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Efficacy and Safety of Atypical Antipsychotics in Bipolar Disorder With Comorbid Substance Dependence

A Systematic Review

Sepede, Gianna, MD, PhD*; Lorusso, Marco, MD*; Spano, Maria Chiara, MD*; Di Nanno, Piero, MD*; Di Iorio, Giuseppe, MD, PhD*†; Di Giannantonio, Massimo, MD*†

doi: 10.1097/WNF.0000000000000297
Review Article

Objectives Bipolar disorder (BD) patients with a comorbid substance use disorder (SUD) are notoriously difficult to treat. Atypical antipsychotics (AAPs) are widely prescribed in BD, but their efficacy in patients with comorbid SUD is still debated. The aim of the present article is to systematically review the literature findings on the efficacy and safety of AAPs in BD patients with comorbid SUD.

Methods We searched PubMed to identify original studies focused on the treatment of dual diagnosed BD with AAPs.

Results Ten articles met our inclusion/exclusion criteria, involving a total of 969 subjects, 906 affected by BD and 793 with comorbid SUD: 4 were randomized controlled trials, 4 were open label trials and 2 were observational studies, published between 2002 and 2017. The most commonly abused substances were alcohol and cocaine. The AAPs used to treat patients were quetiapine (n = 337), asenapine (n = 119), olanzapine (n = 80), risperidone (n = 62), and aripiprazole (n = 48). In terms of safety, AAPs were usually well tolerated. Atypical antipsychotics were usually efficacious on acute mood symptoms, whereas their impact on substance-related issues was reported only in those studies without a placebo comparison.

Conclusions According to our results, even though AAPs are widely used and efficacious in treating the clinical symptoms of BD, there are not enough data to suggest their adjunctive benefit on craving and substance consumption.

*Department of Neuroscience, Imaging and Clinical Science, “G. d’Annunzio” University of Chieti; and

Department of Mental Health, National Health Trust, Chieti, Italy.

Address correspondence and reprint requests to Gianna Sepede, MD, PhD, Universita degli Studi di Chieti, Chieti, Italy; E-mail:;

M.L. and M.C.S. equally contributed.

Conflicts of Interest and Source of Funding: The authors have no conflicts of interest to declare.

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