Download Controversies in Sleep Physiology and Sleep Medicine

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
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