Simvastatin as an Adjunctive Therapy to Risperidone in Treatment of Autism: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

J Child Adolesc Psychopharmacol. 2018 Feb;28(1):82-89. doi: 10.1089/cap.2017.0055. Epub 2017 Jul 18.


Objectives: Providing novel treatments for autism has been a subject of long-standing research. Based on etiopathological findings, we aim at assessing potential therapeutic effects of statins, here simvastatin, on autism symptoms for the first time.

Methods: In this randomized, double-blind, placebo-controlled, parallel-group 10-week clinical trial, 70 drug-free children aged 4 to 12 years old with diagnosis of autistic disorder based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, who had an Aberrant Behavior Checklist-Community (ABC-C) scale irritability subscale score of ≥12, were equally randomized to receive either simvastatin (20-40 mg/day) or placebo as an adjunct to risperidone (1-2 mg/day) whereas administration of both drugs was started simultaneously from baseline. Patients with comorbid psychiatric disorders, active medical conditions, severe intellectual disability, seizure disorders, history of any treatments for autism in the past 6 months, or history of current anti-inflammatory drug consumption were excluded. Primary outcome was defined as the difference in mean change of the ABC-C scale irritability subscale score from baseline to the endpoint ( ; IRCT201602041556N86).

Results: Significant differences in change of the ABC-C scale irritability (mean difference [95% confidence interval (CI)] = -3.45 [-5.37 to -1.54], p = 0.001; Cohen's d = 0.89) and hyperactivity/noncompliance (mean difference [95% CI] = -4.27 [-6.69 to -1.86], p = 0.001; Cohen's d = 0.87) subscales scores were detected between the two arms. No significant difference was detected in case of the other three subscales.

Conclusions: This study provides preliminary evidence for potential therapeutic effects of simvastatin in the treatment of autism that warrants further investigations.

Keywords: autistic disorder; clinical trial; risperidone; simvastatin.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antipsychotic Agents / administration & dosage*
  • Antipsychotic Agents / therapeutic use
  • Autistic Disorder / drug therapy*
  • Autistic Disorder / physiopathology
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Irritable Mood / drug effects
  • Male
  • Psychiatric Status Rating Scales
  • Risperidone / administration & dosage*
  • Risperidone / therapeutic use
  • Simvastatin / administration & dosage*
  • Simvastatin / therapeutic use
  • Treatment Outcome


  • Antipsychotic Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Simvastatin
  • Risperidone

Associated data

  • IRCT/IRCT201602041556N86