Response to antipsychotic drug in acute schizophrenia remains stable over the years
A meta-analysis of all placebo-controlled trials in patients with acute exacerbations of schizophrenia over a 60-year period has found about twice as many patients improving with antipsychotics as with placebo. However, only a subgroup of patients has had a positive response.
Furthermore, “[e]ffect sizes were reduced by industry and increasing placebo response, not decreasing drug response,” according to researchers, adding that drug development may benefit from smaller samples but better-selected patients.
Multiple electronic databases were searched. The primary outcome was overall efficacy, and secondary outcomes included responder and dropout rates; positive, negative and depressive symptoms; quality of life; functioning; and major side effects. Meta-regression was used to analyse potential moderators of efficacy.
A total of 167 double-blind randomized controlled trials met the inclusion criteria, with 28,102 mainly chronic participants. The standardized mean difference (SMD) for overall efficacy was 0.47 (95 percent CI, 0.42 to 0.51). SMD was reduced to 0.38 after accounting for small-trial effects and publication bias.
Significantly more patients in the antipsychotic group, compared with those in the placebo group, had at least a “minimal” (51 vs 30 percent) and a “good” (23 vs 14 percent) response.
Positive symptoms (SMD, 0.45) improved more than negative symptoms (SMD, 0.35) and depression (SMD, 0.27). There was improvement as well in quality of life (SMD, 0.35) and functioning (SMD, 0.34) even in the short term. Antipsychotics had substantially varied side effects.
A total of 16 trial characteristics of the response predictors analysed had changed over the decades. A multivariable meta-regression revealed, however, that only industry sponsorship and increasing placebo response were significant moderators of effect sizes. Drug response remained stable over time, according to researchers.