Use of zolpidem 10 mg as a benzodiazepine substitute in 84 patients with insomnia

Abstract

The antagonistic effects of zolpidem 10 mg on withdrawal symptoms caused by abrupt or gradual discontinuation (half-dose over 4 nights) of triazolam 0·25 mg in patients with chronic insomnia, who had been receiving regular treatment for over one month, were assessed in a randomized, double-blind, placebo-controlled clinical trial in general practice. Eighty-four patients were enrolled, mostly women (67·9%), with a mean age of 54·3±11·0 years. Twenty-one different general practitioners were solicitated for the recruitment. The subjects were randomized into four groups, and all received triazolam 0·25 mg during the run-in phase from day 1 (D1) to day 3 (D3). The following treatments were given from D4 to D7: triazolam 0·125 mg+zolpidem 10 mg (Group 1); zolpidem 10 mg (Group 2); placebo (Group 3); or triazolam 0·125 mg+placebo (Group 4). Groups 1 and 2 received zolpidem 10 mg from D7 to D24, while Groups 3 and 4 received placebo. Finally, all four groups received placebo (blind withdrawal phase) from D25 to D28. The following assessment criteria were used: clinical global impression (CGI) scale completed by the practitioner; patient questionnaire based on routine sleep criteria, wakefulness and daytime alertness. Secondary criteria were sleep diaries and visual analogue scales. Study drop-outs were reported and explained. The effectiveness/tolerance ratio was found to be statistically significant using the CGI (p<0·007) in favour of zolpidem 10 mg. There was no significant difference in patients subjective assessment between the groups except for nightmares (p<0·04) less frequent in patients receiving zolpidem. Zolpidem was found to be more effective than placebo at D21 (CGI) according to sleep diaries; the zolpidem group showed a statistically significant difference as compared to the three other concerning four sleep parameters: number of awakenings, anxiety, sleep duration, energy. Drop-out rates were significantly lower in the zolpidem group than in other ones (p<0·01). Abrupt and gradual triazolam withdrawal over 4 nights induced withdrawal symptoms. Equally no specific phenomena were observed at the end of the trial during the blind withdrawal phase. This study shows that zolpidem 10 mg improves sleep quality and reduces withdrawal symptoms after abrupt or gradual discontinuation of triazolam 0·25 mg in chronic patients with chronic insomnia. Copyright © 1998 John Wiley & Sons, Ltd.