title: A systematic review of combination therapy with stimulants and atomoxetine for attention-deficit/hyperactivity disorder, including patient characteristics, treatment strategies, effectiveness, and tolerability.
abstract: OBJECTIVE
  The purpose of this article was to systematically review the literature on stimulant and atomoxetine combination therapy, in particular: 1) Characteristics of patients with attention-deficit/hyperactivity disorder (ADHD) given combination therapy, 2) treatment strategies used, 3) efficacy and effectiveness, and 4) safety and tolerability.
  
  
  METHODS
  Literature databases (MEDLINE(®), EMBASE, Cochrane Central Register of Controlled Trials, Science Citation Index Expanded, and SciVerse Scopus) were systematically searched using prespecified criteria. Publications describing stimulant and atomoxetine combination therapy in patients with ADHD or healthy volunteers were selected for review. Exclusion criteria were comorbid psychosis, bipolar disorder, epilepsy, or other psychiatric/neurologic diseases that could confound ADHD symptom assessment, or other concomitant medication(s) to treat ADHD symptoms.
  
  
  RESULTS
  Of the 16 publications included for review, 14 reported findings from 3 prospective studies (4 publications), 7 retrospective studies, and 3 narrative reviews/medication algorithms of patients with ADHD. The other two publications reported findings from two prospective studies of healthy volunteers. The main reason for prescribing combination therapy was inadequate response to previous treatment. In the studies of patients with ADHD, if reported, 1) most patients were children/adolescents and male, and had a combined ADHD subtype; 2) methylphenidate was most often used in combination with atomoxetine for treatment augmentation or switch; 3) ADHD symptom control was improved in some, but not all, patients; and 4) there were no serious adverse events.
  
  
  CONCLUSIONS
  Published evidence of the off-label use of stimulant and atomoxetine combination therapy is limited because of the small number of publications, heterogeneous study designs (there was only one prospective, randomized controlled trial), small sample sizes, and geographic bias. Existing evidence suggests, but does not confirm, that this drug combination may benefit some, but not all, patients who have tried several ADHD medications without success.
authors.affiliation: Neuroscience Research, Eli Lilly and Company, Budapest, Hungary. treuert@lilly.com
authors.forename: Tamás
authors.initials: T
authors.lastname: Treuer
authors.forename: Susan Shur-Fen
authors.initials: SS
authors.lastname: Gau
authors.forename: Luis
authors.initials: L
authors.lastname: Méndez
authors.forename: William
authors.initials: W
authors.lastname: Montgomery
authors.forename: Julie A
authors.initials: JA
authors.lastname: Monk
authors.forename: Murat
authors.initials: M
authors.lastname: Altin
authors.forename: Shenghu
authors.initials: S
authors.lastname: Wu
authors.forename: Chaucer C H
authors.initials: CC
authors.lastname: Lin
authors.forename: Héctor J
authors.initials: HJ
authors.lastname: Dueñas
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D004359:Drug Therapy, Combination; D006801:Humans; D011437:Propylamines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000697:Central Nervous System Stimulants; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride
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