Psychiatric Annals

CME Article 

Metabolic Syndrome in Bipolar Disorder: Review and Management

Alana S. Regan, PharmD, BCPP; Stephanie C. Valcourt, MD

Abstract

The increased prevalence of metabolic syndrome in bipolar disorder is multifactorial in etiology and has far-reaching implications on illness course, treatment adherence, functioning, and premature mortality. Treatment with mood-stabilizing and antipsychotic medications may contribute to the development of metabolic syndrome in this population. Among mood stabilizers, both lithium and valproate have been associated with weight gain, whereas lamotrigine and carbamazepine are considered weight neutral. Antipsychotic medications afford variable risks, with olanzapine and clozapine ranking highest and newer agents carrying less risk, including aripiprazole, ziprasidone, lurasidone, and cariprazine. Mechanisms underlying the metabolic risks of these medications are similarly variable and for antipsychotics may include neurotransmitter-receptor interactions, actions at receptors associated with hypothalamic control of food intake, and individual genetic risk factors. Management includes close monitoring and behavioral/lifestyle interventions, followed by pharmacologic interventions including switching medications or adding a medication to mitigate weight gain, among which metformin has been most extensively studied. [Psychiatr Ann. 2020;50(8):334–339.]

Abstract

The increased prevalence of metabolic syndrome in bipolar disorder is multifactorial in etiology and has far-reaching implications on illness course, treatment adherence, functioning, and premature mortality. Treatment with mood-stabilizing and antipsychotic medications may contribute to the development of metabolic syndrome in this population. Among mood stabilizers, both lithium and valproate have been associated with weight gain, whereas lamotrigine and carbamazepine are considered weight neutral. Antipsychotic medications afford variable risks, with olanzapine and clozapine ranking highest and newer agents carrying less risk, including aripiprazole, ziprasidone, lurasidone, and cariprazine. Mechanisms underlying the metabolic risks of these medications are similarly variable and for antipsychotics may include neurotransmitter-receptor interactions, actions at receptors associated with hypothalamic control of food intake, and individual genetic risk factors. Management includes close monitoring and behavioral/lifestyle interventions, followed by pharmacologic interventions including switching medications or adding a medication to mitigate weight gain, among which metformin has been most extensively studied. [Psychiatr Ann. 2020;50(8):334–339.]

Metabolic syndrome is a constellation of metabolic abnormalities (ie, abdominal obesity, elevated triglyceride level, low high-density lipoprotein cholesterol [HDL-C] level, hypertension, and hyperglycemia) that has been associated with elevated risks of diabetes and cardiovascular disease, and its well-established increased prevalence among people with serious mental illness, including bipolar disorder, contributes to rates of increased and premature mortality across this population.1 Prevalence rates of metabolic syndrome among people with bipolar disorder appear similar to those for schizophrenia and major depression2 and range from 10% to more than 60% in the literature,3 with a rate of 37.3% in a large meta-analysis in 2013, with an odds ratio approaching twice that of the general population.4 Among those who progress to cardiovascular disease, onset of illness is 13.7 years earlier in patients with bipolar disorder relative to controls.5 The etiology of this increased prevalence is considered multifactorial and is briefly summarized in this section, to include genetic, neuroendocrine and immunologic, demographic, illness-specific, lifestyle, and iatrogenic considerations.

Among criteria for metabolic syndrome, abdominal obesity is most commonly seen in bipolar disorder, followed in order by hypertension, low HDL-C, high triglycerides, and hyperglycemia.4 Hyperactivity of the hypothalamic-pituitary-adrenal axis including dysregulation of cortisol seen in depression and across affective phases of bipolar disorder has been shown to contribute to abdominal obesity, and cytokines secreted from adipose tissue, together with concurrent elevations in C-reactive protein and other proinflammatory cytokines, may further promote development of metabolic syndrome through decreased insulin sensitivity.3,6 More recently, genome-wide association and candidate gene studies have pointed to pleiotropic genes that are shared between mood disorders and cardiometabolic conditions, with shared genetic pathways involving neuroendocrine signaling, suggesting an underlying genetic vulnerability to common pathophysiological processes.7

