Efficacy of Adding Cyproheptadine to Risperidone in Children with Autistic Disorder: A Randomized Controlled Clinical Trial

The core symptoms of autism are abnormalities in social interaction, communication, and behavior. The involvement of 5-HT has been suggested in neuropsychiatric disorders and particularly in autistic disorder.The aim of this study was to assess the efficacy of cyproheptadine, a 5-HT2 antagonist, in the treatment of autistic disorder. In this double-blind, placebo-controlled trial, we assessed the effects of cyproheptadine plus risperidone in the treatment of autistic disorder.Thirty children between the ages of 3 and 11 years (inclusive) with a DSM-IV-TR clinical diagnosis of autism referred to the child psychiatry clinics at Sheikh and Ebn-e Sina hospitals, Mashhad, were recruited. The children presented with severely disruptive symptoms related to autistic disorder. Patients were randomly allocated to cyproheptadine + risperidone (Group A; 15 patients) and risperidone + placebo (Group B; 15 patients) for an 8-week, double-blind, placebo-controlled study. The doses of risperidone and cyproheptadine were titrated up to 2 mg/day and 0.2 mg/kg/day, respectively. Patients were assessed at baseline and after 4 and 8 weeks of starting medications. The Childhood Autism Rating Scale scores after 4 and 8 weeks were 40.26±2.9 and 38.56±2.38 in group A and 40.2±3.31 and 37.73±2.59 in group B, respectively. The scores improved in both groups, but the difference between them was not significant (F=0.029, d.f= 1, p=0.867). The results suggest that the combination of cyproheptadine with risperidone is not more effective than risperidone alone. However, the results need confirmation by a larger randomized controlled trial.