Effectiveness of Atomoxetine and Stimulant Combination in Attention-Deficit/Hyperactivity Disorder (ADHD) Treatment: A Systematic Review
Abstract
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that can present with inattention, impulsivity, hyperactivity, or any combination of the three. For ADHD treatment, stimulants are widely considered first-line medications, with methylphenidate formulations being the most commonly prescribed. In patients who do not tolerate stimulants at higher doses, non-stimulant augmentation is a potential treatment strategy. Atomoxetine, as the first approved non-stimulant for ADHD by the United States Food and Drug Administration, has also been evaluated in several studies for combination therapies over the years. This review aims to investigate the effectiveness of combining stimulants such as methylphenidate with atomoxetine based on all newer studies, which came after the last major systematic review published in 2013. Six retrospective studies were included based on eligibility criteria among all studies published from 2012 to 2024 that were relevant to the research question. Three out of the six studies contained data regarding efficacy: one reported no significant difference in ADHD severity reduction between atomoxetine monotherapy and combination therapy overall, while two reported significantly decreased ADHD severity among treatment-resistant monotherapy patients after switching to combined methylphenidate and atomoxetine therapy. Four out of the six studies measured adherence: three reported significantly greater adherence with combined therapy…
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