The Effect of Stimulant Medications on Symptom and Treatment Outcomes in Adults With Comorbid Attention-Deficit/Hyperactivity and Substance Use Disorder: A Systematic Review and Meta-Analysis

Objective Symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) are increasingly recognized among adults and frequently co-occur with substance use disorders (SUD). Changing guidelines and complexity of treatment merit a review of approaches for managing this diagnostic overlap among adults. Methods We conducted a systematic review for randomized controlled trials (RCT) and nonrandomized comparative studies (NRCS) focused on the benefits and harms of non-stimulant/nonpharmacological ADHD treatment compared to psychostimulant medications for those with comorbid ADHD and SUD by searching: Medline (via PubMed), Embase, and PsycINFO from inception to December 14, 2023, the Cochrane library from inception to January 30, 2024, and ClinicalTrials.gov from inception to February 23, 2024. After screening, evidence from eligible studies was qualitatively and quantitatively synthesized by a multidisciplinary team of researchers and clinicians. Results Of 6,419 unique records screened, six RCTs and one NRCS were eligible for review, analyzing a total of N = 662 people. There was no evidence of differences in ADHD treatment adherence, substance use, SUD symptom change, or substance abstinence in people with co-occurring ADHD and SUD who were not prescribed stimulant medications compared to people prescribed stimulants (low confidence for all). No significant difference was observed in the proportion of individuals with improved scores on the Clinical Global Improvement scale based on a pooled analysis of three studies (pooled OR = 1.27 [0.32, 5.09]). Although trending in a clinically positive direction, studies provide insufficient evidence (no conclusion) for ADHD symptom change, SUD treatment adherence, medication misuse/diversion, and measures of depression and anxiety. There was no evidence of a difference in various measures of adverse events (strength of evidence not assessed). Conclusions Significant limitations in the evidence base prevent the ability to draw substantial conclusions, and additional inquiry is recommended in future research. Available data, while limited, may indicate increased maintenance in SUD treatment for long-acting stimulants, and there is insufficient data to support the efficacy of non-stimulants for ADHD treatment in SUD patients. Though literature is minimal, a cautious interpretation suggests that current evidence does not support concerns that stimulant medications can precipitate substance-related problems in adults with co-occurring SUD and ADHD.