TREATMENT OF NARCOLEPSY WITH METHAMPHETAMINE

Eight pairs of subjects (each consisting of a narcoleptic and a contro l matched on the basis of age, sex, educational background and job) we re evaluated under the following double-blind, randomized treatment co nditions: baseline, placebo, low dose and high dose methamphetamine. S ubjects were drug-free for 2 weeks prior to beginning the protocol. Me thamphetamine was the only drug taken during the protocol and was give n in a single morning dose of 0, 20 or 40-60 mg to narcoleptics and 0, 5 or 10 mg to controls. The protocol was 28 days long, with each of t he four treatment conditions lasting 4 days followed by 3 days of wash out. Nighttime polysomnography and daytime testing were done during th e last 24 hours of each treatment condition- Daytime sleep tendency wa s assessed with the multiple sleep latency test (MSLT). Daytime perfor mance was assessed with performance tests including a simple, computer -based driving task. Narcoleptics' mean MSLT sleep latency increased f rom 4.3 minutes on placebo to 9.3 minutes on high dose, compared with an increase from 10.4 to 17.1 minutes for controls. Narcoleptics' erro r rate on the driving task decreased from 2.53% on placebo to 0.33% on high dose, compared with a decrease from 0.22% to 0.16% for controls. The effects of methamphetamine on nocturnal sleep were generally dose -dependent and affected sleep continuity and rapid eye movement (REM) sleep. Elimination half life was estimated to be between 15.9 and 22.0 hours. Mild side effects emerged in a dose-dependent fashion and most often involved the central nervous system and gastrointestinal tract. We concluded that methamphetamine caused a dose-dependent decrease in daytime sleep tendency and improvement in performance in both narcole ptics and controls. Methamphetamine at doses of 40-60 mg allowed narco leptics to function at levels comparable to those of unmedicated contr ols.