title: 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.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors: Clinical Pharmacy Department, Ormož Psychiatric hospital, Ptujska Cesta 33, 2270 Ormož, Slovenia, European Union. Electronic address: matejstuhec@gmail.com.
authors: Matej
authors: M
authors: Stuhec
authors: Chair of Social Pharmacy, Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia, European Union.
authors: Barbara
authors: B
authors: Munda
authors: Department of Psychiatry, Faculty of Medicine, University Ljubljana, Vrazov trg 2, 1104 Ljubljana, Slovenia, European Union.
authors: Vesna
authors: V
authors: Svab
authors: Chair of Social Pharmacy, Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia, European Union.
authors: Igor
authors: I
authors: Locatelli
mesh_terms: D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use*; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D016642:Bupropion / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use; D002648:Child; D057186:Comparative Effectiveness Research; D003913:Dextroamphetamine / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000069478:Lisdexamfetamine Dimesylate; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use*; D010342:Patient Acceptance of Health Care / Q000706:statistics & numerical data*; D011437:Propylamines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000697:Central Nervous System Stimulants; D011437:Propylamines; D016642:Bupropion; D008774:Methylphenidate; D000069445:Atomoxetine Hydrochloride; D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine
keywords: Acceptability; Attention deficit hyperactivity disorder; Bupropion; Child and adolescent psychiatry; Efficacy; Meta-analysis