Tomoxetine

NEW YORK -- Two investigational drugs show promise for treating attention-deficit hyperactivity disorder in children, according to poster presentations at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

Dr. John H. Heiligenstein reported on two multicenter trials that found tomoxetine, a selective noradrenergic enhancer, to be significantly more effective than placebo and comparable with methylphenidate in alleviating attention-deficit hyperactivity disorder (ADHD) symptoms.

Noradrenergic dysfunction is believed to play a role in the pathophysiology of ADHD, but drugs aimed at this system might have cardiac effects. Tomoxetine is highly selective: It enhances noradrenergic transmission by blocking norepinephrine transporter but has minimal affinity for other receptors, he said.

The two studies compared symptoms in 7- to 13-year-old children with ADHD: 129 received 9 weeks of tomoxetine, 38 received methylphenidate, and 124 received placebo, said Dr. Heiligenstein of Lilly Research Laboratories, Indianapolis.

Improvements were significantly greater with tomoxetine than with placebo on the total ADHD rating scale and the inattentive and hyperactive/impulsive subscales. Overall, 61% of patients on tomoxetine had a reduction of 25% or more in ADHD rating scores, nearly double the rate (32%) with placebo. Outcomes were similar with tomoxetine and methylphenidate.

Among adverse effects, anorexia alone was reported significantly more often with tomoxerine than placebo. The noradrenergic drug was not associated with clinically significant changes in laboratory values or cardiac repolarization, he said.

In a separate presentation, GW320659--an investigational compound resembling the major active metabolite of bupropion--appeared safe and effective in 46 children with ADHD whose mean age was 9 years, said Dr. Joseph Devaugh-Geiss, vice president of neurology and psychiatry clinical development at Glaxo Wellcome Inc., Research Triangle Park, N.C.

Bupropion, an antidepressant that enhances noradrenergic and dopaminergic neurotransmission, has been found effective in children and adults with ADHD. Preclinical studies suggest that GW320659 has similar effects but less seizure potential than the antidepressant, he said.

In the open trial, 51 children were enrolled for a titration phase of 7 weeks, in which GW320659 was administered up to the highest tolerated dose or 15 mg/day; 46 children remained on the drug for a treatment phase of 4 additional weeks.

At the end of this period, 35 (76%) of the children were "much improved" or "very much improved" on the Clinical Global Impression scale and had clinically significant improvements in parent or teacher ratings of ADHD symptoms. Parent and teacher ratings of symptoms dropped to within normal limits by the end of treatment.

Adverse events included headache (31%), gastrointestinal discomfort (25%), mood disorders (20%), sleep disorders (18%), and nausea and vomiting (12%). These were "typically mild or moderate, and resolved without sequelae," he said.

Subjects had a mean increase of 10 beats per minute in heart rate, and 5-6 mm Hg in blood pressure.

COPYRIGHT 2001 International Medical News Group
COPYRIGHT 2001 Gale Group