Comparison of the Effects of Zaleplon, Zolpidem, and Triazolam on Memory, Learning, and Psychomotor Performance

Abstract

Twenty-four healthy male and female subjects, who participated in this randomized, double-blind, crossover study, received single nighttime doses of zaleplon 10 mg (therapeutic dose), zaleplon 20 mg, zolpidem 10 mg (therapeutic dose), zolpidem 20 mg, triazolam 0.25 mg (positive control), and placebo. Subjective behavioral ratings and psychomotor tests were completed before and 1.25 and 8.25 hours after administration of the study drug. The Immediate and Delayed Word Recall tests and the Digit Span Test were used to assess memory. The Digit-Symbol Substitution Test, Paired Associates Learning Test, and Divided Attention Test were used to assess other cognitive skills. Zaleplon 10 mg did not produce any significant changes in memory or learning compared with placebo. All other active treatments, including zolpidem 10 mg, caused psychomotor impairment at the 1.25-hour test battery. Zolpidem 20 mg (twice the therapeutic dose) produced more psychomotor impairment at the 1.25-hour assessment than did any of the other active treatments, including zaleplon 20 mg. At the 8.25-hour time point, test scores for subjects who received zaleplon 10 mg and 20 mg did not differ from the test scores for those who received placebo. However, cognitive impairment persisted up to the 8.25-hour observation for subjects who were administered triazolam 0.25 mg and zolpidem 20 mg. Adverse events associated with the use of zaleplon were transient and mild-to-moderate in severity. Overall, this study shows that zaleplon is a safe hypnotic that does not affect memory, learning, or psychomotor skills associated with vigilance.

Effects of prolonged‐release melatonin, zolpidem, and their combination on psychomotor functions, memory recall, and driving skills in healthy middle aged and elderly volunteers

“…These effects were seen across measures of attention, memory, and motor coordination. They are consistent with previous studies, where 10 mg of zolpidem at daytime or night-time was found to produce significant impairments of psychomotor performances, attention, and memory from 1-5 h (Berlin et al, 1993;Danjou et al, 1999;Hindmarch et al, 2001) but no residual effects at 8 h or more after administration (Berlin et al, 1993;Fairweather et al, 1992) although delayed memory might be impaired up to 8.25 h after a bedtime administration (Troy et al, 2000). Driving abilities were also impaired 2 h after zolpidem intake, with standard deviations of both speed limit deviation, absolute speed deviation and ideal route deviation, and the number of collisions being significantly affected.…”

Nelotanserin, a Novel Selective Human 5-Hydroxytryptamine2A Inverse Agonist for the Treatment of Insomnia

“…The efficacy of these compounds is tied to their exposure, i.e., agents with longer half-lives might be better suited to address sleep maintenance insomnias, but they also tend to have more significant next-day hangover effects that are associated with psychomotor and memory impairments (Drover, 2004). Agents like zaleplon, which have a very short half-life of approximately 1 h, are very useful for sleep-onset insomnia and have no hangover effects, but they are not ideal for sleep maintenance (Troy et al, 2000;Walsh et al, 2000). Inverse agonism of the 5HT 2A receptor seems to produce sleep maintenance without residual psychomotor impairment upon wakening.…”

Effect of Repeated Gaboxadol Administration on Night Sleep and Next-Day Performance in Healthy Elderly Subjects

“…In view of its short elimination half-life, one may not have expected residual effects. However, as documented for a number of benzodiazepines (Hindmarch and Ott, 1984) and zolpidem (Roth et al, 1995;Troy et al, 2000;Hindmarch et al, 2001), hypnotic substances with short half-lives are not necessarily free from residual effects. Moreover, as the sleep effects of gaboxadol appear longer-lasting in aged (present study; Lancel et al, 2001) than in young subjects (Faulhaber et al, 1997;Mathias et al, 2001), its elimination half-life probably increases with advancing age.…”