title: Systematic evidence synthesis of treatments for ADHD in children and adolescents: indirect treatment comparisons of lisdexamfetamine with methylphenidate and atomoxetine.
abstract: OBJECTIVE
  Systematically review and synthesize the clinical evidence of treatments for attention deficit hyperactivity disorder (ADHD) by indirectly comparing established treatments in the UK with a drug recently approved in Europe (lisdexamfetamine [LDX]).
  
  
  METHODS
  
  
  
  METHODS
  children and adolescents.
  
  
  METHODS
  Europe. Comparators: methylphenidate (MPH), atomoxetine (ATX), and dexamphetamine (DEX). Electronic databases and relevant conference proceedings were searched for randomized, controlled clinical trials evaluating efficacy and safety of at least one of the comparators and LDX. Quality assessments for each included trial were performed using criteria recommended by the Centre for Reviews and Dissemination. Network meta-analysis methods for dichotomous outcomes were employed to evaluate treatment efficacy.
  
  
  METHODS
  Response, as defined by either a reduction from baseline of at least 25% in the ADHD Rating Scale [ADHD-RS] total score or, separately, as assessed on the Clinical Global Impression-Improvement [CGI-I] scale, and safety (all-cause withdrawals and withdrawal due to adverse events).
  
  
  RESULTS
  The systematic review found 32 trials for the meta-analysis, including data on LDX, ATX, and different formulations of MPH. No trials for DEX meeting the inclusion criteria were found. Sufficient data were identified for each outcome: ADHD-RS, 16 trials; CGI-I, 20 trials; all-cause withdrawals, 28 trials; and withdrawals due to adverse events, 27 trials. The relative probability of treatment response for CGI-I (95% confidence intervals [CI]) for ATX versus LDX was 0.65 (0.53-0.78); for long-acting MPH versus LDX, 0.82 (0.69-0.97); for intermediate release MPH versus LDX, 0.51 (0.40-0.65); and for short-acting MPH versus LDX, 0.62 (0.51-0.76). The relative probabilities of ADHD-RS treatment response also favored LDX.
  
  
  CONCLUSIONS
  For the treatment of ADHD, the synthesis of efficacy data showed statistically significant better probabilities of response with LDX than for formulations of MPH or ATX. The analysis of safety data proved inconclusive due to low event rates. These results may be limited by the studies included, which only investigated the short-term efficacy of medications in patients without comorbid disorders.
authors.affiliation: BresMed Health Solutions , Sheffield , UK.
authors.forename: N S
authors.initials: NS
authors.lastname: Roskell
authors.forename: J
authors.initials: J
authors.lastname: Setyawan
authors.forename: E A
authors.initials: EA
authors.lastname: Zimovetz
authors.forename: P
authors.initials: P
authors.lastname: Hodgkins
mesh_terms: D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use*; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D002648:Child; D003913:Dextroamphetamine / Q000627:therapeutic use*; D018765:Dopamine Uptake Inhibitors / Q000627:therapeutic use*; D005060:Europe; D006801:Humans; D000069478:Lisdexamfetamine Dimesylate; D008774:Methylphenidate / Q000627:therapeutic use*; D015233:Models, Statistical; D011437:Propylamines / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D011437:Propylamines; D008774:Methylphenidate; D000069445:Atomoxetine Hydrochloride; D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine
keywords: Adolescent; Atomoxetine; Attention deficit hyperactivity disorder; Child; Lisdexamfetamine dimesylate; Meta-analysis; Methylphenidate