• Derek J Baughman, Crista M Watson, Jonathan W Beich, May N Joresa Herboso, Liana K Cuttie, and Ari-Beth C Marlyne.
• Medical Director-Primary Care, Barksdale AFB, 2nd Medical Group, Barksdale AFB, LA 71110, USA.
• Mil Med. 2024 May 18; 189 (5-6): e1343e1352e1343-e1352.

IntroductionIn addition to the higher burden of mental health disease in the military, there is a compounding antecedent association between behavioral health comorbidities and the treatment of attention-deficit/hyperactivity disorder (ADHD) in this population. Despite the low prevalence of new-onset ADHD in adults globally, the rate of stimulant (i.e., amphetamines) prescription is increasing. Stimulants can exacerbate mental health disease (often masquerading as ADHD symptomatology), precluding optimal treatment of the underlying etiology and imposing unnecessary dangerous side effects. This study aimed to evaluate the long-term safety and efficacy of stimulants for managing adult ADHD.MethodsA nine-member multidisciplinary team reviewed a PubMed search with the terms "adult," "ADHD," and "stimulant." Targeted PubMed and Google Scholar searches for "adult ADHD" paired with Food and Drug Administration -approved ADHD medications and Google Scholar literature using forward and reverse snowballing methods were performed for high-quality studies focusing on long-term treatment in ADHD. An evidence table and clinical algorithm were developed from the review.ResultsOf the 1,039 results, 50 articles were fully reviewed, consisting of 21 descriptive and experimental studies, 18 observational, and 11 systematic reviews and meta-analyses. Illustrative cases within the structured discussion of the results highlighted ADHD and psychiatric comorbidities, risks, harms, and benefits of stimulant use, medication mechanisms of action, and limitations of the current evidence.DiscussionThe dearth of high-quality studies on long-term ADHD management in adults fails to establish a causal relationship between stimulant use and physiological harm. Despite mixed evidence supporting the benefit of stimulants, there is clear evidence regarding the risk of harm. The serious risks of stimulants include arrhythmias, myocardial infarction, stroke/transient ischemic attack, sudden death, psychosis, and worsening of behavioral health disease. Additionally, there is a possible long-term risk of harm due to chronic sympathetic load (i.e., cardiovascular system remodeling). Stimulants pose a greater risk for addiction and abuse compared to other evidence-based nonstimulant medications that have similar effectiveness. Both stimulants and nonstimulants might promote favorable neuroanatomical changes for long-term improvement of ADHD symptoms, but nonstimulants (atomoxetine) have the pharmacological advantage of also mitigating the effects of sympathetic load (sympatholysis) and anxiety (anxiolysis). Given the physiological uncertainty of extended stimulant use for adults, especially older adults with vulnerable cardiovascular systems, clinicians should proceed cautiously when considering initiating or sustaining stimulant therapy. For long-term treatment of ADHD in adults, clinicians should consider nonstimulant alternatives (including behavioral therapy) due to the comparatively lower side effect risk and the possible additional benefit in patients with behavioral health comorbidities.ConclusionLong-term safety of stimulant use for adults with ADHD is uncertain, as existing studies are limited in quality and duration. This is particularly important for military populations with higher rates of mental health conditions. Managing ADHD and related conditions requires prioritizing cardiovascular safety, especially for older adults. Nonstimulant options can be helpful, especially in comorbid psychiatric disease. Before treating ADHD, ruling out and controlling other behavioral health conditions is essential to avoid masking or worsening underlying issues and reducing unnecessary medication side effects.© The Association of Military Surgeons of the United States 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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