Exercise to enhance antipsychotic effectiveness and mitigate metabolic harm: systematic review and meta-analysis

Antipsychotics are first-line treatments for schizophrenia and related psychotic disorders but are frequently accompanied by cardiometabolic adverse effects (weight gain, hypertension, dyslipidaemia, hyperglycaemia). We assessed whether supervised exercise interventions enhance psychopathology outcomes and reduce antipsychotic-related metabolic harm in adults receiving antipsychotic treatment medication.

Systematic review and meta-analysis.

We searched PubMed, Web of Science, and Scopus following PRISMA 2020 (PROSPERO CRD420251139904). Randomised controlled trials (RCTs) published since 2000 that tested supervised exercise in people receiving antipsychotics were eligible.

Two reviewers selected studies using PICOS criteria, assessed methodological quality with the Revised Cochrane risk-of-bias tool for randomised trials (RoB 2), and pooled effects with random-effects models, expressed as mean differences (MD) with 95% CIs. The certainty of evidence was assessed with GRADE.

Twenty-eight studies (n = 1119) and four additional analyses met inclusion criteria. Exercise significantly improved negative symptoms (MD -3·078, 95% CI -4·457 to -1·699; p < 0·001), general psychopathology (-2·178, -4·140 to -0·216, p = 0·034), and PANSS total score (-7·069, -13·290 to -0·849; p = 0·030). Effects on positive symptoms were not significant (-1·220, -2·462 to 0·022; p = 0·053). Exercise reduced body weight (-1·620, -3·080 to -0·159; p = 0.034), body fat percentage (-1·250, -2·174 to -0·327; p = 0·020) and waist circumference (-1·420, -2·646 to -0·195; p = 0·032), with no material change in BMI. No significant effects were observed for systolic, diastolic blood pressure or fasting glucose. Lipid outcomes were largely null, with limited and inconsistent evidence, including a small increase in total cholesterol. Based on GRADE assessment, the certainty of evidence was moderate for negative symptoms, general psychopathology, body weight, body fat percentage, and waist circumference, with low to very low for the remaining outcomes.

Supervised exercise may be a beneficial adjunct to antipsychotic treatment, improving core psychopathology, particularly negative symptoms, and favourably shifting body composition by reducing adiposity and central fat, although the magnitude of change did not reach clinically meaningful thresholds. High-quality, adequately powered RCTs using multicomponent exercise and comprehensive metabolic endpoints are needed to determine effects on blood pressure, lipid profile, and glucose regulation.

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