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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

Authors


  • This study (CN138-189) is registered at: http://www.ClinicalTrials.gov; identifier: NCT00261443.

  • A preliminary report of this work was presented at the 163rd Annual Meeting of the American Psychiatric Association, May 22-27, 2010, New Orleans, LA, USA.

  • RM, LR, BM, and KT are employees of Bristol-Myers Squibb. AK, the PI of more than 330 clinical trials sponsored by more than 55 pharmaceutical companies and 30 clinical research organizations, has done no compensated consulting or speaking on their behalf; and was a PI during the Aripiprazole 189 Adjunctive Therapy Clinical Trial, enrolling 74 patients. WC and RS are employees of Otsuka Pharmaceutical Development & Commercialization, Inc.

Corresponding author:
Ronald Marcus, M.D.
Bristol-Myers Squibb
5 Research Parkway
Wallingford, CT 06492, USA
Fax: +1 203 677 7695
E-mail: ronald.marcus@bms.com

Abstract

Marcus R, Khan A, Rollin L, Morris B, Timko K, Carson W, Sanchez R. 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.
Bipolar Disord 2011: 13: 133–144. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S.

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Objectives:  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.

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