Tailor ADHD treatment to individual patient’s needs

November 2006

ATLANTA – The treatment options for attention-deficit hyperactivity disorder have evolved over the years, which may have left pediatricians wondering which agents are right for their patients.

The key to treatment is helping parents see ADHD as a chronic illness and setting goals for treatment with patients and parents of their patients, according to Martin T. Stein, MD, of the University of California, San Diego.

When selecting an initial medication, Stein said, pediatricians must consider efficacy, adverse events, duration of action, coexisting behavior conditions, cost and potential for abuse. Age is also a consideration, he said.

In 2001, the AAP published evidence-based guidelines for ADHD management in Pediatrics (108:1033). In the guidelines, the Academy noted that there are strong data for the use of stimulants in ADHD treatment. Stein said that atomoxetine HCl (Strattera, Eli Lilly) will likely be included in the updated guideline.

Before selecting which agent to use, Stein said the first step is to ascertain from patients what their goals for treatment are. He said patients often tell their doctors they hope to improve their social relationships, academic performance, self-esteem, reduce the symptoms and improve the disturbances in functioning that accompany ADHD.

Stein said that parents should also play a key role in the discussion and referred to two AAP publications: “Understanding ADHD,” a brochure, and the book “ADHD: A Complete and Authoritative Guide.” He said discussions with parents should focus on treatment goals. Start by outlining the nature of ADHD to frame the discussion, he suggested.

“ADHD is both a biological condition and a response to a situational problem,” he said. “In our evolutionary history, having ADHD was probably protective. Being hyperactive and hypervigilant meant that you didn’t have dangerous animals coming into your cave at night … but in our contemporary society, when we put our kids into a classroom of 30 to 35 kids, we’re no longer hunter and gatherers anymore. ADHD behaviors may be seen as a response to that change in ecology.”

There are more than 200 randomized control trials showing the efficacy of stimulants in reducing the core symptoms of ADHD. Stimulants work by regulating dopamine in the brain. Seventy percent of children with ADHD respond to the first stimulant they are prescribed. Half of those who respond poorly to the first will respond to the second one their doctors try, Stein said. Family history may be a strong predictor of which medications will work in particular patients. He added, however, “we have no phenotype to find out which patients will respond to one medication or the other.”

In terms of dosing these medications, Stein said the first phase should be titrating. He said he starts stimulant medications low and titrates upward, depending on dose response and adverse events. He said most patients begin stimulants with a seven-day-a-week dosage, since ADHD symptoms can “affect performance in school and social interactions at home as well.”

Stein said there are four major stimulants available that are long-acting: Concerta (McNeil), Focalin XR (Novartis), Metadate (CellTech) and Ritalin (Novartis). The duration is 12 hours for the first two, and eight hours for the second two. Concerta comes in a capsule while the others can all be sprinkled. Concerta is different than the other medications in that it is an immediate-release overcoat at 22%, whereas Ritalin LA is an immediate release at 50%.

“Pay attention so that if you have a child who is very hyperactive in the morning while taking Concerta, Ritalin LA may be helpful,” Stein said.

Discussing amphetamines, Stein said there are three intermediate release formulations: Adderall, Dexedrine and Dexadrine spansules and one extended-release formulation Adderall XR (Shire). There are some patients who are risky populations to prescribe amphetamines, Stein said, such as adolescents who may want to abuse stimulants.

Stein said it is important to consider the individual patient when considering which of these medications to use, and he said he uses both types of stimulants in his practice. He said he has not yet tried the recently approved methylphenidate patch, Daytrana (Noven) in his practice, but he said its slow release formulation and the benefit of bypassing oral administration in the resistant child may have some advantages.

Regardless of which medication used, Stein said several trials have shown the efficacy of all of these medications in ADHD patients. The MTA study was a multimodal treatment study of 579 children with ADHD, who were given prescription medications, behavior management or both. In that study, researchers achieved the best result on core ADHD symptoms with either medication alone or medication in combination with behavioral therapy. In that study, behavioral therapy alone was not as effective as the other two forms of treatment.

Stein said that atomoxetine, a non-stimulant medication, is comparable to stimulants in both its effect on core ADHD behaviors and its adverse event profiles.

He said to consider atomoxetine when there is treatment failure or intolerable adverse events with the stimulants. He also said these treatments are a good alternative when parents are against the use of a stimulant in their child. He also said to consider this medication when there is significant sleep disturbance or significant early morning hyperactivity.

In terms of titrating atomoxetine, Stein said it is different from stimulants in that you have to start with about .5 mg/kg per day for three to five days, and you can increase up to about 1.2 or 1.4 mg/kg per day. He said officials at Lilly have reported safety data as high as 1.8, but caution is warranted. He said this medication might take three to six weeks to have detectable effects.

Coexisting conditions

Stein said that there have been studies that show anxiety and ADHD occur together in up to 20% of patients, conduct disorders and ADHD in up to 10% of patients, and that as many as 20% to 30% of patients with ADHD have learning disorders.

He said some studies have looked at buproprion in patients with ADHD and depression, and found some efficacy.

Stein touched upon the debate between two FDA advisory boards earlier this year that certain medications should include strong warnings regarding potential cardiovascular and psychiatric risks.

In March, the FDA’s Pediatric Advisory Committee stopped short of recommending a black box warning to highlight cardiovascular risks, which another FDA panel, the Drug Safety and Risk Management Advisory Committee suggested in adults. The pediatric committee, composed of outside experts, felt that the cardiovascular events were not of a similar risk in children as adults, except for children with cardiovascular abnormalities.

The panel also declined to support a black box warning for psychiatric risks such as aggression and suicide, saying it did not want to scare patients or parents from effective treatment. Instead, it proposed that the risk of psychiatric events and aggression be described in the warning section of labeling of all ADHD medications.

For more information:

• Stein MT. Psychopharmacology of ADHD. Session #F370. Presented at: 2006 National Conference and Exhibition Program. Oct. 7-10, 2006. Atlanta.