Meta-analysis: Pharmacologic Treatment of Restricted and Repetitive Behaviors in Autism Spectrum Disorders.
2020
Abstract Objective To examine the efficacy of pharmacological treatments for restricted and repetitive behaviors (RRBs) in autism spectrum disorder (ASD). Method We searched PubMed, Embase, and CENTRAL to identify all double-blind, randomized, placebo-controlled trials that examined the efficacy of pharmacological agents in the treatment of autism spectrum disorders and measured restricted and repetitive behaviors as an outcome. Our primary outcome was standardized mean difference in rating scales of RRBs. Results We identified 64 randomized, placebo-controlled trials involving 3,499 participants with ASD. Antipsychotics significantly improved RRB outcomes compared to placebo [standardized mean difference (SMD)=0.28 (95% Confidence Interval (CI): 0.08-0.49), z=2.77, p=0.01] demonstrating a small effect size. Larger significant positive effects on RRBs in ASD were seen in individual studies with fluvoxamine, buspirone, bumetanide, divalproex, guanfacine, and folinic acid that have not been replicated. Other frequently studied pharmacological treatments in ASD including oxytocin, omega-3 fatty acids, selective serotonin reuptake inhibitors (SSRI) and methylphenidate did not demonstrate significant benefit in reducing RRB compared to placebo [oxytocin: SMD=0.23 (95% CI: -0.01-0.47), z=1.85, p= 0.06; omega-3 fatty acids: SMD = 0.19 (95% CI: -0.05-0.43), z= 1.54, p = 0.12; SSRI: SMD=0.09 (95% CI: -0.21-0.39), z=0.60, p=0.56; methylphenidate: SMD=0.18 (95% CI: -0.11-0.46), z=1.23, p=0.22]. Conclusion The results of the present meta-analysis suggest that currently available pharmacological agents have at best only a modest benefit for the treatment of RRBs in ASD with the most evidence supporting antipsychotic medications. Additional RCTs with standardized study designs and consistent and specific assessment tools for RRBs, are needed to further understand how we can best help ameliorate these behaviors in individuals with ASD.
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