For children with attention deficit-hyperactivity disorder (ADHD), use of prescription stimulant medication to manage their symptoms was not associated with later substance use, according to a longitudinal analysis.
Using a causal analytic method to account for age and other time-varying characteristics, including household income, behavior problems, and parental support, there was no evidence showing that current (B range -0.62 to 0.34) or prior stimulant treatment (B range -0.06 to 0.70) or their interaction (B range -0.49 to 0.86) were associated with substance use in adulthood, reported Brooke Molina, PhD, of the University of Pittsburgh, and co-authors.
Models adjusting for confounding by demographic, clinical, and familial factors also showed no evidence that more years of stimulant treatment (B range -0.003 to 0.04) or continuous, uninterrupted stimulant treatment (B range -0.25 to -0.03) were associated with later substance use, including heavy drinking, marijuana use, and daily cigarette smoking, among other substance uses, they noted in .
Similar results were also observed for substance use disorder.
"Parents and providers can be reassured that we found no evidence of increased risk of substance use or substance use disorder when children are prescribed stimulant medications for ADHD," Molina told 鶹ý.
"Because this study took into account the many reasons that medication and substance use may seem connected, it extended the literature base in an important way," she added. "For example, just age alone is associated with decreased use of prescribed stimulant medication and increased substance use over time, which can make them correlated for reasons besides one causing the other."
Molina and co-authors used prospective longitudinal data from the randomized Multimodal Treatment Study of ADHD (MTA), which followed patients with ADHD over a 16-year period from childhood through adolescence into early adulthood.
"We know, from multiple studies, including several others from the MTA, that ADHD is a risk factor for substance use disorders," Molina said. In their introduction, the authors noted that "early exposure to stimulants may cause neurobiological and behavioral sensitization to other drugs and thus increase the risk for harmful substance use."
However, "our confidence is now increased that prescribing stimulants in childhood does not contribute to this problem," Molina said.
"Parents and providers should remember that ADHD is a chronic condition that needs treatment throughout life. Stimulant medication, along with other treatments like parent and teacher training and individual and group therapies for adults, should regularly be considered to maximize the best outcomes, including reducing risk of substance use disorder," she continued.
MTA was conducted at six sites in the U.S. and one site in Canada. It was initially designed to be a 14-month randomized clinical trial of medication and behavior therapy for ADHD, but the study eventually transitioned into a longitudinal observational study. Participants were enrolled from 1994 through 1996.
In total, the researchers included 579 children (mean age at baseline 8.5). Participants were mostly male (80%) and white (61%). Children ages 7 to 9 with DSM-IV combined-type ADHD were repeatedly assessed until a mean age of 25 years.
Stimulant treatment for ADHD was measured prospectively from baseline for 16 years, for a total of 10 assessments, first using parent report, and then young adult report.
The proportion of adolescents using stimulant medication decreased through adolescence, from close to 60% at the 2- and 3-year assessments to 7.2% on average in early adulthood.
Mean percentages across the 12-, 14-, and 16-year follow-up assessments were 36.5% for daily smoking, 29.6% for marijuana use at least weekly, 21.1% for heavy drinking at least weekly, and 6.2% for other substance use at least monthly.
Limitations included a lack of medical records to verify medication history, Molina and team noted. Furthermore, they said, though the study sample included females (20%) and African Americans (20%) and Hispanics (8%), the study was "insufficiently powered for a strong test of moderation by sex, race, or ethnicity."
Disclosures
The Multimodal Treatment Study of Children with ADHD was a National Institute of Mental Health (NIMH) cooperative agreement randomized clinical trial, continued under an NIMH contract as a follow-up study and finally under a National Institute on Drug Abuse contract followed by a data analysis grant.
Molina reported grants from the NIMH and National Institute on Drug Abuse during the conduct of the study. Co-authors reported multiple relationships with various government entities, foundations, and pharmaceutical companies.
Primary Source
JAMA Psychiatry
Molina BSG, et al "Association between stimulant treatment and substance use through adolescence into early adulthood" JAMA Psychiatry 2023; DOI: 10.1001/jamapsychiatry.2023.2157.