Antipsychotic treatment is commonly associated with weight gain, disturbances in glucose and lipid metabolism, and an increased risk of cardiovascular disease, representing a major clinical challenge in long-term psychiatric care. In recent years, randomised controlled trials have evaluated a range of non-pharmacological interventions targeting antipsychotic drug-related metabolic outcomes. However, substantial variability exists across studies in terms of intervention components, outcome measures, and reported effects, resulting in marked heterogeneity of the available evidence. A systematic synthesis of evidence derived from randomised controlled trials is therefore warranted. This review was conducted in accordance with the PRISMA 2020 guidelines. Multiple English-language databases were systematically searched to identify randomised controlled trials conducted in populations receiving antipsychotic treatment that examined the relationship between non-pharmacological interventions and metabolic-related outcomes. Study selection was performed based on predefined inclusion and exclusion criteria. Data were extracted on study characteristics, intervention components, intervention duration, and primary metabolic outcomes. Methodological quality of the included studies was assessed using the Joanna Briggs Institute (JBI) critical appraisal tool for randomised controlled trials. A total of 42 randomised controlled trial publications were included. The included studies were conducted across multiple countries and regions, with considerable variation in sample size. Study populations were predominantly adults, with a small number of trials including adolescents. Most studies focused on schizophrenia and related spectrum disorders, while some included individuals with bipolar disorder or mixed diagnoses of severe or serious mental illness. Participants were generally characterised by existing metabolic abnormalities or an elevated risk of antipsychotic drug-related metabolic disturbances. Based on the primary intervention focus, the included evidence was classified into four categories: comprehensive lifestyle interventions (n = 18), nutritional supplementation and dietary pattern interventions (n = 11), structured exercise interventions (n = 3), and behavioural, psychological, health education or service-based interventions (n = 10). Intervention duration ranged from 6 weeks to 12 months, with some studies incorporating follow-up assessments after the active intervention phase, extending up to 24 months. The most frequently assessed metabolic outcomes were body weight, body mass index, and waist circumference. Measures of glycaemic indices, lipid profiles, and blood pressure were also commonly reported; however, across different studies and intervention types, results were generally inconsistent or heterogeneous. While some studies observed reductions in weight-related measures, changes in glucose, lipid, and blood pressure outcomes showed poor consistency across trials. Current randomised controlled trial evidence indicates that non-pharmacological interventions targeting antipsychotic drug-related metabolic abnormalities are highly diverse with respect to intervention composition, study design, and outcome assessment, and that findings vary substantially across studies. Future research should focus on clarifying core intervention components, standardising key metabolic outcome measures, and extending follow-up durations to improve the interpretability and comparability of the evidence and to provide a clearer foundation for subsequent research and practice. Not applicable.
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