Objectives: To study loxapine prospectively in doses of up to 15mg daily in adolescents and adults with ASD, aggression and irritability. Secondly, to measure brain derived neurotrophic factor (BDNF) as a potential biomarker of neurogenesis, controlling for platelet count and BMI.
Methods: We performed an exploratory prospective 12-week open trial of add-on loxapine in subjects aged 13 to 65 years with ASD, aggression and irritability above 14 points on the Aberrant Behavior Checklist-Irritability (ABC-I) subscale. Loxapine was added and flexibly dosed up to 15mg daily, starting with 5mg alternate days for the first 3 weeks to minimize akathisia. From weeks 1 to 6 other medications were tapered if possible, while from weeks 6 to 12 all medication doses were held stable.The primary outcome response measure was the Clinical Global Impressions scale-Improvement (CGI-I), with response defined as CGI-I of Much Improved or Very Much Improved. Secondary outcome response measures were the ABC-I, Repetitive Behavior scale-Revised, and the Quality of Life scale. Serum BDNF was assayed from samples collected at baseline and final study visits.
Results: Sixteen subjects were enrolled; 13 completed. Eleven were males and 5 were females. Mean age was 21.6 years (range 13 to 39). Mean final loxapine dose was 8.6 mg/day(2.5to 15). By week 6, 8 (50%) were rated as Much Improved and by week 12, 15 (94%) were rated as Much Improved. On ABC-I, 6 subjects (38%) responded by week 6, and 8 (50%) by week 12, using a 25% score reduction as response. Mean BMI scores did not increase. Side effects were minimal. Prolactin elevation did not occur. BDNF levels increased in all but one subject, to a significant degree, p=0.035.
Conclusions: Low dose loxapine shows promise as a new treatment for aggression and irritability in ASD. Loxapine response was rapid, however it could be started and increased to 5mg daily after a week in future trials for an even more rapid response. Prospective, double-blind placebo-controlled trials of loxapine dosed at 5 to 15 mg/day targeting aggression and irritability in ASD are warranted. Loxapine may increase BDNF as a potential biomarker of neurotrophic effects, although larger randomized controlled trials with placebo comparisons are needed.
See more of: Treatment Trials: Behavioral Interventions
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