Fluvoxamine and clomipramine in the treatment of cataplexy. The treatment of accessory symptoms in narcolepsy: a double-blind cross-over study of a selective serotonin re-uptake inhibitor (femoxetine) versus placebo. Ritanserin improves sleep quality in narcolepsy. Narcolepsy. Ritanserin, a 5-HT2 receptor blocker, as add-on treatment in narcolepsy.
Fluvoxamine 25-200 mg daily and clomipramine 25-200 mg daily were given for separate three week periods to 18 subjects with narcolepsy and cataplexy. Both drugs improved cataplexy but not narcolepsy. Fluvoxamine was less active than clomipramine, but both drugs abolished cataplexy in individual subjects. Gastrointestinal side effects prevented treatment with fluvoxamine in five subjects. All patients completed the clomipramine phase of the trial, but two men complained of delayed ejaculation. Fluvoxamine is a more potent inhibitor of 5-hydroxytryptamine (5-HT) reuptake in some systems, but not in others. It is therefore uncertain whether the greater anticataplectic effect of clomipramine is due to a greater inhibition of 5-HT reuptake or to other mechanisms. A randomized, double-blind cross-over trial was carried out in 10 patients with narcolepsy to evaluate the effect of 600 mg femoxetine versus placebo. In comparison to placebo, femoxetine treatment resulted in a significant decrease in both the number and severity score of cataplectic attacks per day. There were also significantly fewer attacks of sleep paralysis, whilst the effects on nightmare and hypnogenic hallucinations were minor. The frequency of sleep attacks decreased slightly during femoxetine treatment, but the overall estimated sleep time during the day and excessive daytime sleepiness remained un-affected. An ambulatory sleep recording for 48 h one week after the start of the femoxetine and placebo period showed that femoxetine treatment resulted in a significant decrease in the total time spent in REM sleep. The side-effects of femoxetine were restricted to transient nausea in 2 patients. It is concluded that femoxetine or other selective serotonin reuptake inhibitors may be a useful alternative for narcoleptic patients who experience troublesome side-effects with tricyclic antidepressants. 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. Narcolepsy is a neurological condition with a prevalence of up to 1 per 1,000 that is characterized by irresistible bouts of sleep. Associated features include the pathological manifestations of rapid-eye-movement (REM) sleep: cataplexy, sleep paralysis, hypnagogic hallucinations, and abnormal sleep-onset REM periods and disturbed nocturnal sleep. The condition is strongly associated with the HLA-DR2 and DQw1 phenotype. The phenomenology of narcolepsy is discussed, and diagnostic procedures are reviewed. Treatment modalities involving central nervous system stimulants for somnolence and tricyclic drugs for REM-sleep abnormalities are discussed. Sleep laboratory studies on the treatment efficacy of methylphenidate, pemoline, dextroamphetamine, protriptyline, and viloxazine are presented. Data suggest that: (1) methylphenidate and dextroamphetamine objectively improve somnolence; (2) pemoline, at doses up to 112.5 mg, is less effective in controlling somnolence but may improve certain aspects of performance; and (3) protriptyline and viloxazine are effective anticataplectic agents that produce little improvement in somnolence. In a double-blind placebo-controlled trial, ritanserin (a 5-HT2 receptor blocker) 5 mg/day or placebo was added to the usual medication in 28 patients with narcolepsy during 4 wk. The effect was assessed by means of polysomnography, daily and weekly subjective evaluations, and Multiple sleep latency tests (MSLT). During the night ritanserin increased the amount of nonrapid eye movement slow wave sleep and reduced wakefulness after sleep onset. It improved the feeling of being refreshed in the morning after awakening and reduced subjective daytime sleepiness. The drug did not significantly influence sleep latency in the MSLT.
Since the last version of this review no new studies were found.
There was no good quality evidence that antidepressants are effective for narcolepsy or improve quality of life. Despite the clinical consensus recommending antidepressants for cataplexy there is scarce evidence that antidepressants have a positive effect on this symptom. There is a clear need for well-designed randomised controlled trials to assess the effect of antidepressants on narcolepsy.