Study design and patient characteristics and outcome in acute mania clinical trials

Abstract

The objective of this systematic review was to identify trial design and patient characteristics associated with symptom improvement in acute mania clinical trials. Drug trials in acute mania that used the Young Mania Rating Scale (YMRS) score as the primary endpoint were identified using a systematic search strategy. Details of the trial, patient population, and treatment assignment were recorded. Covariates associated with change in YMRS were analyzed using a multiple regression model. A total of 41 studies, comprising 89 treatment arms and 10,471 patients, were selected for this analysis. Three variables were statistically significantly associated with change in YMRS score: treatment assignment, baseline mania score, and study location. Compared with placebo, greater mean (95% confidence interval) reductions in YMRS score were noted for all three active treatment arms [-4.7 (-6.4 to -3.0) for mood stabilizers; -5.9 (-7.6 to -4.2) for antipsychotics; and -8.3 (-10.2 to -6.4) for combined mood stabilizer/antipsychotics; all comparisons p < 0.0001]. Greater changes in YMRS score were associated with higher baseline YMRS scores (p = 0.002) and with studies performed outside of the USA (p= 0.02). Year of study publication was not associated with YMRS score change. Study size, number of study sites, YMRS score required for study entry, inclusion of patients with mixed mania or treatment resistance, and enrollment of inpatients versus outpatients had no significant influence on change in YMRS score. These findings may assist in the design of future drug trials for acute mania.