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Sleep. 16(3): 199-20 1 © 1993 American Sleep Disorders Association and Sleep Research Society Controversies in Sleep Physiology and Sleep Medicine This series of presentations will review some controversies in sleep medicine and physiology. This section will appear periodically in this journal to review different perspectives. In this issue three clinicians experienced in the treatment of narcolepsy present their perspectives on the use of stimulant medication in narcolepsy. In medicine there frequently is no "right" or "wrong" way to treat a patient. At times physicians looking at the same data may interpret that data quite differently. As the readership is aware, amphetamine medications are not available in many parts of the world. Yet amphetamines may be highly efficacious in narcolepsy. The purpose of the three presentations is to present the European perspective (Drs. Parkes and Dahlitz), the conventional American perspective (Dr. Guilleminault) and a perspective that focuses on the abolition of sleepiness (Drs. Mitler, Erman and Hajdukovic). The reader is encouraged to examine the data and to reach his or her own conclusion. -Meir Kryger, Section Editor Amphetamines and Narcolepsy 1. Amphetamines and Narcolepsy: Use a/the Stanford Database Christian Guilleminault Stanford University Sleep Disorders Clinic and Research Center, Stanford, California, U.S.A. The use of amphetamines in medicine has been subject to controversy worldwide. Several European countries have banned amphetamines because of their side effects, and the U.S. has considered banning its medical use. The countries that do allow amphetamines often require triplicate prescriptions and drug agency surveillance of prescription patterns, prescription amounts and patient identities. Little research has been done on new stimulant medications over the years. However, probably in recognition of the negative effects of the amphetamine ban on narcoleptics, several countries are now considering market release of selegiline, a putative monoamineoxidase (MAO) inhibitor whose metabolite is amphetamine. France recently released modafinil, a drug with a pharmacologic profile similar to that of an alpha-l agonist, for use as a stimulant. Many hope that it will prove to be less addictive than amphetamines. There are many controversies concerning prescription of amphetamines in narcolepsy due to their potential addictive effects, their use as recreational drugs and the mental and cardiovascular side effects reported with them. Historic reports on amphetamines have varied. In 1935 Prinzmetal and Bloomberg (1) were the first to report an addiction to amphetamines in narcoleptic patients. However, Parkes reported in 1975 on patients who had taken amphetamines for 30 or 40 years without ill effects. Parkes et al. (2) reported that response to amphetamines varies between subjects. In their study, similar blood levels of amphetamines were achieved in both good and poor responders. Age of onset of narcolepsy, and frequency and duration of narcoleptic attacks did not seem to be important variables. Also, 113 of the patients rapidly became tolerant of amphetamines and had to double their dosage to maintain control of symptoms. Reasons for this between-patient variation in tolerance are poorly understood (2,3). Gunne and Anggard (4) found that the plasma elimination rate for amphetamines was increased in drugdependent versus drug-naive subjects. With long-term treatment an increased drug affinity for tissues also seems to occur. Controversies also exist between clinicians and between excessively sleepy patients concerning the end points of therapeutic success and the acceptability of unwanted effects. Some clinicians believe that the aim of therapy is not for patients to be awake and alert all day, but for them to be awake and alert when they need to be awake and alert. Other clinicians believe that patients should be optimally alert all day and that when patients are on proper treatment, they will not require naps and will accept a certain level of side effects to reach this goal. On the other side, some patients will not accept even mild tremulousness, even though they may be much 199