Novel Study Designs for Clinical Trials in Mood Disorders

The standard double-blind, placebo-controlled trials in mood disorders frequently yield uninterpretable results, due in part to high placebo responses. Previous studies have shown that the advantage of the mood disorder treatment over placebo decreased as the degree of symptom reduction with placebo increased.This chapter will review the single-blind placebo washout design, the crossover design, the randomized play-the-winner adaptive clinical trial, the progressive adaptive elimination of high placebo response sites design, the progressive adaptive elimination of high dropout sites design, and the sequential, parallel comparison design (SPCD).This chapter reviews the methods aimed at addressing excessive placebo responses and related novel study designs for in clinical trials. In particular, SPCD is a novel study design aimed at reducing both the placebo response rate and the sample size requirement to evaluate the efficacy of new therapeutic compounds.To enhance signal detection, trials should be enriched using adaptive designs and lower the placebo response. The SPCD is a novel study design with two phases of treatment, aimed at reducing both the placebo response rate and the sample size requirement.