining a neutral tone and avoiding medical jargon.¹³ For instance, we frequently use the term “denied” in medical documentation, as in “Mr. X denied cough, sore throat, fever or chills.” However, in psychiatric notes, if a patient “denied alcohol use,” the colloquial interpretation of this word could imply a tone of distrust toward the patient. A more sensitive way to document this might be: “When screened, reported no alcohol use.” If a patient divulges information and then asks you to omit this from their chart, but you do not feel comfortable doing so, explain what and why you must include the information in the chart.¹⁴

Third, if you receive a subpoena or other document requesting privileged information, first contact the patient and inform them of the request, and then seek legal consultation through your employer or malpractice insurer.¹⁵ Not all subpoenas are valid and enforceable, so it is important for an attorney to examine the subpoena; in addition, the patient’s attorney may choose to challenge the subpoena and limit the disclosure of privileged information.

Finally, inform legislatures and courts about the potential harm of automatic waivers in custody proceedings. A judge’s examination of the psychiatric records, as in Friedenberg, is not an adequate safeguard. A judge is not a trained mental health professional and may deem “relevant” information to be nearly everything: a history of abuse, remote drug or alcohol use, disclosure of a past crime, or financial troubles. We advocate for courts to follow the Maryland model, where a spouse does not automatically waive privilege if filing for divorce or custody. If mental health becomes an issue in a case, then the court may seek an independent psychiatric examination. The independent examiner will have access to patient records but will be in a better position to determine which details are relevant in determining diagnosis and parental fitness, and to render an opinion to the court.

CASE CONTINUED

You inform Mrs. W about a possible exception to privilege in divorce and custody cases. She decides to first talk with a family law attorney before proceeding with treatment. You defer your diagnosis and wait to see if she wants to proceed with treatment. Unfortunately, she does not return to your office.

Bottom Line

Some states limit the confidentiality and privilege of parents who are in psychiatric treatment and also involved in divorce and child custody cases. Psychiatrists should be mindful of these exceptions, and discuss them with patients at the onset of treatment.

Related Resources

• Legal Information Institute. Child custody: an overview. www.law.cornell.edu/wex/child_custody
• Melton GB, Petrila J, Poythress NG, et al. Child custody in divorce. In: Melton GB, Petrila J, Poythress NG, et al. Psychological evaluations for the courts. Guilford Press; 2018:530-533.

Mrs. W, age 35, presents to your clinic seeking treatment for anxiety and depression. She has no psychiatric history but reports feeling sad, overwhelmed, and stressed. Mrs. W has been married for 10 years, has 2 young children, and is currently pregnant. She recently discovered that her husband has been having an affair. Mrs. W tells you that she feels her marriage is unsalvageable and would like to ask her husband for a divorce, but worries that he will “put up a fight” and demand full custody of their children. When you ask why, she states that her husband is “pretty narcissistic” and tends to become combative when criticized or threatened, such as a recent discussion they had about his affair that ended with him concluding that if she were “sexier and more confident” he would not have cheated on her.

As Mrs. W is talking, you recall a conversation you recently overheard at a continuing medical education event. Two clinicians were discussing how their records had been subpoenaed in a child custody case, even though the patient’s mental health was not contested. You realize that Mrs. W’s situation may also fit under this exception to confidentiality or privilege. You wonder if you should have disclosed this possibility to her at the outset of your session and wonder what you should say now, because she is clearly in distress and in need of psychiatric treatment. On the other hand, you want her to be fully informed of the potential repercussions if she continues with treatment.

Confidentiality and privilege allow our patients to disclose sensitive details in a safe space. The psychiatrist’s duty is to keep the patient’s information confidential, except in limited circumstances. The patient’s privilege is their right to prevent someone in a special confidential relationship from testifying against them or releasing their private records. In certain instances, a patient may waive or be forced to waive privilege, and a psychiatrist may be compelled to testify or release treatment records to a court. This article reviews exceptions to confidentiality and privilege, focusing specifically on a little-known exception to privilege that arises in divorce and child custody cases. We discuss relevant legislation and provide recommendations for psychiatrists to better understand how to discuss these legal realities with patients who are or may go through a divorce or child custody case.

Understanding confidentiality and privilege

Confidentiality and privilege are related but distinct concepts. Confidentiality relates to the overall trusting relationship created between 2 parties, such as a physician and their patient, and the duty on the part of the trusted individual to keep information private. Privilege refers to a person’s specific legal right to prevent someone in that confidential, trusting relationship from testifying against them in court or releasing confidential records. Privilege is owned by the patient and must be asserted or waived by the patient in legal proceedings. The concepts of confidentiality and privilege are crucial in creating an open, candid therapeutic environment. Many courts, including the US Supreme Court,¹ have recognized the importance of confidentiality and privilege in establishing a positive therapeutic relationship between a psychotherapist and a patient. Without confidentiality and privilege, patients would be less likely to share sensitive yet clinically important information.

Commonly encountered exceptions to confidentiality (Table 1²) and privilege (Table 2) exist in medical practice. Psychiatrists should discuss these exceptions with patients at the outset of clinical treatment. A little-known exception to privilege that may compel a psychiatrist to disclose confidential records can occur in child custody proceedings. In certain states, the mere filing of a child custody claim constitutes an exception to physician-patient privilege. In these states, the parent filing for divorce and custody may automatically waive privilege and thus compel disclosure of psychiatric records, even if their mental health is not in question. The following recent Ohio Supreme Court case illustrates this exception.

Friedenberg v Friedenberg (2020)

Friedenberg v Friedenberg³ addressed the issue of privilege and release of mental health treatment records in custody disputes. Belinda Torres Friedenberg and Keith Friedenberg were married with 4 minor children. Mrs. Friedenberg filed for divorce in 2016, requesting custody of the children and spousal support. In response, Mr. Friedenberg also filed a complaint seeking custody. Mr. Friedenberg subpoenaed mental health treatment records for Mrs. Friedenberg, who responded by filing a request to prevent the release of these records given physician-patient privilege. Mr. Friedenberg argued that Mrs. Friedenberg had placed her physical and mental health at issue when she filed for divorce and custody. At no point did Mr. Friedenberg allege that Mrs. Friedenberg’s mental health made her an unfit parent. The court agreed with Mr. Friedenberg and compelled disclosure of Mrs. Friedenberg’s psychiatric records, stating it is “hard to imagine a scenario where the mental health records of a parent would not be relevant to issues around custody and the best interests of the children.” The judge reviewed Mrs. Friedenberg’s psychiatric records privately and released records deemed relevant to the custody proceedings. On appeal, the Ohio Supreme Court agreed with this approach, holding that a parent’s mental fitness is always an issue in child custody cases, even if not asserted by either party. The court further held that unnecessary disclosure of sensitive information was prevented by the judge’s private review of records before deciding which records to release to the opposing spouse.

Waiver of physician-patient privilege

Waiver of physician-patient privilege in custody and divorce proceedings varies by state (Table 3^3-6). The Friedenberg decision highlights the most restrictive approach, where the mere filing of a divorce and child custody request automatically waives privilege. Some states, such as Indiana,⁴ follow a similar scheme to Ohio. Other states are silent on this issue or explicitly prohibit a waiver of privilege, asserting that custody disputes alone do not trigger disclosure without additional justifications, such as aberrant parental behaviors or other historical information concerning for abuse, neglect, or lack of parental fitness, or if a parent places their mental health at issue.⁷

Continue to: Once privilege is waived...

Once privilege is waived, the next step is to determine who should examine psychiatric records, deem relevance, and disclose sensitive information to the court and the opposing party. A judge may make this determination, as in the Friedenberg case. Alternatively, an independent psychiatric examiner may be appointed by the court to examine one or both parties; to obtain collateral information, including psychiatric records; and to submit a report to the court with medicolegal opinions regarding parental fitness. For example, in Maryland,⁶ the mere filing of a custody suit does not waive privilege. If a parent’s mental health is questioned, the judge may order an independent psychiatric examination to determine the parent’s fitness, thus balancing the best interests of the child with the parent’s right to physician-patient privilege.

The problem with automatic waivers

The foundation of the physician-patient relationship is trust and confidentiality. While this holds true for every specialty, perhaps it is even more important in psychiatry, where our patients routinely disclose sensitive, personal information in hopes of healing. Patients may not be aware of exceptions to confidentiality, or only be aware of the most well-known exceptions, such as the clinician’s duty to report abuse, or to warn a third party about risk of harm by a patient. Furthermore, clinicians and patients alike may not be aware of less-common exceptions to privilege, such as those that may occur in custody proceedings. This is critically important in light of the high number of patients who are or may be seeking divorce and custody of their children.

As psychiatric clinicians, it is highly likely that we will see patients going through divorce and custody proceedings. In 2018, there were 2.24 marriages for every divorce,⁸ and in 2014, 27% of all American children were living with a custodial parent, with the other parent living elsewhere.⁹ Divorce can be a profoundly stressful time; thus, it would be expected that many individuals going through divorce would seek psychiatric treatment and support.

Our concern is that the Friedenberg approach, which results in automatic disclosure of sensitive mental health information when a party files for divorce and custody, could deter patients from seeking psychiatric treatment, especially those anticipating divorce. Importantly, because women are nearly twice as likely as men to experience depression and anxiety¹⁰ and are more likely to seek treatment, this approach could disproportionately impact them.¹¹ In general, an automatic waiver policy may create an additional obstacle for individuals who are already reticent to seek treatment.

How to handle these situations

As a psychiatrist, you should be familiar with your state’s laws regarding exceptions to patient-physician privilege, and should discuss exceptions at the outset of treatment. However, you will need to weigh the potential negative impacts of this information on the therapeutic relationship, including possible early termination. Furthermore, this information may impact a patient’s willingness to disclose all relevant information to mental health treatment if there is concern for later court disclosure. How should you balance these concerns? First, encourage patients to ask questions and raise concerns about confidentiality and privilege.¹² In addition, you may direct the patient to other resources, such as a family law attorney, if they have questions about how certain information may be used in a legal proceeding.

Continue to: Second, you should be...

Second, you should be transparent regarding documentation of psychiatric visits. While documentation must meet ethical, legal, and billing requirements, you should take care to include only relevant information needed to make a diagnosis and provide indicated treatment while maintaining a neutral tone and avoiding medical jargon.¹³ For instance, we frequently use the term “denied” in medical documentation, as in “Mr. X denied cough, sore throat, fever or chills.” However, in psychiatric notes, if a patient “denied alcohol use,” the colloquial interpretation of this word could imply a tone of distrust toward the patient. A more sensitive way to document this might be: “When screened, reported no alcohol use.” If a patient divulges information and then asks you to omit this from their chart, but you do not feel comfortable doing so, explain what and why you must include the information in the chart.¹⁴

Third, if you receive a subpoena or other document requesting privileged information, first contact the patient and inform them of the request, and then seek legal consultation through your employer or malpractice insurer.¹⁵ Not all subpoenas are valid and enforceable, so it is important for an attorney to examine the subpoena; in addition, the patient’s attorney may choose to challenge the subpoena and limit the disclosure of privileged information.

Finally, inform legislatures and courts about the potential harm of automatic waivers in custody proceedings. A judge’s examination of the psychiatric records, as in Friedenberg, is not an adequate safeguard. A judge is not a trained mental health professional and may deem “relevant” information to be nearly everything: a history of abuse, remote drug or alcohol use, disclosure of a past crime, or financial troubles. We advocate for courts to follow the Maryland model, where a spouse does not automatically waive privilege if filing for divorce or custody. If mental health becomes an issue in a case, then the court may seek an independent psychiatric examination. The independent examiner will have access to patient records but will be in a better position to determine which details are relevant in determining diagnosis and parental fitness, and to render an opinion to the court.

CASE CONTINUED

You inform Mrs. W about a possible exception to privilege in divorce and custody cases. She decides to first talk with a family law attorney before proceeding with treatment. You defer your diagnosis and wait to see if she wants to proceed with treatment. Unfortunately, she does not return to your office.

Bottom Line

Some states limit the confidentiality and privilege of parents who are in psychiatric treatment and also involved in divorce and child custody cases. Psychiatrists should be mindful of these exceptions, and discuss them with patients at the onset of treatment.

Related Resources

• Legal Information Institute. Child custody: an overview. www.law.cornell.edu/wex/child_custody
• Melton GB, Petrila J, Poythress NG, et al. Child custody in divorce. In: Melton GB, Petrila J, Poythress NG, et al. Psychological evaluations for the courts. Guilford Press; 2018:530-533.

The evolution of illness prevention, diagnosis, and treatment has involved an increased appreciation for the clinical utility of longitudinal assessment. This has included the implementation of screening evaluations for high base rate medical conditions, such as cancer, that involve considerable morbidity and mortality.

Unfortunately, the mental health professions have been slow to embrace this approach. Baseline assessment with psychological/neuropsychological screening tests and more comprehensive test batteries to clarify diagnostic status and facilitate treatment planning is far more the exception than the rule in mental health care. This seems to be the case despite the strong evidence supporting this practice as well as multiple surveys indicating that psychiatrists and other physicians report a high level of satisfaction with the findings and recommendations of psychological/neuropsychological test reports.^1-3

There is a substantial literature that reviews the relative indications and contraindications for initial psychological/neuropsychological test evaluations.^4-7 However, there is a paucity of clinical and evidence-based information regarding criteria for follow-up assessment. Moreover, there are no consensus guidelines to inform decision-making regarding this issue.

In general, good clinical practice for baseline assessment and reexamination should include administration of both psychological and neuropsychological tests. Based on clinical experience, this article addresses the relative indications and contraindications for psychological/neuropsychological test reassessment of adults seen in psychiatric care. It also outlines suggested time frames for such reevaluations, based on the patient’s clinical status and circumstances.

Why are patients not referred for reassessment more often?

There are several reasons patients are not referred for follow-up testing, beginning with the failure, at times, of the psychologist to state in the recommendations section of the test report whether a reassessment is indicated, under what circumstances, and within what time frame. Empirical data is lacking, but predicated on clinical experience, even when a strong and unequivocal recommendation is made for reassessment, only a very small percentage of patients are seen for follow-up evaluation.

There are numerous reasons why this occurs. The patient and/or the psychiatrist may overlook or forget about the recommendation for reassessment, particularly if it was embedded in a lengthy list of recommendations and the suggested time frame for the reassessment was several years away. The patient and the psychiatrist may decide against going forward with a reexamination, for a variety of substantive reasons. The patient might decline, against medical advice, to be retested. The patient may fail to make or keep an appointment for the follow-up reexamination. The patient might leave treatment and become lost to follow-up. The patient might not be able to find an appropriate psychologist. The insurance company may decline to authorize follow-up testing.⁸

Indications for reevaluation

Follow-up testing generally is indicated in the following circumstances:

Patients who are likely to soon improve or worsen. Reassessment is indicated when, based on the initial evaluation, the patient has been identified as having a neuropsychiatric disorder that is likely to improve or worsen over the next year or 2 due to the natural trajectory of the condition and the degree to which it may respond to treatment.

Continue to: Patients who are likely...

Patients who are likely to improve include those with mental status changes referable to ≥1 medical and/or neuropsychiatric factors that are considered at least partially treatable and reversible. Patients who fall within this category include those who have mild to moderately severe head trauma or stroke, have a suspected or known medication- or substance-induced altered mental status, appear to have depression-related cognitive difficulties, or have an initial or recurrent episode of idiopathic psychosis.

Patients whose conditions can be expected to worsen over time include those with a mild neurocognitive disorder or major neuro­cognitive disorder of mild severity that is considered referable to a progressive neurodegenerative illness such as Alzheimer’s disease based on family and personal history, their psychometric test profile, and other factors, including findings from positron emission tomography scanning.

Older patients who were referred primarily due to a strong family history of major neurocognitive disorder but with no clear-cut concerning findings on baseline testing warrant reevaluation in the event of the emergence of significant cognitive and/or psychiatric symptoms and/or a functional decline since the baseline examination.

Patients who have been seen for initial test evaluations prior to interventions such as neuro­surgery (including psychosurgery), electroconvulsive therapy (ECT), transcranial magnetic stimulation, cognitive rehabilitation, etc.

Patients undergoing a substantial transition. Reevaluation is appropriate for a broad range of patients experiencing difficulties when undergoing a significant lifestyle transition or change in level of care. This includes patients considering a return to school or work after a prolonged absence due to neuropsychiatric illness, or for whom there are questions regarding the need for a change in their level of everyday care. The latter includes patients who are returning to home care from assisted living, or transferring from home-based services to assisted living or a skilled nursing facility.

Continue to: What about patients with psychiatric disorders?

What about patients with psychiatric disorders? A “grey area” pertains to reassessment of patients with neuropsychiatric disorders such as schizophrenia and related psychotic disorders, bipolar disorder, major depressive disorder, and obsessive-compulsive disorder. Patients with these conditions often have high rates of cognitive/neuropsychological impairment on baseline testing, even when they appear to be improving from a psychiatric perspective, are reasonably stable, and may even be in remission.^9-12

These deficits are frequently a mix of pre-illness, prodromal, and early-stage illness– related neurocognitive difficulties that, for the most part, remain stable over time. That said, there is emerging evidence of worsening cognitive change over time following a first episode of psychosis for some patients with schizophrenia.¹³

In general, reevaluation should be considered for patients with a family and/or personal history of cognitive/neuropsychological impairment, structural brain abnormalities on neuroimaging, a concerning cognitive/neuropsychological profile, or any other factors that raise the index of suspicion for a possible progressive deteriorative course of illness.^13,14

Patients with personality disorders who have had a baseline psychometric evaluation do not clearly warrant reassessment unless they develop medical and/or psychosocial difficulties that are often linked to problematic personality traits/patterns and that result in significant and persistent mental status changes. For example, reassessment might be indicated for a patient with borderline personality disorder who has new-onset or worsening cognitive and/or psychiatric complaints/symptoms after sustaining a head injury while intoxicated and embroiled in a domestic conflict triggered by anger and fears related to abandonment and separation.

Reevaluation also should be considered when a patient with a personality disorder has had a baseline assessment and subsequently completes an intensive, long-term treatment program that is likely to improve their clinical status. In this context, retesting may help document these gains. Examples of such programs/services include residential psychiatric and/or substance abuse care, object relational/psychodynamically-based psychotherapy, an extended course of dialectical behavioral therapy, or a related coping skills/distress tolerance psychotherapy.

Continue to: Contraindications for reassessment

Contraindications for reassessment

Retesting generally is not indicated in the following circumstances:

Patients with advanced major neurocognitive disorder. Reassessment is not indicated for such patients when there are no new questions regarding diagnosis, prognosis, level of care, and/or related disposition issues.

Patients with transient episodes of poor functioning. For the most part, reassessment is not helpful for patients with well-established diagnoses and treatment plans who, based on their history, experience time-limited, recurrent episodes of poor functioning and then reliably return to their baseline with ongoing psychiatric care. This includes patients with borderline personality disorder and other personality difficulties with histories of transient decompensation in response to psychosocial and psychodynamic triggers.

Patients who do not improve or worsen over time. Reassessment is not indicated when there has been no clear, sustained improvement or worsening of a patient’s clinical status over an extended time, and a protracted change is not anticipated. In this situation, reassessment is unlikely to yield clinically useful information beyond what is already known or meaningfully impact case formulation and treatment planning.

The Table^9-14 summarizes the relative indications and contraindications for psychological/neuropsychological reexamination.

Continue to: Time frames for reassessment

Time frames for retesting vary considerably depending on factors such as diagnostic status, longitudinal course, treatment parameters, and recent/current life circumstances.

