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

Abstract

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.

A review of atomoxetine effects in young people with developmental disabilities

“…However, this somewhat muted response rate is consistent with what has been reported with psychostimulants in children with ASD (RUPP, 2005) and in children with intellectual disability (Aman, Buican, & Arnold, 2003). Indeed as in Mazzone et al's (2011) study of ATX, Aman et al (2003) found that lower IQ was associated with a poorer response rate to methylphenidate in children with ID and ADHD. It suggests that response rates to noradrenergic and dopaminergic ADHD medicines may be diminished in young people with IDD relative to responses of TD children with ADHD.…”

Adherence, persistence, and medication discontinuation in patients with attention-deficit/hyperactivity disorder &ndash; a systematic literature review

“…Other factors – such as symptom control, parent/caregiver’s decision to discontinue, dislike of medication, and dosing inconvenience – were reported less frequently. Discontinuation reasons for children and adolescents treated with nonstimulants were detailed in only four studies 66–69. All four of these studies cited treatment ineffectiveness/suboptimal response, three cited adverse effects, and one cited poor adherence to treatment as reasons for discontinuation.…”

Safety of medicines used for ADHD in children: a review of published prospective clinical trials

“…After excluding three studies that did not report any data concerning AEs,17 27 31 one interim analysis29 and one study presented as an abstract in a congress,24 11 studies were evaluated 16 18–23 25 26 28 30…”

“…Three studies were retrospective chart reviews,16 21 25 two analysed data collected prospectively in an Italian register18 28 and six were prospective trials 19 20 22 23 26 30…”