Sleep Medicine 5 (2004) 509–511

www.elsevier.com/locate/sleep

Case report
Concomitant use of modafinil and tranylcypromine in a patient
with narcolepsy: a case report
William Eric Clemonsa,*, Eugene Makelab,1, John Youngb,1
a
Michael S. Aldrich Sleep Disorders Laboratory, Department of Neurology, University of Michigan, 8D 8702 University Hospital,
Box 0117, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0117, USA
b
West Virginia University, 930 Chestnut Ridge Road, Morgantown, WV 26505, USA
Received 20 May 2003; received in revised form 15 June 2004; accepted 16 June 2004

Abstract

This is a case report of a patient with narcolepsy treated simultaneously with modafinil and tranylcypromine. The concurrent use of these
two medications is normally contraindicated based on theoretical concerns. To our knowledge this is the first report of the combined use of
these two medications in a patient for any reason. This combination of medications was particularly effective in the treatment of the patient’s
narcoleptic symptoms and was well tolerated, with no evidence of the potential cardiovascular side effects. Due to modafinil’s lack of
sympathomimetic activity and unique pharmacological profile, it may be well tolerated with monoamine oxidase inhibitor’s (MAOI’s) in
humans with respect to hemodynamic parameters and concerns of hypertensive crisis. Further investigation would help clarify cardiovascular
safety issues in using this combined therapy. We believe that with proper informed consent from the patient and careful monitoring, a
combination of an MAOI and modafinil may be a viable treatment alternative in refractory cases of narcolepsy.
q 2004 Elsevier B.V. All rights reserved.

Keywords: Narcolepsy; MAO inhibitor; Modafinil; Tranylcypromine

1. Introduction The psychostimulants are sympathomimetics that stimu-

Monoamine oxidase inhibitors (MAOI) are known to
be an effective treatment alternative for narcolepsy,
causing reductions in cataplexy attacks, sleep paralysis,
and hypnagogic hallucinations [1]. Clinically, the MAOI’s
are infrequently used, due to concern for hypertensive
crisis and poor patient tolerance. The concurrent use
of MAOI’s with modafinil has been cautioned based on
theoretical interactions with other agents that
have pharmacologic similarities. As yet no interaction
studies have been performed [2,3]. We report on the
concomitant use of modafinil and tranylcypromine in a
narcoleptic patient who had no apparent adverse drug
reaction.
* Corresponding author. Tel.: C1-734-936-9068; fax: C1-734-936-
5377.
E-mail address: ec2285@msn.com (W.E. Clemons).
1
Tel.: C1-304-293-2411; fax: C1-304-293-8724.
1389-9457/$ - see front matter q 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.sleep.2004.06.006
late the release of norepinephrine, serotonin, and dopamine
and additionally block their reuptake. The psychomotor
activation associated with these medications is attributed to
their dopaminergic activity; and the sympathomimetic
effects, to their noradrenergic activity [4].
Modafinil is chemically unrelated to the other central
nervous stimulants and has a pharmacologic profile that is
quite different from that of the sympathomimetic amines.
Modafinil does not display sympathomimetic activity in
rat models and appears to have minimal effect on
cardiovascular and hemodynamic parameters. The exact
mechanism through which it promotes wakefulness is
unknown. There is some evidence that it may increase
extracellular dopamine via a hypocretin receptor in an
independent manner in narcoleptic dogs and this may be
responsible for its wake-promoting action [5]. Addition-
ally, there is a report of modafinil blocking the reuptake
of noradrenaline at the noradrenergic terminals on sleep-
promoting neurons from the ventrolateral preoptic nucleus