While empirical data is lacking regarding this matter, based on clinical experience, reevaluation in 18 to 24 months is generally appropriate for patients with neuro­psychiatric conditions who are likely to gradually improve or slowly worsen over this time. Still, reexamination can be sooner (within 12 to 18 months) for patients who have experienced a more rapid and steep negative change in clinical status than initially anticipated.

For most patients with major mental illness, reexamination in 3 to 5 years is probably a reasonable time interval, barring a poorly understood and clinically significant negative change in functioning that warrants a shorter time frame. This suggested time frame would allow for sufficient time to better gauge improvement, stability, or deterioration in functioning and whether the reason(s) for referral have evolved. On the other hand, this time interval is somewhat arbitrary given the lack of empirical data. Therefore, on a case-by-case basis, it would be helpful for psychiatrists to consult with their patients and preferably with the psychologist who completed the baseline evaluation to determine a reasonable interval between assessments.

For patients who have undergone long-term/intensive treatment, reassessment in 3 or 6 months to as long as 1 year after the patient completes the program should be considered. Patients who undergo medical interventions such as neurosurgery or ECT—which can be associated with short-term, at least partially reversible negative effects on mental status—reassessment usually is most helpful when initiated as one or more screening level examinations for several weeks, followed by a comprehensive psychometric reassessment at the 3- to 6-month mark.

Suggestions for future research

Additional research is needed to ascertain the attitudes and opinions of psychiatrists and other physicians who use psychometric test data regarding how psychologists can most effectively communicate a recommendation for reassessment in their reports and clarify the ways psychiatrists can productively address this issue with their patients. Survey research of this kind should include questions about the frequency with which psychiatrists formally refer patients for retesting, and estimates of the rate of follow-through.

Continue to: It also would be desirable...

It also would be desirable to investigate factors that may facilitate follow-through with recommendations for reassessment, or, conversely, identify reasons that psychiatrists and their patients may decide to forgo reassessment. It would be important to try to obtain information regarding the optimum time frames for such reevaluation, depending on the patient’s circumstances and other variables. Evidence-based data pertaining to these issues would contribute to the development of consensus guidelines and a standard of care for psychological/neuropsychological test reevaluation.

Bottom Line

Only a very small percentage of patients referred for follow-up psychological/ neuropsychological test reevaluation actually undergo reexamination. Such retesting may be most helpful for certain patient populations, such as those who are likely to soon improve or worsen, were referred based on a family history of major cognitive disorder but have no concerning findings on baseline testing, or are undergoing a substantial life transition.

Related Resources

• Thom R, Farrell HM. Neuroimaging in psychiatry: potentials and pitfalls. Current Psychiatry. 2019;18(12):27-28;33-34.
• Papakostas GI. Cognitive symptoms in patients with major depressive disorder and their implications for clinical practice. J Clin Psychiatry. 2014;75(1):8-14.
• American Board of Professional Neuropsychology. https://abn-board.com

The evolution of illness prevention, diagnosis, and treatment has involved an increased appreciation for the clinical utility of longitudinal assessment. This has included the implementation of screening evaluations for high base rate medical conditions, such as cancer, that involve considerable morbidity and mortality.

Unfortunately, the mental health professions have been slow to embrace this approach. Baseline assessment with psychological/neuropsychological screening tests and more comprehensive test batteries to clarify diagnostic status and facilitate treatment planning is far more the exception than the rule in mental health care. This seems to be the case despite the strong evidence supporting this practice as well as multiple surveys indicating that psychiatrists and other physicians report a high level of satisfaction with the findings and recommendations of psychological/neuropsychological test reports.^1-3

There is a substantial literature that reviews the relative indications and contraindications for initial psychological/neuropsychological test evaluations.^4-7 However, there is a paucity of clinical and evidence-based information regarding criteria for follow-up assessment. Moreover, there are no consensus guidelines to inform decision-making regarding this issue.

In general, good clinical practice for baseline assessment and reexamination should include administration of both psychological and neuropsychological tests. Based on clinical experience, this article addresses the relative indications and contraindications for psychological/neuropsychological test reassessment of adults seen in psychiatric care. It also outlines suggested time frames for such reevaluations, based on the patient’s clinical status and circumstances.

Why are patients not referred for reassessment more often?

There are several reasons patients are not referred for follow-up testing, beginning with the failure, at times, of the psychologist to state in the recommendations section of the test report whether a reassessment is indicated, under what circumstances, and within what time frame. Empirical data is lacking, but predicated on clinical experience, even when a strong and unequivocal recommendation is made for reassessment, only a very small percentage of patients are seen for follow-up evaluation.

There are numerous reasons why this occurs. The patient and/or the psychiatrist may overlook or forget about the recommendation for reassessment, particularly if it was embedded in a lengthy list of recommendations and the suggested time frame for the reassessment was several years away. The patient and the psychiatrist may decide against going forward with a reexamination, for a variety of substantive reasons. The patient might decline, against medical advice, to be retested. The patient may fail to make or keep an appointment for the follow-up reexamination. The patient might leave treatment and become lost to follow-up. The patient might not be able to find an appropriate psychologist. The insurance company may decline to authorize follow-up testing.⁸

Indications for reevaluation

Follow-up testing generally is indicated in the following circumstances:

Patients who are likely to soon improve or worsen. Reassessment is indicated when, based on the initial evaluation, the patient has been identified as having a neuropsychiatric disorder that is likely to improve or worsen over the next year or 2 due to the natural trajectory of the condition and the degree to which it may respond to treatment.

Continue to: Patients who are likely...

Patients who are likely to improve include those with mental status changes referable to ≥1 medical and/or neuropsychiatric factors that are considered at least partially treatable and reversible. Patients who fall within this category include those who have mild to moderately severe head trauma or stroke, have a suspected or known medication- or substance-induced altered mental status, appear to have depression-related cognitive difficulties, or have an initial or recurrent episode of idiopathic psychosis.

Patients whose conditions can be expected to worsen over time include those with a mild neurocognitive disorder or major neuro­cognitive disorder of mild severity that is considered referable to a progressive neurodegenerative illness such as Alzheimer’s disease based on family and personal history, their psychometric test profile, and other factors, including findings from positron emission tomography scanning.

Older patients who were referred primarily due to a strong family history of major neurocognitive disorder but with no clear-cut concerning findings on baseline testing warrant reevaluation in the event of the emergence of significant cognitive and/or psychiatric symptoms and/or a functional decline since the baseline examination.

Patients who have been seen for initial test evaluations prior to interventions such as neuro­surgery (including psychosurgery), electroconvulsive therapy (ECT), transcranial magnetic stimulation, cognitive rehabilitation, etc.

Patients undergoing a substantial transition. Reevaluation is appropriate for a broad range of patients experiencing difficulties when undergoing a significant lifestyle transition or change in level of care. This includes patients considering a return to school or work after a prolonged absence due to neuropsychiatric illness, or for whom there are questions regarding the need for a change in their level of everyday care. The latter includes patients who are returning to home care from assisted living, or transferring from home-based services to assisted living or a skilled nursing facility.

Continue to: What about patients with psychiatric disorders?

What about patients with psychiatric disorders? A “grey area” pertains to reassessment of patients with neuropsychiatric disorders such as schizophrenia and related psychotic disorders, bipolar disorder, major depressive disorder, and obsessive-compulsive disorder. Patients with these conditions often have high rates of cognitive/neuropsychological impairment on baseline testing, even when they appear to be improving from a psychiatric perspective, are reasonably stable, and may even be in remission.^9-12

These deficits are frequently a mix of pre-illness, prodromal, and early-stage illness– related neurocognitive difficulties that, for the most part, remain stable over time. That said, there is emerging evidence of worsening cognitive change over time following a first episode of psychosis for some patients with schizophrenia.¹³

In general, reevaluation should be considered for patients with a family and/or personal history of cognitive/neuropsychological impairment, structural brain abnormalities on neuroimaging, a concerning cognitive/neuropsychological profile, or any other factors that raise the index of suspicion for a possible progressive deteriorative course of illness.^13,14

Patients with personality disorders who have had a baseline psychometric evaluation do not clearly warrant reassessment unless they develop medical and/or psychosocial difficulties that are often linked to problematic personality traits/patterns and that result in significant and persistent mental status changes. For example, reassessment might be indicated for a patient with borderline personality disorder who has new-onset or worsening cognitive and/or psychiatric complaints/symptoms after sustaining a head injury while intoxicated and embroiled in a domestic conflict triggered by anger and fears related to abandonment and separation.

Reevaluation also should be considered when a patient with a personality disorder has had a baseline assessment and subsequently completes an intensive, long-term treatment program that is likely to improve their clinical status. In this context, retesting may help document these gains. Examples of such programs/services include residential psychiatric and/or substance abuse care, object relational/psychodynamically-based psychotherapy, an extended course of dialectical behavioral therapy, or a related coping skills/distress tolerance psychotherapy.

Continue to: Contraindications for reassessment

Contraindications for reassessment

Retesting generally is not indicated in the following circumstances:

Patients with advanced major neurocognitive disorder. Reassessment is not indicated for such patients when there are no new questions regarding diagnosis, prognosis, level of care, and/or related disposition issues.

Patients with transient episodes of poor functioning. For the most part, reassessment is not helpful for patients with well-established diagnoses and treatment plans who, based on their history, experience time-limited, recurrent episodes of poor functioning and then reliably return to their baseline with ongoing psychiatric care. This includes patients with borderline personality disorder and other personality difficulties with histories of transient decompensation in response to psychosocial and psychodynamic triggers.

Patients who do not improve or worsen over time. Reassessment is not indicated when there has been no clear, sustained improvement or worsening of a patient’s clinical status over an extended time, and a protracted change is not anticipated. In this situation, reassessment is unlikely to yield clinically useful information beyond what is already known or meaningfully impact case formulation and treatment planning.

The Table^9-14 summarizes the relative indications and contraindications for psychological/neuropsychological reexamination.

Continue to: Time frames for reassessment

Time frames for retesting vary considerably depending on factors such as diagnostic status, longitudinal course, treatment parameters, and recent/current life circumstances.

While empirical data is lacking regarding this matter, based on clinical experience, reevaluation in 18 to 24 months is generally appropriate for patients with neuro­psychiatric conditions who are likely to gradually improve or slowly worsen over this time. Still, reexamination can be sooner (within 12 to 18 months) for patients who have experienced a more rapid and steep negative change in clinical status than initially anticipated.

For most patients with major mental illness, reexamination in 3 to 5 years is probably a reasonable time interval, barring a poorly understood and clinically significant negative change in functioning that warrants a shorter time frame. This suggested time frame would allow for sufficient time to better gauge improvement, stability, or deterioration in functioning and whether the reason(s) for referral have evolved. On the other hand, this time interval is somewhat arbitrary given the lack of empirical data. Therefore, on a case-by-case basis, it would be helpful for psychiatrists to consult with their patients and preferably with the psychologist who completed the baseline evaluation to determine a reasonable interval between assessments.

For patients who have undergone long-term/intensive treatment, reassessment in 3 or 6 months to as long as 1 year after the patient completes the program should be considered. Patients who undergo medical interventions such as neurosurgery or ECT—which can be associated with short-term, at least partially reversible negative effects on mental status—reassessment usually is most helpful when initiated as one or more screening level examinations for several weeks, followed by a comprehensive psychometric reassessment at the 3- to 6-month mark.

Suggestions for future research

Additional research is needed to ascertain the attitudes and opinions of psychiatrists and other physicians who use psychometric test data regarding how psychologists can most effectively communicate a recommendation for reassessment in their reports and clarify the ways psychiatrists can productively address this issue with their patients. Survey research of this kind should include questions about the frequency with which psychiatrists formally refer patients for retesting, and estimates of the rate of follow-through.

Continue to: It also would be desirable...

It also would be desirable to investigate factors that may facilitate follow-through with recommendations for reassessment, or, conversely, identify reasons that psychiatrists and their patients may decide to forgo reassessment. It would be important to try to obtain information regarding the optimum time frames for such reevaluation, depending on the patient’s circumstances and other variables. Evidence-based data pertaining to these issues would contribute to the development of consensus guidelines and a standard of care for psychological/neuropsychological test reevaluation.

Bottom Line

Only a very small percentage of patients referred for follow-up psychological/ neuropsychological test reevaluation actually undergo reexamination. Such retesting may be most helpful for certain patient populations, such as those who are likely to soon improve or worsen, were referred based on a family history of major cognitive disorder but have no concerning findings on baseline testing, or are undergoing a substantial life transition.

Related Resources

• Thom R, Farrell HM. Neuroimaging in psychiatry: potentials and pitfalls. Current Psychiatry. 2019;18(12):27-28;33-34.
• Papakostas GI. Cognitive symptoms in patients with major depressive disorder and their implications for clinical practice. J Clin Psychiatry. 2014;75(1):8-14.
• American Board of Professional Neuropsychology. https://abn-board.com

The evolution of illness prevention, diagnosis, and treatment has involved an increased appreciation for the clinical utility of longitudinal assessment. This has included the implementation of screening evaluations for high base rate medical conditions, such as cancer, that involve considerable morbidity and mortality.

Unfortunately, the mental health professions have been slow to embrace this approach. Baseline assessment with psychological/neuropsychological screening tests and more comprehensive test batteries to clarify diagnostic status and facilitate treatment planning is far more the exception than the rule in mental health care. This seems to be the case despite the strong evidence supporting this practice as well as multiple surveys indicating that psychiatrists and other physicians report a high level of satisfaction with the findings and recommendations of psychological/neuropsychological test reports.^1-3

There is a substantial literature that reviews the relative indications and contraindications for initial psychological/neuropsychological test evaluations.^4-7 However, there is a paucity of clinical and evidence-based information regarding criteria for follow-up assessment. Moreover, there are no consensus guidelines to inform decision-making regarding this issue.

In general, good clinical practice for baseline assessment and reexamination should include administration of both psychological and neuropsychological tests. Based on clinical experience, this article addresses the relative indications and contraindications for psychological/neuropsychological test reassessment of adults seen in psychiatric care. It also outlines suggested time frames for such reevaluations, based on the patient’s clinical status and circumstances.

Why are patients not referred for reassessment more often?

There are several reasons patients are not referred for follow-up testing, beginning with the failure, at times, of the psychologist to state in the recommendations section of the test report whether a reassessment is indicated, under what circumstances, and within what time frame. Empirical data is lacking, but predicated on clinical experience, even when a strong and unequivocal recommendation is made for reassessment, only a very small percentage of patients are seen for follow-up evaluation.

There are numerous reasons why this occurs. The patient and/or the psychiatrist may overlook or forget about the recommendation for reassessment, particularly if it was embedded in a lengthy list of recommendations and the suggested time frame for the reassessment was several years away. The patient and the psychiatrist may decide against going forward with a reexamination, for a variety of substantive reasons. The patient might decline, against medical advice, to be retested. The patient may fail to make or keep an appointment for the follow-up reexamination. The patient might leave treatment and become lost to follow-up. The patient might not be able to find an appropriate psychologist. The insurance company may decline to authorize follow-up testing.⁸

Indications for reevaluation

Follow-up testing generally is indicated in the following circumstances:

Patients who are likely to soon improve or worsen. Reassessment is indicated when, based on the initial evaluation, the patient has been identified as having a neuropsychiatric disorder that is likely to improve or worsen over the next year or 2 due to the natural trajectory of the condition and the degree to which it may respond to treatment.

Continue to: Patients who are likely...

Patients who are likely to improve include those with mental status changes referable to ≥1 medical and/or neuropsychiatric factors that are considered at least partially treatable and reversible. Patients who fall within this category include those who have mild to moderately severe head trauma or stroke, have a suspected or known medication- or substance-induced altered mental status, appear to have depression-related cognitive difficulties, or have an initial or recurrent episode of idiopathic psychosis.

Patients whose conditions can be expected to worsen over time include those with a mild neurocognitive disorder or major neuro­cognitive disorder of mild severity that is considered referable to a progressive neurodegenerative illness such as Alzheimer’s disease based on family and personal history, their psychometric test profile, and other factors, including findings from positron emission tomography scanning.

Older patients who were referred primarily due to a strong family history of major neurocognitive disorder but with no clear-cut concerning findings on baseline testing warrant reevaluation in the event of the emergence of significant cognitive and/or psychiatric symptoms and/or a functional decline since the baseline examination.

Patients who have been seen for initial test evaluations prior to interventions such as neuro­surgery (including psychosurgery), electroconvulsive therapy (ECT), transcranial magnetic stimulation, cognitive rehabilitation, etc.

Patients undergoing a substantial transition. Reevaluation is appropriate for a broad range of patients experiencing difficulties when undergoing a significant lifestyle transition or change in level of care. This includes patients considering a return to school or work after a prolonged absence due to neuropsychiatric illness, or for whom there are questions regarding the need for a change in their level of everyday care. The latter includes patients who are returning to home care from assisted living, or transferring from home-based services to assisted living or a skilled nursing facility.

Continue to: What about patients with psychiatric disorders?

What about patients with psychiatric disorders? A “grey area” pertains to reassessment of patients with neuropsychiatric disorders such as schizophrenia and related psychotic disorders, bipolar disorder, major depressive disorder, and obsessive-compulsive disorder. Patients with these conditions often have high rates of cognitive/neuropsychological impairment on baseline testing, even when they appear to be improving from a psychiatric perspective, are reasonably stable, and may even be in remission.^9-12

These deficits are frequently a mix of pre-illness, prodromal, and early-stage illness– related neurocognitive difficulties that, for the most part, remain stable over time. That said, there is emerging evidence of worsening cognitive change over time following a first episode of psychosis for some patients with schizophrenia.¹³

In general, reevaluation should be considered for patients with a family and/or personal history of cognitive/neuropsychological impairment, structural brain abnormalities on neuroimaging, a concerning cognitive/neuropsychological profile, or any other factors that raise the index of suspicion for a possible progressive deteriorative course of illness.^13,14

Patients with personality disorders who have had a baseline psychometric evaluation do not clearly warrant reassessment unless they develop medical and/or psychosocial difficulties that are often linked to problematic personality traits/patterns and that result in significant and persistent mental status changes. For example, reassessment might be indicated for a patient with borderline personality disorder who has new-onset or worsening cognitive and/or psychiatric complaints/symptoms after sustaining a head injury while intoxicated and embroiled in a domestic conflict triggered by anger and fears related to abandonment and separation.

Reevaluation also should be considered when a patient with a personality disorder has had a baseline assessment and subsequently completes an intensive, long-term treatment program that is likely to improve their clinical status. In this context, retesting may help document these gains. Examples of such programs/services include residential psychiatric and/or substance abuse care, object relational/psychodynamically-based psychotherapy, an extended course of dialectical behavioral therapy, or a related coping skills/distress tolerance psychotherapy.

Continue to: Contraindications for reassessment

Contraindications for reassessment

Retesting generally is not indicated in the following circumstances:

Patients with advanced major neurocognitive disorder. Reassessment is not indicated for such patients when there are no new questions regarding diagnosis, prognosis, level of care, and/or related disposition issues.

Patients with transient episodes of poor functioning. For the most part, reassessment is not helpful for patients with well-established diagnoses and treatment plans who, based on their history, experience time-limited, recurrent episodes of poor functioning and then reliably return to their baseline with ongoing psychiatric care. This includes patients with borderline personality disorder and other personality difficulties with histories of transient decompensation in response to psychosocial and psychodynamic triggers.

