title: 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.
abstract: OBJECTIVE
  To examine the efficacy and safety of adjunctive armodafinil for major depressive episodes associated with bipolar I disorder.
  
  
  METHODS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT01072929.
authors.affiliation: 10524 Euclid Ave, Room 12-135, Cleveland, OH 44106 joseph.calabrese@uhhospitals.org.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Calabrese
authors.forename: Mark A
authors.initials: MA
authors.lastname: Frye
authors.forename: Ronghua
authors.initials: R
authors.lastname: Yang
authors.forename: Terence A
authors.initials: TA
authors.lastname: Ketter
mesh_terms: D000328:Adult; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001714:Bipolar Disorder / Q000188:drug therapy*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D010919:Placebos; D016896:Treatment Outcome; D064690:Wakefulness-Promoting Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D001559:Benzhydryl Compounds; D010919:Placebos; D064690:Wakefulness-Promoting Agents; D000077408:Modafinil