Use of a novel adjunctive clinical trial design to examine efficacy, safety of armodafinil for the treatment of bipolar i depression

Patients in randomized, controlled trials of bipolar depression are generally not representative of a clinical population. This study attempted to examine a large sample of patients more representative of patients seen in clinical practice. This report presents baseline patient characteristics from a Phase 3 study examining adjunctive armodafinil for the treatment of a major depressive episode associated with bipolar I disorder (NCT01072929). To assess the safety and efficacy of adjunctive armodafinil 150 mg/day in a heterogeneous sample of patients, this 8-week, double-blind, placebo-controlled, multicenter study evaluated adult patients with bipolar I disorder who were currently experiencing a major depressive episode while taking 1-2 maintenance therapies (mood stabilizers and/or second-generation antipsychotics). The study was conducted at 70 centers in 10 countries from January 2010 to March 2012. Of 786 patients screened, 433 were randomized. Baseline disease severity as assessed by mean (SD) IDS-C30total scores was characteristic of moderate depression (43.6 [6.93] and 43.2 [7.76] for the placebo and 150 mg groups, respectively). The most common concomitant treatments were valproate, lithium, and lamotrigine. Patients in the placebo and armodafinil 150 mg groups experienced their first depressive episode 13.8 (SD 10.24) and 14.5 (SD 11.73) years prior to screening, respectively. The number of distinct regimens of adjunctive treatments will also be reported. Because the design allowed a wider range of adjunctive maintenance therapies, subjects enrolled in this study may be more representative of patients in clinical practice. The diversity of therapeutic regimens encountered in this study may improve external validity/generalizability without sacrificing assay sensitivity, although a large sample size was necessary. Further studies are needed to explore how research on bipolar depression treatments can improve external validity by employing more inclusive designs without sacrificing assay sensitivity.