title: Efficacy of aripiprazole adjunctive to lithium or valproate in the long-term treatment of patients with bipolar I disorder with an inadequate response to lithium or valproate monotherapy: a multicenter, double-blind, randomized study.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of aripiprazole (ARI) adjunctive to lithium (Li) or valproate (Val) (ARI+Li / Val) compared with placebo (PLB) adjunctive to Li or Val (PLB+Li / Val) as maintenance therapy for patients with bipolar I disorder who had an inadequate response to Li or Val monotherapy.
  
  
  METHODS
  Patients with a current manic/mixed episode received Li or Val for at least 2 weeks. Those with an inadequate response [Young Mania Rating Scale (YMRS) total score ≥ 16 and ≤ 35% decrease from baseline at 2 weeks] received adjunctive single-blind ARI plus mood stabilizer. Patients who achieved stability [YMRS and Montgomery-Åsberg Depression Rating Scale (MADRS) score ≤ 12] for 12 consecutive weeks were randomized to double-blind ARI (10-30 mg/day) or PLB+Li / Val. Relapse was monitored for 52 weeks. Adverse events (AEs) were also evaluated.
  
  
  RESULTS
  A total of 337 patients were randomized to ARI+ Li / Val (n=168) or PLB+Li / Val (n=169). The Kaplan-Meier relapse rate at 52 weeks was 17% with ARI+Li / Val and 29% with PLB+Li / Val. ARI+Li / Val significantly delayed time to any relapse compared with PLB+Li / Val; hazard ratio=0.54 (95% confidence interval: 0.33-0.89; log-rank p=0.014). The most common AEs ≥ 5%(ARI+Li / Val versus PLB+Li / Val) were headache (13.2% versus 10.8%), weight increase (9.0% versus 6.6%), tremor (6.0% versus 2.4%), and insomnia (5.4% versus 9.6%).
  
  
  CONCLUSIONS
  Continuation of ARI+Li / Val treatment increased the time to relapse to any mood episode compared with Li or Val monotherapy, and was relatively well tolerated during the one-year study. These findings suggest that there is a long-term benefit in continuing ARI adjunctive to a mood stabilizer after sustained remission is achieved.
authors: Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, USA. ronald.marcus@bms.com
authors: Ronald
authors: R
authors: Marcus
authors: Arif
authors: A
authors: Khan
authors: Linda
authors: L
authors: Rollin
authors: Beth
authors: B
authors: Morris
authors: Karen
authors: K
authors: Timko
authors: William
authors: W
authors: Carson
authors: Raymond
authors: R
authors: Sanchez
mesh_terms: D000328:Adult; D018692:Antimanic Agents / Q000627:therapeutic use*; D000068180:Aripiprazole; D001714:Bipolar Disorder / Q000188:drug therapy*; D016001:Confidence Intervals; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D008094:Lithium / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D015363:Quinolones / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014635:Valproic Acid / Q000627:therapeutic use*
chemical_list: D018692:Antimanic Agents; D010879:Piperazines; D015363:Quinolones; D014635:Valproic Acid; D000068180:Aripiprazole; D008094:Lithium