Background     Stimulants are amphetamines or amphetamine-like drugs. These include illegal substances such as cocaine and illegally manufactured and distributed methamphetamine, as well as the prescription medications methylphenidate and dextroamphetamine that are used for a variety of FDA-approved and off-label indications (e.g., attention–deficit/hyperactivity disorder [ADHD], cancer-related fatigue) (1). Rates of stimulant misuse and stimulant use disorders (StUDs) are rising, and stimulants are involved in 32% of fatal overdose deaths (2,3). This Fast Fact discusses assessment and management strategies for patients with a serious illness who are impacted by nonmedical stimulant use and/or StUD.

Definitions    StUD is a pattern of regular stimulant use (whether prescription, methamphetamine, and/or cocaine) that leads to clinically significant impairment in functioning or distress within a 12-month period (4). As with other substance use disorders, StUD criteria include a persistent desire to use, inability to cut down or control use, cravings, and use leading to recurrent social or interpersonal consequences that impact quality of life (4). While tolerance and withdrawal are included as diagnostic criteria for StUD, these clinical manifestations are not diagnostic of StUD in isolation. Nonmedical stimulant use refers to the use of prescribed or non-prescribed stimulants in ways that are not sanctioned by a prescriber, or are otherwise dangerous or harmful, without such use meeting criteria for StUD.

Assessment   When assessing stimulant use, clinicians should utilize open-ended, nonjudgemental questions and perform a comprehensive substance use history. They should also examine for comorbid psychiatric conditions as you would for any other assessment of a substance use disorder (5-7). Many psychostimulants are controlled 2 substances (e.g., methylphenidate, dextroamphetamine); as such, when prescribing psychostimulants, clinicians should utilize best safe prescribing practices such as reviewing state prescribing databases and scheduling frequent visits (8).

Management of stimulant use disorder     Promotion of recovery as well as support in use reduction for patients with StUD can have a positive impact on quality of life (9). Treatment of co-occurring substance use disorders (e.g., alcohol, opioid) and psychiatric conditions is essential and provides opportunity to improve patients’ lives even if treatment of StUD is less effective (10). 

• Non-pharmacologic treatments: Strong evidence supports behavioral strategies as first-line treatments for StUDs. These include contingency management (a type of learning in which positive behaviors are incentivized and reinforced), motivational interviewing, and cognitive behavioral therapy (6), usually provided by a psychotherapist or substance use treatment counselor. Access to these resources in the community, however, can be limited.
• Pharmacologic treatments: Unlike opioid use disorder, there are no approved medications to treat StUD. The American Society of Addiction Medicine/American Academy of Addiction Psychiatry (ASAM/AAAP) provide evidence-based recommendations for the off-label use of medications for StUD (6). Mirtazapine, topiramate, bupropion, naltrexone, sustained release methylphenidate, and bupropion-naltrexone in combination have shown promise (7,11,12).  For the most part, prescription of these treatments for StUD are provided by psychiatrists and addiction specialists.

Management considerations in palliative care    There is need for more evidence-based guidelines to aid clinicians when caring for patients impacted by symptoms from a serious illness who have concomitant substance misuse and/or substance use disorders including StUD. Pain management in a patient with a serious illness and StUD for whom opioids are appropriate can be especially challenging.  Management strategies include optimization of non-opioids for pain, treating psychiatric comorbidities, and collaboration with addiction medicine/psychiatry when possible (5). ASAM/AAAP guidelines support the careful use of prescription stimulants to treat ADHD even in patients with StUD.  Among a cohort of palliative care and addiction experts, continuing opioids for cancer-related pain with increased monitoring (e.g., more frequent visits, short-course prescriptions) was felt to be appropriate for some patients with advanced cancer and evidence of nonmedical stimulant use via urine drug testing, regardless of prognosis (13). However, it is unclear how clinicians should navigate prescribing opioids when indicated for symptom management in patients with severe StUD. Clinicians must make individualized treatment decisions to balance the risks and benefits of opioids for someone with high-risk stimulant use. It is also important to use patient-first language when discussing addiction with patients (see Fast Fact #429) and to optimize support from the multidisciplinary team, which can include social workers, chaplains, and peer addiction support specialists when available, to address stigma and existential contributions to suboptimally controlled symptoms (14). To reduce the risk of psychostimulant diversion, the FDA has published resources for patients, families, clinicians, and hospice agencies regarding the safe disposal of controlled substances such as psychostimulants should the patient not need the medication anymore (8).

