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Atomoxetine Versus Placebo for Cognitive Deficits in Stimulant Use Disorder: A Systematic Review.

Douglas Barroso·Martin Kotochinsky·Mateus Rodrigues Alessi·Wellgner Fernandes Oliveira Amador·Diogo Carrazzoni Godoi·Rohan Sabloak·Samuel Izaias Dos Santos Pereira·Yusuf-Zain Ansari·Karolina Guedes Amorim·Gabriel Barbosa·Alvaro Texeira
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Abstract

BACKGROUND: Stimulant use disorder (StUD), particularly involving cocaine and amphetamines, is associated with significant cognitive impairments that impede recovery and increase relapse risk. Atomoxetine, a selective norepinephrine reuptake inhibitor, has been proposed as a potential treatment given its role in enhancing executive function and its established efficacy in attention-deficit/hyperactivity disorder (ADHD). This systematic review aimed to evaluate the efficacy, cognitive, and mood effects of atomoxetine compared with placebo in individuals with StUD. METHODS: A comprehensive literature search of PubMed, Cochrane CENTRAL, and Embase databases was conducted to identify randomized controlled trials (RCTs) evaluating atomoxetine for StUD. Eligible studies compared atomoxetine with placebo and assessed outcomes related to cognition (attention and response inhibition), stimulant use or abstinence, mood symptoms, and safety. Data were extracted and synthesized qualitatively due to methodological heterogeneity across studies. RESULTS: Nine RCTs met the inclusion criteria. Findings on cognitive outcomes were inconsistent: Some studies reported improvements in attentional bias and inhibitory control, while others showed no significant effects. Atomoxetine did not significantly reduce stimulant use, craving, or sustain abstinence compared with placebo. Limited mood-related benefits were observed, particularly among male participants, although results were variable. Across studies, atomoxetine was well tolerated, with most adverse events mild and transient. CONCLUSION: Despite a compelling neurobiological rationale and evidence of modest cognitive and mood benefits, atomoxetine has not demonstrated consistent efficacy as a monotherapy for StUD. Its favorable safety profile may warrant further investigation in carefully defined populations, such as individuals with comorbid ADHD or in combination with behavioral interventions.

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Atomoxetine HydrochlorideHumansAdrenergic Uptake InhibitorsCognitive DysfunctionCognitive EnhancementCentral Nervous System StimulantsAttention Deficit Disorder with HyperactivityRandomized Controlled Trials as TopicCocaine-Related DisordersAmphetamine-Related Disordersamphetaminesatomoxetinecocainecognitionexecutive functionnorepinephrinestimulant use disordersystematic reviewSystematic ReviewJournal ArticleReview

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Douglas Barroso, Martin Kotochinsky, Mateus Rodrigues Alessi, Wellgner Fernandes Oliveira Amador, Diogo Carrazzoni Godoi, Rohan Sabloak, Samuel Izaias Dos Santos Pereira, Yusuf-Zain Ansari, Karolina Guedes Amorim, Gabriel Barbosa, Alvaro Texeira. 2026-05-29. Atomoxetine Versus Placebo for Cognitive Deficits in Stimulant Use Disorder: A Systematic Review.. https://doi.org/10.1177/29767342261443842

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Amphetamine-Related Disorders subjectCocaine subjectCocaine-Related Disorders subjectCognition subjectCognitive Dysfunction subjectCognitive Enhancement subjectExecutive Function subjectHumans subjectJournal Article subjectSystematic Review; Journal Article; Review resourceSystematic reviews study

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