Background: Current therapies for bipolar depression are associated with limited efficacy and undesirable adverse events (AEs). This study examined the use of armodafinil as an adjunctive therapy for the treatment of bipolar depression. Methods: Adults diagnosed with bipolar I disorder currently experiencing a major depressive episode that broke through mood stabilizers were randomized to armodafinil 150, 200 mg, or placebo. Primary outcome was mean change from baseline to week 8 in the 30-Item Inventory of Depressive Symptomatology-Clinician-rated (IDS-C30) total score. Results: 433 patients were randomized (n=199 placebo, n=201 armodafinil 150 mg, n=33 armodafinil 200 mg). The 200-mg armodafinil group was discontinued early. At week 8 endpoint, armodafinil 150-mg compared to placebo yielded a significantly greater decrease in mean IDS-C30 total score (–21.7 vs. –17.9; P=0.0097) and a significantly higher IDS-C30 responder (≥50% decrease from baseline) rate (46.2% vs. 34.2%; P=0.0147, number needed to treat = 9). Adverse events (AE) associated with armodafinil treatment included headache, insomnia, diarrhea, and nausea. Mania, insomnia, and anxiety scores were similar between all treatment groups. At final visit, 1.6% (3/186) of armodafinil 150 mg and 4.4% (8/183) of placebo patients had ≥7% weight gain from baseline (number needed to harm = -37), and 5.6% (11/198) of armodafinil 150-mg and 4.0% (8/199) of placebo patients discontinued due to AE (number needed to harm = 50). Discussion: Adjunctive armodafinil 150 mg significantly improved depressive symptoms compared with placebo in patients with bipolar I disorder and was well tolerated.
Terence Ketter, MD
Joseph Calabrese, MD
Ronghua Yang, PhD
Mark Frye, MD
Teva Pharmaceutical Industries Ltd.