Dose-response studies of lormetazepam: efficacy, side effects, and rebound insomnia.

Lormetazepam, an investigational hypnotic, was evaluated for efficacy and withdrawal phenomena in doses of 0.5, 1.0, 1.5, and 2.0 mg in four separate sleep laboratory protocols, each including four placebo baseline nights, seven drug nights, and three placebo withdrawal nights. A moderate degree of efficacy was shown across the four doses, but this was quite variable. There was no dose-response effect for efficacy for either the first three or last three nights of this short-term administration period. In general, there was less efficacy on the later drug nights, indicating a potential for the development of tolerance over a relatively short period of time. Following drug withdrawal, there was a dose-related worsening of sleep above baseline levels (rebound insomnia). The peak degree of worsening of sleep following drug withdrawal was more than two times greater than the peak degree of improvement of sleep with drug administration.