Evolving methodologies in bipolar disorder maintenance research

Background During the development of a new treatment for bipolar disorder, maintenance studies are used to evaluate the ability of the putative mood stabiliser to prevent relapse and recurrence of further episodes. Comparisons with the early bipolar disorder maintenance studies indicate that the methodologies of recent trials have evolved substantially. Aims To review the methods used in the first- and second-generation maintenance studies, highlighting the differences of the various designs. Method Literature review. Results Methods that have evolved the most include patient enrolment, randomisation schemes and the use of outcome measures and statistical analyses. In addition, regulatory and commercial issues have also influenced study design. Conclusion There is little consensus on the methodology of bipolar disorder maintenance studies. As the integration of newer therapies into routine clinical practice is dependent on the evidence from controlled studies, it is essential that future maintenance trials in bipolar disorder achieve adequate methodological rigour without sacrificing overall feasibility.