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

- Safe, well-tolerated treatments for bipolar I depression are limited.
- Over 6 months, open-label adjunctive armodafinil was generally safe and well tolerated.
- Mean measures for emergence of mania, suicidality, anxiety, or insomnia did not worsen.
- Results suggest a positive risk profile of adjunctive armodafinil in bipolar I depression.
- Adjunctive armodafinil efficacy remains to be established, and it does not have an FDA indication for bipolar I depression.

BackgroundSafe/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.MethodsCompleters 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).Results867 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.LimitationsLack of placebo control.ConclusionsAdjunctive 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.