Background: Assessment of therapeutic interventions in bipolar disorder is complicated by rapid, complex clinical changes, high placebo-response rates, and varying times to specific levels of clinical recovery that may not be adequately reflected in averaged rating-scale scores particularly in acute mania, calling for improved methods to evaluate treatment responses. Chengappa et al. (1) propose operational criteria for specific outcomes based on rating-scale data from two placebo-controlled trials of olanzapine in mania.
Methods: These trials and other recent research were considered in commenting on the design, conduct, analysis and interpretation of experimental therapeutic trials in mania and to optimize olanzapine versus placebo contrasts by systematically varying end-point criteria for mania (YMRS) and depression (HDRS) ratings.
Results: Olanzapine versus placebo responses were optimally separated at scores of 10 for final paired mania and depression ratings, or 5 for each rating scale considered separately.
Conclusions: Use of empirically determined end-points derived from standard rating scales used in experimental therapeutics research in mood disorders can improve both outcome-assessment and separation of active treatment from placebo responses in acute mania.