Evidence-Based Reviews

Monoamine oxidase inhibitors: Forgotten treatment for depression

Current Psychiatry. 2012 December;11(12):20-26

References

1. Balon R, Mufti R, Arfken CL. A survey of prescribing practices for monoamine oxidase inhibitors. Psychiatr Serv. 1999;50(7):945-947.

2. Nolen WA, van de Putte JJ, Dijken WA, et al. Treatment strategy in depression. II. MAO inhibitors in depression resistant to cyclic antidepressants: two controlled crossover studies with tranylcypromine versus L-5-hydroxytryptophan and nomifensine. Acta Psychiatr Scand. 1988;78(6):676-683.

3. McGrath PJ, Stewart JW, Harrison W, et al. Treatment of tricyclic refractory depression with a monoamine oxidase inhibitor antidepressant. Psychopharmacol Bull. 1987;23(1):169-172.

4. Amsterdam JD. Monoamine oxidase inhibitor therapy in severe and resistant depression. Psychiatr Ann. 2006;36(9):607-613.

5. Schildkraut JJ. The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am J Psychiatry. 1965;122(5):509-522.

6. Kennedy SH, Holt A, Baker GB. Monoamine oxidase inhibitors. In: Sadock BJ Sadock VA, eds. Kaplan and Sadock’s comprehensive textbook of psychiatry. 8th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005: 1076–1080.

7. EMSAM [package insert]. Napa CA: Dey Pharm LP; 2011.

8. Amsterdam JD, Chopra M. Monoamine oxidase inhibitors revisited. Psychiatric Ann. 2001;31(6):361-370.

9. Quitkin FM, Stewart JW, McGrath PJ, et al. Phenelzine versus imipramine in the treatment of probable atypical depression: defining syndrome boundaries of selective MAOI responders. Am J Psychiatry. 1988;145(3):306-311.

10. Vallejo J, Gasto C, Catalan R, et al. Double-blind study of imipramine versus phenelzine in melancholias and dysthymic disorders. Br J Psychiatry. 1987;151:639-642.

11. White K, Razani J, Cadow B, et al. Trancylpromine vs. nortriptyline vs. placebo in depressed outpatients: a controlled trial. Psychopharmacology (Berl). 1984;82(3):258-262.

12. Thase ME, Frank E, Mallinger AG, et al. Treatment of imipramine-resistant recurrent depression, III: efficacy of monoamine oxidase inhibitors. J Clin Psychiatry. 1992;53(1):5-11.

13. Himmelhoch JM, Thase ME, Mallinger AG, et al. Tranylcypromine versus imipramine in anergic bipolar depression. Am J Psychiatry. 1991;148(7):910-916.

14. Rothschild AJ. ed. The evidence-based guide to antidepressant medications. Arlington, VA: American Psychiatric Publishing, Inc.; 2012:15–20.

15. Ravaris CL, Nies A, Robinson DS, et al. A multiple-dose, controlled study of phenelzine in depression-anxiety states. Arch Gen Psychiatry. 1976;33(3):347-350.

16. Cockhill LA, Remick RA. Blood pressure effects of monoamine oxidase inhibitors—the highs and lows. Can J Psychiatry. 1987;32(9):803-808.

17. Shulman KI, Walker SE. A reevaluation of dietary restrictions for irreversible monoamine oxidase inhibitors. Psychiatr Ann. 2001;31(6):378-384.

18. Gardner DM, Shulman KI, Walker SE, et al. The making of a user friendly MAOI diet. J Clin Psychiatry. 1996;57(3):99-104.

19. Keck PE, Jr, Carter WP, Nierenberg AA, et al. Acute cardiovascular effects of tranylcypromine: correlation with plasma drug, metabolite, norepinephrine, and MHPG levels. J Clin Psychiatry. 1991;52(6):250-254.

20. Micromedex Healthcare Series [UMass Memorial Healthcare Intranet System]. Version 5.1. Greenwood Village CO: Thomson Reuters (Healthcare) Inc.

21. American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder third edition. http://psychiatryonline.org/content.aspx?bookid=28&sectionid=1667485. Published October 2010. Accessed October 26, 2012.

22. McGrath PJ, Stewart JW, Fava M, et al. Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report. Am J Psychiatry. 2006;163(9):1531-1541; quiz 1666.

23. Nelson JC, Byck R. Rapid response to lithium in phenelzine non-responders. Br J Psychiatry. 1982;141:85-86.

24. Guze BH, Baxter LR, Jr, Rego J. Refractory depression treated with high doses of monoamine oxidase inhibitor. J Clin Psychiatry. 1987;48(1):31-32.

