Placebo response in pharmacological and dietary supplement trials of autism spectrum disorder (ASD): systematic review and meta-regression analysis

Study answer

What this study found

Placebo produced substantial improvements across core ASD symptoms: social-communication difficulties (SMC −0.32; 95% CI −0.39 to −0.25), repetitive behaviors (SMC −0.23; 95% CI −0.32 to −0.15), and overall core symptoms (SMC −0.36; 95% CI −0.46 to −0.26). About 19% of participants were at least much improved with placebo (CGI-I). Larger placebo responses were linked to caregiver ratings, lower risk of bias, flexible dosing, larger sample sizes and more sites, earlier publication year, and higher baseline irritability, with some effects varying by domain. No clear difference by age group.…

Study & population

86 randomized, placebo-controlled trials (pharmacological and dietary supplements) comparing with placebo; most were double-blind and parallel design; cross-over data used only from the first phase to avoid carryover effects.

Key limitation

Focus on placebo effects in core symptoms only; wide heterogeneity of scales and CGI anchoring; moderators of drug–placebo differences not analyzed; reliance on aggregate data with potential ecological bias; many eligible studies lacked data; cross-over data limited to first phase; majority of trials pediatric;…

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Original abstract