Dose-response effects of zaleplon as compared with triazolam (0.25 mg) andplacebo in chronic primary insomnia

The effects of two nights of treatment with the short-acting benzodiazepine receptor agonist zaleplon, triazolam, or placebo was assessed in chronic p rimary insomniacs using two concurrent, multi-center, randomized, double-bl ind. Latin Square crossover studies. Study 1 (n = 47) compared zaleplon (10 and 40 mg) to triazolam (0.25 mg) and placebo. Study 2 (n = 36) compared z aleplon (20 and 60 mg) to triazolam (0.25 mg) and placebo. For each study, polysomnographically recorded sleep parameters and patient reports of sleep quality were collected during baseline and two consecutive nights during t he four treatment phases in each study. All doses of zaleplon produced sign ificant decreases in latency to persistent sleep. Although no minimally eff ective dose could be determined, dose-response effects were apparent. Triaz olam 0.25 mg produced a decrease in latency to persistent sleep that was: c omparable to that of zaleplon 10 mg. Only the triazolam dose and the 60 mg dose of zaleplon produced significant increases in total sleep time over pl acebo. Zaleplon 40 and 60 mg and triazolam produced decreases in the percen tage of REM sleep compared to placebo. Patient reports of efficacy were con sistent with objective findings. In addition, all doses of zaleplon tended to increase while triazolam decreased the percentage of stage 3/4 sleep. Th ere was no evidence of residual daytime impairment for any of the zaleplon doses, however, triazolam administration produced significant impairment in performance on a digit copying test. A higher number of adverse events wer e seen with the 40 and 60 mg doses of zaleplon compared to triazolam (0.25) and placebo. At higher doses, zaleplon is more effective than triazolam at reducing latency to persistent sleep in chronic insomnia and is not associ ated with the decrease in slow-wave sleep or residual impairment observed w ith triazolam. However increases in total sleep time were apparent only at doses which produced concomitant increases in the number of adverse events. In contrast, triazolam (0.25 mg) produced increases in total sleep time (s imilar to 25 min) and decreases in latency to persistent sleep at a dose of 0.25 mg. Copyright (C) 2000 John Wiley & Sons, Ltd.