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 appearing within 3 days from the abrupt discontinuation of benzodiazepines (mainly short-acting), following long term use and abuse of these hypnotics. Zolpidem is an imidazopyridine, that binds selectively at ω1-receptor subtypes within the GABAA receptor supramolecular complex. 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 (three Italian centres) was aimed at assessing the symptoms/signs of rebound 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 were statistically significant [p = 0.0064 for Total Sleep Time (TST) and p = 0.0051 for Sleep Efficiency (SE%)] differences between triazolam- and zolpidem-treated patients during the first withdrawal night versus 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) showed a statistically significantly (p = 0.0083) different pattern, during the first withdrawal night, remaining decreased after zolpidem (37.5 min) but suddenly increasing after triazolam (17.3 min). Also the subjective time to fall asleep changed with a statistically significant difference (p = 0.042), being increased after triazolam (8.6 min) and decreased after zolpidem (20.8 min). The results of the study demonstrate the presence of clear rebound insomnia after triazolam discontinuation, whereas such a drawback is absent with zolpidem. This allows the abrupt discontinuation of zolpidem without any need for a tapering procedure and without any risk of pharmacological dependence.