Whereas longer illness duration has not been demonstrated to be associated with increased risk of metabolic syndrome among patients with bipolar disorder, it has been noted to have an increased prevalence in older patients.4 And although some studies have shown an increased risk of obesity, particularly abdominal obesity, among women versus men with bipolar disorder,8 there has not been a clear association with increased risk of metabolic syndrome among women with bipolar disorder across studies.4,9

Metabolic syndrome has been demonstrated to be more prevalent in people with past or current depressive syndromes; among patients with bipolar disorder, depressive burden in particular has been associated with obesity, and metabolic syndrome has been shown to be associated with a lifetime history of suicide attempts, at least in the United States.3 Possibly, bipolar depression symptoms (for example, hyperphagia, fatigue, hypersomnia/insomnia) may contribute to lifestyle factors that increase risk of metabolic syndrome and cardiovascular disease, including overeating and limited activity/exercise,3 in addition to increased rates of cigarette smoking and alcohol use.4 Regarding course of illness, abdominal obesity has been correlated with worse scores on measures of disease severity and global functioning.10 Notably, antipsychotic and mood-stabilizing medications approved for treatment of bipolar disorder contribute toward increased risk of metabolic syndrome for which treatment must be individualized and inclusive of risk-reduction approaches.

Treatment Challenges in Bipolar Disorder

Since the emergence of lithium, pharmacotherapeutic options for bipolar disorder have advanced to include an array of antiepileptics and typical and atypical antipsychotics as first-line treatments. Despite a growing armamentarium, medication tolerability, drug-drug interactions, toxicity, and side effects often surface and can undermine treatment success, posing a challenge for patients and clinicians. Aside from contributing to metabolic syndrome, psychotropic-induced weight gain is a common cause of treatment nonadherence in bipolar disorder, as reported by nearly 60% of patients with self-reported treatment nonadherence.11 This further contributes to relapse, hospitalizations, and increased morbidity.11 Weight gain can also have negative psychosocial implications such as impaired self-image, low self-esteem, and lessened social interactions.12 It is imperative that pharmacotherapeutic options are not only effective but tolerable enough for patients to be able to sustain adequate treatment durations. This requires a thorough understanding of metabolic side effects, including pharmacologic mechanisms, relative risks between agents, and mitigation and management strategies.

Mood Stabilizers

Weight gain associated with lithium treatment has been linked to nonadherence. A 2018 retrospective cohort study appraising causes of lithium discontinuation in patients with bipolar disorder found that more than 60% of discontinuations were due to adverse effects, and up to 12% of those were due to weight gain.13 Lithium-induced weight gain is experienced by about one-fourth of patients,12 most commonly during the first 2 years of treatment before plateauing, averaging 4.5 to 12 kg,12 and is greatest in patients who are already obese.14 Increases in weight appear to be dose-dependent, showing a greater risk at plasma levels >0.8 mmol/L.12,15 The exact frequency, extent, and timing of lithium-induced weight gain are somewhat varied in the literature. In a meta-analysis of 14 trials, significant weight gain >7% was found to be more frequent in patients receiving lithium than placebo (odds ratio 1.89, 1.27–2.82, P = .002).16 Tondo et al.17 evaluated the effect of long-term lithium therapy over 8 to 48 years (mean 18) in 312 adults with bipolar disorder. After 31 to 48 years of treatment, mean body mass index (BMI) increased modestly from 25.9 at baseline to 26.6 kg/m2.17 However, the most significant change in BMI occurred during the first year of treatment, increasing from 25.9 to 27.9 kg/m2.17 An additional metabolic outcome included an increase in mean glucose from 88 to 122 mg/dL, at 0.79% per year, with the most significant increases occurring during years 6 to 10 of treatment.17 The exact mechanism of lithium-induced weight gain is unknown. Possible mechanisms include edema; a slowed metabolic rate due to hypothyroidism, underlining the importance of regular thyroid function monitoring; polyuria leading to polydipsia, increasing the intake of high-calorie, sugar-sweetened beverages; and direct appetite stimulation at the hypothalamus.12,13 Lithium is not directly associated with dyslipidemia, hypertension, or diabetes mellitus, although these comorbidities can occur secondary to weight gain.15 Dyslipidemia may also occur secondary to lithium-induced hypothyroidism.15

