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Letter to the Editor   |    
Modafinil Augmentation of Phenelzine for Residual Fatigue in Dysthymia
ADAM KELLER ASHTON, M.D.
Am J Psychiatry 2004;161:1716-a-1717. doi:10.1176/appi.ajp.161.9.1716-a

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.

Ms. A was a 54-year-old Caucasian woman who was seen for the treatment of dysthymia, which had lasted 6 years. She had not improved after psychotherapy with three different therapists and did not respond to treatment with adequate trials of 80 mg/day of fluoxetine, 300 mg/day of extended-release venlafaxine, 600 mg/day of nefazodone, 62.5 mg of mirtazapine at bedtime, and 100 mg/day of clomipramine. She had a partial response to a trial of tranylcypromine, 30 mg b.i.d., and a more significant response with phenelzine, 30 mg t.i.d. Clinical improvement was further enhanced with lamotrigine augmentation at 200 mg b.i.d., although she had no evidence of bipolar symptoms according to her history. Ms. A essentially described remission of depressive symptoms lasting 1 year with this combination but continued to describe fatigue and hypersomnolence, whereby she could sleep all night and part of the day. These complaints did not appear to be brought on by her medication. Neither she nor her husband described signs of a sleep disorder, such as snoring or restlessness. Modafinil was added to her regimen, and Ms. A described rapid clinical improvement in energy and motivation, taking 100 mg/day to the extent that she felt more productive. She described no side effects or any sign of hypertensive reaction and was stable with this combination for at least 6 months.

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.

Himmelhoch JM: Monoamine oxidase inhibitors, in Comprehensive Textbook of Psychiatry, 6th ed. Edited by Kaplan HI, Sadock BJ. Baltimore, Williams & Wilkins, 1995, p 2045
 
Physicians’ Desk Reference, 58th ed. Montvale, NJ, Thomson PDR, 2004
 
Nierenberg AA, Keefe VR, Leslie VC, Alpert JE, Pava JA, Worthington JJ, Rosenbaum JF, Fava M: Residual symptoms in depressed patients who respond acutely to fluoxetine. J Clin Psychiatry  1999; 60:221–225
[PubMed]
[CrossRef]
 
Menza JA, Kaufman KR, Castellanos A: Modafinil augmentation of antidepressant treatment in depression. J Clin Psychiatry  2000; 61:378–381
[PubMed]
[CrossRef]
 
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References

Himmelhoch JM: Monoamine oxidase inhibitors, in Comprehensive Textbook of Psychiatry, 6th ed. Edited by Kaplan HI, Sadock BJ. Baltimore, Williams & Wilkins, 1995, p 2045
 
Physicians’ Desk Reference, 58th ed. Montvale, NJ, Thomson PDR, 2004
 
Nierenberg AA, Keefe VR, Leslie VC, Alpert JE, Pava JA, Worthington JJ, Rosenbaum JF, Fava M: Residual symptoms in depressed patients who respond acutely to fluoxetine. J Clin Psychiatry  1999; 60:221–225
[PubMed]
[CrossRef]
 
Menza JA, Kaufman KR, Castellanos A: Modafinil augmentation of antidepressant treatment in depression. J Clin Psychiatry  2000; 61:378–381
[PubMed]
[CrossRef]
 
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