Placebo response in pharmacological and dietary supplement trials of autism spectrum disorder (ASD): systematic review and meta-regression analysis.
Spyridon Siafis, Oğulcan Çıray, Johannes Schneider-Thoma and 13 others
PMID 32847616WHAT IT FOUND
About 20% of people with autism improved substantially on placebo alone in medication and supplement trials.
Caregiver ratings showed larger placebo responses than clinician observations, suggesting expectations influence perceived progress more than actual symptom change.
Key findings
01The overall positive response rate to placebo, defined as at least much improvement, was 19%.
02Larger placebo responses in social-communication difficulties were associated with caregiver ratings compared to clinician ratings.
03Placebo response was substantial and comparable across core symptom domains.
STILL TO COME
How it was doneWhat they foundWhat it means for SLPs
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What it does not show
The analysis relied on aggregate data from trials, which limits the ability to account for individual participant characteristics. There was considerable heterogeneity in the scales used to measure core symptoms across the included studies. Many predictors of placebo response were identified through exploratory meta-regressions, which are prone to false positives and ecological fallacy. Data on baseline severity and other participant factors were missing in a significant number of studies. The review excluded behavioral and multimodal interventions, so findings apply only to pharmacological and dietary supplement trials.
Declared interests
The study was funded by multiple organizations including the Innovative Medicines Initiative, Spanish Ministry of Science, CIBERSAM, and several private foundations (Familia Alonso, Alicia Koplowitz, Mutua Madrileña). No specific author conflicts of interest were declared in the provided text.
The easy way to misread this
Do not interpret the 19% placebo response rate as evidence that the active treatments in these trials were ineffective. This figure represents the improvement seen in the placebo groups, which serves as the baseline against which drug effects must be measured to determine true efficacy.