Irene Bighelli, Georgia Salanti, Maximilian Huhn, Johannes Schneider-Thoma, Marc Krause, Cornelia Reitmeir, Sofia Wallis, Felicitas Schwermann, Gabi Pitschel-Walz, Corrado Barbui, Toshi A Furukawa, Stefan Leucht

Psychological treatments are increasingly regarded as useful interventions for schizophrenia. However, a comprehensive evaluation of the available evidence is lacking and the benefit of psychological interventions for patients with current positive symptoms is still debated. The present study aimed to evaluate the efficacy, acceptability and tolerability of psychological treatments for positive symptoms of schizophrenia by applying a network meta-analysis approach, that can integrate direct and indirect comparisons. We searched EMBASE, MEDLINE, PsycINFO, PubMed, BIOSIS, Cochrane Library, World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov for randomized controlled trials of psychological treatments for positive symptoms of schizophrenia, published up to January 10, 2018. We included studies on adults with a diagnosis of schizophrenia or a related disorder presenting positive symptoms. The primary outcome was change in positive symptoms measured with validated rating scales. We included 53 randomized controlled trials of seven psychological interventions, for a total of 4,068 participants receiving the psychological treatment as add-on to antipsychotics. On average, patients were moderately ill at baseline. The network meta-analysis showed that cognitive behavioural therapy (40 studies) reduced positive symptoms more than inactive control (standardized mean difference, SMD=-0.29; 95% CI: -0.55 to -0.03), treatment as usual (SMD=-0.30; 95% CI: -0.45 to -0.14) and supportive therapy (SMD=-0.47; 95% CI: -0.91 to -0.03). Cognitive behavioural therapy was associated with a higher dropout rate compared with treatment as usual (risk ratio, RR=0.74; 95% CI: 0.58 to 0.95). Confidence in the estimates ranged from moderate to very low. The other treatments contributed to the network with a lower number of studies. Results were overall consistent in sensitivity analyses controlling for several factors, including the role of researchers' allegiance and blinding of outcome assessor. Cognitive behavior therapy seems to be effective on positive symptoms in moderately ill patients with schizophrenia, with effect sizes in the lower to medium range, depending on the control condition.