In the first head-to-head comparison of two popular ADHD drugs in a classroom setting, researchers say that children treated with the stimulant drug Adderall XR showed greater improvements in their behavior and attention than those getting Strattera, the first nonstimulant medication FDA-approved to treat ADHD.
Some 200 children aged 6 to 12 -- already diagnosed with ADHD -- took part in the three-week study, presented this week at the annual meeting of the American Psychiatric Association. The research was funded by Shire Pharmaceuticals Group, the maker of Adderall XR.
"The bottom line is, we saw a lot of significant differences in how well these medications work in a simulated classroom setting," says lead researcher Sharon Wigal, Ph.D., director of clinical trials at the Child Development Center of the University of California, Irvine. "The children who received Adderall XR were better behaved and focused, and these effects lasted longer. They were better able to sit in the classroom and not disrupt other kids."
But a medical advisor for Eli Lilly & Co., which makes Strattera, questions the way the study was conducted and says its findings produce a "significant inconsistency" with previous research done on his company's drug.
How the study was done
For this study, the children were first placed on a placebo drug for three days to negate any effects of medications they may have been taking. They were then randomly assigned once-daily treatment of either Adderall XR, an extended-release formulation of mixed amphetamines, or Strattera, approved in November 2002 as the first nonstimulant drug to treat ADHD in children and adults.
The children were then monitored in three weekly sessions in a simulated classroom environment, each lasting 12 hours. With each week, the doses of both drugs were increased according to manufacturer recommendations, and the kids' behavior was measured by a standard ADHD assessment tool every 2 1/2 hours during each session.
"With Strattera, we saw improvements during the first week, but we didn't see those effects continue during the second or third week," Wigal tells WebMD. "With Adderall XR, the improvements were consistent across each of the study days."
She also notes that Adderall-treated patients performed better on a timed math test. "They were able to answer twice as many problems compared to (the study's start), but we didn't see that kind of improvement in those getting Strattera."
Study length and patient selection play roles
But psychiatrist Dr. Calvin R. Sumner, medical advisor for Lilly Research Labs and Neurosciences, says both the study's length and patient selection played key roles in the results. Lilly is a WebMD sponsor.
For one thing, Wigal's trial lasted only three weeks -- a short period by most medical research standards. And, says Sumner, that's especially important when studying Strattera.
"With Strattera, you see changes within the first couple of weeks, but you don't appreciate the full benefits of the drug for four to six weeks," he tells WebMD. "The rate it reaches its full benefit is a longer time than with Adderall XR."
Another problem: Sumner, who attended the APA conference and reviewed the research, says that children diagnosed with the most common symptom of ADHD -- inattention -- were intentionally excluded from the trial.
"One of the things put forward in this trial is that attention improved better with Adderall XR. But attention was not a systematic problem among patients in the trial to begin with," he says. "If you sufficiently limit your study population as they have, you may be looking at different things than what you see in overall trials of ADHD. It's hard to know with this trial if you're looking at a group of kids who are representative of the broader world of what really is ADHD."
Drugs work differently
Both drugs have been proven effective in treating ADHD, believed to affect at least 2 million American children and marked by symptoms of inattention, impulsiveness, and/or hyperactivity. But they work in different ways.
Adderall XR, approved only for use in children, is a mixture of four amphetamines that is thought to help restore the balance of two chemicals -- dopamine and norepinephrine -- in areas of the brain that control the ability to focus and pay attention.
But unlike stimulants, Strattera affects only norepinephrine and not dopamine, giving it its nonstimulating effect. It is also taken once daily and is FDA-approved for use in children, teens, and adults with ADHD.
In Wigal's study, both drugs produced few side effects. Not surprisingly, with Adderall XR, the children were more likely to have problems falling asleep, whereas those on Strattera were more prone to daytime drowsiness, she says.
Still, Sumner says he is "curious" why Wigal's study showed that Strattera's benefits seemed to level off after a first-week improvement blip.
"This is a significant inconsistency to what has been demonstrated with Strattera in six longer, double-blind, placebo-controlled trials that demonstrate significant improvement in attention and behavior over time."