ADHD Research Today is a free monthly online journal that collates and summarizes the latest research about ADHD, including details on attention-deficit hyperactivity disorder, drugs, treatment, symptoms.

CYP2D6 and clinical response to atomoxetine in children and adolescents with ADHD.

Michelson D, Read HA, Ruff DD, Witcher J, Zhang S, McCracken J

Lilly Research Laboratories, Indianapolis, USA. david_michelson@merck.com

BACKGROUND: Atomoxetine, a selective norepinephrine reuptake inhibitor effective in the treatment of attention-deficit/hyperactivity disorder (ADHD), is metabolized through the cytochrome P-450 2D6 (CYP2D6) enzyme pathway, which is genetically polymorphic in humans. Variations in plasma atomoxetine exposures can occur because of genetic variation or as a consequence of coadministration with drugs that inhibit CYP2D6. METHOD: We examined the effects of CYP2D6 on the efficacy, safety, and tolerability of atomoxetine in children and adolescents using pooled data from atomoxetine clinical trials. RESULTS: At endpoint, poor metabolizers had markedly greater reductions in mean symptom severity scores compared with extensive metabolizers (p < .05). Poor metabolizers had greater increases in heart rate and diastolic blood pressure (p < .001) and smaller increases in weight (p < .05) than extensive metabolizers. Several adverse events, including decreased appetite and tremor, were more frequent in poor metabolizers (p < .05). CONCLUSIONS: These results suggest that CYP2D6 poor metabolizers taking atomoxetine in doses up to 1.8 mg/kg/day are likely to have greater efficacy, greater increases in cardiovascular tone, and some differences in tolerability compared with CYP2D6 extensive metabolizers taking similar doses.

Published 23 January 2007 in J Am Acad Child Adolesc Psychiatry, 46(2): 242-51.
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