Patients who do not improve or worsen over time. Reassessment is not indicated when there has been no clear, sustained improvement or worsening of a patient’s clinical status over an extended time, and a protracted change is not anticipated. In this situation, reassessment is unlikely to yield clinically useful information beyond what is already known or meaningfully impact case formulation and treatment planning.

The Table^9-14 summarizes the relative indications and contraindications for psychological/neuropsychological reexamination.

Continue to: Time frames for reassessment

Time frames for retesting vary considerably depending on factors such as diagnostic status, longitudinal course, treatment parameters, and recent/current life circumstances.

While empirical data is lacking regarding this matter, based on clinical experience, reevaluation in 18 to 24 months is generally appropriate for patients with neuro­psychiatric conditions who are likely to gradually improve or slowly worsen over this time. Still, reexamination can be sooner (within 12 to 18 months) for patients who have experienced a more rapid and steep negative change in clinical status than initially anticipated.

For most patients with major mental illness, reexamination in 3 to 5 years is probably a reasonable time interval, barring a poorly understood and clinically significant negative change in functioning that warrants a shorter time frame. This suggested time frame would allow for sufficient time to better gauge improvement, stability, or deterioration in functioning and whether the reason(s) for referral have evolved. On the other hand, this time interval is somewhat arbitrary given the lack of empirical data. Therefore, on a case-by-case basis, it would be helpful for psychiatrists to consult with their patients and preferably with the psychologist who completed the baseline evaluation to determine a reasonable interval between assessments.

For patients who have undergone long-term/intensive treatment, reassessment in 3 or 6 months to as long as 1 year after the patient completes the program should be considered. Patients who undergo medical interventions such as neurosurgery or ECT—which can be associated with short-term, at least partially reversible negative effects on mental status—reassessment usually is most helpful when initiated as one or more screening level examinations for several weeks, followed by a comprehensive psychometric reassessment at the 3- to 6-month mark.

Suggestions for future research

Additional research is needed to ascertain the attitudes and opinions of psychiatrists and other physicians who use psychometric test data regarding how psychologists can most effectively communicate a recommendation for reassessment in their reports and clarify the ways psychiatrists can productively address this issue with their patients. Survey research of this kind should include questions about the frequency with which psychiatrists formally refer patients for retesting, and estimates of the rate of follow-through.

Continue to: It also would be desirable...

It also would be desirable to investigate factors that may facilitate follow-through with recommendations for reassessment, or, conversely, identify reasons that psychiatrists and their patients may decide to forgo reassessment. It would be important to try to obtain information regarding the optimum time frames for such reevaluation, depending on the patient’s circumstances and other variables. Evidence-based data pertaining to these issues would contribute to the development of consensus guidelines and a standard of care for psychological/neuropsychological test reevaluation.

Bottom Line

Only a very small percentage of patients referred for follow-up psychological/ neuropsychological test reevaluation actually undergo reexamination. Such retesting may be most helpful for certain patient populations, such as those who are likely to soon improve or worsen, were referred based on a family history of major cognitive disorder but have no concerning findings on baseline testing, or are undergoing a substantial life transition.

Related Resources

• Thom R, Farrell HM. Neuroimaging in psychiatry: potentials and pitfalls. Current Psychiatry. 2019;18(12):27-28;33-34.
• Papakostas GI. Cognitive symptoms in patients with major depressive disorder and their implications for clinical practice. J Clin Psychiatry. 2014;75(1):8-14.
• American Board of Professional Neuropsychology. https://abn-board.com

The diagnosis of bipolar II disorder is one of the most common challenges in psychiatric practice. Bipolar II disorder is frequently misdiagnosed as major depressive disorder (MDD) because symptoms of transient hypomanic episodes are either insufficiently probed or are rather vague. However, there are many valuable biographical clues that can expedite the diagnosis of bipolar II disorder.

The late Hagop S. Akiskal, MD, who passed away in January 2021, was an internationally recognized expert in mood disorders, and a dear friend for decades. He was a keen observer of human behavior who delved into the “life stories” of patients seeking help for depression. By thinking “outside the DSM box,” Dr. Akiskal was the first to recognize and codify a variety of behavioral and biographical clues for the bipolar spectrum (of which he was a pioneer) in patients presenting with a chief complaint of depression. He proposed a colorful set of behavioral stigmata in most patients with bipolar II disorder by carefully canvassing the life experiences of the patients he treated in the mood disorder clinic he established in the 1970s, which is believed to have been the first mood specialty clinic in the country.

Based on a review of >1,000 patients in his clinic who presented with depressive symptoms and were ultimately diagnosed as bipolar II disorder, Dr. Akiskal highlighted what he labeled as “behavioral activation, flamboyance and extravagance” among those patients. He referred to the cluster of those behaviors as “the soft spectrum” of bipolar disorder, which manifests in a set of distinctive behaviors in addition to depressive symptoms. He found that research tools such as the DSM-based Structured Clinical Interview often fail and frequently lead to a misdiagnosis of bipolar II disorder as MDD. This often condemns the patient to multiple failed trials of antidepressant monotherapy, and a delay in improvement, thus increasing the risk of job loss, disrupted relationships, and even suicide.

Over 3 decades, Dr. Akiskal developed the Mood Clinic Data Questionnaire (MCDQ) to systematize unstructured observations of patients presenting with a chief complaint of depression. His tool expedites the diagnosis of bipolar II disorder by understanding the patient as an individual, revealing personal and behavioral features consistent with what he labeled as episodic “hyperthymia” within the context of recurrent depression. This “social and behavioral phenotype,” as Dr. Akiskal called it, is rarely observed among patients with MDD.

By examining many patients with bipolar II disorder, Dr. Akiskal identified several “triads” of behavioral traits in the patients’ biographical history and in some of their close blood relatives as well. He also noticed that temperamentally, patients with bipolar II disorder thrive on “activity” and lovingly referred to themselves as “activity junkies.” Some of them may qualify as workaholics.

Biographical features that suggest bipolar II disorder

Here is a summary of the unique biographical features of patients with bipolar II disorder that Dr. Akiskal described:

Multilingual. Speaking ≥3 languages is unusual among individuals born in the United States, but often encountered among those with bipolar II disorder.

Continue to: Eminence

Eminence. Patients with bipolar II disorder, as well as their family members, tend to have leadership roles and prominence in journalism, media, and entertainment, fields that require interpersonal charm and eloquence. Those are common features of the “hyperthymic” temperament.

Creativity. Artists, poets, painters, and musicians who experience depression are more likely to have bipolar II disorder than MDD.

Biographical instability and/or excess. This is exemplified by going to 3 colleges and not necessarily obtaining a degree, or by frequently changing one’s line of work or city of residence. A classic example is a professor of medicine who also practices law and regularly sings in the opera, or a physician who is board-certified in 3 distinct specialties.

Activity junkies. Examples include a person with boundless energy, such as a novelist who writes 3 books a year or a professional who regularly works 12 hours a day without getting exhausted but seeks treatment for depressive episodes.

Multiple substances of abuse, such as nicotine, alcohol, stimulants, and opiates.

Continue to: Multiple psychiatric comorbidities

Multiple psychiatric comorbidities, such as having 3 types of anxiety (panic attacks, social phobia, and obsessive-compulsive disorder) or bulimia, seasonal depression, and anxiety.

Multiple pleasure-seeking or “outrageous” behaviors, such as compulsive gambling, sexual addiction, car racing, or skydiving. Another example is having a history of shoplifting, paraphilia, or arrest for participating in a riot, all of which are suggestive of antisocial traits in a patient seeking help for depression.

Sexual excesses, such as dating or having sex with ≥3 individuals concurrently, sometimes on the same day, or demanding sexual intercourse from a partner several times a day. Dr. Akiskal suggested that “sexual prowess” may represent an evolutionary advantage for the perpetuation of bipolar II disorder.

Marital history, such as a history of ≥3 marriages, or maintaining ≥2 families in different cities without being married.

Flamboyance and/or ornamentation. Examples might include wearing loud, colorful clothing (especially red), wearing ≥3 rings, or having piercings in ≥3 different body parts (tongue, nipples, navel, genitalia). Having elaborate tattoos across the body is no longer unique to “hyperthymic” persons with bipolar II disorder because tattoos have become far more common in the general population than they were in the 1970s. However, some take their tattoos to extremes.

Continue to: The above behaviors...

The above behaviors are condensed in a list that Dr. Akiskal called “the rule of 3” in patients with depression (Table¹). Not all patients with bipolar II disorder will meet all the criteria of the rule of 3, but the first item in the mental status exam (appearance) alone may reflect the “soft bipolar spectrum,” such as garish clothing, red sneakers, multiple rings, bizarre hair coloring, and multiple piercings. This might prompt the clinician to ask further questions about hypomanic episodes as well as other personal behaviors related to the rule of 3.

Dr. Akiskal’s contributions to psychiatry are legendary in their originality, creativity, and clinical relevance. The rule of 3 is but one of his clinical concepts that may help identify many individuals with bipolar II disorder who are misdiagnosed as having MDD and prescribed a treatment that does not help or may exacerbate their illness course and worsen their outcome.

Based on the referrals of patients who are “treatment-resistant” to our Resident Mood Clinic, there are numerous persons in the country with bipolar II disorder (possibly millions) who are mislabeled with MDD and receiving the wrong treatments, to which they failed to respond. Their lifestyles and behaviors can provide valuable clinical insights into their true psychopathology, and that will lead to developing the right treatment plan.

The diagnosis of bipolar II disorder is one of the most common challenges in psychiatric practice. Bipolar II disorder is frequently misdiagnosed as major depressive disorder (MDD) because symptoms of transient hypomanic episodes are either insufficiently probed or are rather vague. However, there are many valuable biographical clues that can expedite the diagnosis of bipolar II disorder.

The late Hagop S. Akiskal, MD, who passed away in January 2021, was an internationally recognized expert in mood disorders, and a dear friend for decades. He was a keen observer of human behavior who delved into the “life stories” of patients seeking help for depression. By thinking “outside the DSM box,” Dr. Akiskal was the first to recognize and codify a variety of behavioral and biographical clues for the bipolar spectrum (of which he was a pioneer) in patients presenting with a chief complaint of depression. He proposed a colorful set of behavioral stigmata in most patients with bipolar II disorder by carefully canvassing the life experiences of the patients he treated in the mood disorder clinic he established in the 1970s, which is believed to have been the first mood specialty clinic in the country.

Based on a review of >1,000 patients in his clinic who presented with depressive symptoms and were ultimately diagnosed as bipolar II disorder, Dr. Akiskal highlighted what he labeled as “behavioral activation, flamboyance and extravagance” among those patients. He referred to the cluster of those behaviors as “the soft spectrum” of bipolar disorder, which manifests in a set of distinctive behaviors in addition to depressive symptoms. He found that research tools such as the DSM-based Structured Clinical Interview often fail and frequently lead to a misdiagnosis of bipolar II disorder as MDD. This often condemns the patient to multiple failed trials of antidepressant monotherapy, and a delay in improvement, thus increasing the risk of job loss, disrupted relationships, and even suicide.

Over 3 decades, Dr. Akiskal developed the Mood Clinic Data Questionnaire (MCDQ) to systematize unstructured observations of patients presenting with a chief complaint of depression. His tool expedites the diagnosis of bipolar II disorder by understanding the patient as an individual, revealing personal and behavioral features consistent with what he labeled as episodic “hyperthymia” within the context of recurrent depression. This “social and behavioral phenotype,” as Dr. Akiskal called it, is rarely observed among patients with MDD.

By examining many patients with bipolar II disorder, Dr. Akiskal identified several “triads” of behavioral traits in the patients’ biographical history and in some of their close blood relatives as well. He also noticed that temperamentally, patients with bipolar II disorder thrive on “activity” and lovingly referred to themselves as “activity junkies.” Some of them may qualify as workaholics.

Biographical features that suggest bipolar II disorder

Here is a summary of the unique biographical features of patients with bipolar II disorder that Dr. Akiskal described:

Multilingual. Speaking ≥3 languages is unusual among individuals born in the United States, but often encountered among those with bipolar II disorder.

Continue to: Eminence

Eminence. Patients with bipolar II disorder, as well as their family members, tend to have leadership roles and prominence in journalism, media, and entertainment, fields that require interpersonal charm and eloquence. Those are common features of the “hyperthymic” temperament.

Creativity. Artists, poets, painters, and musicians who experience depression are more likely to have bipolar II disorder than MDD.

Biographical instability and/or excess. This is exemplified by going to 3 colleges and not necessarily obtaining a degree, or by frequently changing one’s line of work or city of residence. A classic example is a professor of medicine who also practices law and regularly sings in the opera, or a physician who is board-certified in 3 distinct specialties.

Activity junkies. Examples include a person with boundless energy, such as a novelist who writes 3 books a year or a professional who regularly works 12 hours a day without getting exhausted but seeks treatment for depressive episodes.

Multiple substances of abuse, such as nicotine, alcohol, stimulants, and opiates.

Continue to: Multiple psychiatric comorbidities

Multiple psychiatric comorbidities, such as having 3 types of anxiety (panic attacks, social phobia, and obsessive-compulsive disorder) or bulimia, seasonal depression, and anxiety.

Multiple pleasure-seeking or “outrageous” behaviors, such as compulsive gambling, sexual addiction, car racing, or skydiving. Another example is having a history of shoplifting, paraphilia, or arrest for participating in a riot, all of which are suggestive of antisocial traits in a patient seeking help for depression.

Sexual excesses, such as dating or having sex with ≥3 individuals concurrently, sometimes on the same day, or demanding sexual intercourse from a partner several times a day. Dr. Akiskal suggested that “sexual prowess” may represent an evolutionary advantage for the perpetuation of bipolar II disorder.

Marital history, such as a history of ≥3 marriages, or maintaining ≥2 families in different cities without being married.

Flamboyance and/or ornamentation. Examples might include wearing loud, colorful clothing (especially red), wearing ≥3 rings, or having piercings in ≥3 different body parts (tongue, nipples, navel, genitalia). Having elaborate tattoos across the body is no longer unique to “hyperthymic” persons with bipolar II disorder because tattoos have become far more common in the general population than they were in the 1970s. However, some take their tattoos to extremes.

Continue to: The above behaviors...

The above behaviors are condensed in a list that Dr. Akiskal called “the rule of 3” in patients with depression (Table¹). Not all patients with bipolar II disorder will meet all the criteria of the rule of 3, but the first item in the mental status exam (appearance) alone may reflect the “soft bipolar spectrum,” such as garish clothing, red sneakers, multiple rings, bizarre hair coloring, and multiple piercings. This might prompt the clinician to ask further questions about hypomanic episodes as well as other personal behaviors related to the rule of 3.

Dr. Akiskal’s contributions to psychiatry are legendary in their originality, creativity, and clinical relevance. The rule of 3 is but one of his clinical concepts that may help identify many individuals with bipolar II disorder who are misdiagnosed as having MDD and prescribed a treatment that does not help or may exacerbate their illness course and worsen their outcome.

Based on the referrals of patients who are “treatment-resistant” to our Resident Mood Clinic, there are numerous persons in the country with bipolar II disorder (possibly millions) who are mislabeled with MDD and receiving the wrong treatments, to which they failed to respond. Their lifestyles and behaviors can provide valuable clinical insights into their true psychopathology, and that will lead to developing the right treatment plan.

The diagnosis of bipolar II disorder is one of the most common challenges in psychiatric practice. Bipolar II disorder is frequently misdiagnosed as major depressive disorder (MDD) because symptoms of transient hypomanic episodes are either insufficiently probed or are rather vague. However, there are many valuable biographical clues that can expedite the diagnosis of bipolar II disorder.

The late Hagop S. Akiskal, MD, who passed away in January 2021, was an internationally recognized expert in mood disorders, and a dear friend for decades. He was a keen observer of human behavior who delved into the “life stories” of patients seeking help for depression. By thinking “outside the DSM box,” Dr. Akiskal was the first to recognize and codify a variety of behavioral and biographical clues for the bipolar spectrum (of which he was a pioneer) in patients presenting with a chief complaint of depression. He proposed a colorful set of behavioral stigmata in most patients with bipolar II disorder by carefully canvassing the life experiences of the patients he treated in the mood disorder clinic he established in the 1970s, which is believed to have been the first mood specialty clinic in the country.

Based on a review of >1,000 patients in his clinic who presented with depressive symptoms and were ultimately diagnosed as bipolar II disorder, Dr. Akiskal highlighted what he labeled as “behavioral activation, flamboyance and extravagance” among those patients. He referred to the cluster of those behaviors as “the soft spectrum” of bipolar disorder, which manifests in a set of distinctive behaviors in addition to depressive symptoms. He found that research tools such as the DSM-based Structured Clinical Interview often fail and frequently lead to a misdiagnosis of bipolar II disorder as MDD. This often condemns the patient to multiple failed trials of antidepressant monotherapy, and a delay in improvement, thus increasing the risk of job loss, disrupted relationships, and even suicide.

Over 3 decades, Dr. Akiskal developed the Mood Clinic Data Questionnaire (MCDQ) to systematize unstructured observations of patients presenting with a chief complaint of depression. His tool expedites the diagnosis of bipolar II disorder by understanding the patient as an individual, revealing personal and behavioral features consistent with what he labeled as episodic “hyperthymia” within the context of recurrent depression. This “social and behavioral phenotype,” as Dr. Akiskal called it, is rarely observed among patients with MDD.

By examining many patients with bipolar II disorder, Dr. Akiskal identified several “triads” of behavioral traits in the patients’ biographical history and in some of their close blood relatives as well. He also noticed that temperamentally, patients with bipolar II disorder thrive on “activity” and lovingly referred to themselves as “activity junkies.” Some of them may qualify as workaholics.

Biographical features that suggest bipolar II disorder

Here is a summary of the unique biographical features of patients with bipolar II disorder that Dr. Akiskal described:

Multilingual. Speaking ≥3 languages is unusual among individuals born in the United States, but often encountered among those with bipolar II disorder.

Continue to: Eminence

Eminence. Patients with bipolar II disorder, as well as their family members, tend to have leadership roles and prominence in journalism, media, and entertainment, fields that require interpersonal charm and eloquence. Those are common features of the “hyperthymic” temperament.

Creativity. Artists, poets, painters, and musicians who experience depression are more likely to have bipolar II disorder than MDD.

Biographical instability and/or excess. This is exemplified by going to 3 colleges and not necessarily obtaining a degree, or by frequently changing one’s line of work or city of residence. A classic example is a professor of medicine who also practices law and regularly sings in the opera, or a physician who is board-certified in 3 distinct specialties.

Activity junkies. Examples include a person with boundless energy, such as a novelist who writes 3 books a year or a professional who regularly works 12 hours a day without getting exhausted but seeks treatment for depressive episodes.

Multiple substances of abuse, such as nicotine, alcohol, stimulants, and opiates.

Continue to: Multiple psychiatric comorbidities

Multiple psychiatric comorbidities, such as having 3 types of anxiety (panic attacks, social phobia, and obsessive-compulsive disorder) or bulimia, seasonal depression, and anxiety.

Multiple pleasure-seeking or “outrageous” behaviors, such as compulsive gambling, sexual addiction, car racing, or skydiving. Another example is having a history of shoplifting, paraphilia, or arrest for participating in a riot, all of which are suggestive of antisocial traits in a patient seeking help for depression.

Sexual excesses, such as dating or having sex with ≥3 individuals concurrently, sometimes on the same day, or demanding sexual intercourse from a partner several times a day. Dr. Akiskal suggested that “sexual prowess” may represent an evolutionary advantage for the perpetuation of bipolar II disorder.

Marital history, such as a history of ≥3 marriages, or maintaining ≥2 families in different cities without being married.