Similar to lithium, valproate discontinuation and poor treatment adherence are frequently attributed to weight gain. The incidence of valproate-induced weight gain ranges from 10% to 70%,18 averaging at about one-half of patients, gaining a mean of 6 kg,19 and women tend to gain more weight compared to men.10 Torrent et al.12 estimated that weight gain with valproate ranges from 3 to 10 kg over the first 3 to 12 months, but patients could possibly gain up to 20 kg over a longer duration of treatment. Weight gain appears to be dose-dependent, as it has shown to be more likely at plasma levels >125 mcg/mL,14 and the extended-release formulation appears to cause less severe weight gain than other formulations.19 The exact mechanism behind valproate-induced weight gain is unknown, but it is hypothesized to involve increases in insulin secretion, appetite, and energy storage resulting in weight gain.19 A 2016 population-based cohort study of patients with bipolar disorder showed greater rates of significant weight gain (hazard ratio [HR] 1.62; 95% confidence interval [CI] 1.31–2.01; P < .001), hypertension (HR 1.19; 95% CI 0.90–1.58; P = .274), and type 2 diabetes mellitus (HR 1.08; 95% CI 0.83–1.42; P = 0.586) with valproate when compared to lithium, although not all of these results were statistically significant.20 Unlike lithium, valproate has been associated with glucose intolerance, hypertension, and increases in triglycerides, apart from weight gain.15 Valproate is also associated with the development of polycystic ovary syndrome and subsequent insulin resistance.14

Lamotrigine and carbamazepine are considered weight neutral, with some evidence displaying weight loss properties, and can be considered as lower risk alternatives if adequate mood stability can be achieved without lithium or valproate.14,15 Carbamazepine has been shown to play a role in dyslipidemia via CYP51A1 enzyme induction, leading to loss of feedback inhibition on 3-hydroxy-3-methylglutaryl-CoA reductase, and increasing cholesterol production.15 A neutral effect on lipids has been observed with lamotrigine.21

Antipsychotics

Antipsychotic drugs are mainstays of treatment for bipolar disorder and are often used alone or in combination with mood-stabilizing medications. Comprehensive reviews comparing metabolic risks of antipsychotics have been conducted in patients with schizophrenia, as reviewed below, whereas this data in bipolar disorder remain limited. In a head-to-head meta-analysis of metabolic side effects of atypical antipsychotics, increases in weight, cholesterol, and glucose appeared to cluster into three groups, ranking highest- to lowest-risk: olanzapine and clozapine > quetiapine and risperidone > aripiprazole and ziprasidone.22 In a 2013 meta-analysis of 15 antipsychotic drugs, olanzapine was associated with significantly more weight gain than most other drugs, and all drugs produced more weight gain than placebo except for haloperidol, lurasidone, and ziprasidone.23 Specifically, clozapine, iloperidone, chlorpromazine, quetiapine, risperidone, and paliperidone were associated with significantly more weight gain than haloperidol, ziprasidone, lurasidone, aripiprazole, and asenapine (although asenapine did not differ significantly from paliperidone). Among D2 partial agonists specifically, propensity for weight gain with cariprazine may be lower than that of aripiprazole.24

The rate of weight gain with atypical antipsychotics appears to be greatest over the first 6 months of treatment, with some evidence that it subsequently may not plateau.25 The relationship between antipsychotic dose and metabolic risk is less clear and may not be generalizable; although there is some evidence to suggest that clozapine and olanzapine may have serum concentration-dependent metabolic effects, the data for risperidone are controversial, and there is no evidence that aripiprazole, quetiapine, or ziprasidone have dose-dependent effects.26

Mechanisms underlying weight gain with antipsychotics are multifactorial and not fully understood, although they may include neurotransmitter-receptor interactions (with more evidence for histamine H1 receptor antagonism, serotonin 5-HT2C receptor antagonism or inverse agonism, and muscarinic M3 antagonism; also secondary effects of hypothalamic/mesolimbic dopamine D2 receptor antagonism and synergistic effects of noradrenergic alpha-1 receptor antagonism) and actions at receptors associated with the hypothalamic control of food intake (via altered expressions of anorexigenic hormones such as leptin and orexigenic hormones including adiponectin and ghrelin).27 Genetic variability in receptor targets of antipsychotics (to include single nucleotide polymorphisms in the serotonin 5-HT2C receptor [HTR2C], dopamine D2 [DRD2] receptor, and adrenoreceptor alpha-2A receptor [ADRA2A] genes), hypothalamic control of food intake and body weight (to include the melanocortin-4 receptor [MC4R] gene), among other heritable risk factors for obesity and metabolic disturbances, likely explains the profoundly variable weight gain seen among people receiving treatment with the same antipsychotic.27 A potentially protective pharmacological effect common to lower-weight gain antipsychotics including aripiprazole, lurasidone, and ziprasidone is partial agonism at serotonin 5-HT1A receptors, whose effects on body weight oppose those of 5-HT2C receptors, and which may explain the potential for aripiprazole to diminish the weight gain from higher-risk agents such as clozapine.27

