ADHD Treatment Strategies Linked to Life-Cycle Stage

Cognitive impairments are robustly associated with ADHD across the lifespan, according to Rosemary Tanneck, Ph.D., senior scientist at the Hospital for Sick Children in Toronto, Ontario, and an associate professor of psychiatry at the University of Toronto. Growing evidence suggests such impairments may underlie and give rise to behavioral symptoms of ADHD. Failure to consider cognitive impairments, Tanneck said, may result in inadequate consideration of a treatment plan.

One computerized test to assess executive function requires subjects to respond to every letter except “x,” while another measures both whether subjects can stop responding to a stimulus and how fast they can stop. In another, subjects are asked to name the color of a word in which the letters may be green while the print says “blue.”

Although it is commonly believed that impulsivity triggers fast responses, children, adolescents, and adults with ADHD commonly react more slowly on such tests than matched controls without ADHD, and give more variable and inaccurate responses. The variability often is the best discriminator between ADHD and control groups, Tanneck said, although it is not specific to ADHD. It also occurs in dyslexia and learning disorders.

People with ADHD also manifest difficulties with working memory: the ability to briefly retain, associate, and manipulate information such as phone numbers or directions. Researchers once thought attention was necessary to enable concentration, she said, but working memory now is seen as crucial to helping the mind focus.

Studies show that substance abusers have a high prevalence of ADHD and that ADHD is a risk factor for substance abuse, said Timothy Wilens, M.D., director of substance abuse services in pediatric psychopharmacology at the Massachusetts General Hospital in Boston.

About 27 percent of the general population, he said, has a lifetime risk of alcohol or drug addiction. Some 55 percent of adults with ADHD—a rate he termed “extraordinarily high”—have such problems.

Preliminary findings from a six-week open-label trial in 28 subjects show bupropion benefits adults with both ADHD and substance abuse, Wilens said. It significantly reduced ADHD symptoms according to physician assessment, and substance abuse by objective measures such as urine tests and self-reports.

Bupropion was well tolerated, he said. There were no reports of interaction between bupropion and substances of abuse. Participants who continue to maintain sobriety, Wilens said, report the medication provides an “anticraving” effect that helps them abstain. Two in five subjects failed to complete the trial, he noted, highlighting the need to stabilize the addiction first and then tackle the ADHD.

Debate continues over whether childhood treatment of ADHD with stimulants protects patients from later substance abuse, or, conversely, predisposes them to it. Wilens described a longitudinal family genetics study at Massachusetts General Hospital. The study included 117 children who had ADHD and took medications, typically stimulants, starting around age 10 or 11; 45 children with ADHD but no medication exposure; and 344 non-ADHD controls. Researchers followed the children until late adolescence.

Only 12 percent of the medicated ADHD group developed a substance abuse disorder in mid-adolescence, while 30 percent of those not on medications did so. Three other studies with long-term follow-up support this finding, Wilens said. These data, he asserted, “are among the strongest in child psychiatry showing the preventive influence of treatment on the later development of substance abuse.”

David Michelson, M.D., discussed an investigational new drug for ADHD, atomoxetine, a nonstimulant medication. Initially called “tomoxetine,” the drug was renamed to avoid confusion with the anticancer agent tamoxiphen, said Michelson, who is medical director for atomoxetine at Eli Lilly and Company.

Atomoxetine’s single active metabolite is cleared from the body in less than one hour. Nearly all of the drug is excreted in urine. Its half-life is around four hours in fast metabolizers, and about 15 to 20 hours in slow metabolizers. A dose of around 01.2 mg/kg/day appears to be effective in both adults and children. It has been given twice daily in all studies. Because the medication is a nonstimulant, Michelson said, late-day dosing is not problematic.

Four placebo-controlled studies have been completed to date, including one in adults with ADHD by Spencer and colleagues published in the American Journal of Psychiatry in 1998. The other three studies involved children. All have shown robust separation between atomoxetine and placebo, Michaelson said. Parents report they are less drained by activities required to care for a child with ADHD who is taking atomoxetine. About 10 percent to 15 percent of 270 users in published studies experienced loss of appetite and weight. Further studies in both adults and children are in progress. If atomoxetine were to be approved for the treatment of ADHD, it would be the first nonstimulant agent in this category. ▪