To the Editor: Monoamine oxidase inhibitors (MAOIs) are sometimes required to treat refractory depressive disorders (1). Although effective, they require careful attention to concomitant medicines and foods to avoid a hypertensive crisis or other severe reactions (2, pp. 2557–2559). Modafinil is an agent used to promote wakefulness in patients suffering from excessive daytime somnolence (2, pp. 1160–1162). Most patients with depression complain of fatigue even after antidepressant treatment (3). Modafinil augmentation has been used to enhance antidepressant response (4). We know of no interaction studies that have been performed to evaluate the safety or efficacy of combining modafinil with an MAOI. I report what I believe to be the first published case of the use of modafinil to combat excessive daytime somnolence in a patient successfully treated for dysthymia with phenelzine and lamotrigine.

This report may be the first to describe a safe and effective combination of modafinil and an MAOI. There are some obvious limitations. The patient did not have a sleep study performed, so perhaps modafinil was treating an underlying sleep disorder, although no change in nighttime sleep was described. A placebo control would have been helpful, although years of taking other agents did not elicit this kind of response. Long-term safety cannot be guaranteed. Perhaps a drug interaction had not had time to develop, although usually this kind of adverse reaction can occur after as little as a single dose, and this individual had already taken hundreds of doses. Further study on the safety and usefulness of modafinil augmentation with MAOIs would be helpful. Despite these drawbacks, this case does suggest that some individuals taking MAOIs may be able to derive clinical benefit to manage the persistent fatigue and hypersomnolence that may occur during treatment of depressive disorders by adding modafinil.