Atomoxetin

Additional information

In children and adolescents, Attention Deficit Hyperactivity Disorder (ADHD) is more commonly diagnosed in boys, with the sex ratio ranging from 2:1 to 10:1 [1-4], with higher male-to-female ratios found in clinical versus population-based samples. The male-to-female ratio is smaller in adult clinical samples than in childhood and adolescent samples [5]. In women, hyperactivity/impulsivity and conduct problems were stronger predictors of clinical diagnosis and prescriptions of pharmacological treatment, compared to men [6]. Girls more often than boys have ADHD with mainly attention deficit disorder and more rarely clear hyperactivity/impulsivity problems. Therefore, the diagnosis in girls/women may be more difficult to recognize and be less likely to receive pharmacological treatment, and males with ADHD are more likely to receive ADHD medication than females with ADHD [6-9].

Pharmacokinetics and dosing

No differences in atomoxetine pharmacokinetics have been seen between boys/men and girls/women, and no sex differentiation in dosing has been recommended by the pharmaceutical company [10].

Effects

Even though earlier studies of ADHD treatment included few females, recent RCTs to demonstrate efficacy in the newer ER preparations have enrolled reasonable numbers of females [11].

A meta-analysis of nine studies including 1150 patients on atomoxetine and 678 patients on placebo (sex ratio not specified) evaluating efficacy and safety of atomoxetine in children and adolescents showed that male sex was associated with a smaller reduction in ADHD symptoms. This suggests that atomoxetine may be more efficacious in female ADHD patients [12].

Long-term response to atomoxetine in adult ADHD was analyzed in a double-blind trial followed by a three-year open-label study (247 men, 137 women). During the double-blind phase, patient’s sex had an impact on treatment effect. Women showed the greatest difference in improvement versus men on emotional dysregulation. In the end on the open-label phase, women had greater improvement on the hyperactivity/impulsivity section of both outcome measure scales WRAADDS and CAARS [13].

Pooled data from five atomoxetine clinical trials (658 boys, 136 girls) showed that atomoxetine was effective in improving some aspects of patient-reported HR-QoL (health-related quality of life) in both sexes. Patient’s sex did not influence treatment outcome [14]. Also, another study (338 boys, 83 girls) showed that atomoxetine improved ADHD-related difficulties (and hence the quality of life) as perceived by patients, parents and physicians was similar in boys and girls [15].

Adverse effects

When dose-dependent effects of atomoxetine on the corrected QT interval (QTc) was examined in Japanese adult ADHD patients (26 men, 15 women), there was a positive correlation between atomoxetine dosage and prolongation of QTc only in women. There was no correlation between plasma concentrations of atomoxetine and the QTc in either women or men [16].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).