Flamboyance and/or ornamentation. Examples might include wearing loud, colorful clothing (especially red), wearing ≥3 rings, or having piercings in ≥3 different body parts (tongue, nipples, navel, genitalia). Having elaborate tattoos across the body is no longer unique to “hyperthymic” persons with bipolar II disorder because tattoos have become far more common in the general population than they were in the 1970s. However, some take their tattoos to extremes.

Continue to: The above behaviors...

The above behaviors are condensed in a list that Dr. Akiskal called “the rule of 3” in patients with depression (Table¹). Not all patients with bipolar II disorder will meet all the criteria of the rule of 3, but the first item in the mental status exam (appearance) alone may reflect the “soft bipolar spectrum,” such as garish clothing, red sneakers, multiple rings, bizarre hair coloring, and multiple piercings. This might prompt the clinician to ask further questions about hypomanic episodes as well as other personal behaviors related to the rule of 3.

Dr. Akiskal’s contributions to psychiatry are legendary in their originality, creativity, and clinical relevance. The rule of 3 is but one of his clinical concepts that may help identify many individuals with bipolar II disorder who are misdiagnosed as having MDD and prescribed a treatment that does not help or may exacerbate their illness course and worsen their outcome.

Based on the referrals of patients who are “treatment-resistant” to our Resident Mood Clinic, there are numerous persons in the country with bipolar II disorder (possibly millions) who are mislabeled with MDD and receiving the wrong treatments, to which they failed to respond. Their lifestyles and behaviors can provide valuable clinical insights into their true psychopathology, and that will lead to developing the right treatment plan.

Many psychiatrists conceptualize mental illnesses, including psychotic disorders, across a continuum where their borders can be ambiguous.¹ The same can be said of individual symptoms such as delusions, where the line separating clear-cut pathology from nonpathological or subclinical “delusion-like beliefs” is often blurred.^2,3 However, the categorical distinction between mental illness and normality is fundamental to diagnostic reliability and crucial to clinical decisions about whether and how to intervene.

Conspiracy theory beliefs are delusion-like beliefs that are commonly encountered within today’s political landscape. Surveys have consistently revealed that approximately one-half of the population believes in at least 1 conspiracy theory, highlighting the normality of such beliefs despite their potential outlandishness.⁴ Here are 3 questions you can ask to help differentiate conspiracy theory beliefs from delusions.

1. What is the evidence for the belief?

Drawing from Karl Jaspers’ conceptualization of delusions as “impossible” and “unshareable,” the DSM-5 distinguishes delusions from culturally-sanctioned shared beliefs such as religious creeds.³ Whereas delusions often arise out of anomalous subjective experiences, individuals who come to believe in conspiracytheories have typically sought explanations and found them from secondary sources, often on the internet.⁵ Despite the familiar term “conspiracy theorist,” most who believe in conspiracy theories aren’t so much theorizing as they are adopting counter-narratives based on assimilated information. Unlike delusions, conspiracy theory beliefs are learned, with the “evidence” to support them easily located online.

2. Is the belief self-referential?

The stereotypical unshareability of delusions often hinges upon their self-referential content. For example, while it is easy to find others who believe in the Second Coming, it would be much harder to convince others that you are the Second Coming. Unlike delusions, conspiracy theories are beliefs about the world and explanations of real-life events; their content is rarely, if ever, directly related to the believer.

Conspiracy theory beliefs involve a negation of authoritative accounts that is rooted in “epistemic mistrust” of authoritative sources of information.⁵ While conspiratorial mistrust has been compared with paranoia, with paranoia found to be associated with belief in conspiracy theories,⁶ epistemic mistrust encompasses a range of justified cultural mistrust, unwarranted mistrust based on racial prejudice, and subclinical paranoia typical of schizotypy. The more self-referential the underlying paranoia, the more likely an associated belief is to cross the boundary from conspiracy theory to delusion.⁷

3. Is there overlap?

Conspiracy theory beliefs and delusions are not mutually exclusive. “Gang stalking” offers a vexing example of paranoia that is part shared conspiracy theory, part idiosyncratic delusion.⁸ Reliably disentangling these components requires identifying the conspiracy theory component as a widely-shared belief about government surveillance, while carefully analyzing the self-referential component to determine credibility and potential delusionality.

Many psychiatrists conceptualize mental illnesses, including psychotic disorders, across a continuum where their borders can be ambiguous.¹ The same can be said of individual symptoms such as delusions, where the line separating clear-cut pathology from nonpathological or subclinical “delusion-like beliefs” is often blurred.^2,3 However, the categorical distinction between mental illness and normality is fundamental to diagnostic reliability and crucial to clinical decisions about whether and how to intervene.

Conspiracy theory beliefs are delusion-like beliefs that are commonly encountered within today’s political landscape. Surveys have consistently revealed that approximately one-half of the population believes in at least 1 conspiracy theory, highlighting the normality of such beliefs despite their potential outlandishness.⁴ Here are 3 questions you can ask to help differentiate conspiracy theory beliefs from delusions.

1. What is the evidence for the belief?

Drawing from Karl Jaspers’ conceptualization of delusions as “impossible” and “unshareable,” the DSM-5 distinguishes delusions from culturally-sanctioned shared beliefs such as religious creeds.³ Whereas delusions often arise out of anomalous subjective experiences, individuals who come to believe in conspiracytheories have typically sought explanations and found them from secondary sources, often on the internet.⁵ Despite the familiar term “conspiracy theorist,” most who believe in conspiracy theories aren’t so much theorizing as they are adopting counter-narratives based on assimilated information. Unlike delusions, conspiracy theory beliefs are learned, with the “evidence” to support them easily located online.

2. Is the belief self-referential?

The stereotypical unshareability of delusions often hinges upon their self-referential content. For example, while it is easy to find others who believe in the Second Coming, it would be much harder to convince others that you are the Second Coming. Unlike delusions, conspiracy theories are beliefs about the world and explanations of real-life events; their content is rarely, if ever, directly related to the believer.

Conspiracy theory beliefs involve a negation of authoritative accounts that is rooted in “epistemic mistrust” of authoritative sources of information.⁵ While conspiratorial mistrust has been compared with paranoia, with paranoia found to be associated with belief in conspiracy theories,⁶ epistemic mistrust encompasses a range of justified cultural mistrust, unwarranted mistrust based on racial prejudice, and subclinical paranoia typical of schizotypy. The more self-referential the underlying paranoia, the more likely an associated belief is to cross the boundary from conspiracy theory to delusion.⁷

3. Is there overlap?

Conspiracy theory beliefs and delusions are not mutually exclusive. “Gang stalking” offers a vexing example of paranoia that is part shared conspiracy theory, part idiosyncratic delusion.⁸ Reliably disentangling these components requires identifying the conspiracy theory component as a widely-shared belief about government surveillance, while carefully analyzing the self-referential component to determine credibility and potential delusionality.

Many psychiatrists conceptualize mental illnesses, including psychotic disorders, across a continuum where their borders can be ambiguous.¹ The same can be said of individual symptoms such as delusions, where the line separating clear-cut pathology from nonpathological or subclinical “delusion-like beliefs” is often blurred.^2,3 However, the categorical distinction between mental illness and normality is fundamental to diagnostic reliability and crucial to clinical decisions about whether and how to intervene.

Conspiracy theory beliefs are delusion-like beliefs that are commonly encountered within today’s political landscape. Surveys have consistently revealed that approximately one-half of the population believes in at least 1 conspiracy theory, highlighting the normality of such beliefs despite their potential outlandishness.⁴ Here are 3 questions you can ask to help differentiate conspiracy theory beliefs from delusions.

1. What is the evidence for the belief?

Drawing from Karl Jaspers’ conceptualization of delusions as “impossible” and “unshareable,” the DSM-5 distinguishes delusions from culturally-sanctioned shared beliefs such as religious creeds.³ Whereas delusions often arise out of anomalous subjective experiences, individuals who come to believe in conspiracytheories have typically sought explanations and found them from secondary sources, often on the internet.⁵ Despite the familiar term “conspiracy theorist,” most who believe in conspiracy theories aren’t so much theorizing as they are adopting counter-narratives based on assimilated information. Unlike delusions, conspiracy theory beliefs are learned, with the “evidence” to support them easily located online.

2. Is the belief self-referential?

The stereotypical unshareability of delusions often hinges upon their self-referential content. For example, while it is easy to find others who believe in the Second Coming, it would be much harder to convince others that you are the Second Coming. Unlike delusions, conspiracy theories are beliefs about the world and explanations of real-life events; their content is rarely, if ever, directly related to the believer.

Conspiracy theory beliefs involve a negation of authoritative accounts that is rooted in “epistemic mistrust” of authoritative sources of information.⁵ While conspiratorial mistrust has been compared with paranoia, with paranoia found to be associated with belief in conspiracy theories,⁶ epistemic mistrust encompasses a range of justified cultural mistrust, unwarranted mistrust based on racial prejudice, and subclinical paranoia typical of schizotypy. The more self-referential the underlying paranoia, the more likely an associated belief is to cross the boundary from conspiracy theory to delusion.⁷

3. Is there overlap?

Conspiracy theory beliefs and delusions are not mutually exclusive. “Gang stalking” offers a vexing example of paranoia that is part shared conspiracy theory, part idiosyncratic delusion.⁸ Reliably disentangling these components requires identifying the conspiracy theory component as a widely-shared belief about government surveillance, while carefully analyzing the self-referential component to determine credibility and potential delusionality.

Mrs. D, age 67, has a history of major depressive disorder. She has had adequate treatment trials with duloxetine, mirtazapine, and sertraline; each failed to produce remission. She is currently prescribed paroxetine, 40 mg/d, and aripiprazole, 10 mg/d, with good efficacy. She also has a history of hypertension and seasonal allergies, for which she receives amlodipine, 10 mg/d, and loratadine, 10 mg/d, respectively.

Mrs. D’s depressive symptoms were well controlled until 2 months ago, when she fell and fractured her hip. With encouragement from her prescriber, she enrolled in a partial hospitalization program for more intensive psychotherapy. During a medication education session, she is surprised to learn that antidepressants may affect bone health.

During a medication management meeting with her prescriber, Mrs. D asks about the risk of osteoporosis, and whether her antidepressant could have contributed to her hip fracture.

Bone is a dynamic tissue that undergoes a continuous process of remodeling. Osteoblasts are responsible for bone formation, whereas osteoclasts are responsible for bone resorption. Osteocytes—the predominant cell type in bone—along with cytokines, hormones, and growth factors help to orchestrate these actions.¹ Serotonin is increasingly recognized as a factor in bone homeostasis. Bone synthesizes serotonin, expresses serotonin transporters, and contains a variety of serotonin receptors.²

Serotonin serves many physiologic functions outside of the CNS, and it appears to have opposing actions on bone metabolism (Table 1^1,3). Peripheral (gut-derived) serotonin inhibits bone formation through its effects on osteoblasts, whereas the actions of serotonin in the CNS promote bone growth through inhibitory effects on sympathetic output.² Selective serotonin reuptake inhibitor (SSRI) enhancement of peripheral serotonin and its negative effect on bone may outweigh the benefits caused by SSRI enhancement of central serotonin neurotransmission.¹ In vitro data suggest SSRIs inhibit osteoblast and osteoclast function, theoretically decreasing bone turnover and increasing fracture risk.⁴ Other data indicate SSRI treatment may decrease procollagen type 1 N-terminal propeptide, a peripheral marker of bone formation.⁵ Both SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs) have been associated with lower cortical bone mineral density (BMD).⁶Table 2^7,8 details the relative affinity of select antidepressants for the serotonin transporter.

What the evidence says

Evidence for the correlation between fractures and serotonergic antidepressant use is mixed. One meta-analysis found a significant association between SSRIs and fractures, suggesting a 1.62-fold increased risk.¹³ Another meta-analysis investigated SSRIs and SNRIs and the risk of fracture.¹⁴ The SSRIs had a 1.67-fold increased risk; however, a lack of studies prohibited making conclusions about SNRIs. The number needed to harm was calculated at 85, 46, and 19 with 1, 2, and 5 years of SSRI exposure, respectively. A third meta-analysis found increased fracture risk related to depression and reported a hazard ratio of 1.26 after adjusting for confounders.⁹ This analysis suggests depression affects fracture risk and may limit the interpretation of causation from SSRI use. Studies included in these meta-analyses had significant heterogeneity.

Continue to: The effect of SSRIs...

The effect of SSRIs vs non-SSRIs on BMD also has been studied. The SSRIs were associated with significantly reduced BMD of the lumbar spine but not the total hip or femoral neck as compared to non-SSRIs; however, this BMD loss was not examined in relation to the presence of fractures. Older patients had more pronounced bone loss.¹⁵ Conversely, another meta-analysis examined BMD in women receiving SSRIs or tricyclic antidepressants.¹⁰ Neither medication class was associated with lower BMD at measured locations, including lumbar spine, femoral neck, and total hip. This analysis was limited by the lack of available trials; only 4 were included.

Other recent research has continued to explore the relationship between antidepressants and fracture in various patient populations. In a study of patients receiving maintenance dialysis treatment, short- and long-term SSRI use increased hip fracture risk. The authors speculated that short-term risk may be mediated by adverse effects that increase fall risk (eg, hyponatremia, orthostasis), whereas long-term risk may be influenced by changes in bone homeostasis.¹⁶ In two 6-month analyses of fluoxetine treatment in patients following an acute stroke, fluoxetine increased the risk of bone fractures.^17,18 Finally, in women with osteoporosis receiving risedronate or teriparatide, in both groups a higher fracture risk was observed for patients who were also receiving an SSRI or SNRI.¹⁹

Monitor BMD and educate patients about bone health

Available literature has not identified any clear risk factors for fracture with SSRI use. Guidelines suggest monitoring BMD in patients with risk factors for osteoporosis, if clinically indicated, as well as monitoring BMD in those receiving long-term antidepressant treatment.^20-22 Educate patients on strategies that promote optimal bone health, such as consuming a balanced diet that meets the recommended dietary allowance of calcium, vitamin D, and limits soda consumption. Teach patients to avoid tobacco and excessive alcohol use because both adversely impact BMD. Maintaining a healthy weight, physical activity, and adequate sleep also support bone health.¹¹ Instruct patients receiving antidepressants to report unexplained bone pain, tenderness, swelling, or bruising because these symptoms may be indicative of fracture.

CASE CONTINUED

Mrs. D’s age, sex, and depression place her at higher risk of fracture. Paroxetine is the only SSRI that has bone fracture listed as a precaution in its labeling.²³ In addition, it is the most anticholinergic SSRI and may have contributed to her fall. Switching to bupropion by cross titration may benefit Mrs. D because bupropion is not serotonergic. Little data exist regarding the effects of bupropion on bone. Her prescriber monitors Mrs. D’s BMD periodically, and educates her on dietary considerations. He also recommends calcium, 1,200 mg/d, and vitamin D, 800 IU/d, to help prevent fractures,²⁴ and that she continue physical therapy exercises and increase physical activity as tolerated.

Related Resources

• Cosman F, de Beur SJ, LeBoff MS, et al. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. 2014;25(10):2359-2581.
• Dodd S, Mitchell PB, Bauer M, et al. Monitoring for antidepressant-associated adverse events in the treatment of patients with major depressive disorder: an international consensus statement. World J Biol Psychiatry. 2018;19(5):330-348.
• Fernandes BS, Hodge JM, Pasco JA, et al. Effects of depression and serotonergic antidepressants on bone: mechanisms and implications for the treatment of depression. Drugs Aging. 2016;33(1):21-25.
• US National Library of Medicine. DailyMed. https://dailymed.nlm.nih.gov/dailymed

Drug Brand Names

Amitriptyline • Elavil
Amlodipine • Norvasc
Aripiprazole • Abilify
Bupropion • Wellbutrin
Citalopram • Celexa
Clomipramine • Anafranil
Desipramine • Norpramin
Doxepin • Silenor, Sinequan
Duloxetine • Cymbalta
Escitalopram • Lexapro
Fluoxetine • Prozac
Fluvoxamine • Luvox
Imipramine • Tofranil
Levomilnacipran • Fetzima
Loratadine • Claritin
Mirtazapine • Remeron
Nortriptyline • Pamelor
Paroxetine • Paxil
Risedronate • Actonel
Sertraline • Zoloft
Teriparatide • Forteo
Trazodone • Desyrel
Venlafaxine • Effexor
Vortioxetine • Trintellix

Mrs. D, age 67, has a history of major depressive disorder. She has had adequate treatment trials with duloxetine, mirtazapine, and sertraline; each failed to produce remission. She is currently prescribed paroxetine, 40 mg/d, and aripiprazole, 10 mg/d, with good efficacy. She also has a history of hypertension and seasonal allergies, for which she receives amlodipine, 10 mg/d, and loratadine, 10 mg/d, respectively.

Mrs. D’s depressive symptoms were well controlled until 2 months ago, when she fell and fractured her hip. With encouragement from her prescriber, she enrolled in a partial hospitalization program for more intensive psychotherapy. During a medication education session, she is surprised to learn that antidepressants may affect bone health.

During a medication management meeting with her prescriber, Mrs. D asks about the risk of osteoporosis, and whether her antidepressant could have contributed to her hip fracture.

Bone is a dynamic tissue that undergoes a continuous process of remodeling. Osteoblasts are responsible for bone formation, whereas osteoclasts are responsible for bone resorption. Osteocytes—the predominant cell type in bone—along with cytokines, hormones, and growth factors help to orchestrate these actions.¹ Serotonin is increasingly recognized as a factor in bone homeostasis. Bone synthesizes serotonin, expresses serotonin transporters, and contains a variety of serotonin receptors.²

Serotonin serves many physiologic functions outside of the CNS, and it appears to have opposing actions on bone metabolism (Table 1^1,3). Peripheral (gut-derived) serotonin inhibits bone formation through its effects on osteoblasts, whereas the actions of serotonin in the CNS promote bone growth through inhibitory effects on sympathetic output.² Selective serotonin reuptake inhibitor (SSRI) enhancement of peripheral serotonin and its negative effect on bone may outweigh the benefits caused by SSRI enhancement of central serotonin neurotransmission.¹ In vitro data suggest SSRIs inhibit osteoblast and osteoclast function, theoretically decreasing bone turnover and increasing fracture risk.⁴ Other data indicate SSRI treatment may decrease procollagen type 1 N-terminal propeptide, a peripheral marker of bone formation.⁵ Both SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs) have been associated with lower cortical bone mineral density (BMD).⁶Table 2^7,8 details the relative affinity of select antidepressants for the serotonin transporter.

What the evidence says

Evidence for the correlation between fractures and serotonergic antidepressant use is mixed. One meta-analysis found a significant association between SSRIs and fractures, suggesting a 1.62-fold increased risk.¹³ Another meta-analysis investigated SSRIs and SNRIs and the risk of fracture.¹⁴ The SSRIs had a 1.67-fold increased risk; however, a lack of studies prohibited making conclusions about SNRIs. The number needed to harm was calculated at 85, 46, and 19 with 1, 2, and 5 years of SSRI exposure, respectively. A third meta-analysis found increased fracture risk related to depression and reported a hazard ratio of 1.26 after adjusting for confounders.⁹ This analysis suggests depression affects fracture risk and may limit the interpretation of causation from SSRI use. Studies included in these meta-analyses had significant heterogeneity.

Continue to: The effect of SSRIs...

