Efficacy and tolerability of adjunctive modafinil/armodafinil in bipolar depression: A meta-analysis of randomized controlled trials

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

Research output: Contribution to journalReview articlepeer-review

6 Scopus citations


Objective: 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. Methods: 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. Results: 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). Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)109-120
Number of pages12
JournalBipolar disorders
Issue number2
StatePublished - Mar 1 2020


  • armodafinil
  • augmentation strategy
  • bipolar depression
  • meta-analysis
  • modafinil

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


Dive into the research topics of 'Efficacy and tolerability of adjunctive modafinil/armodafinil in bipolar depression: A meta-analysis of randomized controlled trials'. Together they form a unique fingerprint.

Cite this