Tiagabine enhances slow wave sleep and sleep maintenance in primary insomnia.
OBJECTIVE
To evaluate the effect of tiagabine on sleep and next-morning alertness and performance in adult patients with primary insomnia.


METHODS
Patients with primary insomnia, as defined by Diagnostic and Statistical Manual of Mental Disorders--Fourth Edition (DSM-IV), received tiagabine 4, 8, 12, 16 mg, and placebo in a randomized, double-blind, five-period, Latin square, crossover study. Efficacy was assessed using polysomnographic and self-report techniques; residual effects were evaluated using the Digit Symbol Substitution Test (DSST) and the Rey Auditory Verbal Learning Test (RAVLT).


RESULTS
Fifty-eight patients (40f, 18m; mean age 46.6+/-8.0 years) were randomized. Results showed a significant dose-dependent increase in slow wave sleep percentage with all tiagabine doses, a trend toward a dose-dependent increase in total sleep time, and no effect on latency to persistent sleep. Wake after sleep onset also decreased in a dose-dependent manner, with the 16-mg dose differing significantly from placebo. The tolerability profiles of tiagabine 4 and 8 mg were similar to placebo. The most common adverse events reported following tiagabine 12 and 16 mg were dizziness and nausea. Residual effects were only apparent at 12- and 16-mg doses.


CONCLUSIONS
Tiagabine increased slow wave sleep and reduced wake after sleep onset in a dose-dependent manner. Tiagabine dosages up to 8 mg did not compromise next-morning alertness and psychomotor performance in adult patients with primary insomnia. Further investigation of tiagabine doses up to 8 mg is warranted.
Walsh
James K
JK
St. John's Mercy/St. Luke's Hospitals, Sleep Medicine and Research Center, Chesterfield, MO 63017, and Department of Psychology, St. Louis University, St. Louis, MO 63130, USA. jwalsh@stlo.mercy.net
Zammit
Gary
G
Schweitzer
Paula K
PK
Ondrasik
John
J
Roth
Thomas
T
D000328:Adult; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009557:Nipecotic Acids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D017286:Polysomnography; D012890:Sleep / Q000187:drug effects*; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*; D012894:Sleep Stages / Q000187:drug effects; D000078308:Tiagabine; D014851:Wakefulness / Q000187:drug effects
D018755:GABA Agonists; D009557:Nipecotic Acids; D000078308:Tiagabine