Combination Therapy

Studies show an increase in weight gain when adding an antipsychotic to mood stabilizer monotherapy, but not when adding a mood stabilizer to antipsychotic monotherapy. A 2015 cross-sectional study of 626 patients found that treatment with valproate plus an antipsychotic was not associated with a statistically significant increase in metabolic side effects when compared to antipsychotic monotherapy.18 Conversely, when comparing adding either olanzapine or placebo to lithium or valproate therapy, weight gain was more common in the combination group compared to mood stabilizer monotherapy (20% versus 6%).12

Management Strategies

Given the incidence of metabolic syndrome in this patient population, a systematic screening and treatment approach is recommended regardless of medication regimen.21 First-line lifestyle interventions (eg, cognitive-behavioral therapy, nutrition counseling, exercise programs, social support) have proven effective in preventing and treating weight gain.28 When behavioral interventions are insufficient, pharmacologic interventions may be indicated. Transitioning to a mood stabilizer or antipsychotic with a lower metabolic risk is recommended if the causative agent has only minimal therapeutic advantage over the lower risk alternative.21 Medications to assist with weight management are recommended in patients with a BMI ≥30 kg/m2, or in patients with a BMI ≥27 kg/m2 and a weight-related morbidity (eg, diabetes mellitus, hypertension, dyslipidemia).21Table 1 describes potential pharmacologic options. Metformin has been studied most extensively in this patient population.14 Orlistat has not shown significant results in psychotropic-induced weight gain, although it has been effective in general population studies.29 Sympathomimetic agents such as phentermine and modafinil should be used with caution due to potential for inducing hypomania/mania.21 The other elements of metabolic syndrome such as hypertension, dyslipidemia, and hyperglycemia, need to be monitored and addressed, keeping in mind that they may occur in the absence of weight gain and may not be resolved by the aforementioned lifestyle changes and weight loss treatments.21

Pharmacologic Management Optionsa

Table 1.

