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Jump to Key Points Stimulant-based pharmacotherapies were associated with significant alleviation of symptoms in patients with co-occurring attention-deficit/hyperactivity disorder (ADHD) and stimulant use disorder compared with placebo, new research suggested.
A meta-analysis of six randomized controlled trials (RCTs) and more than 400 adult patients with both disorders showed that methylphenidate and mixed amphetamine salts (MAS), especially high-dose methylphenidate, were linked to greater improvement in ADHD symptoms than placebo.
High-dose MAS was also linked to greater odds of achieving continuous abstinence from stimulants. Although pharmacotherapy as a whole was associated with increased odds of stimulant-negative urine tests, high-dose MAS was linked to the greatest increase in negative tests.
Additionally, safety outcomes were comparable between the active treatment and placebo groups.
- Stimulant pharmacotherapy improved ADHD symptoms vs placebo in comorbid stimulant use disorder.
- Methylphenidate and MAS showed benefit; high-dose methylphenidate strongest for ADHD symptoms.
- High-dose MAS had highest odds of stimulant abstinence and negative urine tests.
- Overall safety similar to placebo; insomnia and ↓ appetite were more frequent.
- Optimized stimulant dosing may help, but misuse/diversion monitoring remains essential.
“These findings support consideration of optimized stimulant dosing” when treating these co-occurring conditions, Henrique N.P. Oliva, MD, PhD, Department of Psychiatry at Yale University School of Medicine, New Haven, Connecticut, and colleagues wrote.
However, “further trials are warranted to refine clinical recommendations,” they added.
The findings were published online on August 31 in The Journal of Clinical Psychiatry.
Substantial Treatment ‘Gap’
ADHD often co-occurs with various substance use disorders. In fact, ADHD prevalence is around 20% vs 6.8% in adults with cocaine and methamphetamine use disorders vs the general population, the investigators noted.
There are currently no FDA-approved pharmacotherapies for stimulant use disorder, although various options are used off-label, which makes clinical management of the co-occurring conditions challenging, they added.
In their network meta-analysis, the researchers included six RCTs that assessed treatments for comorbid ADHD and stimulant use disorder in 456 total patients. These treatments included methylphenidate, MAS, and bupropion.
Results showed superior outcomes for both higher-dose methylphenidate and MAS.
MAS was linked to greater odds of achieving abstinence than placebo (odds ratio [OR], 8.45; P = .0005), and its 80-mg dose was ranked highest for abstinence within the network meta-analysis framework (P-score = .846).
Pharmacotherapy overall showed increased odds of negative urine tests over the treatment period (OR, 1.65; P = .05), with the highest probability linked to the 80-mg MAS dose (P-score = .89).
Pathway to Better Outcomes?
ADHD symptom severity was also significantly improved with pharmacologic treatment as a whole vs control treatment (standardized mean difference, -0.59; P = .001), with the greatest improvement linked to the methylphenidate 180-mg dose (P-score = .899).
There were no significant differences in overall clinical global impression scores between the treatment and control groups, but heterogeneity was deemed substantial.
Although five of six trials showed no retention rate differences between active and placebo groups, one study did show higher retention for participants receiving methylphenidate (51 vs 18 days; P = .001).
There were higher risks for the pharmacologic treatments than for placebo for insomnia (risk ratio [RR], 2.37; P = .002) and decreased appetite (RR, 3.11; P = .04); however, there were no significant between-group differences for other adverse events, including headache, nausea, fatigue, dry mouth, or elevated blood pressure.
For adults with both co-occurring conditions, “optimized dose stimulant pharmacotherapy may improve ADHD symptoms and stimulant use outcomes but should be paired with careful monitoring for insomnia, decreased appetite, cardiovascular effects, and misuse or diversion,” the investigators wrote.
“ADHD symptom improvement may be one pathway through which stimulant pharmacotherapy supports reductions in stimulant use, but prospective studies are needed to clarify this relationship,” they added.
The study was funded by the National Institute on Drug Abuse and by the State of Connecticut, Department of Mental Health and Addiction Services. Disclosure information for the study investigators is available in the original study publication.
