Am J Psychiatry 164:684, April 2007
Acute Chorea and Hyperthermia After Concurrent Use of Modafinil and
Tranylcypromine
MICHAL VYTOPIL, M.D., RAM MANI, M.D., ASHISH ADLAKHA, M.D. and JAY-JIGUANG
ZHU, M.D.
The combination of monoamine oxidase inhibitors (MAOIs) and sympathomimetic
psychostimulants can produce hypertensive crisis and serotonin syndrome.
To our knowledge, similar reactions have never been described with modafinil
and MAOIs, presumably because modafinil lacks sympathomimetic effects
of amphetamine and methylphenidate. We report a case of a patient with
acute chorea, confusion, and hyperthermia that developed after concurrent
use of modafinil and tranylcypromine.
A 34-year-old Caucasian female was admitted to our facility because
of chorea and confusion. She had a 15-year history of refractory depression,
which had been stable on high-dose tranylcypromine (80 mg daily). Three
days prior to admission, she began taking modafinil 200 mg daily to improve
wakefulness in the setting of increased workload. She had not taken modafinil
on a regular basis before this.
On the morning of admission, her parents noted that she appeared restless.
Seven hours later, she was sent to the emergency room by her coworkers
because she was behaving "strange[ly]" and had "tics."
At presentation, her verbal responses were in single words and inappropriate.
Severe choreiform movements of all four limbs, lip smacking, and rhythmic
rapid tongue protrusions were observed. Her neck was in opisthotonus with
rhythmic bilateral rotations.
The patient was admitted to our intensive care unit. Tranylcypromine
and modafinil were discontinued. A head CT scan, CSF analysis, EEG, laboratory
tests, and toxicology screens were unrevealing. The patient was started
on a regiment of cyproheptadine for presumed serotonin syndrome. Her temperature
rose to 38° C 24 hours after presentation, remained elevated for 24
hours, and then normalized spontaneously. Other vital signs remained normal
throughout her stay. The patient’s symptoms resolved within 48 hours
of admission.
A recent case report of modafinil combined with tranylcypromine suggests
that such treatment is safe (1). In our patient, symptoms developed three
days after modafinil was added to tranylcypromine and resolved two days
after discontinuation of both. Since other etiologies of self-limited
chorea were excluded, we presume the symptoms were precipitated by concurrent
use of modafinil and tranylcypromine.
Orofacial and limb dyskinesias have been reported with modafinil (2).
Some studies indicate that modafinil has a central dopaminergic effect
(3), which could explain the occurrence of dyskinesias. Other studies
demonstrate that modafinil increases cortical serotonin levels by enhancing
the efficacy of serotonin release mechanism (4). We hypothesize that tranylcypromine
produced acute dyskinesias, confusion, and hyperthermia in our patient
by augmenting central dopaminergic and serotoninergic activity of modafinil.
We feel that hyperthermia and confusion represent an incomplete form of
serotonin syndrome.
This case illustrates the need for a study on safety of combining modafinil
with MAOIs.
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