PHARMACOTHERAPIES FOR CO-OCCURRING STIMULANT USE DISORDER AND ADHD: A NETWORK META-ANALYSIS

Importance: Stimulant use disorder (StUD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur, complicating treatment decisions and raising concerns regarding stimulant prescribing. Evidence guiding pharmacologic management of individuals with both conditions remains limited.

Objective

To evaluate the efficacy and safety of pharmacotherapies for adults with cooccurring StUD and ADHD using network meta-analysis. Data Sources: PubMed, Embase, Scopus, Web of Science, and ClinicalTrials.gov were searched through January 28, 2026 for randomized controlled trials (RCTs). Study Selection: Eligible studies were RCTs enrolling adults with both StUD and ADHD; six trials published between 2002 and 2015 met inclusion criteria. Data Extraction and Synthesis: Outcomes included stimulant abstinence, negative urine toxicology, ADHD symptom severity, and global clinical improvement. Interventions were methylphenidate, mixed amphetamine salts (MAS), and bupropion. Random-effects network meta-analyses were conducted using standardized mean differences (SMDs) and odds ratios (ORs); treatment ranking was assessed with P-scores.

Results

Higher-dose stimulant regimens demonstrated superior outcomes across multiple domains. MAS showed the greatest benefit for continuous abstinence versus placebo (OR = 8.45; 95% CI, 2.55–27.98; p = 0.0005), with the 80-mg dose ranking highest (P-score = 0.87). Pharmacotherapy also increased the odds of negative urine toxicology (OR = 1.65; 95% CI, 1.01–2.71; p = 0.05), again favoring higher-dose MAS (P-score = 0.93). ADHD symptoms were significantly reduced overall (SMD = –0.59; 95% CI, –0.94 to –0.23; I² = 43%), with the greatest improvement observed for methylphenidate 180 mg (P-score = 0.91). CGI improvement did not differ significantly from placebo. Lower-dose methylphenidate and bupropion demonstrated smaller or inconsistent effects. Adverse events were generally mild to moderate and comparable to placebo.

Conclusions

In adults with co-occurring StUD and ADHD, stimulant-based pharmacotherapies, particularly higher-dose MAS and methylphenidate, were associated with improved stimulant-use outcomes and ADHD symptom control. These findings support consideration of optimized stimulant dosing with careful monitoring in this population, while highlighting the need for larger, contemporary trials.