25. Robinson DS, Gilmor ML, Yang Y, et al. Treatment effects of selegiline transdermal system on symptoms of major depressive disorder: a meta analysis of short term, placebo controlled, efficacy trials. Psychopharmacol Bull. 2007;40(3):15-28.

26. Keller MB, Lavori PW, Rice J, et al. The persistent risk of chronicity in recurrent episodes of nonbipolar major depressive disorder: a prospective follow-up. Am J Psychiatry. 1986;143(1):24-28.

Insomnia and day-night shifting—sleeping during the day and staying awake at night—are common and patients often cite these as reasons for discontinuing MAOIs. Many patients who respond to MAOIs report periods of substantial sleepiness in the mid to late afternoon. Table 3²⁰ provides a more complete list of reported side effects and their frequencies.

Table 3

MAOIs: Stay vigilant for side effects

Medication	Common side effects
Isocarboxazid	Anxiety, blurred vision, constipation, dizziness, headache, insomnia, mania, somnolence, weight gain, xerostomia
Phenelzine	Constipation, disorder of ejaculation and/or orgasm, dizziness, edema, fatigue, headache, hyperreflexia, impotence, elevated values on liver function tests, orthostatic hypotension, sleep disorders, somnolence, tremor, weight gain, xerostomia
Selegiline transdermal	Application site reaction, decreased systolic blood pressure, diarrhea, headache, indigestion, insomnia, orthostatic hypotension, weight loss, xerostomia
Tranylcypromine	Agitation, anxiety, constipation, diarrhea, dizziness, headache, impotence, insomnia, loss of appetite, mania, nausea, orthostatic hypotension, somnolence, weight gain, xerostomia
MAOIs: monoamine oxidase inhibitors Source: Adapted from reference 20

Practice guidelines

The American Psychiatric Association’s practice guidelines for treating major depression state that MAOIs are effective in treating subgroups of patients with MDD with atypical features who have failed TCA trials.²¹ These guidelines also state that MAOIs have been shown to be effective treatment for some patients who have failed other antidepressants. However, for TRD patients who have not responded to SSRIs or SNRIs, the effectiveness of MAOIs compared with other strategies is unclear.²²

Clinical Point

Practice guidelines state MAOIs are effective for patients with depression with atypical features who have failed tricyclic antidepressants

One study found adding lithium to an MAOI may provide more rapid or more efficacious response than MAOI monotherapy.²³ Guze et al²⁴ evaluated the effects of high-dose MAOI treatment for 2 TRD patients; both patients improved without any side effects.

MAOIs have been used for >6 decades, and published studies continue to document their efficacy and safety when patients are monitored appropriately.^{11,12,14,15,25} However, based on our observations we suspect MAOIs are underutilized in clinical practice today. We are concerned that such practices can trickle down into residency training programs. Psychiatric residents typically do not receive adequate training in prescribing MAOIs, largely because many training faculty are not prescribing MAOIs themselves. Despite MAOIs’ limitations, concerns about an increased risk of suicide in patients with TRD²⁶ and the high likelihood of a poor outcome associated with persistent nonresponse to prior treatments must be weighed against the relatively low risk of a hypertensive event with MAOIs.⁶

Clinical Point

Studies continue to document MAOIs’ safety and efficacy when patients are monitored appropriately

Related Resources

McCabe-Sellers BJ, Staggs CG, Bogle ML. Tyramine in foods and monoamine oxidase inhibitor drugs: a crossroad where medicine, nutrition, pharmacy, and food industry converge. Journal of Food Composition and Analysis. 2006;19(suppl):S58-S65.
Fiedorowicz JG, Swartz KL. The role of monoamine oxidase inhibitors in current psychiatric practice. J Psychiatr Pract. 2004;10(4):239-248.

Drug Brand Names

Clomipramine • Anafranil
Epinephrine • Adrenalin, EpiPen
Fluoxetine • Prozac
Imipramine • Tofranil
Isocarboxazid • Marplan
Lithium • Eskalith, Lithobid
Nifedipine • Adalat, Afeditab
Phenelzine • Nardil
Phentolamine • OraVerse, Regitine
Selegiline • EMSAM
Tranylcypromine • Parnate

Disclosures

Dr. Kosinski reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Rothschild receives grant or research support from Cyberonics, the National Institute of Mental Health, St. Jude Medical, and Takeda, and is a consultant to Allergan, Eli Lilly and Company, GlaxoSmithKline, Noven Pharmaceuticals, Pfizer Inc., Shire Pharmaceuticals, and Sunovion.