Nov. 4, 2003 (New Orleans) -- Twice-daily atomoxetine has been shown in a pilot study to minimally decrease wet nights for pediatric patients with nocturnal enuresis, researchers reported here Monday at the American Academy of Pediatrics National Conference and Exhibition.
Douglas Kelsey, MD, from Eli Lilly and Company Research Laboratories, presented data from an 87-patient study. Atomoxetine is approved by the U.S. Food and Drug Administration to treat attention deficit-hyperactivity disorder (ADHD), and in clinical studies for that use, relief of bed-wetting was an unexpected benefit, said Dr. Kelsey. He and a colleague at Eli Lilly, the drug's maker, decided to test the drug's efficacy in a group of patients with nocturnal enuresis, he said.
"We felt like we had to at least do an exploratory study," Dr. Kelsey told Medscape.
In that trial, children aged six to 18 who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for nocturnal enuresis were randomly assigned to atomoxetine or placebo, with doses given in the morning and in the late afternoon.
Children with a documented history of psychosis, or who had taken antipsychotic drugs within four weeks of the study's start were excluded. Concomitant use of other medications or therapies, including biofeedback, was barred.
The study subjects were primarily male and white. Nineteen of the 44 atomoxetine-treated patients and 22 of the placebo-treated subjects had ADHD, which is a frequently occurring comorbid condition with nocturnal enuresis, with up to 30% of ADHD children also experiencing bed-wetting, Dr. Kelsey told meeting attendees.
The primary outcome measure was change from baseline on the Day Night Log-Parent Report. At baseline, patients in the atomoxetine arm had a mean of 1.51 dry nights, and placebo patients a mean of 1.01. By the study's end at one week, the atomoxetine group had a mean increase of 1.5 dry nights compared with 0.6 for the placebo group. That difference was only slightly significant ( P = .02).
Six atomoxetine patients had no dry nights compared with 17 patients in the placebo group. Eight subjects taking atomoxetine had seven dry nights, while none of the placebo patients had a dry week.
Adverse events were minimal. Headache was the most reported effect, affecting nine atomoxetine-treated patients compared with four patients who received placebo. Nausea and decreased appetite were also reported by similar small numbers of patients in both groups.
Atomoxetine is an inhibitor of the presynaptic norepinephrine transporter, and it increases the contractility of muscle in the bladder, Dr. Kelsey told Medscape. He said he believes that the drug is at least, or more, potent that current therapies such as imipramine, and it is better-tolerated. It is not clear, however, how the drug is working in nocturnal enuresis.
"We need to understand how it's working," Steven J. Skoog, MD, FAAP, from the Oregon Health & Sciences University in Portland, told Medscape. "Is it through the bladder or through treating the ADHD?"
Dr. Skoog characterized the pilot study as "exciting," but he added, "...I don't think we have proof." Many of the questions about atomoxetine's efficacy in bed-wetting could be answered easily in larger studies, he said.
"We certainly need to do other trials," agreed Dr. Kelsey. But, he added, he's not certain whether the company will devote resources to further study.
Eli Lilly & Co. funded the study.
AAP 2003 National Conference and Exhibition: Poster 43. Presented November 3, 2003.
Reviewed by Gary D. Vogin, MD
Alicia Ault is a freelance writer for Medscape.
Medscape Medical News © 2003
Cite this: Atomoxetine Shows Promise Against Nocturnal Enuresis - Medscape - Nov 04, 2003.