Adjunctive armodafinil for major depressive episodes associated with bipolar i disorder

Background In a previous study, adjunctive armodafinil 150 mg/day significantly improved depressive symptoms associated with bipolar I disorder. Methods Multicenter, double-blind study of patients with a major depressive episode despite bipolar I disorder maintenance therapy randomized to adjunctive placebo or adjunctive armodafinil 150 or 200 mg/day for 8 weeks; for logistical reasons, assignment to armodafinil 200 mg/day was discontinued early. Primary efficacy was measured by change from baseline to week 8 in 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C₃₀) total score. Results Patients were randomized to adjunctive placebo (n=230), adjunctive armodafinil 150 mg/day (n=232), or adjunctive armodafinil 200 mg/day (n=30; analyzed for safety only). Least-square mean change in IDS-C₃₀ total score was numerically superior for adjunctive armodafinil 150 mg/day vs adjunctive placebo, but was not statistically significant (p=0.13). Armodafinil was well-tolerated. Adverse events (AEs) observed in >5% with adjunctive armodafinil 150 mg/day and more frequently than with adjunctive placebo were headache (16% [38/231] vs 13% [30/229]) and nausea (7% [17/231] vs 2% [5/229]). The most common AEs with adjunctive armodafinil 200 mg/day were diarrhea and dry mouth (17% [5/30] each vs 6% [13/229] and 1% [3/229], respectively, with adjunctive placebo). Limitations Early study discontinuation for logistical reasons by the sponsor limited adjunctive armodafinil 200-mg/day assessment. Conclusions FDA-approved bipolar I depression treatments are limited. Adjunctive armodafinil 150 mg/day reduced depressive symptoms associated with bipolar I disorder to a greater extent than adjunctive placebo, although the difference failed to reach statistical significance. Safety data indicate treatment with adjunctive armodafinil was well-tolerated.