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ADHD Meds Tied to Lower Substance Abuse Risk

Use of medications to treat attention-deficit/hyperactivity disorder (ADHD) is associated with a lower current risk for substance-related events, new research suggests.

"When doctors are weighing the risks and benefits of ADHD medication, they might want to consider our study, which provides more documentation that these medications are not likely to increase substance-related problems," study author Brian D'Onofrio, PhD, Indiana University, Bloomington, told Medscape Medical News.

"There's a huge concern among some in the medical profession and the general public that ADHD medication causes substance abuse," he told Medscape Medical News.

"There might be subsections of the population where that might be true, but our findings are not consistent with the hypothesis that taking ADHD medications actually causes people to have more substance-related problems."

The study was published online June 29 in the American Journal of Psychiatry.

Largest Study to Date

In what is reportedly the largest study yet to examine whether ADHD medications are associated with differences in risk for substance-related problems, the investigators used the Truven Health MarketScan Commercial Claims and Encounters (MarketScan) databases of deidentified inpatient, outpatient, and prescribed drug claims. MarketScan includes data on millions of insured people across the United States.

From this resource, the researchers identified almost 3 million individuals aged 13 years or older who received either an ADHD diagnosis or treatment for ADHD with a stimulant or with the nonstimulant atomoxetine (Strattera, Lilly) from 2005 to 2014.

The mean age of the study group was about 25 years. The patients were followed for about 16 months.

The investigators first compared substance-related events in people with ADHD to those in persons without the disorder. They identified these events through health insurance claims for emergency department diagnoses of a substance-related problem.

"We know that ADHD is associated with a host of negative outcomes, including substance-related problems," said Dr D'Onofrio. "When you look at medications, you have to consider whether the indication for the medication ? the diagnosis itself ? is associated with these bad outcomes."

They found that male and female ADHD patients were more likely to have at least one substance-related event than were male and female control persons (2.69% increased odds for males; 3.30% increased odds for females).

The researchers also investigated associations between ADHD medications and substance-related events. These associations were distinguished on the basis of the sex of the patients.

In both sexes, they carried out population-level and within-individual examinations in ADHD patients with and without prior substance use disorder, with no other psychiatric medications, and with no psychotherapy. They also investigated first events only.

In the within-individual models, the researchers compared periods during which medications were used with periods during which no medications were used.

"These models compared months in which an individual received medication with months in which that same individual did not receive medication," the authors write.

"Because each individual served as his or her own comparison, these models were free of confounding from all factors that were constant within the individual over time (eg, genetics, earlier environmental influences," they add.

In addition to concurrent associations (ie, associations occurring within the same month), the researchers identified associations between ADHD medication use and substance-related events occurring 2 years later.

Reduced Substance Abuse Risk

At the population level, the adjusted odds of substance-related events were 19% lower among male patients (odds ratio [OR] = 0.81; 95% confidence interval [CI] = 0.79 - 0.83) and 11% lower among female patients (OR, 0.89; 95% CI, 0.87 - 0.92) during months in which medications were used relative to months in which they were not used.

In within-individual comparisons, adjusted models showed that use of ADHD medication was associated with 35% lower odds of concurrent substance-related events among men (OR, 0.65; 95% CI, 0.64 - 0.67) and 31% lower odds among women (OR, 0.69; 95% CI, 0.67 - 0.71).

A number of sensitivity analyses supported these associations. For example, among patients with prior diagnoses of substance use disorder, the concurrent associations were somewhat attenuated but remained statistically significant, except in the unadjusted model for male patients.

Importantly, starting and stopping use of antidepressants were not associated with fewer substance abuse events.

"One of the things we struggled with in this paper was whether the lower substance abuse events were just a matter of going on or off any type of medication, and we found that there seems to be something specific about the ADHD medications," said Dr D'Onofrio.

In the long-term examination, adjusted population models showed minor increases in risk for substance-related events among female patients. However, in adjusted within-individual models, ADHD medication predicted a 19% reduction in the odds of substance-related events 2 years later among male patients (OR, 0.81; 95% CI, 0.78 - 0.85) and a 14% reduction among female patients (OR, 0.86; 95% CI, 0.82 - 0.91).