The effect of SSRIs vs non-SSRIs on BMD also has been studied. The SSRIs were associated with significantly reduced BMD of the lumbar spine but not the total hip or femoral neck as compared to non-SSRIs; however, this BMD loss was not examined in relation to the presence of fractures. Older patients had more pronounced bone loss.¹⁵ Conversely, another meta-analysis examined BMD in women receiving SSRIs or tricyclic antidepressants.¹⁰ Neither medication class was associated with lower BMD at measured locations, including lumbar spine, femoral neck, and total hip. This analysis was limited by the lack of available trials; only 4 were included.

Other recent research has continued to explore the relationship between antidepressants and fracture in various patient populations. In a study of patients receiving maintenance dialysis treatment, short- and long-term SSRI use increased hip fracture risk. The authors speculated that short-term risk may be mediated by adverse effects that increase fall risk (eg, hyponatremia, orthostasis), whereas long-term risk may be influenced by changes in bone homeostasis.¹⁶ In two 6-month analyses of fluoxetine treatment in patients following an acute stroke, fluoxetine increased the risk of bone fractures.^17,18 Finally, in women with osteoporosis receiving risedronate or teriparatide, in both groups a higher fracture risk was observed for patients who were also receiving an SSRI or SNRI.¹⁹

Monitor BMD and educate patients about bone health

Available literature has not identified any clear risk factors for fracture with SSRI use. Guidelines suggest monitoring BMD in patients with risk factors for osteoporosis, if clinically indicated, as well as monitoring BMD in those receiving long-term antidepressant treatment.^20-22 Educate patients on strategies that promote optimal bone health, such as consuming a balanced diet that meets the recommended dietary allowance of calcium, vitamin D, and limits soda consumption. Teach patients to avoid tobacco and excessive alcohol use because both adversely impact BMD. Maintaining a healthy weight, physical activity, and adequate sleep also support bone health.¹¹ Instruct patients receiving antidepressants to report unexplained bone pain, tenderness, swelling, or bruising because these symptoms may be indicative of fracture.

CASE CONTINUED

Mrs. D’s age, sex, and depression place her at higher risk of fracture. Paroxetine is the only SSRI that has bone fracture listed as a precaution in its labeling.²³ In addition, it is the most anticholinergic SSRI and may have contributed to her fall. Switching to bupropion by cross titration may benefit Mrs. D because bupropion is not serotonergic. Little data exist regarding the effects of bupropion on bone. Her prescriber monitors Mrs. D’s BMD periodically, and educates her on dietary considerations. He also recommends calcium, 1,200 mg/d, and vitamin D, 800 IU/d, to help prevent fractures,²⁴ and that she continue physical therapy exercises and increase physical activity as tolerated.

Related Resources

• Cosman F, de Beur SJ, LeBoff MS, et al. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. 2014;25(10):2359-2581.
• Dodd S, Mitchell PB, Bauer M, et al. Monitoring for antidepressant-associated adverse events in the treatment of patients with major depressive disorder: an international consensus statement. World J Biol Psychiatry. 2018;19(5):330-348.
• Fernandes BS, Hodge JM, Pasco JA, et al. Effects of depression and serotonergic antidepressants on bone: mechanisms and implications for the treatment of depression. Drugs Aging. 2016;33(1):21-25.
• US National Library of Medicine. DailyMed. https://dailymed.nlm.nih.gov/dailymed

Drug Brand Names

Amitriptyline • Elavil
Amlodipine • Norvasc
Aripiprazole • Abilify
Bupropion • Wellbutrin
Citalopram • Celexa
Clomipramine • Anafranil
Desipramine • Norpramin
Doxepin • Silenor, Sinequan
Duloxetine • Cymbalta
Escitalopram • Lexapro
Fluoxetine • Prozac
Fluvoxamine • Luvox
Imipramine • Tofranil
Levomilnacipran • Fetzima
Loratadine • Claritin
Mirtazapine • Remeron
Nortriptyline • Pamelor
Paroxetine • Paxil
Risedronate • Actonel
Sertraline • Zoloft
Teriparatide • Forteo
Trazodone • Desyrel
Venlafaxine • Effexor
Vortioxetine • Trintellix

Mrs. D, age 67, has a history of major depressive disorder. She has had adequate treatment trials with duloxetine, mirtazapine, and sertraline; each failed to produce remission. She is currently prescribed paroxetine, 40 mg/d, and aripiprazole, 10 mg/d, with good efficacy. She also has a history of hypertension and seasonal allergies, for which she receives amlodipine, 10 mg/d, and loratadine, 10 mg/d, respectively.

Mrs. D’s depressive symptoms were well controlled until 2 months ago, when she fell and fractured her hip. With encouragement from her prescriber, she enrolled in a partial hospitalization program for more intensive psychotherapy. During a medication education session, she is surprised to learn that antidepressants may affect bone health.

During a medication management meeting with her prescriber, Mrs. D asks about the risk of osteoporosis, and whether her antidepressant could have contributed to her hip fracture.

Bone is a dynamic tissue that undergoes a continuous process of remodeling. Osteoblasts are responsible for bone formation, whereas osteoclasts are responsible for bone resorption. Osteocytes—the predominant cell type in bone—along with cytokines, hormones, and growth factors help to orchestrate these actions.¹ Serotonin is increasingly recognized as a factor in bone homeostasis. Bone synthesizes serotonin, expresses serotonin transporters, and contains a variety of serotonin receptors.²

Serotonin serves many physiologic functions outside of the CNS, and it appears to have opposing actions on bone metabolism (Table 1^1,3). Peripheral (gut-derived) serotonin inhibits bone formation through its effects on osteoblasts, whereas the actions of serotonin in the CNS promote bone growth through inhibitory effects on sympathetic output.² Selective serotonin reuptake inhibitor (SSRI) enhancement of peripheral serotonin and its negative effect on bone may outweigh the benefits caused by SSRI enhancement of central serotonin neurotransmission.¹ In vitro data suggest SSRIs inhibit osteoblast and osteoclast function, theoretically decreasing bone turnover and increasing fracture risk.⁴ Other data indicate SSRI treatment may decrease procollagen type 1 N-terminal propeptide, a peripheral marker of bone formation.⁵ Both SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs) have been associated with lower cortical bone mineral density (BMD).⁶Table 2^7,8 details the relative affinity of select antidepressants for the serotonin transporter.

What the evidence says

Evidence for the correlation between fractures and serotonergic antidepressant use is mixed. One meta-analysis found a significant association between SSRIs and fractures, suggesting a 1.62-fold increased risk.¹³ Another meta-analysis investigated SSRIs and SNRIs and the risk of fracture.¹⁴ The SSRIs had a 1.67-fold increased risk; however, a lack of studies prohibited making conclusions about SNRIs. The number needed to harm was calculated at 85, 46, and 19 with 1, 2, and 5 years of SSRI exposure, respectively. A third meta-analysis found increased fracture risk related to depression and reported a hazard ratio of 1.26 after adjusting for confounders.⁹ This analysis suggests depression affects fracture risk and may limit the interpretation of causation from SSRI use. Studies included in these meta-analyses had significant heterogeneity.

Continue to: The effect of SSRIs...

The effect of SSRIs vs non-SSRIs on BMD also has been studied. The SSRIs were associated with significantly reduced BMD of the lumbar spine but not the total hip or femoral neck as compared to non-SSRIs; however, this BMD loss was not examined in relation to the presence of fractures. Older patients had more pronounced bone loss.¹⁵ Conversely, another meta-analysis examined BMD in women receiving SSRIs or tricyclic antidepressants.¹⁰ Neither medication class was associated with lower BMD at measured locations, including lumbar spine, femoral neck, and total hip. This analysis was limited by the lack of available trials; only 4 were included.

Other recent research has continued to explore the relationship between antidepressants and fracture in various patient populations. In a study of patients receiving maintenance dialysis treatment, short- and long-term SSRI use increased hip fracture risk. The authors speculated that short-term risk may be mediated by adverse effects that increase fall risk (eg, hyponatremia, orthostasis), whereas long-term risk may be influenced by changes in bone homeostasis.¹⁶ In two 6-month analyses of fluoxetine treatment in patients following an acute stroke, fluoxetine increased the risk of bone fractures.^17,18 Finally, in women with osteoporosis receiving risedronate or teriparatide, in both groups a higher fracture risk was observed for patients who were also receiving an SSRI or SNRI.¹⁹

Monitor BMD and educate patients about bone health

Available literature has not identified any clear risk factors for fracture with SSRI use. Guidelines suggest monitoring BMD in patients with risk factors for osteoporosis, if clinically indicated, as well as monitoring BMD in those receiving long-term antidepressant treatment.^20-22 Educate patients on strategies that promote optimal bone health, such as consuming a balanced diet that meets the recommended dietary allowance of calcium, vitamin D, and limits soda consumption. Teach patients to avoid tobacco and excessive alcohol use because both adversely impact BMD. Maintaining a healthy weight, physical activity, and adequate sleep also support bone health.¹¹ Instruct patients receiving antidepressants to report unexplained bone pain, tenderness, swelling, or bruising because these symptoms may be indicative of fracture.

CASE CONTINUED

Mrs. D’s age, sex, and depression place her at higher risk of fracture. Paroxetine is the only SSRI that has bone fracture listed as a precaution in its labeling.²³ In addition, it is the most anticholinergic SSRI and may have contributed to her fall. Switching to bupropion by cross titration may benefit Mrs. D because bupropion is not serotonergic. Little data exist regarding the effects of bupropion on bone. Her prescriber monitors Mrs. D’s BMD periodically, and educates her on dietary considerations. He also recommends calcium, 1,200 mg/d, and vitamin D, 800 IU/d, to help prevent fractures,²⁴ and that she continue physical therapy exercises and increase physical activity as tolerated.

Related Resources

• Cosman F, de Beur SJ, LeBoff MS, et al. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. 2014;25(10):2359-2581.
• Dodd S, Mitchell PB, Bauer M, et al. Monitoring for antidepressant-associated adverse events in the treatment of patients with major depressive disorder: an international consensus statement. World J Biol Psychiatry. 2018;19(5):330-348.
• Fernandes BS, Hodge JM, Pasco JA, et al. Effects of depression and serotonergic antidepressants on bone: mechanisms and implications for the treatment of depression. Drugs Aging. 2016;33(1):21-25.
• US National Library of Medicine. DailyMed. https://dailymed.nlm.nih.gov/dailymed

Drug Brand Names

Amitriptyline • Elavil
Amlodipine • Norvasc
Aripiprazole • Abilify
Bupropion • Wellbutrin
Citalopram • Celexa
Clomipramine • Anafranil
Desipramine • Norpramin
Doxepin • Silenor, Sinequan
Duloxetine • Cymbalta
Escitalopram • Lexapro
Fluoxetine • Prozac
Fluvoxamine • Luvox
Imipramine • Tofranil
Levomilnacipran • Fetzima
Loratadine • Claritin
Mirtazapine • Remeron
Nortriptyline • Pamelor
Paroxetine • Paxil
Risedronate • Actonel
Sertraline • Zoloft
Teriparatide • Forteo
Trazodone • Desyrel
Venlafaxine • Effexor
Vortioxetine • Trintellix

CASE Unresponsive after a presumed seizure

Mr. F, age 44, has schizophrenia. He is brought to the hospital by ambulance after he is found on the ground outside of his mother’s house following a presumed seizure and fall. On arrival to the emergency department, he is unresponsive. His laboratory values are significant for a sodium level of 110 mEq/L (reference range: 135 to 145 mEq/L), indicating hyponatremia.

HISTORY Fixated on purity

Mr. F’s mother reports that Mr. F had an unremarkable childhood. He was raised in a household with both parents and a younger sister. Mr. F did well academically and studied engineering and physics in college. There was no reported history of trauma or substance use.

During his senior year of college, Mr. F began experiencing paranoia, auditory hallucinations, and religious delusions. He required hospitalization and was diagnosed with schizophrenia. Following multiple hospitalizations over 5 years, he moved in with his mother, who was granted guardianship.

His mother said Mr. F’s religious delusions were of purity and cleansing the soul. He spent hours memorizing the Bible and would go for days without eating but would drink large amounts of water. She said she thought this was due to his desire to flush out imperfections.

In the past 3 years, Mr. F has been hospitalized several times for severe hyponatremia. At home, his mother attempted to restrict his water intake. However, Mr. F would still drink out of sinks and hoses. Mr. F’s mother reports that over the past month he had become more isolated. He would spend entire days reading the Bible, and his water intake had further increased.

Prior medication trials for Mr. F included haloperidol, up to 10 mg twice per day; aripiprazole, up to 20 mg/d; and risperidone, up to 6 mg nightly. These had been effective, but Mr. F had difficulty with adherence. He did not receive a long-acting injectable (LAI) antipsychotic initially due to lack of access at the rural clinic where he was treated, and later due to his mother’s preference for her son to receive oral medications. Prior to his current presentation, Mr. F’s medication regimen was olanzapine, 10 mg twice a day; perphenazine, 8 mg twice a day; and long-acting propranolol, 60 mg/d. Mr. F had no other chronic medical problems.

EVALUATION Hyponatremia, but why?

Mr. F is intubated and admitted to the surgical service for stabilization due to injuries from his fall. He has fractures of his right sinus and bilateral nasal bones, which are managed nonoperatively. He is delirious, with waxing and waning attention, memory disturbances, and disorientation. His psychotropic medications are held.

Continue to: Imaging of his head...

Imaging of his head does not reveal acute abnormalities suggesting a malignant or paraneoplastic process, and there are no concerns for ongoing seizures. An infection workup is negative. His urine toxicology is negative and blood alcohol level is 0. His sodium normalizes after 3 days of IV fluids and fluid restriction. Therefore, further tests to differentiate the causes of hyponatremia, such as urine electrolytes and urine osmolality, are not pursued.

[polldaddy:10910406]

The authors’ observations

The differential diagnosis for hyponatremia is broad in the setting of psychiatric illness. Low sodium levels could be due to psychotropic medications, psychiatrically-driven behaviors, or an underlying medical problem. Our differential diagnosis for Mr. F included iatrogenic syndrome of inappropriate antidiuretic hormone (SIADH), diabetes insipidus, or psychogenic polydipsia, a form of primary polydipsia. Other causes of primary polydipsia are related to substances, such as heavy beer intakeor use of 3,4-methylenedioxymethamphetamine (MDMA, also known as “ecstasy”), or brain lesions,¹ but these causes were less likely given Mr. F’s negative urine toxicology and head imaging.

While psychogenic polydipsia is due to increased water consumption, both SIADH and diabetes insipidus are due to alterations in fluid homeostasis.^2,3 Table 1^2-4 outlines distinguishing characteristics of SIADH, diabetes insipidus, and psychogenic polydipsia. Urine studies were not pursued because Mr. F’s sodium resolved and acute concerns, such as malignancy or infection, were ruled out. Mr. F’s hyponatremia was presumed to be due to psychogenic polydipsia because of his increased fluid intake and normalization of sodium with hypertonic fluids and subsequent fluid restriction. During this time, he was managed on the surgical service; the plan was to pursue urine studies and possibly a fluid challenge if his hyponatremia persisted.

EVALUATION Delirium resolves, delusions persist

While Mr. F is on the surgical service, the treatment team focuses on stabilizing his sodium level and assessing for causes of altered mental status that led to his fall. Psychiatry is consulted for management of his agitation. Following the gradual correction of his sodium level and extubation, his sensorium improves. By hospital Day 5, Mr. F’s delirium resolves.

During this time, Mr. F’s disorganization and religious delusions become apparent. He spends much of his time reading his Bible. He has poor hygiene and limited engagement in activities of daily living. Due to his psychosis and inability to care for himself, Mr. F is transferred to the psychiatric unit with consent from his mother.

Continue to: TREATMENT Olanzapine and fluid restriction

In the psychiatric unit, Mr. F is restarted on olanzapine, but not on perphenazine due to anticholinergic effects and not on propranolol due to continued orthostatic hypotension. Five days later, he is at his baseline level of functioning with residual psychosis. His fluid intake is restricted to <1.5 L per day and he is easily compliant.

Mr. F’s mother is comfortable with his discharge home on a regimen of olanzapine, 25 mg/d, and the team discusses the fluid restrictions with her. The treatment team suggests initiating an LAI before Mr. F is discharged, but this is not pursued because his mother thinks he is doing well with the oral medication. She wants to monitor him with the medication changes in the clinic before pursuing an LAI; however, she is open to it in the future.

The authors’ observations

Approximately 20% of patients with schizophrenia may experience psychogenic polydipsia.^4,5 The cause of psychogenic polydipsia in patients with serious mental illness is multifactorial. It may stem from malfunction of the hypothalamic-pituitary axis, which leads to alterations in antidiuretic hormone secretion and function.^4-6

Mr. F’s case highlights several challenges associated with treating psychogenic polydipsia in patients with serious mental illness. Antipsychotics with high dopamine affinity, such as risperidone and haloperidol, may increase the risk of psychogenic polydipsia, while antipsychotics with lower dopamine affinity, such as clozapine, may decrease the occurrence.⁵ Antipsychotics block postsynaptic dopamine receptors, which can induce supersensitivity by increasing presynaptic dopamine release in the hypothalamic areas, where thirst regulation occurs. This increase in dopamine leads to increased thirst drive and fluid intake.³

Quetiapine or clozapine may have been a better antipsychotic choice because these agents have lower D2 receptor affinity, whereas olanzapine has intermediate binding to D2 receptors.^6,7 However, quetiapine and clozapine are more strongly associated with orthostasis, which was a concern during Mr. F’s hospitalization. The weekly laboratory testing required with clozapine use would have been an unfeasible burden for Mr. F because he lived in a rural environment. Perphenazine was not continued due to higher D2 affinity and anticholinergic effects, which can increase thirst.⁶

Continue to: In addition to switching...

In addition to switching to an antipsychotic with looser D2 binding, other medications for treating polydipsia have been studied. It is hypothesized that the alpha-2 adrenergic system may play a role in thirst regulation. For example, mianserin, an alpha-2 antagonist, may decrease water intake. However, studies have been small and inconsistent.^8,9 Propranolol,¹⁰ a beta adrenergic receptor blocker; irbesartan,¹¹ an angiotensin-II receptor blocker; demeclocycline,¹² a tetracycline that inhibits antidiuretic hormone action; and naltrexone,⁹ a mu opioid antagonist, have been studied with inconclusive results and a variety of adverse effects^5,7,13 (Table 2^8-13).

Behavioral interventions for patients with psychogenic polydipsia include fluid restriction, twice-daily weight checks, cognitive-behavioral therapy, and reinforcement schedules, which may be useful but less realistic due to need for increased supervision.^11,12 Patient and family education on the signs of hyponatremia are important to prevent serious complications, such as those Mr. F experienced.

OUTCOME Repeated hospitalizations

Mr. F is discharged with follow-up in our psychiatry clinic and attends 1 appointment. At that time, his mother reports that Mr. F is compliant with his medication and has limited fluid intake. However, over the next 2 months, he is admitted to our psychiatric unit twice with similar presentations. Each time, the treatment team has extensive discussions with Mr. F’s mother about strategies to limit his water intake and the possibility of residential placement due to his need for a higher level of care. Although she acknowledges that nursing home placement may be needed in the future, she is not ready to take this step.

Three months later, Mr. F returns to our hospital with severe abdominal pain and is found to have a perforated bowel obstruction. His sodium is within normal limits on presentation, and the psychiatry team is not involved during this hospitalization. Mr. F is treated for sepsis and undergoes 3 exploratory laparotomies with continued decline in his health. He dies during this hospitalization. The cause of Mr. F’s perforated bowel obstruction is not determined, and his family does not pursue an autopsy.

