Abstract
IMPORTANCE: Psychedelic-assisted therapy (PAT) is a novel intervention for depressive symptoms, typically delivered with additional psychological therapy sessions. Quantitative evidence on how this concomitant therapy contributes to treatment outcomes is limited, highlighting the need for a systematic synthesis. OBJECTIVE: To evaluate whether the quantity of psychological therapy is associated with symptom reduction in PAT for depressive symptoms. DATA SOURCES: PubMed, PsycINFO, and Scopus databases were searched from inception to June 16, 2025. STUDY SELECTION: The analysis included controlled clinical trials involving adults with depressive symptoms who received PAT using classic serotonergic psychedelics (eg, psilocybin or lysergic acid diethylamide). Within these trials, psychedelic dosing sessions were embedded in therapeutic sessions before (preparation) and after (integration). Studies were excluded if they used microdosing as the primary intervention, involved naturalistic or purely pharmacological administration, or did not report therapy session count or duration. Qualitative studies, reviews, case reports, and conference abstracts were also excluded. Of the 226 records identified, 42 full texts were assessed by 2 independent reviewers, of which 12 met inclusion criteria. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and assessed risk of bias according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Multilevel random-effects meta-analysis and multilevel metaregressions were conducted using robust variance estimation. MAIN OUTCOMES AND MEASURES: The primary outcomes were standardized mean differences (Hedges g) in depressive symptoms at all available posttreatment time points. Metaregression analyses assessed associations of different metrics of psychological therapy quantity (duration in hours, number of sessions, and total duration in weeks) with treatment outcomes. RESULTS: The 12 included trials had a total sample of 733 participants (365 female [49.8%]; mean [SD] age, 43.1 [6.2] years). PAT showed a large overall effect size in reducing depressive symptoms compared with control conditions (Hedges g = -0.84; 95% CI, -1.15 to -0.54; P < .001). More preparation therapy hours were significantly associated with greater symptom reduction (β = -0.13; 95% CI, -0.24 to -0.01; P = .04). No significant associations were found for hours of postdosing integration (β = -0.02; 95% CI, -0.08 to 0.05; P = .53) or total session count (β = -0.01; 95% CI, -0.09 to -0.08; P = .86). Longer follow-up periods, measured in weeks from substance administration, were generally associated with smaller treatment effect sizes (β = 0.02; 95% CI, 0.01 to 0.04; P = .003). Risk of bias was high in the majority (9 [75%]) of studies, mostly due to ineffective blinding. CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis of controlled clinical trials investigating PAT for depressive symptoms, a greater quantity of preparation therapy was associated with significantly larger reductions of depressive symptoms. These findings highlight a potential key role of preparation in optimizing PAT outcomes. The observed association primarily reflects quantitative aspects of therapy exposure rather than qualitative or process-related dimensions of the therapeutic interaction. Additional systematic research is needed to clarify this association and optimize all therapeutic components within psychedelic interventions.