• Open Access

Aripiprazole monotherapy in patients with rapid-cycling bipolar I disorder: an analysis from a long-term, double-blind, placebo-controlled study

Authors


  • DisclosuresDavid J. Muzina: Honoraria received for speaking, consultation and advisory board participation from AstraZeneca, GlaxoSmithKline and Pfizer. Research/educational grant support has been received from: Abbott Labs, AstraZeneca, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer and Repligen Corp. Chinedu Momah: Former employee of Bristol-Myers Squibb. James M. Eudicone: Employee of Bristol-Myers Squibb. Andrei Pikalov: Employee of Otsuka America Pharmaceutical Inc. Robert D. McQuade: Employee of Otsuka Pharmaceutical Development & Commercialization, Inc. Ronald N. Marcus: Employee of Bristol-Myers Squibb. Raymond Sanchez: Former employee of Bristol-Myers Squibb. Berit X. Carlson: Employee of Bristol-Myers Squibb.

  • Previous presentation Presented as a poster at the 7th International Conference on Bipolar Disorder (ICBD), 7–9 June 2007, Pittsburgh, Pennsylvania, USA.

  • Clinical trial registry information
    ClinicalTrial.gov Identifier NCT00036348.

  • Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

David J. Muzina,
Cleveland Clinic Lerner College of Medicine, 9500 Euclid Avenue, P57, Cleveland, OH 44195, USA
Tel.: + 1 216 444 5810
Fax: + 1 216 636 1515
Email: muzinad@ccf.org

Summary

Aims:  Rapid-cycling bipolar disorder is difficult to treat and associated with greater morbidity than non-rapid-cycling disease. This post hoc analysis evaluated 28 patients with rapid-cycling bipolar I disorder from a 100-week, double-blind, placebo-controlled study assessing long-term efficacy, safety and tolerability of aripiprazole in patients with bipolar I disorder (most recently manic/mixed).

Methods:  Following ≥ 6 consecutive weeks’ stabilisation with open-label aripiprazole, patients were randomised (1 : 1) to aripiprazole or placebo. Patients completing 26 weeks treatment without relapse could continue for a further 74 weeks. Primary end-point was time to relapse for manic, mixed or depressive symptoms, defined as discontinuation due to lack of efficacy. Safety assessments included adverse event (AE) monitoring and changes in weight and lipid, glucose and prolactin levels.

Results:  Of the 28 patients (aripiprazole, n = 14; placebo, n = 14) with rapid-cycling bipolar disorder, 12 (aripiprazole, n = 7; placebo, n = 5) completed the initial 26-week treatment period and three (all aripiprazole treated) completed the 100-week, double-blind period. Time to relapse was significantly longer with aripiprazole vs. placebo at week 26 [log-rank p = 0.033; 26-week hazard ratio = 0.21 (95% CI: 0.04, 1.03)] and week 100 [log-rank p = 0.017; 100-week hazard ratio = 0.18 (95% CI: 0.04, 0.88)]. The most commonly reported AEs with aripiprazole during the 100 weeks (≥ 10% incidence and twice placebo) were anxiety (n = 4), sinusitis (n = 4), depression (n = 3) and upper respiratory infection (n = 3). One aripiprazole-treated patient discontinued due to an AE (akathisia). There were no significant between-group differences in mean changes in weight or metabolic parameters.

Conclusion:  In this small, post hoc subanalysis, aripiprazole maintained efficacy and was generally well tolerated in the long-term treatment of rapid-cycling bipolar disorder. Further research with prospectively designed and adequately powered trials is warranted.

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