Comparative Trial Shows Advantages to Once-Daily Methylphenidate Over Once-Daily Atomoxetine
Paula Moyer, Medscape

May 5, 2004 (New York) — The first head-to-head comparative study of once-daily atomoxetine (Strattera) with sustained-release methylphenidate (Concerta, OROS methylphenidate) shows that children with attention deficit hyperactivity disorder (ADHD) get more symptom relief from the methylphenidate formulation, according to findings presented here at the 15th annual meeting of the American Psychiatric Association.

"We received a lot of requests for comparison from both parents of children with ADHD and from treating physicians," said principal investigator Jason Kemner, MPH, in a telephone interview. "We found a significant difference in reduction of symptoms between the two groups. The difference was evident in the first week of the study and widened as the study progressed." Dr. Kemner is manager of outcomes research at McNeil Consumer and Specialty Pharmaceuticals in Fort Washington, Pennsylvania.

The investigators randomized 1,300 patients with ADHD aged six to 12 years to a three-week trial of either sustained-release methylphenidate or once-daily atomoxetine in an open-label study funded by McNeil. The ratio of children to each group of the study was 2:1 methylphenidate to atomoxetine. The patients were either newly diagnosed or had been suboptimally managed on current treatment. To be included in the trial, participants had to have an Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS) score of at least 24 and a Clinical Global Impressions–Severity of Illness (CGI-S) score of more than 3.

All of the subjects have completed the study; the investigators have analyzed the data on 651 subjects. There were 422 patients in the methylphenidate group and 229 in the atomoxetine group. The children in each group had similar ADHD-RS scores, a mean of 39.77 in the methylphenidate group and 38.87 in the atomoxetine group. In the methylphenidate group, therapy was started at 18 mg once daily and was titrated upward as deemed necessary by the physician. Similarly, atomoxetine was initiated at 0.5 mg/kg daily and was titrated upward if the physician considered it necessary.

At the first visit, children in the methylphenidate group had a mean ADHD-RS score reduction of 11.50 compared with a reduction of 8.55 in the atomoxetine group (P < .0006), with a mean difference in scores of 2.95. At the second visit, the mean reduction in score for the methylphenidate arm was 16.17 compared with 12.49 for the atomoxetine group (P < .0001), with a mean difference of 3.58 in scores between the two groups. At the third and final visit, children in the methylphenidate group had a mean score reduction over baseline of 21.10 compared with 15.94 for the atomoxetine group (P < .0001, with a mean difference of 5.16 between the groups.

Based on the CGI-I scale, the investigators found that 71.7% of patients in the methylphenidate group responded to treatment compared with 56.1% of those in the atomoxetine group (P < .0001). They found that 20.1% of those in the methylphenidate group and 23.6% of those in the atomoxetine group experienced treatment-related adverse effects and concluded that the two groups had similar experiences with these effects.

"When a child with ADHD responds quickly to a medication, it gives everyone confidence," David W. Goodman, MD, who was not involved in the study, told Medscape in a telephone interview. He is an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University School of Medicine in Baltimore and the director of the Adult Attention Deficit Disorder Center of Maryland in Lutherville.

"This study is interesting because often the reluctance to start a medication is resolved when a benefit is seen within a few days of starting treatment," Dr. Goodman said. "The physician can then recruit the patient's and parent's cooperation and adherence to treatment."

APA 157th Annual Meeting: Abstract NR451. Presented May 4, 2004.