17 Salahuddin, Nurul Husna Herlitzius, Emilia Schütz, Alexandra Siafis, Spyridon Priller, Josef Leucht, Stefan Bighelli, Irene AG Priller JAMA psychiatry JAMA psychiatry AMA Chicago, Ill. 2168-622X 10.1001/jamapsychiatry.2025.4390 English 353 4 83 Substance use disorder (SUD) is commonly found in individuals with schizophrenia, with a high co-occurrence rate of approximately 41.7%. Despite this high prevalence, people with both schizophrenia and SUD are frequently excluded from clinical trials and systematic reviews; this special group is particularly challenging to treat and imposes a significant economic burden on health care systems.To evaluate the efficacy, acceptability, and tolerability of psychological and psychosocial interventions in patients with schizophrenia and co-occurring SUD.The Cochrane Schizophrenia Group registry was searched up to January 13, 2025. Data analysis was performed from March to April 2025.Randomized clinical trials (RCTs) examining psychological and psychosocial interventions compared with control groups in adults with schizophrenia and concomitant SUD were identified. No restrictions were applied regarding the type of substance used, including alcohol, cannabis, nicotine, and stimulants, such as amphetamines.A systematic review and random-effect pairwise meta-analyses were conducted to estimate standardized mean differences (SMD) with 95% confidence intervals and were reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Confidence in the estimate was assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.The primary outcomes were overall symptoms and substance use reduction measured by validated scales at posttreatment.A total of 35 RCTs were included (4136 participants), with 29 trials involving 3831 participants contributing to pairwise meta-analyses comparing psychological and psychosocial interventions with control conditions. Among the 3748 participants with reported sex, 951 (25.4%) were female, and mean (range) age was 37.2 (20.6-57.5) years. A very small effect favoring the intervention group was observed in reducing overall symptoms (SMD, -0.11; 95% CI, -0.27 to 0.05; 13 trials; low confidence in the estimate), mainly driven by nicotine studies. No difference was found between intervention and control groups in reducing all types of substance use (SMD, -0.01; 95% CI, -0.21 to 0.18; 8 trials; moderate confidence). When considered separately, alcohol, cannabis, amphetamines, and other stimulants showed similar no-effect results, while nicotine use indicated a small effect.The findings of this systematic review and meta-analysis suggest that current psychological and psychosocial interventions provide limited benefit in reducing symptoms and no effect in reducing substance use in individuals with schizophrenia and SUD compared to control conditions, with the exception of nicotine use, highlighting the urgent need to develop more effective treatment strategies. PUB:(DE-HGF)16, ; 0, ; Humans Substance-Related Disorders: therapy Substance-Related Disorders: epidemiology Substance-Related Disorders: complications Schizophrenia: therapy Schizophrenia: epidemiology Psychosocial Intervention: methods Comorbidity Psychotherapy: methods Diagnosis, Dual (Psychiatry) Randomized Controlled Trials as Topic Journal Article 2026 DZNE-2026-00354 2026 pmc:PMC12874077 pmid:41637064 https://pub.dzne.de/record/285818 https://doi.org/10.1001/jamapsychiatry.2025.4390