Pharmacologic Management Options

References

  1. Swartz HA, Fagiolini A. Cardiovascular disease and bipolar disorder: risk and clinical implications. J Clin Psychiatry. 2012;73(12):1563–1565. doi:10.4088/JCP.12ac08227 [CrossRef] PMID:23290329
  2. Vancampfort D, Stubbs B, Mitchell AJ, et al. Risk of metabolic syndrome and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder: a systematic review and meta-analysis. World Psychiatry. 2015;14(3):339–347. doi:10.1002/wps.20252 [CrossRef] PMID:26407790
  3. McElroy SL, Keck PE Jr, . Metabolic syndrome in bipolar disorder: a review with a focus on bipolar depression. J Clin Psychiatry. 2014;75(1):46–61. doi:10.4088/JCP.13r08634 [CrossRef] PMID:24502861
  4. Vancampfort D, Vansteelandt K, Correll CU, et al. Metabolic syndrome and metabolic abnormalities in bipolar disorder: a meta-analysis of prevalence rates and moderators. Am J Psychiatry. 2013;170(3):265–274. doi:10.1176/appi.ajp.2012.12050620 [CrossRef] PMID:23361837
  5. Goldstein BI, Fagiolini A, Houck P, Kupfer DJ. Cardiovascular disease and hypertension among adults with bipolar I disorder in the United States. Bipolar Disord. 2009;11(6):657–662. doi:10.1111/j.1399-5618.2009.00735.x [CrossRef] PMID:19689508
  6. de Almeida KM, Moreira CL, Lafer B. Metabolic syndrome and bipolar disorder: what should psychiatrists know?CNS Neurosci Ther. 2012;18(2):160–166. doi:10.1111/j.1755-5949.2011.00240.x [CrossRef] PMID:22070636
  7. Penninx BWJH, Lange SMM. Metabolic syndrome in psychiatric patients: overview, mechanisms, and implications. Dialogues Clin Neurosci. 2018;20(1):63–73. PMID:29946213
  8. Baskaran A, Cha DS, Powell AM, Jalil D, McIntyre RS. Sex differences in rates of obesity in bipolar disorder: postulated mechanisms. Bipolar Disord. 2014;16(1):83–92. doi:10.1111/bdi.12141 [CrossRef] PMID:24467470
  9. McIntyre RS, Danilewitz M, Liauw SS, et al. Bipolar disorder and metabolic syndrome: an international perspective. J Affect Disord. 2010;126(3):366–387. doi:10.1016/j.jad.2010.04.012 [CrossRef] PMID:20541810
  10. Fagiolini A, Chengappa KN, Soreca I, Chang J. Bipolar disorder and the metabolic syndrome: causal factors, psychiatric outcomes and economic burden. CNS Drugs. 2008;22(8):655–669. doi:10.2165/00023210-200822080-00004 [CrossRef] PMID:18601304
  11. Baldessarini RJ, Perry R, Pike J. Factors associated with treatment nonadherence among US bipolar disorder patients. Hum Psychopharmacol. 2008;23(2):95–105. doi:10.1002/hup.908 [CrossRef] PMID:18058849
  12. Torrent C, Amann B, Sánchez-Moreno J, et al. Weight gain in bipolar disorder: pharmacological treatment as a contributing factor. Acta Psychiatr Scand. 2008;118(1):4–18. doi:10.1111/j.1600-0447.2008.01204.x [CrossRef] PMID:18498432
  13. Öhlund L, Ott M, Oja S, et al. Reasons for lithium discontinuation in men and women with bipolar disorder: a retrospective cohort study. BMC Psychiatry. 2018;18(1):37. doi:10.1186/s12888-018-1622-1 [CrossRef] PMID:29415689
  14. Kemp DE. Managing the side effects associated with commonly used treatments for bipolar depression. J Affect Disord. 2014;169(1)(suppl 1):S34–S44. doi:10.1016/S0165-0327(14)70007-2 [CrossRef] PMID:25533913
  15. Abosi O, Lopes S, Schmitz S, Fiedorowicz JG. Cardiometabolic effects of psychotropic medications. Horm Mol Biol Clin Investig. 2018;36(1): /j/hmbci.2018.36.issue-1/hmbci-2017-0065/hmbci-2017-0065.xml. doi:10.1515/hmbci-2017-0065 [CrossRef] PMID:29320364
  16. McKnight RF, Adida M, Budge K, Stockton S, Goodwin GM, Geddes JR. Lithium toxicity profile: a systematic review and meta-analysis. Lancet. 2012;379(9817):721–728. doi:10.1016/S0140-6736(11)61516-X [CrossRef] PMID:22265699
  17. Tondo L, Abramowicz M, Alda M, et al. Long-term lithium treatment in bipolar disorder: effects on glomerular filtration rate and other metabolic parameters. Int J Bipolar Disord. 2017;5(1):27. doi:10.1186/s40345-017-0096-2 [CrossRef] PMID:28480485
  18. Zuo S, Fries BE, Szafara K, Regal R. Valproic acid as a potentiator of metabolic syndrome in institutionalized residents on concomitant antipsychotics: fat chance, or slim to none?P T. 2015;40(2):126–132. PMID:25673963
  19. Martin CK, Han H, Anton SD, Greenway FL, Smith SR. Effect of valproic acid on body weight, food intake, physical activity and hormones: results of a randomized controlled trial. J Psychopharmacol. 2009;23(7):814–825. doi:10.1177/0269881108091595 [CrossRef] PMID:18583434
  20. Hayes JF, Marston L, Walters K, Geddes JR, King M, Osborn DP. Adverse renal, endocrine, hepatic, and metabolic events during maintenance mood stabilizer treatment for bipolar disorder: a population-based cohort study. PLoS Med. 2016;13(8):e1002058. doi:10.1371/journal.pmed.1002058 [CrossRef] PMID:27483368
  21. McIntyre RS, Alsuwaidan M, Goldstein BI, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force. The Canadian Network for Mood and Anxiety Treatments (CANMAT) task force recommendations for the management of patients with mood disorders and comorbid metabolic disorders. Ann Clin Psychiatry. 2012;24(1):69–81. PMID:22303523
  22. Rummel-Kluge C, Komossa K, Schwarz S, et al. Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis. Schizophr Res. 2010;123(2–3):225–233. doi:10.1016/j.schres.2010.07.012 [CrossRef] PMID:20692814
  23. Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. 2013;382(9896):951–962. doi:10.1016/S0140-6736(13)60733-3 [CrossRef] PMID:23810019
  24. Corponi F, Fabbri C, Bitter I, et al. Novel antipsychotics specificity profile: A clinically oriented review of lurasidone, brexpiprazole, cariprazine and lumateperone. Eur Neuropsychopharmacol. 2019;29(9):971–985. doi:10.1016/j.euroneuro.2019.06.008 [CrossRef] PMID:31255396
  25. Bushe CJ, Slooff CJ, Haddad PM, Karagianis JL. Weight change from 3-year observational data: findings from the worldwide schizophrenia outpatient health outcomes database. J Clin Psychiatry. 2012;73(6):e749–e755. doi:10.4088/JCP.11m07246 [CrossRef] PMID:22795214
  26. Simon V, van Winkel R, De Hert M. Are weight gain and metabolic side effects of atypical antipsychotics dose dependent? A literature review. J Clin Psychiatry. 2009;70(7):1041–1050. doi:10.4088/JCP.08r04392 [CrossRef] PMID:19653979
  27. Reynolds GP, McGowan OO. Mechanisms underlying metabolic disturbances associated with psychosis and antipsychotic drug treatment. J Psychopharmacol. 2017;31(11):1430–1436. doi:10.1177/0269881117722987 [CrossRef] PMID:28892404
  28. Dayabandara M, Hanwella R, Ratnatunga S, Seneviratne S, Suraweera C, de Silva VA. Antipsychotic-associated weight gain: management strategies and impact on treatment adherence. Neuropsychiatr Dis Treat. 2017;13:2231–2241. doi:10.2147/NDT.S113099 [CrossRef] PMID:28883731
  29. Fiedorowicz JG, Miller DD, Bishop JR, Calarge CA, Ellingrod VL, Haynes WG. Systematic review and meta-analysis of pharmacological interventions for weight gain from antipsychotics and mood stabilizers. Curr Psychiatry Rev. 2012;8(1):25–36. doi:10.2174/157340012798994867 [CrossRef] PMID:22712004
  30. Marteene W, Winckel K, Hollingworth S, et al. Strategies to counter antipsychotic-associated weight gain in patients with schizophrenia. Expert Opin Drug Saf. 2019;18(12):1149–1160. doi:10.1080/14740338.2019.1674809 [CrossRef] PMID:31564170