"Even when the results failed to support reductions in risk, we found almost no evidence that medication increased risk of substance-related events, including among those with pre-existing substance use disorders" the authors note.

The researchers were not able to differentiate between stimulant and nonstimulant ADHD medications because, said Dr D'Onofrio, "the overwhelming majority of people were prescribed stimulants."

The apparently weaker long-term associations suggest that at least some risk reduction may dissipate over time, according to the authors.

Although long-term associations were less clear among female patients relative to male patients, Dr D'Onofrio stressed that "it wasn't as if the medication was associated with more of these events in females."

The authors note that the study sample was not nationally representative and that differences in associations may reflect characteristics of the patients that were included in the study.

They also note that more female ADHD patients received other psychiatric medications and psychotherapy than did male patients. This, they add, raises the possibility that self-referral for comorbid psychiatric problems may have increased the number of adult female patients that were included in the study.

Alternative Hypothesis

The researchers cautioned that the analyses could not exclude all time-varying confounding effects.

"Our concurrent results could be consistent, for example, with the hypothesis that life events prompt some patients to simultaneously decrease their substance involvement and enter psychiatric treatment, thereby producing noncausal medication associations."

However, they said they do not believe that this hypothesis explains the observed long-term associations. And the finding in a sensitivity analysis that the associations did not hold for selective serotonin reuptake inhibitors may be evidence that this alternative hypothesis "does not entirely explain our results."

In addition, Dr D'Onofrio's research group has uncovered evidence of associations between ADHD medications and lower risk for injuries, car accidents, criminality, depression, and suicide. These findings also weaken the alternative explanation.

Although the dataset is large and longitudinal and derives from a national sample and in designing the study the researchers incorporated multiple features to rule out alternative explanations for the observed associations, the authors stress that the study is still observational.

Dr D'Onofrio also emphasized that the results should not be interpreted as supporting the use of ADHD medications to treat substance-related problems.

"Whether ADHD medications help people who don't have ADHD is a separate question that we are not able to answer."

ADHD medications are not without side effects and are associated with problems such as diversion, he said.

Dr D'Onofrio and his colleagues are using the same large dataset to study other possible associations with ADHD medications, including psychotic episodes. They are also interested in learning whether in certain subgroups of individuals, ADHD medications might be even more protective in terms of substance-related outcomes.

Protective Effect

Commenting on the findings for Medscape Medical News, Steven P. Cuffe, MD, professor and chair, Department of Psychiatry, University of Florida College of Medicine, Jacksonville, said it adds to a growing body of evidence, almost all of which points in the same direction.

"The evidence is getting increasingly strong that at a minimum, the use of ADHD medications does not cause addiction-related problems in people with ADHD, and evidence is accruing that it may be protective," said Dr Cuffe.

The new study results should make clinicians feel more comfortable treating children reaching the age when it was thought that there might be a risk for addiction, said Dr Cuffe.

"It used to be that kids frequently stopped using stimulant medication when they became adolescents because of the risk of addiction, but over time, this practice pattern is really changing."

However, Dr Cuffe noted that this does not minimize the problems regarding diversion associated with stimulants – the risks of these drugs being stolen, given away, or sold to adolescents who do have addiction problems.

Stimulants are also being used by college students to help them concentrate in the hopes of doing well in school.

Dr Cuffe praised the study for including such a large number of participants and for being "comprehensive."

But he did point out some limitations.

"Just because the subjects had a prescription doesn't mean they took it, and it doesn't mean that they took it during the months that the prescription was written for," said Dr Cuffe. "Tons of people start taking it and stop it, and then 3 months later may start taking it again, or they may save it and take it when they have a big exam."

The study was supported by the National Institute of Mental Health, the National Institute of Drug Abuse, the European Union Seventh Framework Programme, the Swedish Research Council for Health, Working Life, and Welfare, and by the Indiana Clinical and Translational Sciences Institute, which is funded by the National Center for Advancing Translational Sciences. Dr D'Onofrio and Dr Cuffe have disclosed no relevant financial disclosures.


ADHD Meds Tied to Lower Substance Abuse Risk - Medscape - Jul 14, 2017

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