Improving the design of maintenance studies for bipolar disorder

Abstract

Background:

In contrast to the trial design of acute mania studies, there is no standard design for bipolar maintenance studies. Over the past 15 years, the design of monotherapy maintenance studies in bipolar disorder has evolved significantly, but recent study designs continue to differ in important ways.

Scope:

We reviewed the design of recent controlled bipolar maintenance studies, using PubMed, from August 2006 to August 2009, examining the strengths and weaknesses of different study design features.

Findings:

Design differences are sufficiently important that the disparate results across maintenance studies may reflect either true differences in medication efficacy or the effects of these design differences on outcome. Design elements such as recent episode polarity, stabilization criteria, using enriched versus nonenriched samples, length of stabilization before randomization, length of experimental phase, and recurrence outcome criteria are critical factors that differ widely across studies and likely play a role in study outcome.

Conclusions:

As consensus for trial designs for bipolar maintenance therapy is developed, it will be easier to develop algorithms for maintenance treatment based on results from studies as opposed to clinical opinions.

Key words:

• Bipolar disorder
• Bipolar maintenance therapy
• Pharmacotherapy
• Relapse
• Stabilization

Transparency

Declaration of funding

The authors of this paper received no funding of any kind for writing this paper, and the idea for the paper originated with the authors.

Declaration of financial/other relationships

M.G. has declared that he has received honoraria in the past from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Inc., Cephalon, Takeda, Otsuka Pharmaceuticals, and Lilly. O.A. has declared that he has no relevant financial relationships. M.A.F. has declared that he is a consultant for Abbott Laboratories, Bristol-Myers Squibb, Lilly, GlaxoSmithKline, Janssen Pharmaceuticals, Organon, and Otsuka Pharmaceuticals; has received research grants from Abbott Laboratories, Cephalon, GlaxoSmithKline, Janssen Pharmaceuticals, and Pfizer, Inc.; has participated in continuing medical education activities for AstraZeneca, Bristol-Myers Squibb, Lilly, GlaxoSmithKline, Organon, and Otsuka Pharmaceuticals; and has received travel funds from Bristol-Myers Squibb, Cephalon, Organon, and Otsuka Pharmaceuticals.

Peer reviewers may receive honoraria from CMRO for their review work. The peer reviewers have disclosed no relevant financial relationships.

Acknowledgments

Linda Felcone has provided editorial and writing support to facilitate the multiple drafts and revisions of the manuscript that authors have contributed for the submission. Linda Felcone followed the authors’ instructions in both preparation of the drafts and the revisions. Funding for the editorial support was provided by Bristol-Myers Squibb. Editorial help was also supplied by MedErgy HealthGroup, Inc. in drafting Figure 1; this was funded by Bristol-Myers Squibb.