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The aim of this study was to evaluate the efficacy and safety of the dopaminergic-enhancing agent modafinil/armodafinil (MoArm) as adjunctive treatment for bipolar depression. A comprehensive search of major electronic databases was conducted to identify randomized controlled trials (RCTs) of adjunctive MoArm that included patients with bipolar I (BP-I) or bipolar II (BP-II) depression. Data for response/remission and all-cause discontinuation were analyzed. Effect size was summarized by relative risk (RR) using a random effect model. Of 58 studies, five RCTs (N = 795 drug, N = 792 placebo) met inclusion criteria. Four armodafinil studies included only BP-I patients and one modafinil study included both bipolar subtypes with limited heterogeneity (I2  = 34%, P = .19; I2  = 18%, P = .30). Compared to placebo, augmentation with MoArm was associated with significantly greater rates of treatment response (RR, 1.18; 95% CI, 1.01-1.37; P = .03) and remission (RR, 1.38; 95% CI, 1.10-1.73; P = .005). All-cause discontinuation was not different than placebo (RR, 1.08; 95% CI, 0.89-1.30; P = .45) with no evidence of increased risk of mood switch or suicide attempts with MoArm (RR, 0.99; 95% CI, 0.39-2.5; P = .98; RR, 1.02; 95% CI, 0.37-2.85; P = .97). This narrower scope meta-analysis of one drug for one disease suggests that adjunctive MoArm may represent a novel therapeutic intervention. Further studies delineating the subtypes of bipolar depression responsive to these novel dopaminergic-enhancing agents are encouraged. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Citation

Nicolas A Nunez, Balwinder Singh, Francisco Romo-Nava, Boney Joseph, Marin Veldic, Alfredo Cuellar-Barboza, Alejandra Cabello Arreola, Jennifer L Vande Voort, Paul Croarkin, Katherine M Moore, Joanna Biernacka, Susan L McElroy, Mark A Frye. Efficacy and tolerability of adjunctive modafinil/armodafinil in bipolar depression: A meta-analysis of randomized controlled trials. Bipolar disorders. 2020 Mar;22(2):109-120

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PMID: 31643130

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