Relative Efficacy of Drugs for the Treatment of Sleepiness in Narcolepsy

Abstract

A survey was conducted on 10 polysomnographic studies on the pharmacologic treatment of the sleepiness of narcolepsy. Three studies employed the MSLT and 7 employed the MWT as their polygraphic measure of sleep tendency. Statistically and clinically significant therapeutic changes were apparent for pemoline, modafinil, dextroamphetamine and methylphenidate. Codeine, ritanserin and protriptyline did show statistically significant effects. The common feature among the drugs that did produce clinically significant improvements seems to be facilitatory action on central catecholaminergic transmission. Within this group of drugs, only methylphenidate and dextroamphetamine brought MWT sleep latencies to approximately 70% of normal levels.

Diurnal actigraphy and stimulant efficacy in narcolepsy

“…In a study of 522 patients with narcolepsy (Sangal et al, 1999), estimates of sleep propensity [Epworth Sleepiness Scale, ESS; Johns, 1991)] were shown to remain unchanged despite objectively measured changes in sleep propensity in the laboratory (Maintenance of Wakefulness Test, MWT). Costly sleep laboratory based procedures such as the Multiple Sleep Latency Test (MSLT) and MWT provide inconsistent results in the evaluation of treatment efficacy of disorders of excessive sleepiness (Mitler et al, 1982(Mitler et al, , 1990(Mitler et al, , 1991(Mitler et al, , 1993. In addition, external validity is questionable due to confounding motivational and environmental factors inherent under laboratory conditions (Broughton et al, 1988;Roth et al, 1994).…”

Clinical features, diagnosis and treatment of narcolepsy

“…18 Amphetamines have been in use since the 1930s and there is little doubt about their efficacy; however, formal evidence for their use is sparse. Mitler and Hajdukovic 34 conducted a post hoc quantitative review of various studies of the pharmacological treatment of excessive daytime sleepiness in narcolepsy. Drugs used in the studies reviewed included methylphenidate, dexamphetamine and modafinil.…”

Treatment of Narcolepsy with Methamphetamine

“…Furthermore, surveys indicate that narcoleptics receiving pharmacological treatment report that they function poorly at work and in social situations (17,18). It is likely that efforts to eliminate pathological somnolence with central nervous system (CNS) stimulants are not attempted due to physician concern regarding side effects and physician reluctance to prescribe doses of stimulants in excess of manufacturer's suggested dosage levels (17,19,20). …”

“…Although our study did not explore the mechanism of action of methamphetamine, the amphetamines in general are thought to act by releasing dopamine and, to some extent, norepinephrine from CNS neurons (21). We and others have speculated that the relative efficacy of drugs in the treatment of narcolepsy is related to the degree to which the drugs act on CNS dopamine systems (20,35,36). Within this group of drugs, our favorable results with methamphetamine may stem from methamphetamine's higher ratio of central to peripheral effects (21).…”

“…In spite of its favorable ratio of central to peripheral effects and clinical reports of its effectiveness (16), methamphetamine does not have narcolepsy listed as an indication (20). At present, methamphetamine is rarely prescribed in the treatment of narcolepsy (17).…”