Mr. Z describes ADHD symptoms from early elementary school to college. He was held back in kindergarten for being “immature,” his academic performance was inconsistent, and he “just got by…by cramming” in high school and college. His school performance pattern does not suggest a learning disability; he did not need special help in 1 subject more than others, and under pressure he could achieve average grades.
Medical review excludes explanations other than ADHD for his inattention, restlessness, and impulsivity. You conclude that Mr. Z meets criteria for ADHD, combined subtype, and discuss medication treatment.
FDA-approved medications
Medication for ADHD is appropriate only if symptoms are impairing. Five effective and generally well-tolerated medications are FDA-approved for adults with ADHD (Table 2):
- extended-release mixed amphetamine (Adderall XR)
- extended-release OROS methylphenidate (Concerta)
- extended-release dexmethylphenidate (Focalin XR)
- atomoxetine (Strattera)
- lisdexamfetamine (Vyvanse).
Efficacy. A meta-analysis of 29 pediatric ADHD trials across 30 years demonstrated greater effect size for stimulant class medications (immediate- and long-acting), compared with nonstimulant medications (including bupropion, atomoxetine, and modafinil).2 This finding is consistent with the American Academy of Child and Adolescent Psychiatry’s recommendation of stimulant medications as first-line agents for pediatric ADHD.3 A similar meta-analysis of 6 controlled studies of methylphenidate-class medications in adults found a large mean effect size (0.9), with greater effects associated with higher doses.4
Atomoxetine, a norepinephrine reuptake inhibitor, is the only nonstimulant medication FDA-approved for ADHD in adults. More than 6,000 children, adolescents, and adults have taken atomoxetine in clinical trials for ADHD (Lilly, prescribing information), with 4 years of open treatment data showing benefit being maintained over time.5
Tolerability. Although ADHD medications are generally well-tolerated by healthy adults, assess for a history of potential contraindications:
- unstable medical condition, hyperthyroidism, glaucoma
- treatment with a monoamine oxidase inhibitor or other pressor agents because of possible effects on blood pressure and heart rate
- use of cytochrome P450 2D6 inhibitors, which may increase atomoxetine steady-state plasma concentrations
- cardiovascular disease or family history of early cardiac disease (Box 1)6,7
- history of or active substance use disorder, such as alcohol dependence, cocaine or heroin abuse
- history of psychosis, bipolar disorder, or an active clinically significant psychiatric comorbidity (major depression, agitated state, suicidality).
Clinically, some patients appear to tolerate 1 class of stimulant (such as methylphenidate or amphetamine) over another. Consider switching to an alternate stimulant if your patient has bothersome side effects—mild low appetite, insomnia, tension, or jitteriness—or has received limited or partial benefit during an initial stimulant trial.
Managing cardiovascular risk of stimulant use in adults
Serious cardiovascular events and sudden death have occurred in adults and children treated with stimulants.6 Agents used for attention-deficit/hyperactivity disorder (ADHD) have not been shown to cause sudden cardiac death, but the FDA requires stimulants’ labeling to warn about this risk in patients with structural cardiac abnormalities. The warning advises against using stimulants in adults with cardiomyopathy, serious heart rhythm abnormalities, or coronary artery disease.
When treating adults with ADHD, look to advisories about cardiovascular monitoring in children with ADHD. Before initiating medications, do a physical exam focused on cardiovascular disease risk factors and obtain a patient and family health history of:
- fainting or dizziness
- sudden or unexplained death in someone young
- sudden cardiac death or “heart attack” in family members age <35 years.
The American Academy of Pediatrics, American Academy of Child and Adolescent Psychiatry, and American Heart Association concur that electrocardiography (ECG) is not mandatory in cardiovascular assessment and monitoring during ADHD pharmacotherapy.7 This author (PH) refers cardiovascular questions to a primary care physician or cardiologist.
During ADHD treatment, monitor vital signs and refer patients with emergent cardiac symptoms or concerns to a cardiologist. Expect increases in blood pressure (1 to 4 mm Hg) and heart rate (2 to 6 bpm) during treatment with methylphenidate and amphetamine-class stimulants as well as with atomoxetine. Do not expect significant changes in ECG parameters (PR, QRS, and QTC intervals).
Extended-release formulations. Early adult studies demonstrated the efficacy of immediate-release stimulants, but adults with ADHD’s inherent deficits in organization and memory may have higher adherence rates and greater success with once-daily, extended-release formulations.8-11 Unless your patient wants to begin with small, short-acting dosages (5 to 10 mg) or desires to target treatment to specific times of day (such as in the morning for administrative work only), many appreciate once-daily formulations. Extended-release formulations also may be the simplest stimulants with which to begin ADHD treatment.