Atomoxetine Versus Placebo for Cognitive Deficits in Stimulant Use Disorder: A Systematic Review
Douglas Barroso1, Martin Kotochinsky2, Mateus Rodrigues Alessi3
1Department of Medicine, State University of Santa Cruz, Ilhéus, Brazil.
Substance Use & Addiction Journal
|May 29, 2026
Summary
Atomoxetine shows modest cognitive and mood benefits for stimulant use disorder (StUD) but does not consistently improve abstinence or reduce use. Further research in specific populations is suggested due to its safety profile.
Area of Science:
- Neuroscience
- Psychiatry
- Pharmacology
Background:
- Stimulant use disorder (StUD) presents significant cognitive challenges, hindering recovery.
- Atomoxetine, a norepinephrine reuptake inhibitor, is explored for its potential to improve executive function in StUD.
- Atomoxetine is approved for attention-deficit/hyperactivity disorder (ADHD).
Purpose of the Study:
- To systematically review the efficacy of atomoxetine versus placebo in treating StUD.
- To assess atomoxetine's impact on cognitive function, stimulant use, and mood in StUD patients.
- To evaluate the safety and tolerability of atomoxetine for StUD.
Main Methods:
- A systematic literature search was performed across major databases (PubMed, Cochrane CENTRAL, Embase).
- Included studies were randomized controlled trials (RCTs) comparing atomoxetine with placebo.
- Outcomes assessed included cognition, stimulant use, abstinence, mood, and safety; data were synthesized qualitatively.
Main Results:
- Nine RCTs were included, showing inconsistent effects on cognitive outcomes like attention and inhibition.
- Atomoxetine did not significantly improve abstinence rates or reduce stimulant use compared to placebo.
- Limited mood benefits were observed, particularly in males; atomoxetine was generally well-tolerated with mild adverse events.
Conclusions:
- Atomoxetine lacks consistent efficacy as a monotherapy for StUD, despite theoretical benefits.
- Its safety profile suggests potential utility in specific populations, such as those with comorbid ADHD.
- Combination therapy with behavioral interventions may warrant further investigation.
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