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Achieving and Sustaining Remission in Bipolar I Disorder with Ziprasidone

A Post Hoc Analysis of a 24-Week, Double-Blind, Placebo-Controlled Study

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Abstract

Background and Objective

A number of operational definitions have been proposed to describe outcomes in bipolar disorders; the criteria used to define terms such as recurrence, relapse, response, remission and recovery have varied both in observational studies and in clinical trials. We carried out a post hoc analysis of rates of symptomatic point remission and sustained remission using four different remission criteria that had been evaluated in a previously published 24-week, double-blind, placebo-controlled study.

Methods

After stabilization for 8 consecutive weeks on open-label ziprasidone plus lithium or valproate, stabilized subjects were randomized to two groups, ziprasidone with lithium or valproate (ziprasidone group), or placebo with lithium or valproate (placebo group) for 16 weeks. Four remission criteria included (i) Mania Rating Scale (MRS) score ≤7, (ii) MRS ≤7 + Montgomery-Åsberg Depression Rating Scale (MADRS) score ≤10, (iii) MRS ≤7 + Clinical Global Impression-Improvement (CGI-I) = 1, (iv) MRS score ≤7 + MADRS score ≤10 + CGI-I score = 1. We examined the percentages of subjects in each treatment group achieving symptomatic point (i.e. at each visit) and sustained (i.e. for ≥8 weeks) remission during the double-blind phase.

Results

At week 24, symptomatic point remission based on the above two more stringent criteria was achieved by 48.0 and 24.4% of the ziprasidone group versus 36.9 and 18.0% of placebo recipients, respectively (p = 0.04 and 0.14). Sustained remission rates at 24 weeks were 42.5 and 18.1% for ziprasidone, respectively (vs 33.3 and 14.4% for placebo, p = 0.04 and 0.21, respectively).

Conclusion

This analysis indicates that ziprasidone plus lithium or valproate treatment showed modest to moderate remission rates at week 24 based on four different remission criteria in terms of symptomatic and sustained remission, despite the stringent criteria. Our findings indicate that ziprasidone may be effective in achieving sustained remission in bipolar I disorder and propose that a better understanding regarding the definition of remission in bipolar disorders should be required in clinical practice since our results showed different remission rates with different remission criteria.

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Acknowledgments

This study was sponsored by Pfizer Inc. Editorial Support was provided by Hajira Koeller, Ph.D. and Joanne Vaughan of PAREXEL and was funded by Pfizer Inc.

Conflict of interest

PSM: consultant for Dey Pharma, Eli Lilly and Company, Forest, Merck, Pfizer, Sunovion; Speaker’s Bureau on Eli Lilly and Company, Forest, Glaxosmithkline, Merck, Pfizer, Sunovion: Stock Ownership in Global Medical Education. CUP: none. COG and FSM are employees of Pfizer Inc.

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Authors and Affiliations

  1. Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea

    Chi-Un Pae

  2. Department of Psychiatry, Duke University Medical Center, Durham, NC, USA

    Chi-Un Pae

  3. Global Medical Education Inc., New York, NY, 10065, USA

    Prakash S. Masand

  4. Pfizer Inc, New York, NY, USA

    Francine S. Mandel & Cedric O’Gorman

Authors
  1. Chi-Un Pae
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  2. Prakash S. Masand
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  4. Cedric O’Gorman
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Correspondence to Chi-Un Pae.

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Pae, CU., Masand, P.S., Mandel, F.S. et al. Achieving and Sustaining Remission in Bipolar I Disorder with Ziprasidone. Clin Drug Investig 32, 747–754 (2012). https://doi.org/10.1007/s40261-012-0009-1

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  • DOI: https://doi.org/10.1007/s40261-012-0009-1

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