Effect of tiagabine on sleep in elderly subjects with primary insomnia: A randomized, double-blind, placebo-controlled study

Subject Objective: This study further evaluated the effects of tiagabine on sleep in elderly subjects with primary insomnia. Methods: Elderly subjects (aged 65-85 years) meeting DSM-IV-TR criteria for primary insomnia were randomly assigned to receive tiagabine 2, 4, 6, or 8 mg or placebo on 2 consecutive nights. Efficacy was assessed using standard polysomnography and a postsleep questionnaire. Additional assessments included the Assessment of Daily Functioning, Digit Symbol Substitution Test (for residual effects), and visual analog scale (for sleepiness/alertness). Results: A total of 207 subjects were randomly assigned to study medication (tiagabine: 2 mg, n = 43; 4 mg, n = 38; 6 mg, n = 45; 8 mg, n = 43; placebo, n = 38). Tiagabine did not significantly effect wake after sleep onset, latency to persistent sleep, or total sleep time compared with placebo (P > .05). Significant increases in Stage 3 + 4 sleep (i.e., slow-wave sleep) were found for tiagabine 4, 6, and 8 mg versus placebo, with a corresponding significant decrease in Stage 1 sleep (P < .05). At 6 and 8 mg, tiagabine also significantly reduced the number of awakenings and increased the ratio of Stage 3 + 4/(Stage 1 +wake after sleep onset). In general, there were no significant effects on subjects' ratings of sleep or daily functioning with tiagabine 2, 4, and 6 mg versus placebo. These 3 doses had tolerability profiles comparable with that of placebo and were not associated with significant residual effects or reduced alertness. The 8-mg dose, however, significantly decreased subjective total sleep time and refreshing quality of sleep, as well as daily functioning. This dose was associated with troublesome adverse events, significant residual effects, and reduced alertness. Conclusions: In elderly subjects with primary insomnia, tiagabine did not have a significant effect on wake after sleep onset, latency to persistent sleep, total sleep time, or the subjective rating of sleep. Tiagabine 4, 6, and 8 mg significantly increased slow-wave sleep, with a corresponding significant decrease in Stage 1 sleep. Tiagabine was generally well tolerated, with doses of less than 6 mg having tolerability profiles generally similar to that of placebo. The 8-mg dose, however, was associated with troublesome adverse events, residual effects, and reduced alertness.