MIAMI BEACH – Three variables–medicine characteristics, efficacy study characteristics, and patient characteristics–should be considered when prescribing for attention-deficit hyperactivity disorder, said Dr. Richard Rubin at the annual meeting of the American Society for Adolescent Psychiatry.
Medicine characteristics include effect duration, influence on comorbidities, individual safety risk, patient acceptance, cost, and access for continuous adherence, said Dr. Rubin, director of the private practice-based Clinical Study Center in Burlington, Vt.
Efficacy study characteristics–such as patient selection, rating measurements used, dosing, and treatment duration–should be considered in regard to how they might limit the findings and apply to patient care.
Patient characteristics important to consider include potential response mediators and moderators.
Compliance, for example, is a mediator that frequently causes problems in achieving desired outcomes. Data from 2004 on the three most commonly prescribed ADHD medications show that refill adherence after 2 months is only 50%. Patient/parent benefit expectations, subjective discomfort complaints, and side-effect fears appear to play an important role in compliance, and should be addressed by prescribers.
Comorbid disorders are common moderators that also require careful evaluation and consideration in ADHD prescribing, said Dr. Rubin at the meeting cosponsored by the University of Texas at Dallas.
Medications specifically approved for ADHD included amphetamine formulations, various methylphenidate products, and atomoxetine (Strattera). Useful medications not approved for ADHD include the antidepressants bupropion, imipramine, and nortriptyline, and the α2-adrenergic agonists clonidine and guanfacine. Pemoline was withdrawn from the market, Dr. Rubin noted.
In the past year, new FDA approvals for adolescents were granted for a 72-g dose of osmotic-release oral system (OROS) methylphenidate, a methylphenidate transdermal system (Daytrana), and extended-release mixed amphetamine salts. An extended-release formulation for dexmethylphenidate (Focalin XR) was also approved for children, adolescents, and adults.
In addition, an “FDA approvable” letter was issued for an ADHD formulation of modafinil (Provigil), he noted.
Other topics Dr. Rubin addressed included:
▸ Stimulant pharmacokinetics and efficacy. One study looking at the effects of weight, age, and gender on mixed amphetamine salts (MAS) pharmacokinetics showed that the area under the curve and Cmax decreased, and half-life increased as weight increased in children, adolescents, and adults. Age and gender had no effect on the parameters, independent of weight.
A 4-week randomized, placebo-controlled study of MAS in 318 adolescents showed those treated with 10–40 mg/day had a mean 17.8-point decrease on the ADHD Rating Scale (ADHD-RS), those treated with 50 mg/day had a mean 16.9-point decrease, and those in the 60-mg group had a mean 14-point decrease, compared with a mean 9.4-point decrease in the placebo group. An OROS methylphenidate dosing study of 177 13- to 18-year-olds with combined type ADHD showed that 38% required the 72-mg dose to achieve at least a 30% ADHD-RS improvement, with a mean change of 15.3.
▸ Schedule II prescribing rules. Federal regulations updated in November 2005 to clarify physician responsibilities state that physicians are not required to see a patient every month or whenever schedule II drugs are prescribed. Prescriptions due for a refill can be mailed to a patient, or mailed or faxed to a pharmacy, but the physician should have a contact with the patient to verify ongoing safety. Physicians cannot provide refill prescriptions dated in advance. The amount of medicine that can be prescribed (for example, a 30- or 90-day supply) is regulated by the state or a third-party payer.
▸ Tricyclics for ADHD. These drugs may still have some selected use in ADHD, for example, with comorbid tics, but the risks for overdose fatality remain. Also, case reports suggest there is a risk for tricyclic-marijuana adverse interactions.
▸ α2 Noradrenergic agonists for ADHD. Clonidine and guanfacine have been shown to be effective when added to stimulants for aggression with ADHD, and also appear effective for tics with ADHD. While the sedative properties of clonidine are commonly used at bedtime after daytime stimulants, physicians should be conscientious about the differential diagnosis and treatment of sleep problems in ADHD adolescents, Dr. Rubin advised.
For example, the ADHD itself, or comorbidities such as anxiety, oppositional defiant disorder, and substance abuse might play a role in sleep problems. Stimulant side effects, a primary sleep disorder such as obstructive apnea, restless legs, or poor sleep-hygiene practices may also be to blame.
▸ Bupropion. This drug is still a useful off-label treatment option for ADHD, particularly in those with substance use disorder, mood disorder, and/or conduct disorder, recent studies suggest. The dose needs to be high enough (450 mg/day for the XL form and 400 mg/day for SR form), and with duration of at least 4 weeks to achieve a 50% reduction in symptoms. The XL once-daily dose is associated with better adherence than the twice-daily SR dose, he noted.