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Psychiatr Clin North Am. 2016 Sep;39(3):477-86. doi: 10.1016/j.psc.2016.04.008. Epub 2016 Jun 17.

Adverse Effects of Second-Generation Antipsychotics as Adjuncts to Antidepressants: Are the Risks Worth the Benefits?

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Mood and Anxiety Treatment and Research Program, Perelman School of Medicine, University of Pennsylvania, 3535 Market Street, Suite 670, Philadelphia, PA 19104-3309, USA. Electronic address:


Over the past decades, several adjunctive therapies have been introduced for treatment-resistant depression (TRD), and these strategies have ebbed and flowed in popularity. Currently, adjunctive therapy with the second-generation antipsychotics (SGAs) is most commonly used by psychiatrists. Four SGAs are FDA approved for indications related to TRD (aripiprazole, brexpiprazole, olanzapine, and quetiapine extended release); some evidence also supports use of risperidone and ziprasidone as adjunctive therapies. This article briefly reviews the role of adjunctive therapy with SGAs in contemporary algorithms for TRD, considering both the evidence of benefit and the adverse effects.


Adjunctive therapy; Adverse effects; Benefits; Risks; Second-generation antipsychotics

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