Efficacy and Safety of Adjunctive Armodafinil in Adults With Major Depressive Episodes Associated With Bipolar I Disorder: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial

Objective: To examine the efficacy and safety of adjunctive armodafinil for major depressive episodes associated with bipolar I disorder.

Method: Adults meeting DSM-IV-TR criteria for bipolar I disorder and currently experiencing a major depressive episode while taking at least 4 weeks of conventional maintenance medication were enrolled in a placebo-controlled evaluation of adjunctive armodafinil 150 or 200 mg (conducted January 2010-March 2012). The primary efficacy measure was change from baseline to week 8 on the 30-item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) total score in the 150-mg armodafinil group versus placebo.

Results: Of 786 patients screened, 433 were randomized (placebo, n = 199; armodafinil 150 mg, n = 201; armodafinil 200 mg, n = 33). The 200-mg armodafinil group was discontinued by protocol amendment due to lower than expected patient enrollment. For the 150-mg armodafinil group versus placebo, there was a significantly greater decrease in least squares mean (standard error of mean [SEM]) IDS-C30 total score at week 8 (-21.7 [1.1] vs -17.9 [1.1]; P = .0097; Cohen d therapeutic effect size = 0.28). The proportion of IDS-C30 responders (≥ 50% decrease from baseline) was significantly higher for the 150-mg armodafinil group versus placebo at final visit (46% [91/197] vs 34% [67/196]; P = .0147). The proportion of IDS-C30 remitters (total score ≤ 11) was 21% (42/197) for armodafinil 150 mg versus 17% (34/196) for placebo (P = .3343) at final visit. Adverse events (AEs) observed in > 5% of either the armodafinil 150 mg or placebo groups and more frequently with 150 mg armodafinil were diarrhea (9% [17/198] vs 7% [13/199]), and nausea (6% [11/198] vs 5% [9/199]), respectively. In the 200-mg armodafinil group, there were 2 serious AEs (n = 1, hepatic failure leading to death; n = 1, acute hepatitis). The death was not considered related to study treatment.

Conclusions: Adjunctive armodafinil 150 mg significantly improved symptoms of major depressive episodes associated with bipolar I disorder versus placebo and was generally well tolerated.

Trial Registration: ClinicalTrials.gov identifier: NCT01072929