The report is a product of the VA/HSR Evidence Synthesis Program.

ADHD and Substance Use Disorders in Adults: A Systematic Review

Takeaway: Rates of attention-deficit/hyperactivity disorder (ADHD) diagnoses among Veterans are increasing. The overall literature did not identify broad evidence of harm associated with the prescription of stimulants for people with ADHD. There are limited data about misuse and diversion of stimulant medications in people with ADHD. Prescribers should consider stimulant medications or other treatments for ADHD after a thorough, individualized discussion of risks versus benefits, and prescriptions should include broad education about the risks of diversion and/or misuse of these medications.

Over the past decade, there has been an increase in the documented prevalence and incidence of attention-deficit/hyperactivity disorder (ADHD) among adults. Prescription psychostimulants are first-line pharmacologic treatments for ADHD in adults. However, there is concern for misuse and diversion of psychostimulants, and concern that these medications may lead to a new substance use disorder (SUD) diagnosis or precipitate substance-related problems in people with co-occurring SUD and ADHD.

In response to a request from the VHA Office of Mental Health, HSR’s Evidence Synthesis Program (ESP) Center in Providence, RI, conducted a systematic review on the incidence of SUD in adults with ADHD who are prescribed psychostimulant medications, as well as the benefits and harms of psychostimulant treatment of ADHD in adults with co-occurring ADHD and SUD.

ESP investigators searched for peer-reviewed articles in Medline, Embase, and PsycINFO from inception to December 14, 2023.

Summary of Findings

Regarding the effect of stimulants on the incidence of SUD, diversion, and misuse in people with ADHD without SUD at baseline:

• Seven studies examined the incidence of SUD in people with ADHD who were prescribed stimulant medication.
• Among adults prescribed stimulants for ADHD, approximately 1 in 7 is newly diagnosed with SUD, although estimates varied drastically across studies.
• Only 1 small study assessed diversion or misuse of stimulants among people prescribed stimulants for ADHD. Diversion was reported in 11% of people and misuse in 10–31% depending on definition.
• Among people prescribed stimulants for ADHD compared to people with ADHD who are not prescribed stimulants, there is no evidence of a difference in the risk of a new SUD in adulthood.
• Among people prescribed stimulants for ADHD compared to those who are not prescribed stimulants, there is insufficient evidence of a difference in the risk of alcohol-specific use disorders (AUD) or non-alcohol substance use or stimulant use disorders.

Regarding the effect of stimulants on ADHD and SUD symptoms and treatment outcomes in people with co-occurring ADHD and SUD:

• Seven studies compared stimulant treatment to other ADHD treatments in people with both ADHD and SUD.
• Among people with co-occurring ADHD and SUD who are prescribed versus not prescribed stimulants, there is no evidence of a difference in ADHD treatment adherence, substance use, SUD symptom change, and abstinence from substance use.
• Among people with co-occurring ADHD and SUD who are prescribed versus not prescribed stimulants, there is insufficient evidence to assess differences in ADHD symptom change, SUD treatment adherence, medication misuse or diversion, and depression or anxiety.

Implications

Given the increasing rates of ADHD diagnoses in the Veteran population, VA needs to provide guidance and education for clinicians who treat ADHD. The overall literature did not identify broad evidence of harm associated with the prescription of stimulants for people with ADHD. Therefore, prescribers should consider stimulant treatment or other treatments for ADHD after a thorough, individualized discussion of risks versus benefits. Prescriptions should include broad education about the risks of diversion and/or misuse of these medications and may benefit from strategies used in opiate use disorder treatment to reduce these risks (e.g., ongoing toxicology screens and/or use of bottle recall/pill counts).

Limitations

Depending on the key question being addressed, ESP investigators required that outcomes or baseline population include SUD diagnosis rather than just substance use, which might limit generalization of the results of this report to all people with ADHD with substance-related problems. The ESP team also included a variety of ADHD and SUD definitions that might have led to a lack of homogeneity among the symptoms of the people included across the studies. Additionally, many of the included studies used older stimulant medications, which may have greater side effects or misuse potential. Relating to diversion and misuse, the review team included only longitudinal studies and those with outcomes in adult populations, which would have excluded cross-sectional studies or those that focused on misuse or diversion in non-adult populations. Finally, studies that examined outcomes in people with comorbid ADHD and SUD included small sample sizes.

Future Research

Longitudinal data with ample sample size and follow-up are needed to examine the long-term outcomes of stimulant exposure as it relates to substance use. Additional longitudinal data are needed on diversion or misuse outcomes in adulthood. Alternatively, to answer the question of whether ADHD stimulant medication use may impact incidence of SUD, predictive modeling studies may be needed to help identify which people may be at increased risk for SUD outcomes. There is also an opportunity for qualitative research to understand the factors that contribute to diversion and misuse; for sufficiently powered randomized trials of people with ADHD and SUD and modern formulations of stimulants; and for research on people with drug-specific SUDs. Finally, future studies should standardize outcome measures.

Citation:

Rieke K, Sereda Y, Mai HJ, et al. ADHD and Substance Use Disorders in Adults: A Systematic Review. Washington, DC: Evidence Synthesis Program, Health Systems Research, Office of Research and Development, Department of Veterans Affairs. VA ESP Project #22-116; 2024.

To view the full report, go to vaww.hsrd.research.va.gov/publications/esp/adult-adhd.cfm (This report is available via intranet only.).

How can VA leadership work with the ESP? Nominations for systematic review topics may be submitted to the program at any time. When you submit a topic nomination form, ESP Coordinating Center staff will work with you to determine the appropriate research approach and ESP product to address your questions of interest. Topics are selected and assigned to an ESP Center based on program capacity and alignment with VA national goals.

This Management Brief is provided to inform you about recent HSR findings that may be of interest. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. If you have any questions or comments about this Brief, please email CIDER. The Center for Information Dissemination and Education Resources (CIDER) is a VA HSR Resource Center charged with disseminating important HSR findings and information to policy makers, managers, clinicians, and researchers working to improve the health and care of Veterans.

This report is a product of VA/HSR's Evidence Synthesis Program (ESP), which was established to provide timely and accurate synthesis of targeted healthcare topics of particular importance to VA managers and policymakers; and to disseminate these reports throughout VA.

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