Conclusions:    Nonmedical stimulant use, misuse of prescription stimulants, and/or StUDs present unique challenges for patients with serious illness. Appropriate screening, awareness of treatment strategies, collaboration with addiction and behavioral medicine experts in a transdisciplinary team model, and judicious safe prescribing practices are essential clinician skills.

References 

1. Mücke M, Mochamat M, Cuhls H, et al. Pharmacological treatments for fatigue associated with palliative care. Cochrane Database Syst Rev. 2015 May 30;2015(5):CD006788. doi: 10.1002/14651858.CD006788.pub3.
2. Friedman J, Shover CL. Charting the fourth wave: Geographic, temporal, race/ethnicity and demographic trends in polysubstance fentanyl overdose deaths in the United States, 2010-2021. Addiction. 2023 Dec;118(12):2477-2485. doi: 10.1111/add.16318.
3. Han B, Jones CM, Volkow ND, et al. Prescription stimulant use, misuse, and use disorders among US adults aged 18 to 64 years. JAMA Psychiatry. 2025 Mar 19:e250054.
4. American Psychiatric Association. (2022). Substance-Related and Addictive Disorders. In Diagnostic and Statistical Manual of Mental Disorders (5th ed., text rev.).
5. Substance Abuse and Mental Health Services Administration. (2020). Treatment of Stimulant Use Disorders. Available at:  https://store.samhsa.gov/sites/default/files/SAMHSA_Digital_Download/PEP20-06-01-001_508.pdf. Accessed Sept 6, 2025.
6. Clinical Guideline Committee (CGC) Members; ASAM Team; AAAP Team; IRETA Team. The ASAM/AAAP Clinical Practice Guideline on the Management of Stimulant Use Disorder. J Addict Med. 2024 May-Jun 01;18(1S Suppl 1):1-56. doi: 10.1097/ADM.0000000000001299.
7. Coffin PO, Suen LW. Methamphetamine toxicities and clinical management. NEJM Evidence. 2023;2(12):EVIDra2300160. doi:10.1056/EVIDra2300160.
8. US FDA.  Prescription stimulant medications: information about FDA’s work to support appropriate use and address the impact of stimulant-related risks, including misuse, addiction, overdose, and diversion.  Updated 7/29/24. Available at:  https://www.fda.gov/information-drug-class/prescription-stimulant-medications.
9. Amin-Esmaeili M, Farokhnia M, Susukida R, et al. Reduced drug use as an alternative valid outcome in individuals with stimulant use disorders: Findings from 13 multisite randomized clinical trials. Addiction. 2024 May;119(5):833-843. doi: 10.1111/add.16409.
10. Perusinghe M, Chen KY, McDermott B. Evidence-based management of depression in palliative care: a systematic review. J Palliat Med. 2021 May;24(5):767-781. doi: 10.1089/jpm.2020.0659.
11. Trivedi MH, Walker R, Ling W, et al. Bupropion and naltrexone in methamphetamine use disorder. N Engl J Med. 2021 Jan 14;384(2):140-153. doi: 10.1056/NEJMoa2020214.
12. Chan B, Kondo K, Freeman M, et al. Pharmacotherapy for cocaine use disorder-a systematic review and meta-analysis. J Gen Intern Med. 2019 Dec;34(12):2858-2873. doi: 10.1007/s11606-019-05074-8.
13. Jones KF, Khodyakov D, Han BH, et al. Expert consensus-based guidance on approaches to opioid management in individuals with advanced cancer-related pain and nonmedical stimulant use. Cancer. 2023 Dec 15;129(24):3978-3986. doi: 10.1002/cncr.34921. Epub 2023 Sep 11. Erratum in: Cancer. 2024 May 15;130(10):1894.
14. Ho J, Nickels K, Childers J. 7Ps: An organized approach to opioid management for patients with OUD and painful serious illness. J Pain Symptom Manage. 2024 May;67(5):e548.

Authors’ Affiliations: University of Utah, Salt Lake City, UT. 
Conflicts of Interest: The authors have not disclosed any relevant conflicts of interest.
Version History:  Originally edited by Drew A Rosielle MD; first electronically published in September 2025.