The authors’ observations

At Mr. F’s final hospital presentation, his sodium was normal. It is possible Mr. F and his mother had found an acceptable fluid restriction routine, and he may have been doing better from a psychiatric perspective, but this will remain unknown.

Continue to: This case highlights...

This case highlights the clinical and ethical complexity of treating patients with psychogenic polydipsia. Because Mr. F no longer had autonomy, we had to determine if his mother was acting in his best interest as his guardian. Guardianship requirements and expectations vary by state. In our state of Missouri, a guardian is appointed by the court to act in the best interest of the ward, and may be a family member (preferred) or state-appointed. The guardian is responsible for providing the ward’s care and is in charge of financial and medical decisions. In Missouri, the guardian must assure the ward resides in the “least restrictive setting reasonably available,” which is the minimum necessary to provide the ward safe care and housing.¹⁴ Full guardianship, as in Mr. F’s case, is different from limited guardianship, which is an option in states such as Missouri. In limited guardianship, the court decides the extent of the guardian’s role in decisions for the ward.^14,15

Mr. F’s mother believed she was acting in her son’s best interest by having him home with his family. She believed by living at home, he would derive more enjoyment from life than living in a nursing home. By the time Mr. F presented to our hospital, he had been living with decompensated schizophrenia for years, so some level of psychosis was likely to persist, even with treatment. Given his increasingly frequent hospitalizations for hyponatremia due to increased water intake, more intense supervision may have been needed to maintain his safety, in line with nonmaleficence. The treatment team considered Mr. F’s best interest when discussing placement and worked to understand his mother’s preferences.

His mother continued to acknowledge the need for changes and adjustments at home. She was receptive to the need for fluid restriction and increased structure at home. Therefore, we felt she continued to be acting in his best interest, and his home would be the least restrictive setting for his care. If Mr. F had continued to require repeated hospitalizations and had not passed away, we would have pursued an ethics consult to discuss the need for nursing home placement and how to best approach this with Mr. F’s mother.

Bottom Line

Patients with serious mental illness who present with hyponatremia should be evaluated for psychogenic polydipsia by assessing their dietary and fluid intakes, along with collateral from family. The use of antipsychotics with high dopamine affinity may increase the risk of psychogenic polydipsia. Behavioral interventions include fluid restriction, weight checks, cognitive-behavioral therapy, and reinforcement schedules.

Related Resources

• Sharp CS, Wilson MP. Hyponatremia. In: Nordstrom KD, Wilson MP, eds. Quick guide to psychiatric emergencies. Springer International Publishing; 2018:115-119. doi:10.1007/ 978-3-319-58260-3_21
• Sailer C, Winzeler B, Christ-Crain M. Primary polydipsia in the medical and psychiatric patient: characteristics, complications and therapy. Swiss Med Wkly. 2017;147:w14514. doi:10.4414/ smw.2017.14514

Drug Brand Names

Amiloride • Midamor
Aripiprazole • Abilify
Clonidine • Catapres
Clozapine • Clozaril
Demeclocycline • Declomycin
Desmopressin • DDAVP
Haloperidol • Haldol
Irbesartan • Avapro
Lithium • Eskalith, Lithobid
Losartan • Cozaar
Mianserin • Tolvon
Naloxone • Narcan
Naltrexone • Revia
Olanzapine • Zyprexa
Perphenazine • Trilafon
Propranolol • Inderal LA
Quetiapine • Seroquel
Risperidone • Risperda

CASE Unresponsive after a presumed seizure

Mr. F, age 44, has schizophrenia. He is brought to the hospital by ambulance after he is found on the ground outside of his mother’s house following a presumed seizure and fall. On arrival to the emergency department, he is unresponsive. His laboratory values are significant for a sodium level of 110 mEq/L (reference range: 135 to 145 mEq/L), indicating hyponatremia.

HISTORY Fixated on purity

Mr. F’s mother reports that Mr. F had an unremarkable childhood. He was raised in a household with both parents and a younger sister. Mr. F did well academically and studied engineering and physics in college. There was no reported history of trauma or substance use.

During his senior year of college, Mr. F began experiencing paranoia, auditory hallucinations, and religious delusions. He required hospitalization and was diagnosed with schizophrenia. Following multiple hospitalizations over 5 years, he moved in with his mother, who was granted guardianship.

His mother said Mr. F’s religious delusions were of purity and cleansing the soul. He spent hours memorizing the Bible and would go for days without eating but would drink large amounts of water. She said she thought this was due to his desire to flush out imperfections.

In the past 3 years, Mr. F has been hospitalized several times for severe hyponatremia. At home, his mother attempted to restrict his water intake. However, Mr. F would still drink out of sinks and hoses. Mr. F’s mother reports that over the past month he had become more isolated. He would spend entire days reading the Bible, and his water intake had further increased.

Prior medication trials for Mr. F included haloperidol, up to 10 mg twice per day; aripiprazole, up to 20 mg/d; and risperidone, up to 6 mg nightly. These had been effective, but Mr. F had difficulty with adherence. He did not receive a long-acting injectable (LAI) antipsychotic initially due to lack of access at the rural clinic where he was treated, and later due to his mother’s preference for her son to receive oral medications. Prior to his current presentation, Mr. F’s medication regimen was olanzapine, 10 mg twice a day; perphenazine, 8 mg twice a day; and long-acting propranolol, 60 mg/d. Mr. F had no other chronic medical problems.

EVALUATION Hyponatremia, but why?

Mr. F is intubated and admitted to the surgical service for stabilization due to injuries from his fall. He has fractures of his right sinus and bilateral nasal bones, which are managed nonoperatively. He is delirious, with waxing and waning attention, memory disturbances, and disorientation. His psychotropic medications are held.

Continue to: Imaging of his head...

Imaging of his head does not reveal acute abnormalities suggesting a malignant or paraneoplastic process, and there are no concerns for ongoing seizures. An infection workup is negative. His urine toxicology is negative and blood alcohol level is 0. His sodium normalizes after 3 days of IV fluids and fluid restriction. Therefore, further tests to differentiate the causes of hyponatremia, such as urine electrolytes and urine osmolality, are not pursued.

[polldaddy:10910406]

The authors’ observations

The differential diagnosis for hyponatremia is broad in the setting of psychiatric illness. Low sodium levels could be due to psychotropic medications, psychiatrically-driven behaviors, or an underlying medical problem. Our differential diagnosis for Mr. F included iatrogenic syndrome of inappropriate antidiuretic hormone (SIADH), diabetes insipidus, or psychogenic polydipsia, a form of primary polydipsia. Other causes of primary polydipsia are related to substances, such as heavy beer intakeor use of 3,4-methylenedioxymethamphetamine (MDMA, also known as “ecstasy”), or brain lesions,¹ but these causes were less likely given Mr. F’s negative urine toxicology and head imaging.

While psychogenic polydipsia is due to increased water consumption, both SIADH and diabetes insipidus are due to alterations in fluid homeostasis.^2,3 Table 1^2-4 outlines distinguishing characteristics of SIADH, diabetes insipidus, and psychogenic polydipsia. Urine studies were not pursued because Mr. F’s sodium resolved and acute concerns, such as malignancy or infection, were ruled out. Mr. F’s hyponatremia was presumed to be due to psychogenic polydipsia because of his increased fluid intake and normalization of sodium with hypertonic fluids and subsequent fluid restriction. During this time, he was managed on the surgical service; the plan was to pursue urine studies and possibly a fluid challenge if his hyponatremia persisted.

EVALUATION Delirium resolves, delusions persist

While Mr. F is on the surgical service, the treatment team focuses on stabilizing his sodium level and assessing for causes of altered mental status that led to his fall. Psychiatry is consulted for management of his agitation. Following the gradual correction of his sodium level and extubation, his sensorium improves. By hospital Day 5, Mr. F’s delirium resolves.

During this time, Mr. F’s disorganization and religious delusions become apparent. He spends much of his time reading his Bible. He has poor hygiene and limited engagement in activities of daily living. Due to his psychosis and inability to care for himself, Mr. F is transferred to the psychiatric unit with consent from his mother.

Continue to: TREATMENT Olanzapine and fluid restriction

In the psychiatric unit, Mr. F is restarted on olanzapine, but not on perphenazine due to anticholinergic effects and not on propranolol due to continued orthostatic hypotension. Five days later, he is at his baseline level of functioning with residual psychosis. His fluid intake is restricted to <1.5 L per day and he is easily compliant.

Mr. F’s mother is comfortable with his discharge home on a regimen of olanzapine, 25 mg/d, and the team discusses the fluid restrictions with her. The treatment team suggests initiating an LAI before Mr. F is discharged, but this is not pursued because his mother thinks he is doing well with the oral medication. She wants to monitor him with the medication changes in the clinic before pursuing an LAI; however, she is open to it in the future.

The authors’ observations

Approximately 20% of patients with schizophrenia may experience psychogenic polydipsia.^4,5 The cause of psychogenic polydipsia in patients with serious mental illness is multifactorial. It may stem from malfunction of the hypothalamic-pituitary axis, which leads to alterations in antidiuretic hormone secretion and function.^4-6

Mr. F’s case highlights several challenges associated with treating psychogenic polydipsia in patients with serious mental illness. Antipsychotics with high dopamine affinity, such as risperidone and haloperidol, may increase the risk of psychogenic polydipsia, while antipsychotics with lower dopamine affinity, such as clozapine, may decrease the occurrence.⁵ Antipsychotics block postsynaptic dopamine receptors, which can induce supersensitivity by increasing presynaptic dopamine release in the hypothalamic areas, where thirst regulation occurs. This increase in dopamine leads to increased thirst drive and fluid intake.³

Quetiapine or clozapine may have been a better antipsychotic choice because these agents have lower D2 receptor affinity, whereas olanzapine has intermediate binding to D2 receptors.^6,7 However, quetiapine and clozapine are more strongly associated with orthostasis, which was a concern during Mr. F’s hospitalization. The weekly laboratory testing required with clozapine use would have been an unfeasible burden for Mr. F because he lived in a rural environment. Perphenazine was not continued due to higher D2 affinity and anticholinergic effects, which can increase thirst.⁶

Continue to: In addition to switching...

In addition to switching to an antipsychotic with looser D2 binding, other medications for treating polydipsia have been studied. It is hypothesized that the alpha-2 adrenergic system may play a role in thirst regulation. For example, mianserin, an alpha-2 antagonist, may decrease water intake. However, studies have been small and inconsistent.^8,9 Propranolol,¹⁰ a beta adrenergic receptor blocker; irbesartan,¹¹ an angiotensin-II receptor blocker; demeclocycline,¹² a tetracycline that inhibits antidiuretic hormone action; and naltrexone,⁹ a mu opioid antagonist, have been studied with inconclusive results and a variety of adverse effects^5,7,13 (Table 2^8-13).

Behavioral interventions for patients with psychogenic polydipsia include fluid restriction, twice-daily weight checks, cognitive-behavioral therapy, and reinforcement schedules, which may be useful but less realistic due to need for increased supervision.^11,12 Patient and family education on the signs of hyponatremia are important to prevent serious complications, such as those Mr. F experienced.

OUTCOME Repeated hospitalizations

Mr. F is discharged with follow-up in our psychiatry clinic and attends 1 appointment. At that time, his mother reports that Mr. F is compliant with his medication and has limited fluid intake. However, over the next 2 months, he is admitted to our psychiatric unit twice with similar presentations. Each time, the treatment team has extensive discussions with Mr. F’s mother about strategies to limit his water intake and the possibility of residential placement due to his need for a higher level of care. Although she acknowledges that nursing home placement may be needed in the future, she is not ready to take this step.

Three months later, Mr. F returns to our hospital with severe abdominal pain and is found to have a perforated bowel obstruction. His sodium is within normal limits on presentation, and the psychiatry team is not involved during this hospitalization. Mr. F is treated for sepsis and undergoes 3 exploratory laparotomies with continued decline in his health. He dies during this hospitalization. The cause of Mr. F’s perforated bowel obstruction is not determined, and his family does not pursue an autopsy.

The authors’ observations

At Mr. F’s final hospital presentation, his sodium was normal. It is possible Mr. F and his mother had found an acceptable fluid restriction routine, and he may have been doing better from a psychiatric perspective, but this will remain unknown.

Continue to: This case highlights...

This case highlights the clinical and ethical complexity of treating patients with psychogenic polydipsia. Because Mr. F no longer had autonomy, we had to determine if his mother was acting in his best interest as his guardian. Guardianship requirements and expectations vary by state. In our state of Missouri, a guardian is appointed by the court to act in the best interest of the ward, and may be a family member (preferred) or state-appointed. The guardian is responsible for providing the ward’s care and is in charge of financial and medical decisions. In Missouri, the guardian must assure the ward resides in the “least restrictive setting reasonably available,” which is the minimum necessary to provide the ward safe care and housing.¹⁴ Full guardianship, as in Mr. F’s case, is different from limited guardianship, which is an option in states such as Missouri. In limited guardianship, the court decides the extent of the guardian’s role in decisions for the ward.^14,15

Mr. F’s mother believed she was acting in her son’s best interest by having him home with his family. She believed by living at home, he would derive more enjoyment from life than living in a nursing home. By the time Mr. F presented to our hospital, he had been living with decompensated schizophrenia for years, so some level of psychosis was likely to persist, even with treatment. Given his increasingly frequent hospitalizations for hyponatremia due to increased water intake, more intense supervision may have been needed to maintain his safety, in line with nonmaleficence. The treatment team considered Mr. F’s best interest when discussing placement and worked to understand his mother’s preferences.

His mother continued to acknowledge the need for changes and adjustments at home. She was receptive to the need for fluid restriction and increased structure at home. Therefore, we felt she continued to be acting in his best interest, and his home would be the least restrictive setting for his care. If Mr. F had continued to require repeated hospitalizations and had not passed away, we would have pursued an ethics consult to discuss the need for nursing home placement and how to best approach this with Mr. F’s mother.

Bottom Line

Patients with serious mental illness who present with hyponatremia should be evaluated for psychogenic polydipsia by assessing their dietary and fluid intakes, along with collateral from family. The use of antipsychotics with high dopamine affinity may increase the risk of psychogenic polydipsia. Behavioral interventions include fluid restriction, weight checks, cognitive-behavioral therapy, and reinforcement schedules.

Related Resources

• Sharp CS, Wilson MP. Hyponatremia. In: Nordstrom KD, Wilson MP, eds. Quick guide to psychiatric emergencies. Springer International Publishing; 2018:115-119. doi:10.1007/ 978-3-319-58260-3_21
• Sailer C, Winzeler B, Christ-Crain M. Primary polydipsia in the medical and psychiatric patient: characteristics, complications and therapy. Swiss Med Wkly. 2017;147:w14514. doi:10.4414/ smw.2017.14514

Drug Brand Names

Amiloride • Midamor
Aripiprazole • Abilify
Clonidine • Catapres
Clozapine • Clozaril
Demeclocycline • Declomycin
Desmopressin • DDAVP
Haloperidol • Haldol
Irbesartan • Avapro
Lithium • Eskalith, Lithobid
Losartan • Cozaar
Mianserin • Tolvon
Naloxone • Narcan
Naltrexone • Revia
Olanzapine • Zyprexa
Perphenazine • Trilafon
Propranolol • Inderal LA
Quetiapine • Seroquel
Risperidone • Risperda

CASE Unresponsive after a presumed seizure

Mr. F, age 44, has schizophrenia. He is brought to the hospital by ambulance after he is found on the ground outside of his mother’s house following a presumed seizure and fall. On arrival to the emergency department, he is unresponsive. His laboratory values are significant for a sodium level of 110 mEq/L (reference range: 135 to 145 mEq/L), indicating hyponatremia.

HISTORY Fixated on purity

Mr. F’s mother reports that Mr. F had an unremarkable childhood. He was raised in a household with both parents and a younger sister. Mr. F did well academically and studied engineering and physics in college. There was no reported history of trauma or substance use.

During his senior year of college, Mr. F began experiencing paranoia, auditory hallucinations, and religious delusions. He required hospitalization and was diagnosed with schizophrenia. Following multiple hospitalizations over 5 years, he moved in with his mother, who was granted guardianship.

His mother said Mr. F’s religious delusions were of purity and cleansing the soul. He spent hours memorizing the Bible and would go for days without eating but would drink large amounts of water. She said she thought this was due to his desire to flush out imperfections.

In the past 3 years, Mr. F has been hospitalized several times for severe hyponatremia. At home, his mother attempted to restrict his water intake. However, Mr. F would still drink out of sinks and hoses. Mr. F’s mother reports that over the past month he had become more isolated. He would spend entire days reading the Bible, and his water intake had further increased.

Prior medication trials for Mr. F included haloperidol, up to 10 mg twice per day; aripiprazole, up to 20 mg/d; and risperidone, up to 6 mg nightly. These had been effective, but Mr. F had difficulty with adherence. He did not receive a long-acting injectable (LAI) antipsychotic initially due to lack of access at the rural clinic where he was treated, and later due to his mother’s preference for her son to receive oral medications. Prior to his current presentation, Mr. F’s medication regimen was olanzapine, 10 mg twice a day; perphenazine, 8 mg twice a day; and long-acting propranolol, 60 mg/d. Mr. F had no other chronic medical problems.

EVALUATION Hyponatremia, but why?

Mr. F is intubated and admitted to the surgical service for stabilization due to injuries from his fall. He has fractures of his right sinus and bilateral nasal bones, which are managed nonoperatively. He is delirious, with waxing and waning attention, memory disturbances, and disorientation. His psychotropic medications are held.

Continue to: Imaging of his head...

Imaging of his head does not reveal acute abnormalities suggesting a malignant or paraneoplastic process, and there are no concerns for ongoing seizures. An infection workup is negative. His urine toxicology is negative and blood alcohol level is 0. His sodium normalizes after 3 days of IV fluids and fluid restriction. Therefore, further tests to differentiate the causes of hyponatremia, such as urine electrolytes and urine osmolality, are not pursued.

[polldaddy:10910406]

The authors’ observations

The differential diagnosis for hyponatremia is broad in the setting of psychiatric illness. Low sodium levels could be due to psychotropic medications, psychiatrically-driven behaviors, or an underlying medical problem. Our differential diagnosis for Mr. F included iatrogenic syndrome of inappropriate antidiuretic hormone (SIADH), diabetes insipidus, or psychogenic polydipsia, a form of primary polydipsia. Other causes of primary polydipsia are related to substances, such as heavy beer intakeor use of 3,4-methylenedioxymethamphetamine (MDMA, also known as “ecstasy”), or brain lesions,¹ but these causes were less likely given Mr. F’s negative urine toxicology and head imaging.

While psychogenic polydipsia is due to increased water consumption, both SIADH and diabetes insipidus are due to alterations in fluid homeostasis.^2,3 Table 1^2-4 outlines distinguishing characteristics of SIADH, diabetes insipidus, and psychogenic polydipsia. Urine studies were not pursued because Mr. F’s sodium resolved and acute concerns, such as malignancy or infection, were ruled out. Mr. F’s hyponatremia was presumed to be due to psychogenic polydipsia because of his increased fluid intake and normalization of sodium with hypertonic fluids and subsequent fluid restriction. During this time, he was managed on the surgical service; the plan was to pursue urine studies and possibly a fluid challenge if his hyponatremia persisted.

EVALUATION Delirium resolves, delusions persist

While Mr. F is on the surgical service, the treatment team focuses on stabilizing his sodium level and assessing for causes of altered mental status that led to his fall. Psychiatry is consulted for management of his agitation. Following the gradual correction of his sodium level and extubation, his sensorium improves. By hospital Day 5, Mr. F’s delirium resolves.

