Additive Effects of Cognitive Remediation and Physical Exercise in Patients with Schizophrenia: Cognitive Improvements.

Cognitive impairment is a clinically important feature of schizophrenia that affects community functioning and responds poorly to pharmacological treatment. Cognitive remediation (CR) and physical exercise (PE) can each improve cognition, but whether their combination provides additive benefits remains uncertain. This systematic review examined cognitive outcomes of interventions combining CR and PE in adults with schizophrenia or other psychotic spectrum disorders. The protocol was registered in PROSPERO (ID: 639266). PubMed was searched for eligible studies, and findings were synthesized narratively because of heterogeneity in designs, interventions, comparators, and outcome measures. Risk of bias was assessed using RoB 2 for randomized trials and ROBINS-I for non-randomized studies. Eleven reports representing 10 underlying studies met the eligibility criteria. Combined CR and PE was associated with improvements in global cognitive performance and in domains including executive function, verbal memory, working memory, and processing speed. Some studies reported benefits over CR alone or PE alone, while three-arm trials provided the most direct, although not uniformly consistent, evidence of superiority over both monotherapies. Four randomized reports raised some concerns regarding risk of bias; three were judged to be at high risk, and all four non-randomized reports were judged to be at serious risk. The single-database search, methodological heterogeneity, and risk-of-bias concerns limit the certainty and generalizability of the findings. Combined CR and PE may provide additional cognitive benefits, but adequately powered trials with appropriate comparators and standardized outcomes are needed to establish additivity.