A recent study in narcolepsy patients has shown that ritanserin, a 5HT2-antagonist, reduced wake after sleep onset times and subjective sleepiness during daytime. To assess the efficacy of this compound in a statistically sufficient number of narcoleptic patients a double-blind, placebo-controlled, European multi-center study on the effects of ritanserin on daytime sleepiness, the feeling of being refreshed in the morning, number of unwanted sleep periods and slow-wave sleep was performed. All 134 narcolepsy patients were allowed to remain on stable concomitant antidepressant, stimulant and gammahydroxybutyrate medication during the trial. Patients were randomly assigned to treatment with 5 mg or 10 mg ritanserin or placebo given once daily for 28 days. Efficacy was measured by two 40-hour polysomnographic recordings, visual analogue scales and physician, partner, parents and patient-rated sleep-wake behavior tests prior to and after the trial. Patients kept diaries on sleepiness, numbers of wanted and unwanted sleep periods, feeling of being refreshed and frequency of narcoleptic symptoms during the entire treatment period. Treatment with 5 and 10 mg ritanserin significantly improved the ‘feeling of being refreshed in the morning,’ but no other narcoleptic symptoms as assessed in the diary. Whereas investigators had the impression that the primary efficacy parameters were not improved by ritanserin, patients reported significant improvements in four out of six parameters, and patients partners in two out of six parameters with 5 mg ritanserin compared to placebo. Both ritanserin doses resulted in a significant increase of nocturnal slow-wave sleep (percentage of total sleep time) and a significant, dose-dependent reduction in NREM stage 1 percentage during daytime sleep. The significant polysomnographic findings were not paralleled by changes in the subjective parameters daytime sleepiness or number of unplanned sleep periods. In contrast to the first study on narcoleptic patients, ritanserin only improved one subjective parameter, but did not improve objective sleep quality or number of ”sleep attacks” or reduce ”wake after sleep onset” during night or daytime sleep. In conclusion, ritanserin may serve as add-on medication for the treatment of impaired sleep quality in narcoleptic patients, but not as a stimulant or hypnotic type of medication.
Key words
Ritanserin - Narcolepsy - 40-hour polysomnographic recording - Slow-wave sleep - Visual analogue scales - Sleep quality
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