Pharmacological and non-pharmacological interventions for irritability in autism spectrum disorder: a systematic review and meta-analysis with the GRADE assessment.
Hangnyoung Choi, Jae Han Kim, Hee Sang Yang and 10 others
PMID 38263251WHAT IT FOUND
For irritability in autism, only risperidone, aripiprazole, and parent training showed a clear benefit over control.
The remaining interventions, including most supplements and newer drugs, did not.
Key findings
01Risperidone and aripiprazole both reduced irritability scores significantly more than placebo, with high certainty of evidence. Risperidone's effect was large (Hedges' g −0.857, 95% CI −1.263 to −0.451) across 6 trials, and aripiprazole's was moderate (Hedges' g −0.559, 95% CI −0.767 to −0.351) across 5 trials.
02Parent training for maladaptive behaviors reduced irritability scores more than inactive control (Hedges' g −0.893, 95% CI −1.184 to −0.602, 6 trials), with an effect size the authors describe as comparable to the two antipsychotics, though rated moderate rather than high certainty.
03Lurasidone, anti-epileptic drugs, valproate, and all dietary supplements tested as standalone treatments (N-acetylcysteine, polyunsaturated fatty acids, omega-3, vitamin D3) did not show a significant benefit over placebo, with certainty of evidence ranging from low to very low.
STILL TO COME
How it was doneWhat they found
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What it does not show
Most individual meta-analyses included only a small number of trials and participants, partly because conducting RCTs in children with autism is difficult. Most participants were under 19, so the findings may not apply to adults with autism. Five of the six parent training trials had a high risk of bias, mainly because the design was open-label, meaning the researchers and families knew who was getting the training. The authors note this may overestimate the effect. Three of the six risperidone trials had some concerns or high risk of bias. The adjuvant drug findings (sulforaphane, topiramate, pentoxifylline, and others) each come from a single trial and carry very low certainty of evidence. Different irritability scales were used across trials (ABC-I, DBC-irritable, ECBI-Intensity), though subgroup analyses suggested this did not materially affect the results.
Declared interests
Funded by the National Center for Mental Health. No industry funding or conflicts of interest are declared.
The easy way to misread this
Do not read the significant results for sulforaphane, topiramate, or the other adjuvant drugs as evidence they work. Each comes from a single trial, and the authors themselves call for replication before these can be considered. The parent training result, while stronger, rests on trials where five of six had a high risk of bias, mainly because the design was open-label.
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