No change. In a 10-year naturalistic study, Biederman et al28 followed 109 children with ADHD age 7 to 12 into adulthood. These children had a developmental reading disorder but no other psychiatric comorbidities. When comparing patients who were treated with methylphenidate (n = 43) with those who did not receive stimulants (n = 66), Bierderman et al found no significant difference between the 2 groups in the prevalence of SUD for any of the 7 drug categories studied.
Decreased risk. Two meta-analyses found children with ADHD who were treated with stimulants and followed until adolescence were 5.8 times less likely to develop SUDs compared with those who did not receive stimulants.28,29 This protective effect diminished when patients were followed into adulthood, but individuals treated with stimulants were 1.4 times less likely to develop SUDs than those not treated with stimulants.30 In a prospective case-control, 5-year follow-up study of 114 patients with ADHD treated with stimulants, Wilens et al31 found significant protective effects of stimulant treatment on the development of any SUD. They found no effects from time of onset or duration of stimulant therapy on subsequent risk of SUDs or cigarette smoking.
One possible explanation for stimulants’ apparently reduced protective effect among adults is for patients with ADHD, stimulant use might delay but not prevent SUDs. It also is likely that by adulthood, loss of parental supervision leads to poor medication adherence and increased susceptibility to SUDs.30
Other studies have found exposure to stimulants may protect against SUDs. Katusic et al23 reviewed medical records for documented SUDs in 295 adults with ADHD treated with stimulants and 84 who did not receive stimulants. They found 20% of patients who received stimulants had a documented SUD compared with 27% of those not treated with stimulants. Barkely et al32 followed 98 stimulant-treated and 21 untreated ADHD patients with a mean age of 15 and 21, respectively. They found stimulant treatment did not increase the risk for substance use or abuse in either group.
ADHD and stimulant abuse
The prevalence of stimulant misuse is as high as 9% in patients in grade school and high school and up to 35% in college-age individuals.33 ADHD patients who misuse stimulants (eg, escalating dose without authorization) or skip stimulant doses to use illicit drugs or alcohol are more likely to sell their medication.34 Immediate-release stimulant formulations are more liable to be abused than extended-release drugs because they achieve earlier peak drug concentrations and dopamine blockade, indicating rapid drug absorption and central drug activity. Close monitoring and use of extended-release formulations are useful deterrents against stimulant abuse.
Clinical recommendations
Detecting and treating SUDs in patients with ADHD can be challenging. Ideally, the best time to assess for ADHD symptoms is after a prolonged abstinence from any influencing substance. However, in most clinical situations this is not practical. A better approach is a longitudinal assessment for ADHD symptoms. Detecting evidence of early childhood onset of ADHD symptoms before the patient began using substances can be helpful in conducting a proper differential diagnosis. Assessing for symptoms of SUDs in early adolescence, along with serial assessment of ADHD symptoms, also can be helpful. Symptoms secondary to ADHD are likely to show a consistent pattern, whereas symptoms secondary to an SUD may be sporadic.
When assessing SUD risk, consider the patient’s clinical condition, history of comorbidities that suggest SUDs, and overall functional status. Collateral information about the patient’s behavior and substance abuse from family members is important. A history of CD, bipolar disorder, or antisocial personality disorder should raise concerns about potential future stimulant abuse or diversion. Close monitoring of patients suspected of having an SUD is essential to detect stimulant abuse or diversion, which often manifests as weight loss, requests for higher doses, requests to switch from long-acting or extended-release formulations to immediate-release formulations, and repeated and suspicious “lost prescriptions.” Close observation for other subtle signs—such as changes in personality or mood and unexplained accidents or injuries—also may be needed.35
Challenges of treating ADHD and co-occurring SUD include poor medication adherence, need for a higher therapeutic stimulant dose, and difficulty in assessing the therapeutic benefit of pharmacotherapy in the presence of an SUD.36 Treating ADHD comorbid with SUD requires a collaborative approach that involves a psychiatrist, family members, and a behavioral care provider in addition to frequent monitoring.34
In the absence of treatment guidelines for treating ADHD with comorbid SUDs, some clinicians prefer to stabilize the SUD before initiating stimulants. Others prefer to use nonstimulants (such as atomoxetine, guanfacine, bupropion, venlafaxine, tricyclic antidepressants, or modafinil) as a first-line treatment. However, nonstimulants have not demonstrated efficacy comparable to that of stimulants for ADHD.35