Treatment of narcolepsy with methamphetamine

Abstract

Eight pairs of subjects (each consisting of a narcoleptic and a control matched on the basis of age, sex, educational background and job) were evaluated under the following double-blind, randomized treatment conditions: baseline, placebo, low dose and high dose methamphetamine. Subjects were drug-free for 2 weeks prior to beginning the protocol. Methamphetamine was the only drug taken during the protocol and was given 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 the four treatment conditions lasting 4 days followed by 3 days of washout. Nighttime polysomnography and daytime testing were done during the last 24 hours of each treatment condition. Daytime sleep tendency was assessed with the multiple sleep latency test (MSLT). Daytime performance was assessed with performance tests including a simple, computer-based driving task. Narcoleptics' mean MSLT sleep latency increased from 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' error 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 narcoleptics and controls. Methamphetamine at doses of 40-60 mg allowed narcoleptics to function at levels comparable to those of unmedicated controls.

FIG. 1

Mean MSLT sleep latencies, in minutes, as a function of experimental condition. The horizontal axis represents the experimental condition: baseline, placebo and 5–60 mg of methamphetamine. The vertical axis represents mean MSLT sleep latency. A point is plotted for each narcoleptic and control subject. The squares connected by lines represent the average for each experimental condition.

FIG. 2

Driving task performance as a function of experimental condition. The horizontal axis represents the experimental conditions: baseline, placebo and 5–60 mg of methamphetamine. The vertical axis represents mean percent of objects hit on the Steer Clear driving task. A point is plotted for each narcoleptic and control subject. The squares connected by lines represent the average for each experimental condition.

FIG. 3

Average of the morning and afternoon serum levels of methamphetamine (horizontal axis) vs. the average MSLT sleep latency (vertical axis) measured during the baseline, placebo, low dose and high dose treatment conditions for narcoleptic and control subjects. Two open circles were generated for narcoleptics in the high dose condition (rightmost circles), one for the five narcoleptics who received 40 mg and one for the three narcoleptics who received 60 mg.