Efficacy and tolerability of nutraceuticals and phytotherapics for antipsychotic-induced weight gain in schizophrenia spectrum disorders: Systematic review and meta-analysis

Antipsychotic drugs frequently cause metabolic complications in people with schizophrenia spectrum disorders, increasing cardiovascular morbidity and contributing to premature mortality; nutraceutical and phytotherapeutic agents may offer accessible adjunctive strategies, but their efficacy in this setting remains uncertain. We conducted a systematic review and meta-analysis (PROSPERO: CRD42024616494) of randomized controlled trials comparing nutraceuticals/phytotherapics with placebo in adults (18–65 years) with schizophrenia spectrum disorders receiving antipsychotics, including interventions lasting at least 4 weeks. Primary outcomes were body weight change and all-cause treatment discontinuation; secondary outcomes included lipid profile, glucose homeostasis, blood pressure, and anthropometric measures. Two independent reviewers extracted data and assessed study quality using the Cochrane Risk of Bias 2 tool, and meta-analyses primarily used random-effects models. Twenty-one trials (1,426 participants) evaluating 16 interventions were included. Omega-3 fatty acids, probiotics combined with dietary fibers, and Liuyu decoction were each associated with reduced body weight versus placebo, while alpha-lipoic acid showed consistent triglyceride reductions across two independent trials and berberine reduced systolic blood pressure. Discontinuation rates did not differ between groups, but risk of bias was frequently substantial, mainly due to blinding limitations and missing data handling. Overall, alpha-lipoic acid for hypertriglyceridemia and berberine for hypertension have the most consistent multi-trial support, whereas single-trial findings for omega-3s, probiotic combinations, and traditional Chinese medicine preparations require replication; heterogeneity and methodological weaknesses currently preclude broad clinical recommendations, though selected nutraceuticals may be considered for specific metabolic targets.