Double-blind, placebo-controlled study of amantadine hydrochloride in the treatment of children with autistic disorder

Objective: To test the hypothesis that amantadine hydrochloride is a safe a nd effective treatment for behavioral disturbances-for example, hyperactivi ty and irritability-in children with autism. Method: Thirty-nine subjects ( intent to treat; 5-19 years old; IQ > 35) had autism diagnosed according to DSM-IV and ICD-10 criteria using the Autism Diagnostic Interview-Revised a nd the Autism Diagnostic Observation Schedule-Generic. The Aberrant Behavio r Checklist-Community Version (ABC-CV) and Clinical Global Impressions (CGI ) scale were used as outcome variables. After a 1-week, single-blind placeb o run-in, patients received a single daily dose of amantadine (2.5 mg/kg pe r day) or placebo for the next week, and then bid dosing (5.0 mg/kg per day ) for the subsequent 3 weeks. Results: When assessed on the basis of parent -rated ABC-CV ratings of irritability and hyperactivity, the mean placebo r esponse rate was 37% versus amantadine at 47% (not significant). However, i n the amantadine-treated group there were statistically significant improve ments in absolute changes in clinician-rated ABC-CVs for hyperactivity (ama ntadine -6.4 versus placebo -2.1; p =.046) and inappropriate speech (-1.9 v ersus 0.4; p =.008). CGI scale ratings were higher in the amantadine group: 53% improved versus 25% (p =.076). Amantadine was well tolerated. Conclusi ons: Parents did not report statistically significant behavioral change wit h amantadine. However, clinician-rated improvements in behavioral ratings f ollowing treatment with amantadine suggest that further studies with this o r other drugs acting on the glutamatergic system are warranted. The design of these and similar drug trials in children with autistic disorder must ta ke into account the possibility of a large placebo response.