Comparative efficacy and acceptability of atomoxetine, lisdexamfetamine, bupropion and methylphenidate in treatment of attention deficit hyperactivity disorder in children and adolescents: a meta-analysis with focus on bupropion

Objectives: There is a lack of comparative effectiveness research among attention deficit hyperactivity disorder (ADHD) drugs in terms of efficacy and acceptability, where bupropion is compared with atomoxetine, lisdexamfetamine and methylphenidate. The main aim of this work was to compare the efficacy and acceptability of these drugs in children and adolescents using a metaanalysis.

Methods: A literature search was conducted to identify double-blind, placebo-controlled, noncrossover studies of ADHD. PubMed/Medline and Clinicaltrials.gov were searched. Comparative drug efficacy to placebo was calculated based on the standardized mean difference (SMD), while the comparative drug acceptability (all cause discontinuation) to placebo was estimated on the odds ratio (OR).

Results: In total 28 trials were included in the meta-analysis. Efficacy in reducing ADHD symptoms compared to placebo was small for bupropion (SMD=-0.32, 95% CI; -0.69, 0.05), while modest efficacy was shown for atomoxetine (SMD=-0.68, 95% CI; -0.76, -0.59) and methylphenidate (SMD=-0.75, 95% CI; -0.98, -0.52) and high efficacy was observed for lisdexamfetamine (SMD=-1.28, 95% CI; -1.84, -0.71). Compared to placebo treatment discontinuation was statistically significantly lower for methylphenidate (OR=0.35, 95% CI; 0.24, 0.52), while it was not significantly different for atomoxetine (OR=0.91, 95% CI; 0.66, 1.24), lisdexamfetamine (OR=0.60, 95% CI, 0.22, 1.65), and bupropion (OR=1.64, 95% CI; 0.5, 5.43).

Limitations: The heterogeneity was high, except in atomoxetine trials. The crossover studies were excluded. The effect sizes at specific time points were not computed. Studies with comorbid conditions, except those reporting on oppositional defiant disorder, were also excluded. All studies involving MPH were combined.

Conclusions: The results suggest that lisdexamfetamine has the best benefit risk balance and has promising potential for treating children and adolescents with ADHD. More research is needed for a better clinical evaluation of bupropion.