Abstract
BackgroundPsychostimulants and non stimulants are effective in the treatment of ADHD. Efficacy of both methylphenidate and atomoxetine has been established in placebo controlled trials. Direct comparison of efficacy is now possible due to availability of results from several head-to-head trials of these two medications.MethodsAll published, randomized, open label or double blind trials, comparing efficacy of methylphenidate with atomoxetine, in treatment of ADHD in children, diagnosed using DSM-IV™ criteria were included. The outcome studied was ADHDRS-IVParent:Inv score. The standardized mean difference (SMD) was used as a measure of effect size.ResultsNine randomized trials comparing methylphenidate and atomoxetine, with a total of 2762 participants were included. Meta-analysis did not find a significant difference in efficacy between methylphenidate and atomoxetine (SMD = 0.09, 95% CI -0.08-0.26) (Z = 1.06, p = 0.29). Synthesis of data from eight trials found no significant difference in response rates (RR = 0.93 95% CI 0.76-1.14, p = 0.49). Sub group analysis showed a significant standardized mean difference favouring OROS methylphenidate (SMD = 0.32, 95% CI 0.12-0.53 (Z = 3.05, p < 0.002). Immediate release methylphenidate was not superior to atomoxetine (SMD = -0.04, 95% CI -0.19-0.12) (Z = 0.46, p = 0.64). Excluding open label trials did not significantly alter the effect size (SMD = 0.08, 95% CI -0.04-0.21) (Z = 1.27, p = 0.20). All-cause discontinuation was used as a measure of acceptability. There was no significant difference in all cause discontinuation between atomoxetine and methylphenidate (RR 1.22, 95% CI 0.87-1.71). There was significant heterogeneity among the studies (p = 0.002, I2 = 67%). Subgroup analysis demonstrated the heterogeneity to be due to the open label trials (p = 0.001, I2 = 81%).ConclusionsIn general atomoxetine and methylphenidate have comparable efficacy and equal acceptability in treatment of ADHD in children and adolescents. However OROS methylphenidate is more effective than atomoxetine and may be considered as first line treatment in treatment of ADHD in children and adolescents.
Highlights
Psychostimulants and non stimulants are effective in the treatment of ADHD
Meta-analysis did not find a significant difference in efficacy between methylphenidate and atomoxetine when standardized mean difference (SMD) was used as a measure of effect size 0.09 (Z = 1.06, p = 0.29)
Sub group analysis Sub group analysis showed a significant standardized mean difference favouring OROS methylphenidate 0.32 (95% CI 0.12-0.53 (Z = 3.05, p < 0.002)
Summary
Psychostimulants and non stimulants are effective in the treatment of ADHD. Efficacy of both methylphenidate and atomoxetine has been established in placebo controlled trials. Structural and functional imaging studies suggest that dysfunction of cingulate, frontal, and parietal cortical regions and imbalances in the dopaminergic and noradrenergic systems, contribute to the pathophysiology of ADHD [1,2]. It is characterized by inattention, hyperactivity and impulsivity. ADHD is associated with co-morbidities such as learning disorders, tics, anxiety, oppositional defiant disorder and conduct disorder [6]. Antisocial behavior, substance abuse, and a variety of problems related to conduct and learning can occur [7]
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