European psychiatry : the journal of the Association of European Psychiatrists · 2026
Magnitude of response in treatment and control groups within psychedelic trials for psychiatric disorders: A meta-analysis.
СтатьяМетаанализСистематический обзорНазвание и аннотация: Перевод в очереди
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Meshkat Shakila, Lin Qiaowei, Sousa-Ho Rachel, Demchenko Ilya, Zeifman Richard J, Fang Howell, Reichelt Amy C, Zhang Yanbo, Burback Lisa, Winkler Olga, Greenshaw Andrew, Monson Candice M, Vermetten Eric, Jetly Rakesh, Lou Wendy, Husain Muhammad Ishrat, Burke Matthew J, Bhat Venkat
Аннотация
BACKGROUND: Psychedelic-assisted psychotherapy has shown potential for psychiatric disorders. However, the magnitude of symptom change in control groups remains poorly understood. We aim to evaluate within-group effects in control groups and compare them to treatment groups in psychedelic trials.
METHODS: A systematic search was conducted up to 1 July 2025. The study protocol was preregistered in PROSPERO (CRD420251111853).
RESULTS: Fourteen randomized controlled trials (n = 643) were included. Direct between-arm meta-analyses showed greater symptom reductions in treatment compared with control across outcomes, including depressive symptoms (number of study arms [k] = 13; SMD = -0.82; 95% CI = -1.17, -0.47; I2 = 60.1%), posttraumatic stress disorder (PTSD) symptoms (k = 10; SMD = -0.89; 95% CI = -1.14, -0.65; I2 = 0%), and anxiety symptoms (k = 5; SMD = -0.66; 95% CI = -0.94, -0.38; I2 = 0%). Subgroup analyses showed limited evidence that effects differed by placebo type for depressive or PTSD symptoms. Descriptive within-group analyses indicated symptom reductions from baseline in both control and treatment groups, with larger within-group improvements observed in treatment groups across outcomes; notably, larger within-group reductions in PTSD symptoms were observed in inactive placebo groups. Sensitivity analyses showed consistent results.
CONCLUSIONS: Control groups in psychedelic trials demonstrated substantial symptom improvement, which may reflect non-specific trial factors (including expectancy and concurrent psychotherapy). These findings emphasize the importance of robust control conditions in psychedelic research and the need for nuanced interpretation of treatment effects.
METHODS: A systematic search was conducted up to 1 July 2025. The study protocol was preregistered in PROSPERO (CRD420251111853).
RESULTS: Fourteen randomized controlled trials (n = 643) were included. Direct between-arm meta-analyses showed greater symptom reductions in treatment compared with control across outcomes, including depressive symptoms (number of study arms [k] = 13; SMD = -0.82; 95% CI = -1.17, -0.47; I2 = 60.1%), posttraumatic stress disorder (PTSD) symptoms (k = 10; SMD = -0.89; 95% CI = -1.14, -0.65; I2 = 0%), and anxiety symptoms (k = 5; SMD = -0.66; 95% CI = -0.94, -0.38; I2 = 0%). Subgroup analyses showed limited evidence that effects differed by placebo type for depressive or PTSD symptoms. Descriptive within-group analyses indicated symptom reductions from baseline in both control and treatment groups, with larger within-group improvements observed in treatment groups across outcomes; notably, larger within-group reductions in PTSD symptoms were observed in inactive placebo groups. Sensitivity analyses showed consistent results.
CONCLUSIONS: Control groups in psychedelic trials demonstrated substantial symptom improvement, which may reflect non-specific trial factors (including expectancy and concurrent psychotherapy). These findings emphasize the importance of robust control conditions in psychedelic research and the need for nuanced interpretation of treatment effects.