SGAS VS MOOD STABILIZERS: THE PARADIGM SHIFT IN CORE TREATMENT FOR BIPOLAR DISORDER

Mood stabilizers have traditionally been regarded as the foundational treatment for bipolar disorder, but recent years have witnessed a growing array of clinical trials revealing their limited breadth of spectrum. Lithium shows greater efficacy for mania than depression and produces robust effects in only a relatively small patient subgroup definable by mania polarity-proneness, positive family history of lithium-responsive bipolar disorder, and the absence of mixed features, rapid cycling, psychosis, or substance use and/or psychiatric comorbidities. Valproate similarly exerts greater antimanic than antidepressant value and has not been shown to prevent recurrences better than placebo. Lamotrigine lacks discernible antimanic acute or prophylactic efficacy and data are inconsistent for its use in acute depressive episodes. Carbamazepine is limited by its hepatic, hematologic and pharmacokinetic adverse effects and lacks data in bipolar depression or maintenance prophylaxis. No other anticonvulsants have demonstrated superiority to placebo as thymoleptics. By contrast, a number of second generation antipsychotics (SGAs) have demonstrated breadth of spectrum across all phases of illness with outcomes that are least noninferior (if not in some cases superior) to mood stabilizers, particularly for depressive episodes and those with mixed features. The availability of long-acting injectable SGA formulations also substantially helps to mitigate the risk for relapse due to treatment nonadherence. As a class, the limitations of SGAs coalesce mainly around 2 areas: long-term cardiometabolic and neurological tolerability, and within-class differences in the treatment or prevention of depressive episodes. This presentation will examine both the relative merits and shortcomings of SGAS as the emerging foundational treatment class for bipolar disorder, with the concept that medications identified as “mood stabilizers” may in fact play a more limited, supplemental, or adjunctive role in both short-and long-term treatment. Examples of within-class agents among both SGAs and mood stabilizers will be reviewed with respect to breadth of spectrum across clinical presentations and choosing patient clinical profiles that correspond to a best fit for a given core treatment approach.

Learning Objective 1: Understand the pharmacodynamic treatment limitations of lithium and anticonvulsant mood stabilizers across phases of bipolar disorder

Learning Objective 2: Recognize the breadth of spectrum, and within-class differences, among second generation antipsychotics as mono-or adjunctive therapies in the treatment of bipolar mania, mixed episodes, depressive episodes, and relapse prevention of both manias and depressions.

References

Rhee TG, Olfson M, Nierenberg AA, et al. 20-Year Trends in the Pharmacologic Treatment of Bipolar Disorder by Psychiatrists in Outpatient Care Settings. Am J Psychiatry 2020; 177: 706-715 Lindström L, Lindström E, Nilsson M, et al. Maintenance therapy with second generation antipsychotics for bipolar disorder - A systematic review and meta-analysis. J Affect Disord 2017; 213: 138-150