During this time, Mr. F’s disorganization and religious delusions become apparent. He spends much of his time reading his Bible. He has poor hygiene and limited engagement in activities of daily living. Due to his psychosis and inability to care for himself, Mr. F is transferred to the psychiatric unit with consent from his mother.

Continue to: TREATMENT Olanzapine and fluid restriction

In the psychiatric unit, Mr. F is restarted on olanzapine, but not on perphenazine due to anticholinergic effects and not on propranolol due to continued orthostatic hypotension. Five days later, he is at his baseline level of functioning with residual psychosis. His fluid intake is restricted to <1.5 L per day and he is easily compliant.

Mr. F’s mother is comfortable with his discharge home on a regimen of olanzapine, 25 mg/d, and the team discusses the fluid restrictions with her. The treatment team suggests initiating an LAI before Mr. F is discharged, but this is not pursued because his mother thinks he is doing well with the oral medication. She wants to monitor him with the medication changes in the clinic before pursuing an LAI; however, she is open to it in the future.

The authors’ observations

Approximately 20% of patients with schizophrenia may experience psychogenic polydipsia.^4,5 The cause of psychogenic polydipsia in patients with serious mental illness is multifactorial. It may stem from malfunction of the hypothalamic-pituitary axis, which leads to alterations in antidiuretic hormone secretion and function.^4-6

Mr. F’s case highlights several challenges associated with treating psychogenic polydipsia in patients with serious mental illness. Antipsychotics with high dopamine affinity, such as risperidone and haloperidol, may increase the risk of psychogenic polydipsia, while antipsychotics with lower dopamine affinity, such as clozapine, may decrease the occurrence.⁵ Antipsychotics block postsynaptic dopamine receptors, which can induce supersensitivity by increasing presynaptic dopamine release in the hypothalamic areas, where thirst regulation occurs. This increase in dopamine leads to increased thirst drive and fluid intake.³

Quetiapine or clozapine may have been a better antipsychotic choice because these agents have lower D2 receptor affinity, whereas olanzapine has intermediate binding to D2 receptors.^6,7 However, quetiapine and clozapine are more strongly associated with orthostasis, which was a concern during Mr. F’s hospitalization. The weekly laboratory testing required with clozapine use would have been an unfeasible burden for Mr. F because he lived in a rural environment. Perphenazine was not continued due to higher D2 affinity and anticholinergic effects, which can increase thirst.⁶

Continue to: In addition to switching...

In addition to switching to an antipsychotic with looser D2 binding, other medications for treating polydipsia have been studied. It is hypothesized that the alpha-2 adrenergic system may play a role in thirst regulation. For example, mianserin, an alpha-2 antagonist, may decrease water intake. However, studies have been small and inconsistent.^8,9 Propranolol,¹⁰ a beta adrenergic receptor blocker; irbesartan,¹¹ an angiotensin-II receptor blocker; demeclocycline,¹² a tetracycline that inhibits antidiuretic hormone action; and naltrexone,⁹ a mu opioid antagonist, have been studied with inconclusive results and a variety of adverse effects^5,7,13 (Table 2^8-13).

Behavioral interventions for patients with psychogenic polydipsia include fluid restriction, twice-daily weight checks, cognitive-behavioral therapy, and reinforcement schedules, which may be useful but less realistic due to need for increased supervision.^11,12 Patient and family education on the signs of hyponatremia are important to prevent serious complications, such as those Mr. F experienced.

OUTCOME Repeated hospitalizations

Mr. F is discharged with follow-up in our psychiatry clinic and attends 1 appointment. At that time, his mother reports that Mr. F is compliant with his medication and has limited fluid intake. However, over the next 2 months, he is admitted to our psychiatric unit twice with similar presentations. Each time, the treatment team has extensive discussions with Mr. F’s mother about strategies to limit his water intake and the possibility of residential placement due to his need for a higher level of care. Although she acknowledges that nursing home placement may be needed in the future, she is not ready to take this step.

Three months later, Mr. F returns to our hospital with severe abdominal pain and is found to have a perforated bowel obstruction. His sodium is within normal limits on presentation, and the psychiatry team is not involved during this hospitalization. Mr. F is treated for sepsis and undergoes 3 exploratory laparotomies with continued decline in his health. He dies during this hospitalization. The cause of Mr. F’s perforated bowel obstruction is not determined, and his family does not pursue an autopsy.

The authors’ observations

At Mr. F’s final hospital presentation, his sodium was normal. It is possible Mr. F and his mother had found an acceptable fluid restriction routine, and he may have been doing better from a psychiatric perspective, but this will remain unknown.

Continue to: This case highlights...

This case highlights the clinical and ethical complexity of treating patients with psychogenic polydipsia. Because Mr. F no longer had autonomy, we had to determine if his mother was acting in his best interest as his guardian. Guardianship requirements and expectations vary by state. In our state of Missouri, a guardian is appointed by the court to act in the best interest of the ward, and may be a family member (preferred) or state-appointed. The guardian is responsible for providing the ward’s care and is in charge of financial and medical decisions. In Missouri, the guardian must assure the ward resides in the “least restrictive setting reasonably available,” which is the minimum necessary to provide the ward safe care and housing.¹⁴ Full guardianship, as in Mr. F’s case, is different from limited guardianship, which is an option in states such as Missouri. In limited guardianship, the court decides the extent of the guardian’s role in decisions for the ward.^14,15

Mr. F’s mother believed she was acting in her son’s best interest by having him home with his family. She believed by living at home, he would derive more enjoyment from life than living in a nursing home. By the time Mr. F presented to our hospital, he had been living with decompensated schizophrenia for years, so some level of psychosis was likely to persist, even with treatment. Given his increasingly frequent hospitalizations for hyponatremia due to increased water intake, more intense supervision may have been needed to maintain his safety, in line with nonmaleficence. The treatment team considered Mr. F’s best interest when discussing placement and worked to understand his mother’s preferences.

His mother continued to acknowledge the need for changes and adjustments at home. She was receptive to the need for fluid restriction and increased structure at home. Therefore, we felt she continued to be acting in his best interest, and his home would be the least restrictive setting for his care. If Mr. F had continued to require repeated hospitalizations and had not passed away, we would have pursued an ethics consult to discuss the need for nursing home placement and how to best approach this with Mr. F’s mother.

Bottom Line

Patients with serious mental illness who present with hyponatremia should be evaluated for psychogenic polydipsia by assessing their dietary and fluid intakes, along with collateral from family. The use of antipsychotics with high dopamine affinity may increase the risk of psychogenic polydipsia. Behavioral interventions include fluid restriction, weight checks, cognitive-behavioral therapy, and reinforcement schedules.

Related Resources

• Sharp CS, Wilson MP. Hyponatremia. In: Nordstrom KD, Wilson MP, eds. Quick guide to psychiatric emergencies. Springer International Publishing; 2018:115-119. doi:10.1007/ 978-3-319-58260-3_21
• Sailer C, Winzeler B, Christ-Crain M. Primary polydipsia in the medical and psychiatric patient: characteristics, complications and therapy. Swiss Med Wkly. 2017;147:w14514. doi:10.4414/ smw.2017.14514

Drug Brand Names

Amiloride • Midamor
Aripiprazole • Abilify
Clonidine • Catapres
Clozapine • Clozaril
Demeclocycline • Declomycin
Desmopressin • DDAVP
Haloperidol • Haldol
Irbesartan • Avapro
Lithium • Eskalith, Lithobid
Losartan • Cozaar
Mianserin • Tolvon
Naloxone • Narcan
Naltrexone • Revia
Olanzapine • Zyprexa
Perphenazine • Trilafon
Propranolol • Inderal LA
Quetiapine • Seroquel
Risperidone • Risperda

In the modern-day practice of medicine, turf wars are more common than one may realize. Presently, an ongoing battle over who should be prescribing and administering ketamine for novel treatment uses is being waged among psychiatrists, anesthesiologists, family physicians, and emergency physicians. Whoever emerges victorious will determine whether psychiatric care is administered in a safe and cost-effective manner, or if it will merely benefit the bottom line of the prescriber. In this article, we discuss how ketamine may have a role for treatment-resistant depression (TRD), and why psychiatrists are uniquely qualified to prescribe and administer this medication for this purpose.

New approaches to treatment-resistant depression

Antidepressant medications, long the mainstay of depression treatment, have been shown to be safe and relatively equally effective, with varying tolerability. However, 33% percent of patients do not achieve remission after 4 trials of antidepressant therapy.¹ Most antidepressant efficacy studies report remission rates of 35% to 40%,² which means many patients require subsequent switching and/or augmentation of their treatment.³ The STAR*D trial demonstrated that after 2 adequate antidepressant trials, the likelihood of remission diminishes.⁴

After a patient’s depression is found to be treatment-resistant, the onus of guiding treatment shifts away from the patient’s primary care physician to the more specialized psychiatrist. Few would question the suitability of a psychiatrist’s expertise in handling complicated and nuanced mental illness. In order to manage TRD, psychiatrists enter a terrain of emerging novel therapies with rapid onset, different mechanisms of action, and parenteral routes of administration.

One such therapy is esketamine, the S-enantiomer of ketamine. The FDA approved the intranasal (IN) formulation of esketamine in March 2019 after the medication had been designated as a breakthrough therapy for TRD in 2013 and studied in 6 Phase III clinical trials.⁵ The S-enantiomer of ketamine is known to bind to the N-methyl-D-aspartate receptor stronger than the R-enantiomer.⁶ The mechanism of action of both stereoisomers on other receptors, such as opioid and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), is the focus of intensive research and remains to be fully elucidated, but initial studies indicate rapid neuroplasticity and synaptogenesis.⁷ What is clear is that this new intervention can provide relief to patients with TRD via a pharmacologically distinct mechanism.⁸

Ketamine may be administered intranasally, intravenously, or orally. A meta-analysis aimed at assessing differences in ketamine efficacy for depression based on route of administration have shown that both IV and IN ketamine are effective, though it is not possible to draw conclusions regarding a direct comparison based on available data.⁹ Despite several landmark published studies, such as those by Zarate et al,¹⁰ IV ketamine is not FDA-approved for TRD.

Continue to: Why psychiatrists?

Psychiatrists have been prescribing IN esketamine, which is covered by most commercial insurances and administered in certified healthcare settings under a Risk Evaluation and Mitigation Strategy program.⁵ However, anesthesiologists and emergency physicians have opened a crop of boutique and concierge health clinics offering various “packages” of IV ketamine infusions for a slew of mental ailments, including depression, anxiety, bipolar disorder, and posttraumatic stress disorder.¹¹ Minimal investigation reveals that these services are being prescribed mainly by practitioners in fields other than psychiatry. Intravenous ketamine has long been used off-label as a treatment for depression not by psychiatrists but by practitioners of anesthesiology or emergency medicine. Although these clinicians are likely familiar with ketamine as an anesthetic, they have no foundation or expertise in the diagnosis and treatment of complex mood disorders. The FDA-approved indication for esketamine falls firmly in the realm of psychiatric treatment. Physicians who have not completed a psychiatry residency have neither the training nor experience necessary to determine whether a patient is a candidate for this treatment.

One potential adverse effect of ketamine is an emergence phenomenon, colloquially named a “K-hole,” that can induce symptoms of psychosis such as disturbing hallucinations. Patients who have a history of psychosis need to be carefully evaluated for appropriateness to receive this treatment.

Furthermore, ketamine treatments administered by physicians who are not psychiatrists are billed not through insurance but mostly via private pay. A patient may therefore be charged $350 to $1,000 per infusion, to be paid out of pocket.¹¹ Tally that up over the standard 6 to 12 initial treatment infusions, followed by maintenance infusions, and these patients with profound depression are potentially building up significant debt. Does this practice align with the ethical principles of autonomy, justice, beneficence, and nonmaleficence that all physicians swore to uphold? Will psychiatrists take a stand against the financial exploitation of a vulnerable group that is desperate to find any potential relief from their depression?

In the modern-day practice of medicine, turf wars are more common than one may realize. Presently, an ongoing battle over who should be prescribing and administering ketamine for novel treatment uses is being waged among psychiatrists, anesthesiologists, family physicians, and emergency physicians. Whoever emerges victorious will determine whether psychiatric care is administered in a safe and cost-effective manner, or if it will merely benefit the bottom line of the prescriber. In this article, we discuss how ketamine may have a role for treatment-resistant depression (TRD), and why psychiatrists are uniquely qualified to prescribe and administer this medication for this purpose.

New approaches to treatment-resistant depression

Antidepressant medications, long the mainstay of depression treatment, have been shown to be safe and relatively equally effective, with varying tolerability. However, 33% percent of patients do not achieve remission after 4 trials of antidepressant therapy.¹ Most antidepressant efficacy studies report remission rates of 35% to 40%,² which means many patients require subsequent switching and/or augmentation of their treatment.³ The STAR*D trial demonstrated that after 2 adequate antidepressant trials, the likelihood of remission diminishes.⁴

After a patient’s depression is found to be treatment-resistant, the onus of guiding treatment shifts away from the patient’s primary care physician to the more specialized psychiatrist. Few would question the suitability of a psychiatrist’s expertise in handling complicated and nuanced mental illness. In order to manage TRD, psychiatrists enter a terrain of emerging novel therapies with rapid onset, different mechanisms of action, and parenteral routes of administration.

One such therapy is esketamine, the S-enantiomer of ketamine. The FDA approved the intranasal (IN) formulation of esketamine in March 2019 after the medication had been designated as a breakthrough therapy for TRD in 2013 and studied in 6 Phase III clinical trials.⁵ The S-enantiomer of ketamine is known to bind to the N-methyl-D-aspartate receptor stronger than the R-enantiomer.⁶ The mechanism of action of both stereoisomers on other receptors, such as opioid and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), is the focus of intensive research and remains to be fully elucidated, but initial studies indicate rapid neuroplasticity and synaptogenesis.⁷ What is clear is that this new intervention can provide relief to patients with TRD via a pharmacologically distinct mechanism.⁸

Ketamine may be administered intranasally, intravenously, or orally. A meta-analysis aimed at assessing differences in ketamine efficacy for depression based on route of administration have shown that both IV and IN ketamine are effective, though it is not possible to draw conclusions regarding a direct comparison based on available data.⁹ Despite several landmark published studies, such as those by Zarate et al,¹⁰ IV ketamine is not FDA-approved for TRD.

Continue to: Why psychiatrists?

Psychiatrists have been prescribing IN esketamine, which is covered by most commercial insurances and administered in certified healthcare settings under a Risk Evaluation and Mitigation Strategy program.⁵ However, anesthesiologists and emergency physicians have opened a crop of boutique and concierge health clinics offering various “packages” of IV ketamine infusions for a slew of mental ailments, including depression, anxiety, bipolar disorder, and posttraumatic stress disorder.¹¹ Minimal investigation reveals that these services are being prescribed mainly by practitioners in fields other than psychiatry. Intravenous ketamine has long been used off-label as a treatment for depression not by psychiatrists but by practitioners of anesthesiology or emergency medicine. Although these clinicians are likely familiar with ketamine as an anesthetic, they have no foundation or expertise in the diagnosis and treatment of complex mood disorders. The FDA-approved indication for esketamine falls firmly in the realm of psychiatric treatment. Physicians who have not completed a psychiatry residency have neither the training nor experience necessary to determine whether a patient is a candidate for this treatment.

One potential adverse effect of ketamine is an emergence phenomenon, colloquially named a “K-hole,” that can induce symptoms of psychosis such as disturbing hallucinations. Patients who have a history of psychosis need to be carefully evaluated for appropriateness to receive this treatment.

Furthermore, ketamine treatments administered by physicians who are not psychiatrists are billed not through insurance but mostly via private pay. A patient may therefore be charged $350 to $1,000 per infusion, to be paid out of pocket.¹¹ Tally that up over the standard 6 to 12 initial treatment infusions, followed by maintenance infusions, and these patients with profound depression are potentially building up significant debt. Does this practice align with the ethical principles of autonomy, justice, beneficence, and nonmaleficence that all physicians swore to uphold? Will psychiatrists take a stand against the financial exploitation of a vulnerable group that is desperate to find any potential relief from their depression?

In the modern-day practice of medicine, turf wars are more common than one may realize. Presently, an ongoing battle over who should be prescribing and administering ketamine for novel treatment uses is being waged among psychiatrists, anesthesiologists, family physicians, and emergency physicians. Whoever emerges victorious will determine whether psychiatric care is administered in a safe and cost-effective manner, or if it will merely benefit the bottom line of the prescriber. In this article, we discuss how ketamine may have a role for treatment-resistant depression (TRD), and why psychiatrists are uniquely qualified to prescribe and administer this medication for this purpose.

New approaches to treatment-resistant depression

Antidepressant medications, long the mainstay of depression treatment, have been shown to be safe and relatively equally effective, with varying tolerability. However, 33% percent of patients do not achieve remission after 4 trials of antidepressant therapy.¹ Most antidepressant efficacy studies report remission rates of 35% to 40%,² which means many patients require subsequent switching and/or augmentation of their treatment.³ The STAR*D trial demonstrated that after 2 adequate antidepressant trials, the likelihood of remission diminishes.⁴

After a patient’s depression is found to be treatment-resistant, the onus of guiding treatment shifts away from the patient’s primary care physician to the more specialized psychiatrist. Few would question the suitability of a psychiatrist’s expertise in handling complicated and nuanced mental illness. In order to manage TRD, psychiatrists enter a terrain of emerging novel therapies with rapid onset, different mechanisms of action, and parenteral routes of administration.

One such therapy is esketamine, the S-enantiomer of ketamine. The FDA approved the intranasal (IN) formulation of esketamine in March 2019 after the medication had been designated as a breakthrough therapy for TRD in 2013 and studied in 6 Phase III clinical trials.⁵ The S-enantiomer of ketamine is known to bind to the N-methyl-D-aspartate receptor stronger than the R-enantiomer.⁶ The mechanism of action of both stereoisomers on other receptors, such as opioid and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), is the focus of intensive research and remains to be fully elucidated, but initial studies indicate rapid neuroplasticity and synaptogenesis.⁷ What is clear is that this new intervention can provide relief to patients with TRD via a pharmacologically distinct mechanism.⁸

Ketamine may be administered intranasally, intravenously, or orally. A meta-analysis aimed at assessing differences in ketamine efficacy for depression based on route of administration have shown that both IV and IN ketamine are effective, though it is not possible to draw conclusions regarding a direct comparison based on available data.⁹ Despite several landmark published studies, such as those by Zarate et al,¹⁰ IV ketamine is not FDA-approved for TRD.

Continue to: Why psychiatrists?

Psychiatrists have been prescribing IN esketamine, which is covered by most commercial insurances and administered in certified healthcare settings under a Risk Evaluation and Mitigation Strategy program.⁵ However, anesthesiologists and emergency physicians have opened a crop of boutique and concierge health clinics offering various “packages” of IV ketamine infusions for a slew of mental ailments, including depression, anxiety, bipolar disorder, and posttraumatic stress disorder.¹¹ Minimal investigation reveals that these services are being prescribed mainly by practitioners in fields other than psychiatry. Intravenous ketamine has long been used off-label as a treatment for depression not by psychiatrists but by practitioners of anesthesiology or emergency medicine. Although these clinicians are likely familiar with ketamine as an anesthetic, they have no foundation or expertise in the diagnosis and treatment of complex mood disorders. The FDA-approved indication for esketamine falls firmly in the realm of psychiatric treatment. Physicians who have not completed a psychiatry residency have neither the training nor experience necessary to determine whether a patient is a candidate for this treatment.

