N-of-1 trials

Background. Benzodiazepines are frequently prescribed for sleep disturbances. However, benzodiazepines are associated with side effects, and may be ineffective when used for a prolonged period of time. Objectives. To investigate for individual patients whether placebo was as effective as temazepam, or whether 10 mg was as effective as 20 mg temazepam, and whether these results influenced their future temazepam use. Methods. A series of randomized double-blind N-of-1 trials were conducted in general practices in The Netherlands for patients who were using temazepam regularly. Each patient received five pairs of treatments consisting of one week of temazepam (10 or 20 mg) and one week of the control intervention (placebo or 10 mg temazepam). Per pair, the sequence of treatments was randomized. Main outcome measures were: time to fall asleep, and the individual main complaint. Results. Twelve out of 15 patients completed their trial. In three patients there was no difference, in five a large difference, and in four a small difference in favour of temazepam. At follow-up, seven patients had stopped or reduced their temazepam use. Conclusion. The results regarding the efficacy of temazepam varied across patients. N-of-1 trials seem to be valuable in patients who are motivated to stop or reduce their temazepam use. They clearly demonstrate the efficacy of temazepam, and may give patients additional confidence to discontinue regular hypnotic use. The value of N-of-1 trials for patients who are less motivated is unclear, as the size of treatment effect does not seem to influence future hypnotic use