Prophylactic pills for antipsychotic-induced weight gain: critical appraisal

SUMMARY Antipsychotic-induced weight gain poses a profound metabolic risk. This critical appraisal evaluates a Cochrane Review on prophylactic pharmacological interventions in schizophrenia spectrum disorders. The review is methodologically rigorous, but the primary evidence base reveals substantial limitations. For the main interventions, the absence of categorical data forced a post hoc reliance on continuous averages, potentially masking individual clinical responses, although exceptions like the trial of olanzapine plus samidorphan did report binary outcomes. Furthermore, the evaluated trials are hindered by inadequate treatment durations and restrictive inclusion criteria, which significantly limit external validity. Concurrently, internal validity and statistical precision are compromised by unclear allocation concealment and small sample sizes. Currently, metformin is the only agent demonstrating clear attenuation of weight gain, yet its long-term cardiometabolic benefits in this demographic remain uncertain. Consequently, routine prophylactic polypharmacy cannot be broadly recommended. Future clinical research must prioritise long-term, guideline-concordant trials with robust categorical end-points, while exploring emerging metabolic agents.