title: Comparative efficacy and acceptability of methylphenidate and atomoxetine in treatment of attention deficit hyperactivity disorder in children and adolescents: a meta-analysis.
abstract: BACKGROUND
  Psychostimulants 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.
  
  
  METHODS
  All 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.
  
  
  RESULTS
  Nine 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%).
  
  
  CONCLUSIONS
  In 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.
authors.affiliation: Department of Psychological Medicine, Faculty of Medicine, University of Colombo, Sri Lanka.
authors.forename: Raveen
authors.initials: R
authors.lastname: Hanwella
authors.forename: Madhri
authors.initials: M
authors.lastname: Senanayake
authors.forename: Varuni
authors.initials: V
authors.lastname: de Silva
mesh_terms: D000293:Adolescent; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D006801:Humans; D008774:Methylphenidate / Q000009:adverse effects / Q000627:therapeutic use*; D011437:Propylamines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000697:Central Nervous System Stimulants; D011437:Propylamines; D008774:Methylphenidate; D000069445:Atomoxetine Hydrochloride
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