ADHD Stimulants Reduce Risk for Cigarette, Drug, Alcohol Use in Adolescents
Contrary to concerns that stimulant medications may increase the risk for subsequent substance abuse in teens, new research suggests that these agents significantly reduce the risk for cigarette smoking as well as alcohol and drug use disorders in adolescent girls with attention-deficit/hyperactivity disorder (ADHD).
In a case-controlled, prospective 5-year follow-up study, investigators at Harvard Medical School in Boston, Massachusetts, found female adolescents treated with stimulant medications for ADHD did not have increased cigarette smoking or substance abuse. In fact, they had more than a 50% decrease in their risk for cigarette smoking and substance use disorders (SUDs).
According to principal investigator Timothy E. Wilens, MD, these findings replicate results of previous research, including a similar study conducted by this group in adolescent boys with ADHD.
“We still have a lack of what I would consider substantial long-term data on stimulant medications in kids. But I think these data, combined with our previous results, are reassuring and show that at least in adolescents, these medications don’t increase the risk of substance abuse and, that in fact, may delay the onset or have a substantial protective effect,” Dr. Wilens told Medscape Psychiatry.
The study is published in the October issue of the Archives of Pediatrics & Adolescent Medicine.
Significant Concerns
Associated with a high risk for comorbid disruptive, mood disorder, and anxiety disorder, ADHD has also been shown to increase the risk for drug and alcohol abuse and dependence.
“We know that in its untreated state ADHD doubles the risk of cigarette smoking and substance abuse over a person’s lifetime,” said Dr. Wilens.
However, stimulants, which are one of the first-line therapies for the disorder, are also potential drugs of abuse, and concerns have been raised by researchers, clinicians, and parents alike that these medications may have the potential to increase the subsequent risk for smoking and drug and alcohol abuse.
“We wanted to determine if stimulant treatment mediated the risk of subsequent substance abuse in girls with ADHD,” said Dr. Wilens.
To examine the effects of early stimulant treatment on the subsequent risk for cigarette smoking and SUDs, the investigators observed 114 female adolescents who met standard diagnostic criteria for ADHD and who were from both pediatric and psychiatric practices.
At 5-year follow-up, participants underwent a psychiatric assessment and diagnostic interviews to collect data on the lifetime use of nicotine, alcohol, marijuana, and other drugs. With the exception of nicotine and alcohol, all substances were referred to as drugs.
For every substance used by a given participant, investigators recorded from both the adolescents and their parents independently the age at first use; lifetime diagnosis of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, abuse or dependence; and age at onset using structured interview data.
Of the total group, 94 participants were treated with stimulants and 20 were not. Study participants ranged in age from 10 to 24 years at 5-year follow-up. Mean age at follow-up was 16.2 years.
“Because this was a naturalistic examination of what occurred with time related to an intervention and was not a randomized trial, it was important to compare the baseline status of kids treated and not treated with stimulants to see if the groups were similar,” said Dr. Wilens.
He added there were no significant differences between the girls treated with stimulants and those who were not with respect to age, socioeconomic status, rates of conduct disorder, parental history of SUDs, frequency of family intactness, or severity of ADHD-potential risk factors for SUD.
Not only did exposure to stimulants not increase the risk for substance abuse in the girls, but investigators also found that this exposure had a significant protective effect.
Possible Biologic Mechanism?
Because of their previous research in boys, this finding was not a surprise, said Dr. Wilens. However, what was unexpected was the magnitude of the effect.
“I was surprised at the level of the risk reduction and that it was so robust in this sample of girls compared to our sample of boys. It appears stimulants offer a pretty substantial protective effect in adolescents, and at the very least, even if it doesn’t continue into adulthood, it may delay the onset of substance abuse in adulthood,” he said.
Although the mechanism by which stimulants may guard against substance abuse is not clear, on the basis of human and animal studies, there are at least a couple of hypotheses. It could be, said Dr. Wilens, that treating ADHD reduces a number of substance abuse risk factors including poor self-esteem, academic underachievement, impulsivity, and risk-taking behaviors.
In addition, he said, recent animal research indicates that early administration of stimulants in rat pups resulted in alterations in dopamine receptors as well as reducing rates of self-administration of cocaine and other illicit drugs, suggesting that a biologic mechanism may be at play.
Dr. Wilens and his team will continue to observe the cohort and are currently analyzing 10-year follow-up data to determine, among other things, whether this effect continues into adulthood.
In the meantime, he said, these findings send a compelling and reassuring message to parents and clinicians.
“Stimulant medications continue to be very safe and over the longer haul the evidence is that, at least in adolescence, they continue to reduce the risk for smoking and substance abuse. However, the jury is still out as to the potential protective effect these medications may have into adulthood and in older individuals who start these medications later in life,” said. Dr. Wilens.
The study was supported by the National Institutes of Health and by the Lilly Foundation. Dr. Wilens has received grant support from Abbott, McNeil, Eli Lilly & Co, the National Institute on Drug Abuse, Merck, and Shire.
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