Resveratrol as adjunctive therapy in treatment of irritability in children with autism: A double-blind and placebo-controlled randomized trial.

Abstract

The underlying pathophysiology of autism spectrum disorder (ASD) has been linked to immune dysregulation, oxidative stress and excitation-inhibition imbalance. Among associated symptoms of ASD, management of irritability has gained considerable attention as it complicates adjustment of ASD patients and thus necessitates its pharmacological treatment. Resveratrol is a plant phytoalexin, which has been demonstrated to have neuroprotective effects through its anti-inflammatory and antioxidant properties. This double-blind, placebo-controlled randomized trial was designed to assess the potential therapeutic effects of resveratrol plus risperidone on irritability of ASD patients. Sixty-two patients were assigned randomly into two groups of resveratrol and placebo. Both groups were treated with risperidone twice daily starting at a dose of 0.5mg with a dose increase of 0.5mg per week (for the first 3weeks). Resveratrol dosage was 250mg twice per day from the beginning of the study. Using the Aberrant Behavior Checklist-Community (ABC-C), patients were assessed for ASD-related behavioural symptoms at baseline, week 5 and week 10. The frequency of adverse events was recorded using a checklist containing 25 possible side effects, including general, gastrointestinal, neurological and cardiovascular complications. Improvements in primary outcome measure (irritability) and three secondary outcome measures (lethargy/social withdrawal, stereotypic behaviour and inappropriate speech subscales) in the resveratrol group were statistically similar to those in the placebo group. The repeated measures analysis showed no time×treatment interaction on these subscale scores. In contrast, patients in the resveratrol group showed greater decline in hyperactivity/non-compliance score as a secondary outcome measure (mean difference [CI=95%]=4.51 [0.10-8.92], t=2.04; P=.04), and repeated measures analysis showed significant effect for time×treatment effect on this subscale score (F=3.81; df=1.30; P=.043). There was no significant difference in number and severity of adverse events between the two groups. This clinical trial demonstrated no significant effect for adjunctive treatment with resveratrol on irritability of patients with ASD. However, it provided preliminary evidence indicating that resveratrol could improve hyperactivity/non-compliance of ASD patients.