Placebo-Controlled Pilot Trial of Mecamylamine for Treatment of Autism Spectrum Disorders

The purpose of this study is to examine the safety and efficacy of mecamylamine for the core symptoms of autism.

This is a placebo-controlled pilot clinical trial of a nicotinic agent based on evidence that a disturbance occurs in nicotinic cholinergic transmission in the brain of autistic children. This pharmacotherapeutic trial will be conducted as a direct result of findings of a nicotinic receptor abnormality in autopsied brain tissue from individuals who suffered from autism. A pharmacological agent, mecamylamine, with specificity for the nicotinic receptors implicated in autism, will be tested in children with autism spectrum disorder. Twenty children who meet inclusion/exclusion criteria will be randomized in a 2:3 ratio to 14 weeks of either matched placebo (n=8) or mecamylamine (n=12). Children randomized to placebo who do not respond will be given the opportunity to enroll in a ten week open label extension. The trial has been completed and published in J. of Child & Adolescent Psychopharmacology.

There will be 12 children in this arm. These children will receive the active medication (mecamylamine).

There will be 8 children in this arm. These children will receive placebo instead of the active medication.

The dosage is titrated at 6 weeks of .5mg, 2 weeks of 2.5 mg, and 6 weeks of 5.0 mg. One pill is taken once daily.

The primary measure will be a global composite derived by calculating the z scores on each measure other than CGI from published norms (or from the baseline descriptives, then averaging the z scores of the various outcome measures for each individual.

Inclusion Criteria: Autistic Disorder or Pervasive Developmental Disorder-Not Otherwise Specified Age 4-12 General good health IQ of >=36 or mental age of >=18 months Parent/caregiver willingness to accompany child to clinic and monitor for side effects Exclusion Criteria: Unstable Seizure Disorder Psychoactive medication in the process of adjustment Antipsychotic medication in previous 3 months before baseline Systemic corticoids (inhalers allowed) Planned beginning of major behavioral intervention in 3 months of study or the 2 months prior to the study.

Arnold LE, Aman MG, Hollway J, Hurt E, Bates B, Li X, Farmer C, Anand R, Thompson S, Ramadan Y, Williams C. Placebo-controlled pilot trial of mecamylamine for treatment of autism spectrum disorders. J Child Adolesc Psychopharmacol. 2012 Jun;22(3):198-205. doi: 10.1089/cap.2011.0056. Epub 2012 Apr 26.