Acute Chorea and Hyperthermia After Concurrent Use of Modafinil and Tranylcypromine

To the Editor: 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 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.