title: Aripiprazole monotherapy in nonpsychotic bipolar I depression: results of 2 randomized, placebo-controlled studies.
abstract: Although most treatment research on bipolar disorder has focused on mania, depressive episodes occur more frequently among patients with bipolar disorder. Here, we report the results of 2 identically designed, 8-week, multicenter, randomized, double-blind, placebo-controlled studies (CN138-096 and CN138-146) to evaluate the efficacy and safety of aripiprazole monotherapy in outpatients with bipolar I disorder experiencing a major depressive episode without psychotic features. Patients were randomized to placebo or aripiprazole (initiated at 10 mg/d, then flexibly dosed at 5-30 mg/d based on clinical effect and tolerability). The primary end point was mean change from baseline to Week 8 (last observation carried forward) in the Montgomery-Asberg Depression Rating Scale total score. In Studies 1 and 2, respectively, 186 and 187 patients were randomized to aripiprazole, and 188 and 188 to placebo. Although statistically significant differences were observed during Weeks 1 to 6, aripiprazole did not achieve statistical significance versus placebo at Week 8 in either study in the change in Montgomery-Asberg Depression Rating Scale total (primary end point). In addition, despite early statistical separation on the Clinical Global Impressions Bipolar Version Severity of Illness-Depression score (key secondary end point), aripiprazole was not superior to placebo at end point. Aripiprazole was associated with a higher incidence of akathisia, insomnia, nausea, fatigue, restlessness, and dry mouth versus placebo. More patients discontinued with aripiprazole versus placebo in Study 1 (46.8% vs 35.1%) and Study 2 (41.2% vs 29.8%). Aripiprazole monotherapy-as dosed in this study design-was not significantly more effective than placebo in the treatment of bipolar depression at end point (Week 8).
authors.affiliation: University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. thase@mail.med.upenn.edu
authors.forename: Michael E
authors.initials: ME
authors.lastname: Thase
authors.forename: Alan
authors.initials: A
authors.lastname: Jonas
authors.forename: Arif
authors.initials: A
authors.lastname: Khan
authors.forename: Charles L
authors.initials: CL
authors.lastname: Bowden
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Wu
authors.forename: Robert D
authors.initials: RD
authors.lastname: McQuade
authors.forename: William H
authors.initials: WH
authors.lastname: Carson
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Marcus
authors.forename: Randall
authors.initials: R
authors.lastname: Owen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068180:Aripiprazole; D001714:Bipolar Disorder / Q000188:drug therapy*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole