Treatment of Narcolepsy: Objective Studies on Methylphenidate, Pemoline, and Protriptyline

Abstract

Summary: Methylphenidate, pemoline, and protriptyline were studied for their treatment efficacy in narcolepsy. A low, intermediate, and high dose level of each drug was studied for 1 week. For methylphenidate the doses were 10, 30, or 60 mg/day; for pemoline, 18.75,56.25, or 112.5 mg/day; and for protriptyline 10, 30, or 60 mg/day. The order of dose levels was random from subject to subject and the daily dose was divided into thirds and taken in identically appearing capsules morning, noon, and afternoon. Subjects were 6 narcoleptic patients studied on methylphenidate (5 women and 1 man; mean age 54.5 + 11.7 years), 7 narcoleptic patients studied on pemoline (5 women and 2 men; mean age 43.0 + 7.1 years), and 4 narcoleptic patients studied on protriptyline (2 women and 2 men; mean age 42.5 + 16.9 years). Testing consisted of day-long sessions occurring at the end of each dose level and involving a clinical status questionnaire as well as maintenance of wakefulness, Wilkinson addition, and Digit-Symbol Substitution tests. Results were compared with 9 control subjects with no sleep disorder (5 women and 4 men; mean age 39.2 + 8.4 years) who were given placebo that was purported to be a "stimulant drug" and tested in a similar manner. Results demonstrated profound differences in ability to stay awake and perform between narcoleptic patients and controls. Data also suggested that methylphenidate significantly improves ability to stay awake. Pemoline seems to improve ability to perform. Protriptyline does not significantly alter ability to stay awake or to perform.

Trial-to-Trial Variance in Choice Reaction Time as a Measure of the Effect of Stimulants During Sleep Deprivation

“…Although amphetamines may ameliorate the effects of sleep deprivation, their side effects, which include short-term modification of the cardiovascular system (e.g., increased blood pressure and possible long-term abuse of the drug), may argue against their use. Several other stimulants (e.g., methylphenidate and pemoline) are medically approved and have been used extensively in the treatment of attention deficit disorder and narcolepsy (Conners & Taylor, 1980;Mitler, Shafor, Hajdukovic, Timms, & Browman, 1986).…”

Use of Stimulants to Ameliorate the Effects of Sleep Loss During Sustained Performance

“…Other stimulants (e.g., methylphenidate and pemoline) have been shown to enhance performance in tedious discrimination or rote learning tasks for children suffering from attention deficit disorder (Peloquin & Klorman, 1986;Rapoport et al, 1980;R. H. Rosenthal & Allen, 1978), in fatigued normal subjects (Gelfand, Clark, Herbert, Gelfand, & Holmes, 1968), and in narcoleptics (Mitler, Shafor, Hajdukovich, Timms, & Browman, 1986). These effects have been attributed to an enhancement of attention, increased motivation, or reduced impulsiveness (Douglas, 1983;R.…”

“…H. Rosenthal & Allen, 1978;Stroufe, 1975). Amphetamine, pemoline, methylphenidate, and caffeine increase sleep latencies (Mitler et al, 1986;Zwyghuizen-Doorenbos, Roehrs, Lipshutz, Timms, & Roth, 1990). Caffeine improved auditory vigilance reaction time (RT) even after a restricted sleep of 5 hr (L. Rosenthal, Roehrs, Zwyghuizen-Doorenbos, Plath, & Roth, 1991).…”

Methylphenidate and Pemoline: Effects on Sleepiness and Mood during Sleep Deprivation

“…These drugs have been used primarily in the treatment of attention deficit disorder and narcolepsy (Conners and Taylor, 1980;Mitler et al, 1986). Both drugs have been shown to be effective in reversing the effects of fatigue on performance (Gelfand et al, 1968, Orzack et al, 1968 Pemoline is an oxizolidine compound.…”