Long-term safety and efficacy of armodafinil in bipolar depression: A 6-month open-label extension study

Terence A. Ketter, Jess Amchin, Mark A. Frye, Nicholas Gross

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Background Safe/well-tolerated treatments for bipolar I depression remain limited. We assessed safety/tolerability of adjunctive open-label armodafinil, a wakefulness-promoting agent evaluated in 3 acute, controlled efficacy studies with variable efficacy results. Methods Completers of three 8-week, double-blind, placebo-controlled adjunctive armodafinil studies (150-200 mg/day added to ongoing stable maintenance doses of 1 or 2 protocol-defined mood stabilizers) in bipolar I depression could enter this 6-month, open-label extension study. Objectives included evaluation of safety/tolerability (primary) and efficacy (secondary). Results 867 patients enrolled; 863 received ≥1 dose of armodafinil and 506 (58%) completed the 6-month study. Headache, insomnia, and anxiety were the most common adverse events (AEs) reported, whereas akathisia, nausea, sedation/somnolence, and weight increase were uncommon. Mean measures assessing emergence of mania, anxiety, insomnia, or suicidality showed no worsening. Discontinuations due to AEs occurred in 57 (7%) patients. Serious AEs occurred in 27 (3%) patients and were considered treatment-related in 8 (1%) patients. Depressive symptoms improved over the 6 months, as did patient functioning. Limitations Lack of placebo control. Conclusions Adjunctive armodafinil was generally safe and well tolerated over 6 months of open-label treatment at 150-200 mg/day when taken with protocol-defined mood stabilizers for bipolar I depression. This 6-month open-label study suggested that armodafinil augmentation of bipolar maintenance therapies may have a favorable risk profile and may improve depressive symptoms in some patients with bipolar I depression.

Original languageEnglish (US)
Pages (from-to)51-57
Number of pages7
JournalJournal of Affective Disorders
StatePublished - Jun 1 2016


  • Armodafinil
  • Bipolar I disorder
  • Bipolar depression
  • Long-term safety
  • Wakefulness

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health


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