Meta-analysis links antipsychotic use to lower mortality and relapse in schizophrenia

A systematic review and meta-analysis of 68 observational studies involving 1,424,455 people with schizophrenia examined antipsychotic use and clinical outcomes. Use was associated with lower all-cause mortality and relapse, but higher risks of cancer, fractures and lung infections; the authors caution that the findings are not causal.

68 observational studies included 1.42 million people.
Use was associated with lower mortality and relapse.
Higher risks were reported for cancer, fractures and lung infections.
Observational findings cannot establish cause and effect.

Researchers searched four databases for observational studies published through May 1, 2026, reporting associations between antipsychotic use and outcomes in people with schizophrenia. Two reviewers assessed study quality and extracted data. Multilevel random-effects models were used to synthesize findings from 68 studies involving 1,424,455 individuals.

Compared with nonuse, antipsychotic use was associated with lower all-cause mortality (pooled estimate, 0.64; 95% CI, 0.54–0.77) and lower relapse risk (0.34; 95% CI, 0.12–0.99). Associations with higher risks were reported for cancer (1.41; 95% CI, 1.17–1.69), fractures (1.35; 95% CI, 1.17–1.56) and lung infections (1.25; 95% CI, 1.04–1.51). Evidence for other outcomes was not statistically significant.

The authors emphasize that the evidence base is limited: several pooled estimates relied on few studies, and results varied by region and study design. Because the included evidence was observational, residual confounding and bias may explain some or all of the associations; the findings do not establish that antipsychotics caused these outcomes. Further rigorous studies are needed to clarify outcome-specific risks and benefits.

In practice

For people with schizophrenia, this synthesis of observational studies found antipsychotic use associated with lower all-cause mortality and relapse, alongside higher observed risks of cancer, fractures and lung infections. These findings may inform discussion of the range of outcomes studied, but they do not establish that medication caused either benefits or harms. Several estimates came from few studies, results varied by region and design, and residual confounding may remain; the evidence does not support changing treatment decisions on its own.

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Source

Molecular Psychiatry: Real-world associations of antipsychotic use with clinical outcomes in schizophrenia: a systematic review and meta-analysis ↗

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