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Good response rare for antipsychotics in acute schizophrenia

Analysis of 60 years of placebo-controlled antipsychotic drug trials indicated approximately twice as many individuals with acute schizophrenia improved with antipsychotics compared with placebo, but not many had a good response.

“Antipsychotics are criticized by distinguished physicians. This criticism makes the lay public, patients, general physicians and policy makers skeptical. The skepticism is driven by the fact that most placebo-controlled studies are conducted by the pharmaceutical industry, which is not trusted, an issue that we examine here,” Stefan Leucht, MD, of Technische Universität München, Munich, and colleagues wrote. “The essence of the argument is that antipsychotic drugs have multiple side effects, but only little efficacy, and that therefore their use should be restricted to a minimum.”

To assess antipsychotic efficacy, researchers conducted a systematic review, Bayesian meta-analysis and meta-regression of efficacy predictors in 167 double-blind, randomized controlled trials among 28,102 individuals with schizophrenia. The majority of participants had chronic schizophrenia.

The standardized mean difference (SMD) for overall efficacy was 0.47 (95% CI, 0.42-0.51); however, accounting for small-trial effects and publication bias reduced the SMD to 0.38.

Fifty-one percent of participants who receive antipsychotics had “minimal” response, compared with 30% in the placebo group.

A “good” response was achieved by 23% of the antipsychotic group and 14% of the placebo group.

Positive symptoms (SMD = 0.45) improved more than negative symptoms (SMD = 0.35) and depression (SMD = 0.27) among the antipsychotic group.

Participants who received antipsychotics exhibited improvements in quality of life (SMD = 0.35) and functioning (SMD = 0.34), even in the short term.

Researchers found significant differences in adverse effects.

Sixteen trial characteristics changed over the decades. However, multivariable meta-regression indicated industry sponsorship and increasing placebo response were the only significant moderators of effect sizes.

Drug response remained consistent over time, according to findings.

“Our results are important on several levels. First, clinicians can expect that approximately two times more patients improve when treated with antipsychotics compared with placebo, but only a minority will experience a good response in the short term,” Leucht and colleagues wrote. “Second, network meta-analyses need to consider possible temporal changes... Third, industry sponsorship has not inflated effect sizes. But there was publication bias, because companies do not always publish inconclusive studies. Increasing placebo response, but not decreasing drug response, contributed to the decreasing effect sizes over time. Finally, sample size and related measures arose several times as significant moderators, and these are modifiable design features for drug development.” – by Amanda Oldt

Disclosure: Leucht reports receiving honoraria for consulting from Roche, TEVA, Otsuka, Lundbeck, and LB Pharma; for lectures from Otsuka, Lundbeck, Janssen, ICON, Lilly, Sanofi Aventis, AOP Orphan, Roche, and Servier; and for a publication from Roche. Please see the study for a full list of relevant financial disclosures.