Lower IQ is Associated with Decreased Clinical Response to Atomoxetine in Children and Adolescents with Attention-Deficit Hyperactivity Disorder

Objectives: Atomoxetine is commonly used to treat attention-deficit hyperactivity disorder (ADHD) in children with a broad range of cognitive abilities. We examined the association between level of cognitive functioning as determined by IQ and clinical response during treatment with atomoxetine. Methods: The records of all the children and adolescents treated with atomoxetine at a university clinic in Catania, Italy, over a 3-year period were examined. A total of 55 clinically referred children and adolescents (aged 5-15 years, 53 males) with ADHD were treated with atomoxetine (10-110 mg/day; mean: 1.28 mg/kg/day) for a period ranging from 2 to 168 weeks (mean: 57.3 +/- SD 39.4, median: 56). The IQ was assessed as part of the diagnostic evaluation prior to starting treatment. During treatment, clinical outcome was rated on the Clinical Global Impression-Improvement (CGI-I) and CGI-Severity (CGI-S) scales. Results: The IQ ranged from 43 to 117 (mean: 80.6 +/- SD 18.6, median: 84). The IQ and final CGI-I scores were negatively correlated (r = -0.68; p < 0.01). Children and adolescents with an IQ <85 were less likely to be responders (defined as a final CGI-I score of 1 or 2) than children and adolescents with an IQ >= 85 (20.71% vs 76.9%; p < 0.001). None of the patients discontinued atomoxetine due to adverse effects, while treatment was discontinued in 20 subjects due to a lack of efficacy or ambivalence of parents about pharmacological treatment. Conclusions: Atomoxetine appears to be less effective in children and adolescents with an IQ <85 than in children and adolescents in the average range of cognitive functioning. This difference is not accounted for by differences in the severity of ADHD symptoms, co-morbidity or reduced tolerability to the medication. These findings suggest that, in order to be fully informative, clinical trials of medications for ADHD should also include children and adolescents functioning in the borderline and cognitive disability range.