Psychopharmacology of aggression in children and adolescents with autism: A critical review of efficacy and tolerability

Background: Autism is characterized by a clinical triad of symptoms that affect social, language, and behavioral domains. Aggression and self-injury may be associated symptoms of autism and can result in significant harm to those affected as well as marked distress for their families. The precise nature of the relationship between aggressive or self-injurious behavior (SIB) and autism remains unclear and as a result, these symptoms are treated with a broad range of pharmacological approaches. This review seeks to systematically and critically examine the evidence for the pharmacological management of aggression and SIB in children with autism spectrum disorders. Method: The entire PubMed database was searched for English language biomedical articles on clinical trials with medication in autism spectrum disorders. Studies were selected based on the following inclusion criteria: (1) randomized placebo-controlled trials; (2) a sample population that included children and adolescents; (3) at least one standardized assessment of aggression as a primary outcome measure of the study. Results: Twenty one trials with 12 medications were identified. Five medications produced significant improvement as compared to placebo, including tianeptine, methylphenidate, risperidone, clonidine, and naltrexone. Only risperidone and methylphenidate demonstrate results that have been replicated across at least two studies. Conclusions: Although many medications have been studied under placebo-controlled conditions, few produce significant improvement. Additional placebo-controlled trials are needed to increase the number of therapeutic options available in the treatment of aggression in autism.