One potential adverse effect of ketamine is an emergence phenomenon, colloquially named a “K-hole,” that can induce symptoms of psychosis such as disturbing hallucinations. Patients who have a history of psychosis need to be carefully evaluated for appropriateness to receive this treatment.

Furthermore, ketamine treatments administered by physicians who are not psychiatrists are billed not through insurance but mostly via private pay. A patient may therefore be charged $350 to $1,000 per infusion, to be paid out of pocket.¹¹ Tally that up over the standard 6 to 12 initial treatment infusions, followed by maintenance infusions, and these patients with profound depression are potentially building up significant debt. Does this practice align with the ethical principles of autonomy, justice, beneficence, and nonmaleficence that all physicians swore to uphold? Will psychiatrists take a stand against the financial exploitation of a vulnerable group that is desperate to find any potential relief from their depression?

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

The Accreditation Council for Graduate Medical Education (ACGME) is en­trusted with assuring that upon graduation every resident is a competent doctor, a trained professional, and prepared to practice in their own field at a level that assures patient safety and meets the standard of care. The American Board of Psychiatry and Neurology (ABPN) is a private company that sells certificates claiming to attest the capacity or competence of the doctor but does not make public the test questions or algorithms used to win its qualifications or approval. The certifying business and the newer Maintenance of Certification (MOC) process developed by ABPN have unfortunately been embraced by ACGME and many hospitals, despite the lack of any good scientific support that board certification or MOC are meaningful for quality of patient care or outcomes. By that I mean there is no evidence that the voluntary board certification process or MOC have been shown to produce better outcomes for patients, save money for the country drowning in an ocean of health care costs, or allow doctors to get paid at a higher level by insurers for the same billing codes compared with those who bill without possessing these qualifications. The only entity that “profits” from the board certification/MOC process is ABPN, a private corporation that is supposed to be a nonprofit, but was sitting on a treasury of more than $140M in assets in 2019,¹ with revenues growing annually. Including the interest earned on the investment and added revenues every year, the estimated total assets of ABPN will be in the range of $150M at the end of 2021!

Collaboration between ACGME and ABPN

The collaboration between ACGME and ABPN for graduate education for designing training programs for residents and fellows, with progressively increasing competencies and their assessments to dovetail with the board examinations offered by ABPN, sounds very legitimate. This arrangement is designed to enhance the quality of training and establish a minimum level of competence in each trainee who completes the training program. However, ACGME is catering to a monopoly recognized by the US Department of Justice (DOJ) Antitrust Division.² ACGME has not entertained other evaluators of competence to discourage competition to the monopolistic ABPN. ACGME is only involved with the accredited training programs and has no business in assessing the continued competence of graduated trainees after they leave the program, although most will voluntarily opt to become board-certified by ABPN. Maintenance of Certification definitely does not come within the purview of “graduate medical education” for ACGME to be getting drawn into this collaboration.

ACGME and ABPN are unregulated and are not member-driven. As such, they operate outside of any real oversight. Their power derives from the status given to them by hospitals, some insurers, and many of our colleagues, who fail to see the reality that they are nothing more than diploma shops.

I am board-certified in psychiatry and child and adolescent psychiatry, and I have participated in obtaining board certification by ABPN in 3 other subspecialties (geriatric, addiction, and forensic). I decided to not participate in MOC for the latter 3 subspecialty certifications beyond 10 and 20 years for my own practical reasons. Obviously, then, I am not at all against initial certifications in any specialty, nor am I opposed to practitioners keeping up with progress in their fields and maintaining their competence. I am opposed to the continued efforts to engage professionals to pay a high price for the repeated MOC, riding on the hard work and earnings of the graduated specialists and continuously suctioning their income over their careers, with no evidence that MOC measures clinical competence or patient outcomes of their subscribers, who pay a chunk of money to the American Board of Medical Specialties (ABMS)/ABPN annually and every 10 years.

MOC and the APA

Many American Psychiatric Association (APA) members are opposed to the APA giving ABPN a piggyback ride to accomplish this profit seeking. This is becoming obvious to many APA members, who see this as a great exploitation.

Over the last 6 years, physicians have begun to question the validity of board certification and MOC by ABPN, mostly as a response to ever-increasing costs to them and ever-increasing revenues to ABPN. While APA members have long pressed the APA to push back against ABPN, the APA Board of Trustees has done the opposite by accepting yearly “unrestricted educational grants” from ABPN. In this manner, ABPN has essentially silenced the APA and has made it ineffective as our member organization in what has become a fight against ABPN’s unchecked power, influence, and intrusion. Every poll conducted by every APA District Branch or subspecialty organization has shown widespread discontent and anger at the ABPN/MOC process and APA’s deliberate inaction. Even when the APA commissioned its own member survey on the topic, wrote the questions, picked who would get the survey, decided which responses to count, and determined what statistics to apply, the results were damning. Despite its obviously transparent machinations, the APA failed to glorify the MOC process.

Continue to: The APA's membership...

The APA’s membership is declining, and the Board of Trustee’s position on MOC is partly to blame. The APA is once again not listening to its members! As a membership-driven organization, the APA must not exclusively support and promote this commercial educational product termed MOC when other, less expensive alternatives are now available. The APA can easily endorse these alternatives, in addition to offering its own less expensive products for attesting maintenance of competence. The latter effort will help eliminate the monopoly held by ABMS/ABPN in this domain and please all members as well as the DOJ.

The APA’s failure to provide less expensive alternatives or at least endorse existing ones despite repeated requests from a large number of APA members has led to frustration and a surge of strong feelings that are expressed on the APA email listservs, and especially that of the MOC caucus. These expressions are legitimate and need to be publicized to the general membership. I have collected the opinions of various loyal, long-standing APA members and put together a separate, yet-unpublished article to drive home the point that APA has resisted breaking the monopoly of ABPN, which the DOJ would encourage organizations such as the APA to do. Instead, APA is acting as an enabler to ABPN to create a multi-million dollar (and eventually a billion dollar) monopolistic industry at their members’ expense, literally endangering the careers of members if they fail to participate when employed by institutions that overvalue the MOC offered by ABPN.

I believe the recent exhibition of “collaboration” between the APA and ABPN is not similar to that between ACGME and ABPN, but is a most blatant effort on the part of the APA to help ABPN build a billion-dollar educational industry over the next 10 to 15 years. One can easily lose sight of this and get lost in the intricacies of how candidates can maintain their competency by obtaining free CME credits. The APA is distracting its members by citing this. They will continue to pay a high price for certification and recertification, with no real discount.

Most of the APA’s 38,000 members are in the dark about the above-mentioned process. They need to do their own research, especially when there are alternatives to the ABPN’s MOC program. They need to insist that the APA stop exclusively promoting ABPN products, and publicize other, much cheaper, alternatives. It will please all APA members to see the ABPN’s monopoly vanish. This is especially the case for younger psychiatrists, who average nearly $250,000 in educational loans. They need to prevent the APA/ABPN collaboration from having a far-reaching effect on their careers and finances, with potentially destructive consequences for their families, employers and—most importantly—their patients. Even some state licensing boards are being tempted to buy into the illusion.

Stop this MOCkery.

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

The Accreditation Council for Graduate Medical Education (ACGME) is en­trusted with assuring that upon graduation every resident is a competent doctor, a trained professional, and prepared to practice in their own field at a level that assures patient safety and meets the standard of care. The American Board of Psychiatry and Neurology (ABPN) is a private company that sells certificates claiming to attest the capacity or competence of the doctor but does not make public the test questions or algorithms used to win its qualifications or approval. The certifying business and the newer Maintenance of Certification (MOC) process developed by ABPN have unfortunately been embraced by ACGME and many hospitals, despite the lack of any good scientific support that board certification or MOC are meaningful for quality of patient care or outcomes. By that I mean there is no evidence that the voluntary board certification process or MOC have been shown to produce better outcomes for patients, save money for the country drowning in an ocean of health care costs, or allow doctors to get paid at a higher level by insurers for the same billing codes compared with those who bill without possessing these qualifications. The only entity that “profits” from the board certification/MOC process is ABPN, a private corporation that is supposed to be a nonprofit, but was sitting on a treasury of more than $140M in assets in 2019,¹ with revenues growing annually. Including the interest earned on the investment and added revenues every year, the estimated total assets of ABPN will be in the range of $150M at the end of 2021!

Collaboration between ACGME and ABPN

The collaboration between ACGME and ABPN for graduate education for designing training programs for residents and fellows, with progressively increasing competencies and their assessments to dovetail with the board examinations offered by ABPN, sounds very legitimate. This arrangement is designed to enhance the quality of training and establish a minimum level of competence in each trainee who completes the training program. However, ACGME is catering to a monopoly recognized by the US Department of Justice (DOJ) Antitrust Division.² ACGME has not entertained other evaluators of competence to discourage competition to the monopolistic ABPN. ACGME is only involved with the accredited training programs and has no business in assessing the continued competence of graduated trainees after they leave the program, although most will voluntarily opt to become board-certified by ABPN. Maintenance of Certification definitely does not come within the purview of “graduate medical education” for ACGME to be getting drawn into this collaboration.

ACGME and ABPN are unregulated and are not member-driven. As such, they operate outside of any real oversight. Their power derives from the status given to them by hospitals, some insurers, and many of our colleagues, who fail to see the reality that they are nothing more than diploma shops.

I am board-certified in psychiatry and child and adolescent psychiatry, and I have participated in obtaining board certification by ABPN in 3 other subspecialties (geriatric, addiction, and forensic). I decided to not participate in MOC for the latter 3 subspecialty certifications beyond 10 and 20 years for my own practical reasons. Obviously, then, I am not at all against initial certifications in any specialty, nor am I opposed to practitioners keeping up with progress in their fields and maintaining their competence. I am opposed to the continued efforts to engage professionals to pay a high price for the repeated MOC, riding on the hard work and earnings of the graduated specialists and continuously suctioning their income over their careers, with no evidence that MOC measures clinical competence or patient outcomes of their subscribers, who pay a chunk of money to the American Board of Medical Specialties (ABMS)/ABPN annually and every 10 years.

MOC and the APA

Many American Psychiatric Association (APA) members are opposed to the APA giving ABPN a piggyback ride to accomplish this profit seeking. This is becoming obvious to many APA members, who see this as a great exploitation.

Over the last 6 years, physicians have begun to question the validity of board certification and MOC by ABPN, mostly as a response to ever-increasing costs to them and ever-increasing revenues to ABPN. While APA members have long pressed the APA to push back against ABPN, the APA Board of Trustees has done the opposite by accepting yearly “unrestricted educational grants” from ABPN. In this manner, ABPN has essentially silenced the APA and has made it ineffective as our member organization in what has become a fight against ABPN’s unchecked power, influence, and intrusion. Every poll conducted by every APA District Branch or subspecialty organization has shown widespread discontent and anger at the ABPN/MOC process and APA’s deliberate inaction. Even when the APA commissioned its own member survey on the topic, wrote the questions, picked who would get the survey, decided which responses to count, and determined what statistics to apply, the results were damning. Despite its obviously transparent machinations, the APA failed to glorify the MOC process.

Continue to: The APA's membership...

The APA’s membership is declining, and the Board of Trustee’s position on MOC is partly to blame. The APA is once again not listening to its members! As a membership-driven organization, the APA must not exclusively support and promote this commercial educational product termed MOC when other, less expensive alternatives are now available. The APA can easily endorse these alternatives, in addition to offering its own less expensive products for attesting maintenance of competence. The latter effort will help eliminate the monopoly held by ABMS/ABPN in this domain and please all members as well as the DOJ.

The APA’s failure to provide less expensive alternatives or at least endorse existing ones despite repeated requests from a large number of APA members has led to frustration and a surge of strong feelings that are expressed on the APA email listservs, and especially that of the MOC caucus. These expressions are legitimate and need to be publicized to the general membership. I have collected the opinions of various loyal, long-standing APA members and put together a separate, yet-unpublished article to drive home the point that APA has resisted breaking the monopoly of ABPN, which the DOJ would encourage organizations such as the APA to do. Instead, APA is acting as an enabler to ABPN to create a multi-million dollar (and eventually a billion dollar) monopolistic industry at their members’ expense, literally endangering the careers of members if they fail to participate when employed by institutions that overvalue the MOC offered by ABPN.

I believe the recent exhibition of “collaboration” between the APA and ABPN is not similar to that between ACGME and ABPN, but is a most blatant effort on the part of the APA to help ABPN build a billion-dollar educational industry over the next 10 to 15 years. One can easily lose sight of this and get lost in the intricacies of how candidates can maintain their competency by obtaining free CME credits. The APA is distracting its members by citing this. They will continue to pay a high price for certification and recertification, with no real discount.

Most of the APA’s 38,000 members are in the dark about the above-mentioned process. They need to do their own research, especially when there are alternatives to the ABPN’s MOC program. They need to insist that the APA stop exclusively promoting ABPN products, and publicize other, much cheaper, alternatives. It will please all APA members to see the ABPN’s monopoly vanish. This is especially the case for younger psychiatrists, who average nearly $250,000 in educational loans. They need to prevent the APA/ABPN collaboration from having a far-reaching effect on their careers and finances, with potentially destructive consequences for their families, employers and—most importantly—their patients. Even some state licensing boards are being tempted to buy into the illusion.

Stop this MOCkery.

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

The Accreditation Council for Graduate Medical Education (ACGME) is en­trusted with assuring that upon graduation every resident is a competent doctor, a trained professional, and prepared to practice in their own field at a level that assures patient safety and meets the standard of care. The American Board of Psychiatry and Neurology (ABPN) is a private company that sells certificates claiming to attest the capacity or competence of the doctor but does not make public the test questions or algorithms used to win its qualifications or approval. The certifying business and the newer Maintenance of Certification (MOC) process developed by ABPN have unfortunately been embraced by ACGME and many hospitals, despite the lack of any good scientific support that board certification or MOC are meaningful for quality of patient care or outcomes. By that I mean there is no evidence that the voluntary board certification process or MOC have been shown to produce better outcomes for patients, save money for the country drowning in an ocean of health care costs, or allow doctors to get paid at a higher level by insurers for the same billing codes compared with those who bill without possessing these qualifications. The only entity that “profits” from the board certification/MOC process is ABPN, a private corporation that is supposed to be a nonprofit, but was sitting on a treasury of more than $140M in assets in 2019,¹ with revenues growing annually. Including the interest earned on the investment and added revenues every year, the estimated total assets of ABPN will be in the range of $150M at the end of 2021!

Collaboration between ACGME and ABPN

The collaboration between ACGME and ABPN for graduate education for designing training programs for residents and fellows, with progressively increasing competencies and their assessments to dovetail with the board examinations offered by ABPN, sounds very legitimate. This arrangement is designed to enhance the quality of training and establish a minimum level of competence in each trainee who completes the training program. However, ACGME is catering to a monopoly recognized by the US Department of Justice (DOJ) Antitrust Division.² ACGME has not entertained other evaluators of competence to discourage competition to the monopolistic ABPN. ACGME is only involved with the accredited training programs and has no business in assessing the continued competence of graduated trainees after they leave the program, although most will voluntarily opt to become board-certified by ABPN. Maintenance of Certification definitely does not come within the purview of “graduate medical education” for ACGME to be getting drawn into this collaboration.

ACGME and ABPN are unregulated and are not member-driven. As such, they operate outside of any real oversight. Their power derives from the status given to them by hospitals, some insurers, and many of our colleagues, who fail to see the reality that they are nothing more than diploma shops.

I am board-certified in psychiatry and child and adolescent psychiatry, and I have participated in obtaining board certification by ABPN in 3 other subspecialties (geriatric, addiction, and forensic). I decided to not participate in MOC for the latter 3 subspecialty certifications beyond 10 and 20 years for my own practical reasons. Obviously, then, I am not at all against initial certifications in any specialty, nor am I opposed to practitioners keeping up with progress in their fields and maintaining their competence. I am opposed to the continued efforts to engage professionals to pay a high price for the repeated MOC, riding on the hard work and earnings of the graduated specialists and continuously suctioning their income over their careers, with no evidence that MOC measures clinical competence or patient outcomes of their subscribers, who pay a chunk of money to the American Board of Medical Specialties (ABMS)/ABPN annually and every 10 years.

MOC and the APA

Many American Psychiatric Association (APA) members are opposed to the APA giving ABPN a piggyback ride to accomplish this profit seeking. This is becoming obvious to many APA members, who see this as a great exploitation.

Over the last 6 years, physicians have begun to question the validity of board certification and MOC by ABPN, mostly as a response to ever-increasing costs to them and ever-increasing revenues to ABPN. While APA members have long pressed the APA to push back against ABPN, the APA Board of Trustees has done the opposite by accepting yearly “unrestricted educational grants” from ABPN. In this manner, ABPN has essentially silenced the APA and has made it ineffective as our member organization in what has become a fight against ABPN’s unchecked power, influence, and intrusion. Every poll conducted by every APA District Branch or subspecialty organization has shown widespread discontent and anger at the ABPN/MOC process and APA’s deliberate inaction. Even when the APA commissioned its own member survey on the topic, wrote the questions, picked who would get the survey, decided which responses to count, and determined what statistics to apply, the results were damning. Despite its obviously transparent machinations, the APA failed to glorify the MOC process.

Continue to: The APA's membership...

The APA’s membership is declining, and the Board of Trustee’s position on MOC is partly to blame. The APA is once again not listening to its members! As a membership-driven organization, the APA must not exclusively support and promote this commercial educational product termed MOC when other, less expensive alternatives are now available. The APA can easily endorse these alternatives, in addition to offering its own less expensive products for attesting maintenance of competence. The latter effort will help eliminate the monopoly held by ABMS/ABPN in this domain and please all members as well as the DOJ.

The APA’s failure to provide less expensive alternatives or at least endorse existing ones despite repeated requests from a large number of APA members has led to frustration and a surge of strong feelings that are expressed on the APA email listservs, and especially that of the MOC caucus. These expressions are legitimate and need to be publicized to the general membership. I have collected the opinions of various loyal, long-standing APA members and put together a separate, yet-unpublished article to drive home the point that APA has resisted breaking the monopoly of ABPN, which the DOJ would encourage organizations such as the APA to do. Instead, APA is acting as an enabler to ABPN to create a multi-million dollar (and eventually a billion dollar) monopolistic industry at their members’ expense, literally endangering the careers of members if they fail to participate when employed by institutions that overvalue the MOC offered by ABPN.

I believe the recent exhibition of “collaboration” between the APA and ABPN is not similar to that between ACGME and ABPN, but is a most blatant effort on the part of the APA to help ABPN build a billion-dollar educational industry over the next 10 to 15 years. One can easily lose sight of this and get lost in the intricacies of how candidates can maintain their competency by obtaining free CME credits. The APA is distracting its members by citing this. They will continue to pay a high price for certification and recertification, with no real discount.

Most of the APA’s 38,000 members are in the dark about the above-mentioned process. They need to do their own research, especially when there are alternatives to the ABPN’s MOC program. They need to insist that the APA stop exclusively promoting ABPN products, and publicize other, much cheaper, alternatives. It will please all APA members to see the ABPN’s monopoly vanish. This is especially the case for younger psychiatrists, who average nearly $250,000 in educational loans. They need to prevent the APA/ABPN collaboration from having a far-reaching effect on their careers and finances, with potentially destructive consequences for their families, employers and—most importantly—their patients. Even some state licensing boards are being tempted to buy into the illusion.

Stop this MOCkery.