Orthostatic hypotension is the most common early side effect of phenelzine and isocarboxazid. Clinically significant hypotension is best managed via dosage adjustment. If that fails, add Na Cl, 1 to 2 grams bid with increased fluids. If that doesn’t work, administer fludrocortisone, 0.1 to 0.4 mg/d. If that fails, administer d-amphetamine, starting with 2.5 to 5 mg/d, and observe carefully for hypertension.
An altered diurnal sleep cycle is another MAOI-related side effect. Some patients get extremely drowsy in the late afternoon but then may have insomnia at night.26 Attempts to alter this odd cycle by changing the timing of administration have generally not helped. We add a stimulant—pemoline (18.75 to 35.5 mg), d-amphetamine (2.5 to 5 mg), methylphenidate (5 to 10 mg), or modafinil (50 to 100 mg)—either in the morning or during afternoon sleepiness, with good effect and no hypertensive crises. We supervise the effect on blood pressure of the first few doses. Another helpful alternative has been to administer trazodone at night to initiate sleep.
THE SEARCH FOR SAFER MAOIs
Efforts over the years have been aimed at developing MAOIs that do not cause the tyramine reaction. One approach—devising reversible inhibitors of monoamine oxidase, which can be displaced from the MAO enzyme by tyramine—has resulted in two drugs (moclobemide and toloxatone) that are available in other parts of the world but not in the United States.27
Brofaromine, a reversible MAOI and an SSRI, looked promising in its clinical trials in Europe and the United States but was withdrawn from development by its manufacturer. A more recent approach to averting the MAOI-associated hypertensive interaction with dietary tyramine has been to deliver the drug parenterally, to spare the gut’s MAO-A.
Selegiline awaits Food and Drug Administration approval to be marketed in the United States as a transdermal preparation.28 The agent in this form would have several virtues, including a more stable blood level than the oral preparation and no clinically meaningful inhibition of intestinal MAO and thus no hypertensive crises.
MAOIs are adrenergic agonists, and dry mouth and constipation can occur as side effects; these can be treated with bethanechol. Edema also occurs, mainly with isocarboxazid and phenelzine, and responds in most cases to modest diuretic doses, such as hydrochlorothiazide, 50 mg/d.
The now-recognized trouble reaching orgasm on SSRIs was first reported to us by women on phenelzine, and this side effect is as difficult to treat with MAOIs as it is with other antidepressants. We have found that sexual dysfunction is less likely to occur with tranylcypromine and selegiline than other MAOIs.
Toward safer MAOIs
Newer reversible MAOIs are in development, and two agents are available (although not in the United States). Delivery systems that reduce the risk of hypertensive crisis also may soon be available (Box 2).27,28
Related resources
- Amsterdam JD, Chopra M. Monoamine oxidase inhibitors revisited. Psychiatric Ann2001;31(6):361-70.
- Treatment with antidepressants. In: Janicak PG, Davis JM, Preskorn SH, Ayd FJ, eds. Principles and practice of psychopharmacotherapy. 3rd ed. Philadelphia: Lippincott, Williams & Wilkins, 2001:215-326.
- Kennedy SH, ed. Clinical Advances in Monoamine Oxidase Inhibitor Therapies. Progress in Psychiatry Series. Washington, DC: American Psychiatric Press, 1994.
Drug brand names
- Isocarboxazide • Marplan
- Moclobemide • Aurorix, Manerix
- Phenelzine • Nardil
- Selegiline • Eldepryl
- Tranylcypromine • Parnate
Disclosure
Dr. Cole reports that he has served as a consultant to SmithKline Beecham Pharmaceuticals, manufacturer of tranylcypromine, and to Somerset Pharmaceuticals, manufacturer of selegiline in the United States. He also has participated in clinical studies of selegiline.
Dr. Bodkin reports that he has served as a consultant to Somerset Pharmaceuticals and has been principal investigator in several multicenter trials of selegiline.