Effect of short-term treatment with gaboxadol on sleep maintenance and initiation in patients with primary insomnia.
OBJECTIVE
To perform an early evaluation of the efficacy and safety of gaboxadol in the treatment of primary insomnia.


METHODS
26 adults (18-65 years) with DSM-IV criteria for primary insomnia were randomly assigned gaboxadol (5 mg, 15 mg) or placebo in a double-blind, crossover study. After a 3-night polysomnographic (PSG) screen, treatment was administered 30 min before bedtime on 2 consecutive nights during 3 separate sessions including PSG. Efficacy analyses (n = 23) were based on the average of Nights 1 and 2, and compared gaboxadol versus placebo. Baseline was the average of Nights 2 and 3 of the screening session. Both gaboxadol doses significantly (P < 0.05) improved mean total sleep time (mean +/- SD: baseline = 368.0 +/- 51.1 min, 15 mg = 420.3 +/- 24.5 min, 5 mg = 419.8 +/- 20.4 min, placebo = 408.7 +/- 30.4 min). Both gaboxadol doses reduced mean wake after sleep onset, although statistical significance was only achieved with 5 mg (baseline = 61.6 +/- 35.4 min, 15 mg = 38.0 +/- 21.1 min, 5 mg = 34.6 +/- 14.3 min, placebo = 43.4 +/- 22.9 min). Gaboxadol 15 mg also significantly reduced mean latency to persistent sleep (baseline = 55.6 +/- 27.0 min, 15 mg = 23.6 +/- 15.1 min, placebo = 30.0 +/- 19.1 min) and enhanced slow wave duration (baseline = 72.4 +/- 20.8 min, 15 mg = 114.0 +/- 37.5 min, placebo = 93.9 +/- 31.3 min) with no significant effects on REM sleep duration. Patient reports (Leeds Sleep Evaluation Questionnaire) of reduced time to sleep and increased sleep quality showed significant improvement with gaboxadol 15 mg. No next-day residual effects were observed with either dose of gaboxadol (assessed 2 h and 9 h after lights on). All adverse events were mild or moderate.


CONCLUSIONS
Gaboxadol 15 mg was effective and generally well tolerated in the short-term treatment of patients with primary insomnia. Gaboxadol also enhanced slow wave sleep duration and had no significant effects on REM sleep duration. These findings suggest that gaboxadol may be a useful treatment for insomnia.
Deacon
Steve
S
H. Lundbeck A/S, International Clinical Research, Valby, Denmark. stde@lundbeck.com
Staner
Luc
L
Staner
Corinne
C
Legters
Annelies
A
Loft
Henrik
H
Lundahl
Jonas
J
D000328:Adult; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D018755:GABA Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D017286:Polysomnography / Q000187:drug effects; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*
D018755:GABA Agonists; D007555:Isoxazoles; C015542:gaboxadol