Comparative efficacy and safety of methylphenidate and atomoxetine for attention-deficit hyperactivity disorder in children and adolescents: Meta-analysis based on head-to-head trials

Introduction: Comparative efficacy and safety are important issues for appropriate drug selection for attention-deficit hyperactivity disorder (ADHD) treatment. Therefore we conducted a meta-analysis, where we compared atomoxetine (ATX) and methylphenidate (MPH) for ADHD treatment in children and adolescents. Method: Literature retrieval was conducted in relevant databases from their inception to April 2016 to select head-to-head trials that compared ATX and MPH in children and adolescents. Outcomes like response rate, ADHD Rating Scale (ADHD-RS) score, and adverse events were compared between ATX and MPH treatments. The standardized mean difference (SMD) and risk ratio (RR) with their corresponding 95% confidence intervals (CIs) were used as the effect size for continuous data or dichotomous data, respectively. Results: Eleven eligible randomized-controlled trials were included, and two of them were double-blind, while the remaining were open-label. Compared to ATX, MPH showed a higher response rate (RR=1.14, 95% CI [1. 09, 1.20]), decreased inattention (SMD=-0.13, 95% CI [-0.25, -0.01]) and lower risk of adverse events (drowsiness: RR=0.17, 95% CI [0.11, 0.26; nausea: RR=0.49; 95% CI [0.29, 0.85; vomiting: RR=0.41, 95% CI [0.27, 0.63]). However, MPH presented a higher risk of insomnia than ATX (RR=2.27, 95% CI [1.63, 3.15], p<.01). Conclusion: Results of the meta-analysis add additional evidence of the effectiveness of both ATX and MPH and suggest that MPH should be a first treatment option in most patients with ADHD.