REBOUND INSOMNIA AFTER ABRUPT DISCONTINUATION OF HYPNOTIC TREATMENT -DOUBLE-BLIND RANDOMIZED COMPARISON OF ZOLPIDEM VERSUS TRIAZOLAM

Rebound insomnia is a transient intense worsening of sleep usually app earing within 3 days from the abrupt discontinuation of benzodiazepine s (mainly short-acting), following long term use and abuse of these hy pnotics. Zolpidem is an imidazopyridine, that binds selectively at ome ga(1)-receptor subtypes within the GABA(A) receptor supramolecular com plex. It has a rapid onset of action and short-elimination half-life; it reduces the latency of sleep and prolongs the duration of sleep in patients with insomnia, without any major effects on sleep stages and rebound effects upon discontinuation. The present multicentre trial (t hree Italian centres) was aimed at assessing the symptoms/signs of reb ound insomnia after discontinuation of either zolpidem or triazolam. A double-blind, randomized, parallel group trial of 20-day duration was carried out in 22 patients suffering from either transient insomnia, or short-term (situational stress) insomnia, or patients who were poor sleepers. The trial consisted of three periods: a 3-day run-in period with placebo, a 14-day active treatment period (zolpidem 10 mg od or triazolam 0.25 mg od), a 3-day withdrawal period with placebo. There w ere statistically significant [p = 0.0064 for Total Sleep Time (TST) a nd p = 0.0051 for Sleep Efficiency (SE%)] differences between triazola m- and zolpidem-treated patients during the first withdrawal night ver sus baseline: TST decreased to 34.5 min after triazolam but increased to 43.8 min after zolpidem, and a similar evolution was shown on SE% ( a decrease of 6.3 per cent after triazolam and an increase of 9.9 per cent after zolpidem). Also the Wake-time After Sleep Onset (WASO) show ed a statistically significantly (p = 0.0083) different pattern, durin g the first withdrawal night, remaining decreased after zolpidem (37.5 min) but suddenly increasing after triazolam (17.3 min). Also the sub jective time to fall asleep changed with a statistically significant d ifference (p = 0.042), being increased after triazolam (8.6 min) and d ecreased after zolpidem (20.8 min). The results of the study demonstra te the presence of clear rebound insomnia after triazolam discontinuat ion, whereas such a drawback is absent with zolpidem. This allows the abrupt discontinuation of zolpidem without any need for a tapering pro cedure and without any risk of pharmacological dependence.