Factors associated with discontinuation in the drug and placebo groups of trials of second generation antipsychotics for acute schizophrenia: A meta-regression analysis: Discontinuation in antipsychotic trials

Abstract

This study investigated factors associated with discontinuation in double-blind, randomized, placebo-controlled trials (DBRPCTs) of second-generation antipsychotics (SGAs) for acute schizophrenia, with a view to establishing what factors were associated with all-cause discontinuation. 77 eligible studies (96 comparisons; n = 22,678) were included in this study. Thirty-one factors potentially affecting all-cause discontinuation, related to the participants, study design, and drugs, were included in a meta-regression analysis that examined the factors associated with discontinuation rates in treatment and placebo groups and/or the treatment–placebo group difference in discontinuation. Smaller improvements in Positive and Negative Syndrome Scale total scores from baseline to endpoint were associated with higher discontinuation rates in both the treatment and placebo groups, and smaller response rates in the treatment group were associated with higher discontinuation rates in the treatment group. These factors were also associated with the treatment–placebo group difference in discontinuation. Although the risk of weight gain from SGA use was not associated with discontinuation rates in either the treatment or placebo groups, SGAs with a risk of weight gain were associated with a larger treatment–placebo group difference in discontinuation, although the reason is unknown. Factors associated with discontinuation rates in both treatment and placebo groups did not influence the treatment–placebo group difference in discontinuation. The efficacy and the risk of weight gain of SGAs seemed to influence treatment–placebo group difference in discontinuation in DBRPCTs of SGAs for acute schizophrenia.