A double-blind, randomized and placebo-controlled study on the polysomnographic withdrawal effects of zopiclone, zolpidem and triazolam in healthy subjects

Rebound effects after withdrawal from hypnotics are believed to trigger the ir chronic use and to enhance the risk of tolerance and dependence. It was the purpose of this study to investigate the acute polysomnographic withdra wal effects after a 4 week treatment with standard doses of the non-benzodi azepine hypnotics zopiclone and zolpidem compared with triazolam and placeb o. Healthy male subjects between 22 and 35 years of age participated in a p arallel study design. They received either zopiclone 7.5 mg (n=11), zolpide m 10 mg (n=11), triazolam 0.25 mg (n=10) or placebo (n=7) over 4 weeks in r andomized and double-blind order. Sleep EEG was registered during 2 nights before treatment under placebo, on days 1, 27 and 28 of treatment and on da ys 29, 30, 41 and 42 under placebo. Total sleep time and sleep efficiency w ere lower in the 1st night after discontinuation of triazolam (p < 0.05, t- test). After withdrawal from zopiclone or zolpidem slight but not significa nt rebound effects concerning sleep continuity were observed. Self-rating s cales showed minimal rebound insomnia after discontinuation of all three hy pnotics. In the placebo group no changes of sleep parameters were observed. Assuming that rebound insomnia is part of a withdrawal reaction, this stud y indicates that the risks of tolerance and dependency are low when adminis tering zopiclone or zolpidem at the recommended doses.