A Systematic Review of Combination Therapy with Stimulants and Atomoxetine for Attention-Deficit/Hyperactivity Disorder, Including Patient Characteristics, Treatment Strategies, Effectiveness, and Tolerability

1 Neuroscience Research, Eli Lilly and Company , Budapest, Hungary .
Journal of child and adolescent psychopharmacology (Impact Factor: 2.93). 04/2013; 23(3). DOI: 10.1089/cap.2012.0093
Source: PubMed


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.

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.

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.

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.

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Available from: Héctor Dueñas, Sep 07, 2015
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    • "Together, these results argue for a potentially useful role for ATO in decreasing relapse-related behaviors versus attenuating the acute rewarding effects of drugs of abuse, and further investigations will be needed to better characterize the therapeutic effects of ATO. However, promising research aimed at quantifying combined treatment effects has shown that using ATO as an adjunctive treatment to the standard treatment for ADHD has yielded better outcomes than standard treatment alone (Treuer et al. 2013; Holzer et al. 2013). Additionally, other research found that substance abuse relapse prevention counseling supplemented with ATO maintained longer abstinence than counseling by itself (Benegal et al. 2013). "
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