Schema therapy versus any control condition for adult mental disorders: a systematic review with meta-analysis and trial sequential analysis

Background Schema therapy is a transdiagnostic psychotherapy targeting complex psychiatric disorders. Previous literature reviews have been on selected mental disorders only and primarily narrative. This systematic review with meta-analysis is the first to synthesize evidence for schema therapy for a wide range of psychiatric disorders. Methods Randomized clinical trials comparing schema therapy with active and passive control conditions were included. Primary outcomes were mental disorder symptoms and quality of life. Secondary outcomes were level of functioning, serious adverse events, and treatment dropout. For the meta-analysis, continuous outcomes were summarized as standardized mean differences and dichotomous outcomes as risk ratio, both presented with their 95% confidence intervals. Results 18 trials (1275 participants) were included. Eight trials were eligible for quantitative synthesis. We found no evidence of a difference between schema therapy and control conditions on the primary outcomes at end of treatment: symptom severity (personality disorders: SMD: -0.55, 95% CI:-1.28-0.18, p  = 0.14; four trials; N = 517; Bayes factor: 0.34; very low certainty) (depression: SMD: -1.11, 95% CI:-3.25 to 1.04, p  = 0.31, two trials; N = 166; Bayes factor: 0.64; very low certainty) and quality of life (SMD: 0.02, 95% CI:-0-14 to 0.19, p  = 0.77; three trials; N = 593; Bayes factor: 367,0; very low certainty), nor on any secondary or exploratory outcomes. Conclusions No evidence for differential effects between schema therapy and control conditions was found for any outcomes. More high-quality trials are needed before schema therapy can be recommended for broader clinical implementation. Study registration The protocol for this study was preregistered on April 22nd, 2025 (PROSPERO CRD420251015725).