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document
Placebo-controlled pilot trial of mecamylamine for treatment of autism spectrum disorders . OBJECTIVE To explore possible benefits of a nicotinic acetylcholine receptor ( nAChR ) agent for autistic symptoms based on postmortem observation of nAChR abnormalities ( deficient α4β2 nAChRs , excess α7 nAChRs ) in brains of patients with autism . METHOD Mecamylamine , because of its safety record in children with other disorders , was chosen for this first exploration . Twenty children with autism spectrum disorder age 4-12 years were randomly assigned for 14 weeks to placebo ( n=8 ) or mecamylamine ( n=12 ) in ascending fixed doses : 0.5 mg/day for 6 weeks , 2.5 mg for 2 weeks , then 5 mg/day for 6 weeks . Improvement was rated by a blinded independent evaluator . Because of small sample , data analysis was descriptive . RESULTS Eighteen participants ( 10 mecamylamine , 8 placebo ) completed the study . All doses were well tolerated ; the only side effect of note was constipation ( 50 % compared with 25 % of placebo group ) . Three children had clinically nonsignificant electrocardiographic QT prolongation . Both groups showed modest to moderate improvement , but differences between groups were negligible . On the primary outcome measure , the Ohio Autism Clinical Impressions Scale , 90 % of the active treatment group showed improvement at some point ( but only 40 % sustained it ) , compared with 62 % on placebo . Of the four in active treatment that sustained improvement , three had a maximum dose of 0.13-0.15 mg/kg/day , while those who regressed had doses ≥0.18 mg/kg/day . Graphed means suggested better outcome with lower mg/kg and longer medication duration . Four parents spontaneously reported reduced hyperactivity and irritability and better verbalization and continued mecamylamine at their own expense . CONCLUSION Mecamylamine appeared to be safe , but not very effective in autism . The suggestion of better results at lower doses and longer exposure warrants consideration for future trials . The next step would be exploration of a more specific α4β2 nAChR agonist , such as varenicline .
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Intervention_Pharmacological
mecamylamine
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Intervention_Pharmacological
nicotinic acetylcholine receptor ( nAChR ) agent
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Outcome_Mental
autism spectrum disorders
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Outcome_Mental
autistic symptoms
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Outcome_Adverse-effects
constipation
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Participant_Condition
autism spectrum disorders .