Temazepam versus Nitrazepam: A Comparative Trial in the Treatment of Sleep Disturbances

Abstract

Introduction Short-acting benzodiazepines are often the first choice drugs in the pharmacological treatment of insomnia, particularly in subjects who live a normal daily working life. Day-time sedation, which impairs mental and physical performance, is in fact one of the major drawbacks of benzodiazepines with a longer half-life. Recently temazepam, one of the shortacting benzodiazepines, has been made available for therapeutic use as a 1% solution in polyethileneglicole (PEG) supplied in soft gelatin capsules. Its pharmacokinetic profile makes it particularly suitable as a sleepinducing agent. The mean plasma levels reach 80% of the peak value as soon as 20 minutes after oral administration, and the drug has a half-life of 6-8 hours (Fucceila 1979). It is eliminated in the urine as the g1ucuronide, forming virtually no active metabolites. On the basis of its pharmacokinetic pattern, with the administration selectivity commonly used in the treatment of insomnia, no cumulation phenomena are usually observed (Fuccella 1979). At the therapeutic dosage, the drug does not give rise to much detectable hang-over the next day (Hindmarch 1975, Hindmarch 1976, Fowler 1977), and even in geriatric patients it appears well tolerated and relatively free from 'morning-after' effects (Middleton 1978). The main aim of this study was to assess the sleep-inducing activity of temazepam and any residual sedation it caused, in comparison with nitrazepam, still a widely used and well documented hypnotic drug. Material and Methods To be eligiblefor the trial, subjects had to have sleep disturbances involving difficulty in falling asleep (onset of sleep longer than 45 minutes) and/or early awakening or mixed type insomnia. Patients with hepatic or renal failure, painful conditions which might interfere with sleep, or the need for concomitant major psychotropic drug or anticonvulsant treatment were excluded. Pregnant women were also not included. Thirty-six subjects were selected, nineteen males and seventeen females, mean age 44·5 years (range 30-59 years). Thirty per cent of these subjects suffered from moderately severe sleep disturbance, and the rest suffered from slight sleep disturbance. The main complaint on admission was the difficulty in falling asleep, the average time required being 65 minutes (range 50-120); the total duration of sleep was on average 6 hours (range 5-7). Only three of these patients were already receiving sleep-inducing or anxiolytic drugs, and these were withdrawn the day before starting the trial. In none of these patients was insomnia a symptom of psychiatric disease, and they were all in hospital for internal medical disorders, mainly involving the cardiovascular system. Basic therapy for these ailments remained unchanged throughout this study. All participants gave their informed consent to taking part in the trial. The three treatments under investigation, namely 20 mg temazepam in soft gelatin capsules, 5 mg nitrazepam in