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

• OSU Autism Rating Scale-DSM-IV [ Time Frame: Baseline, week 6, 8, and 14. ] [ Designated as safety issue: No ]
• Repetitive Behavior Questionnaire [ Time Frame: Baseline, week 2, 4, 6, 8, 10, 12, and 14 ] [ Designated as safety issue: No ]
• Aberrant Behavior Checklist [ Time Frame: Baseline, week 2, 4, 6, 8, 10, 12, and 14. ] [ Designated as safety issue: No ]
• Ohio Autism Clinical Impressions Scale [ Time Frame: Baseline, weeks 1, 2, 4, 6, 7, 8, 9, 10, 12, and 14. ] [ Designated as safety issue: No ]
• Social Responsiveness Scale [ Time Frame: Baseline, weeks 2, 4, 6, 8, 10, 12, and 14. ] [ Designated as safety issue: No ]
• Expressive Vocabulary test-Second Edition [ Time Frame: Baseline and week 14 ] [ Designated as safety issue: No ]
• Adverse Experience checklist and AE log [ Time Frame: Baseline, weeks 1, 2, 4, 6, 7, 8, 9, 10, 12, and 14. ] [ Designated as safety issue: Yes ]
• Cognitive Battery [ Time Frame: baseline, weeks 6, 8, and 14 ] [ Designated as safety issue: No ]

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 was no advantage of active drug over placebo.

• Autistic Disorder
• Pervasive Developmental Disorder

• Drug: mecamylamine
  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.
  Other Name: Inversine
• Drug: placebo
  One pill is taken once daily.

• Experimental: Active Mecamylamine
  There will be 12 children in this arm. These children will receive the active medication (mecamylamine).
  Intervention: Drug: mecamylamine
• Placebo Comparator: Placebo
  There will be 8 children in this arm. These children will receive placebo instead of the active medication.
  Intervention: Drug: placebo

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.