Pharmacologic Management Optionsa

Medication Mechanism Common adverse effects Average weight loss (kg) Indication studied
Amantadine NMDA-receptor antagonism; dopaminergic effects29 Anxiety, agitation, insomnia, exacerbation of psychosis29 −0.229 Antipsychotic-induced weight gain29
GLP-1 agonists (liraglutide, exenatide) Reduces appetite and food intake via activated central and peripheral GLP-1 receptors28 Nausea, vomiting, diarrhea, abdominal pain, injection site reactions (SQ administration)30 −3.730 Antipsychotic-induced weight gain30
Metformin Decreases intestinal glucose absorption, increases insulin sensitivity, reduces hepatic gluconeogenesis, suppresses appetite30 GI (diarrhea, flatulence, indigestion)29 −329 Weight gain associated with mood stabilizers and antipsychotics29
Topiramate Suppresses appetite, increases satiety28 Confusion, dizziness, memory impairment29 −429 Weight gain associated with mood stabilizers and antipsychotics29
Authors

Alana S. Regan, PharmD, BCPP, is a Clinical Pharmacist. Stephanie C. Valcourt, MD, is a Psychiatrist. Both authors are affiliated with McLean Hospital.

Address correspondence to Alana S. Regan, PharmD, BCPP, McLean Hospital, 115 Mill Street, Mail Stop 218, Belmont, MA 02478; email: aregan3@partners.org.

Disclosure: The authors have no relevant financial relationships to disclose.

10.3928/00485713-20200713-01

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