Nine RCTs (1,828 patients) were included in the review: seven RCTs in patients with ADHD with or without ODD (1,615 patients) and two RCTs in patients with co-morbid ADHD plus ODD (213 patients). All of the included studies provided information about withdrawals and drop-outs. Five studies were reported as having appropriate randomisation. Eight studies were double-blinded. The Jadad scores ranged from 3 to 5.
ADHD with or without ODD
Compared with placebo, atomoxetine significantly improved ADHD-RS-IV Total scores (SMD -0.638, 95% CI: -0.761, -0.516), Inattentive symptom scores (SMD -0.558, 95% CI:-0.658, -0.457) and Hyperactive/impulsive symptom scores (SMD -0.548, 95% CI: -0.727, -0.369). Statistically significant heterogeneity was detected for Hyperactive/impulsive symptom scores (p=0.01; I-squared 67%) but not for the other two analyses. The results were similar after adjusting for significant confounding factors.
Compared with placebo, atomoxetine significantly improved CPRS/CTRS-R:S, CGI-S scores, and quality of life and function (results were reported).
The NNT to result in one treatment response was 3.43 (95% CI: 2.79, 4.45) and the NNT to prevent one relapse was 10.30 (95% CI: 5.89, 40.62).
ADHD with ODD
Compared with placebo, atomoxetine significantly reduced or improved ADHD-RS-IV Total, Inattentive symptom scores, Hyperactive/impulsive symptom scores, CGI, parent-rated CPRS-R:S and ODD symptoms in patients with co-morbid ADHD plus ODD (results were reported).
Adverse events.The following adverse events were significantly more common for patients receiving atomoxetine compared with placebo: decrease in appetite (NNH=8.81), somnolence (NNH=19.41), abdominal pain (NNH=22.48), vomiting (NNH=29.96), dyspepsia (NNH=49.38), dizziness (NNH=53.03), fatigue (NNH=62.24), infection (NNH=75.32) and pruritus (NNH=119.5).
Begg’s test showed no evidence of publication bias (p=0.28) but Egger’s test did (p=0.04).
The results of meta-regression analyses were also reported.