PILOT CONTROLLED DOUBLE-BLIND-STUDY OF THE HYPNOTIC EFFECTS OF ZOLPIDEM IN PATIENTS WITH CHRONIC LEARNED INSOMNIA - PSYCHOMETRIC AND POLYSOMNOGRAPHIC EVALUATION

In a pilot double-blind trial in 21 patients with learned or idiopathi c insomnia (DSM-IIIR), patients received placebo for 1 week (nights 1 - 7), either active (zolpidem, 10 mg) or placebo treatment for 2 weeks (nights 8 - 21) and then placebo for a further week (nights 22 - 28). Variables to measure efficacy, rebound and withdrawal were assessed d aily from day 1 to day 28. Polysomnographic recordings together with s leep cycle analysis were performed on nights 7, 21 and 28. Patients tr eated with 10 mg zolpidem for 2 weeks had significantly improved sleep efficiency at the end of the randomised double-blind phase compared w ith the placebo group. Fractionated sleep-cycle analysis showed an inc rease in slow-wave sleep during the first 2-hour cycle after sleep ons et. During the withdrawal placebo week, most of the main sleep variabl es remained relatively stable in the zolpidem group (nights 22 - 28), and deteriorated further in the placebo group. At the end of the withd rawal phase, there was a statistically significant difference between groups, in favour of the zolpidem treatment, in sleep efficiency, tota l sleep time, absolute and percentage of time awake, and percentage of REM sleep. REM sleep, which was normal in both groups at baseline, de creased significantly in the placebo group between nights 22 and 28 (d uring the withdrawal placebo week) compared with the zolpidem treatmen t group, and the number of periods of time awake increased. Minor subj ective complaints were recorded under zolpidem and were comparable wit h those under placebo. Zolpidem seemed to improve some important sleep variables, when assessed both objectively and subjectively. The sleep cycle analysis suggested a possible shift of slow-wave sleep to an ea rlier period of the night, with a more physiological sleep structure. There was no evidence for withdrawal or rebound after stopping the 2 w eeks of zolpidem treatment, but rather signs that the effect of zolpid em outlasted active treatment. The present pilot study justifies a pro spective confirmatory comparison of zolpidem with benzodiazepines in a n adequate number of patients and withdrawal after 6 - 8 weeks of trea tment.