Mood stabilizers and the evolution of maintenance study designs in bipolar I disorder.

The designs employed in bipolar maintenance studies have evolved greatly over the last 28 years. Consequently, there has been minimal consensus set for methods used to demonstrate the ability of any new putative mood stabilizers to prevent relapse and recurrence in bipolar disorder. The methods that have evolved the most include enrollment procedures, randomization schemes, use of outcome measures, statistical analyses, and country-specific commercial and regulatory issues. This article contrasts the various methods employed in first- and second-generation placebo-controlled bipolar I maintenance studies. This article also explores the advantages and disadvantages associated with various designs.