Cyproheptadine in the treatment of autistic disorder: a double-blind placebo-controlled trial

Autism is a childhood-onset disorder of unknown, possibly of multiple aetiologies. The core symptoms of autism are abnormalities in social interaction, communication and behaviour. The involvement of neurotransmitters such as 5-HT has been suggested in neuropsychiatric disorders and particularly in autistic disorder. Increased platelet 5-HT levels were found in 40% of the autistic population, suggesting that hyperserotonaemia may be a pathologic factor in infantile autism. Therefore, it is of interest to assess the efficacy of cyproheptadine, a 5-HT2 antagonist in the treatment of autistic disorder. In this 8-week double-blind, placebo-controlled trial, we assessed the effects of cyproheptadine plus haloperidol in the treatment of autistic disorder.

Children between the ages 3 and 11 years (inclusive) with a DSM IV clinical diagnosis of autism and who were outpatients from a specialty clinic for children at Roozbeh Psychiatric Teaching Hospital were recruited. The children presented with a chief complaint of severely disruptive symptoms related to autistic disorder. Patients were randomly allocated to cyproheptadine + haloperidol (Group A) or haloperidol + placebo (Group B) for an 8-week, double-blind, placebo-controlled study. The dose of haloperidol and cyproheptadine was titrated up to 0.05 and 0.2 mg/kg/day respectively. Patients were assessed by a third-year resident of psychiatry at baseline and after 2, 4, 6 and 8 weeks of starting medication. The primary measure of the outcome was the Aberrant Behaviour Checklist-Community (ABC-C) and the secondary measure of the outcome was the Childhood Autism Rating Scale (relating to people and verbal communication). Side effects and extrapyramidal symptoms were systematically recorded throughout the study and were assessed using a checklist and the Extrapyramidal Symptoms Rating Scale, administered by a resident of psychiatry during weeks 1, 2, 4, 6 and 8.

The ABC-C and the Childhood Autism Rating Scale scores improved with cyproheptadine. The behaviour of the two treatments was not homogeneous across time (groups-by-time interaction, Greenhouse-Geisser correction; F = 7.30, d.f. = 1.68, P = 0.002; F = 8.21, d.f. = 1.19, P = 0.004 respectively). The difference between the two treatments was significant as indicated by the effect of group, and the between-subjects factor (F = 4.17, d.f. = 1, P = 0.048; F = 4.29, d.f. = 1, P = 0.045 respectively). No significant difference was observed between the two groups in terms of extrapyramidal symptoms (P = 0.23). The difference between the two groups in the frequency of side effects was not significant.

The results suggest that the combination of cyproheptadine with a conventional antipsychotic may be superior to conventional antipsychotic alone for children with autistic disorder. However the results need confirmation by a larger randomized controlled trial.