Tiagabine May Be Useful Insomnia Treatment for Adults

Jennifer Reid Holman

June 11, 2004

June 11, 2004 (Philadelphia) — The anticonvulsant drug tiagabine (Gabitril) may be useful for treating adults with primary insomnia, according to preliminary research presented here at the Associated Professional Sleep Societies annual meeting.

In the study presented here, a nightly 8-mg dose of tiagabine for two consecutive nights significantly reduced waking after sleep onset and increased the duration of deeper sleep stages in adults with primary insomnia, without causing objective adverse effects. Lower doses (4 mg and 6 mg) did not have any statistically significant sleep impact, while higher doses (12 mg and 16 mg) lead to some adverse residual effects. The most common were headache, dizziness, and grogginess the next day.

"We consider this preliminary data while we look at figuring out the proper dosages to take forward," said lead investigator James Walsh, PhD, senior scientist in the Sleep Medicine and Research Center at St. John's Mercy Medical Center and St. Luke's Hospital in Chesterfield, Missouri, and clinical professor of psychiatry at St. Louis University. Further study of the 8-mg dose of tiagabine as a sleep-enhancing agent is of particular interest, he said.

This was a crossover, double-blind, placebo-controlled dose-response study of 58 adults with primary insomnia, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and other sleep pattern criteria. Patients were randomized to one of the four treatment groups (4, 8, 12, or 16 mg given 30 minutes before bedtime for two consecutive nights with a 5- to 12-day washout period between treatments). The average age of participants was 47 ± 8 years, the ratio of men to women was 4:7, and other demographics were fairly similar. Fifty patients completed the study; eight patients dropped out primarily due to adverse effects at the higher doses.

In the initial ANCOVA analysis of data, a profound treatment-by-sequence interaction occurred. "The placebo conditions got better and better and better throughout the trial, and it was very, very significant differences," Dr. Walsh told meeting attendees. Thus, this presentation included data only from the first treatment period, including 11 to 12 participants in each of the four dosage groups. (Safety data were reported for all 58 adults who received at least one dose of tiagabine.)

The tiagabine treatment during this first treatment phase had statistically significant effects at both the 8- and 12-mg doses on both reducing the number of minutes spent awake after sleep onset and increasing the minutes of deep slow-wave sleep. Even at the lower 8-mg dose, which produced no adverse effects in any of the participants, the average minutes of slow-wave sleep doubled compared with baseline. These increases were seen both early and throughout the night. "This is a very profound difference," Dr. Walsh explained. "Slow-wave increases are sort of the hallmark of this drug."

The clinical relevance of increasing slow-wave sleep is unknown. "Many of us are designing studies as we sit in our rooms here trying to demonstrate [that] this does play a role," Dr. Walsh said. There is biological evidence to suggest a benefit of increased slow-wave sleep time, he added, and data coming out in the near future may better show this.

Tiagabine is currently approved for controlling partial seizures in adults and children older than 12 years. It is a selective GABA reuptake inhibitor that produces an increase in extracellular GABA by selectively binding to GAT-1, the primary GABA uptake transporter. Such GABAergic drugs have been shown to affect sleep in the past.

The study was funded by Cephalon, Inc., the maker of Gabitril.

APSS 18th Annual Meeting: Abstract 575. Presented June 9, 2004.

Reviewed by Gary D. Vogin, MD

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