DENVER – The anticonvulsant tiagabine (Gabitril) increased slow wave sleep in dose-dependent fashion in a 30-center randomized trial involving 232 adults with primary insomnia, James K. Walsh, Ph.D., reported at the annual meeting of the Associated Professional Sleep Societies.
But whether this drug-induced alteration in sleep architecture will translate into clinical utility for the treatment of insomnia remains an unanswered question. Of note, patients given tiagabine didn't report their sleep as being any deeper, more refreshing, or of better quality than patients on placebo, said Dr. Walsh, director of the sleep medicine and research center at St. Luke's Hospital, St. Louis.
Tiagabine is a selective γ-aminobutyric acid (GABA) reuptake inhibitor that boosts synaptic GABA availability through selective inhibition of the GABA transporter-1 receptor.
The randomized trial compared four doses of tiagabine–4, 6, 8, and 10 mg at bedtime–and a placebo in a two-night polysomnographic study. Slow wave sleep increased from baseline by a mean of 19 minutes with 4 mg of tiagabine, 32 minutes with 6 mg, 40 minutes with 8 mg, and 53 minutes with 10 mg, compared with an 11-minute increase with placebo. A corresponding dose-related decrease in stage 1 sleep with tiagabine was also noted.
The 4- and 6-mg doses of tiagabine had a side effect profile similar to placebo, while dizziness and nausea were the most prominent adverse events noted in patients on 8- and 10-mg doses of the drug.
Patients on the 10-mg dose scored significantly worse than the placebo group on the assessment of daily functioning questionnaire in terms of ability to concentrate and think clearly, sense of physical well-being, and alertness. They also reported notable psychomotor impairment. For these reasons, doses of less than 10 mg will be utilized in further trials evaluating tiagabine efficacy in primary insomnia.
The trial was sponsored by Cephalon Inc.