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Letters to the Editor  |   February 2008
Transdermal Selegiline: New Opportunity for Managing Depression
Author Affiliations
  • Edward H. Tobe, DO
    University of Medicine and Dentistry of New Jersey-School of Osteopathic Medicine, Stratford
Article Information
Psychiatry
Letters to the Editor   |   February 2008
Transdermal Selegiline: New Opportunity for Managing Depression
The Journal of the American Osteopathic Association, February 2008, Vol. 108, 85-86. doi:
The Journal of the American Osteopathic Association, February 2008, Vol. 108, 85-86. doi:
Web of Science® Times Cited: 6
To the Editor: The efficacy of monoamine oxidase inhibitors (MAOIs) in treating patients with mental disorders has long been known. These agents inhibit monoamine oxidase (MAO) enzymes from breaking down the monoamines dopamine, norepinephrine, and serotonin—neurotransmitters in the central nervous system believed to be associated with the genesis and management of mood and anxiety disorders.1 Despite this association, physicians have been reluctant to prescribe MAOIs in oral form because of risks of various adverse events, interactions with other medications, and complications with diet.2 
Monoamine oxidase type A (MAOA) is an enzyme that predominantly metabolizes norepinephrine and serotonin.3,4 The MAOIs can inhibit MAOA in the gastrointestinal tract, interfering with the body's ability to regulate the absorption of tyramine and other vasopressors.1,3,4 This inhibition raises the potential risk of cardiovascular crises (eg, stroke) associated with diet. Consequently, patients taking oral MAOIs must avoid foods rich in vasopressors, including aged cheeses, beef and chicken liver, chocolate, dried sausages, fava beans, Italian green beans, and smoked fish, as well as beer and red and sparkling wines.3,4 
Monoamine oxidase type B (MAOB) predominantly metabolizes dopamine and phenylethylamine.3,4 Medications that inhibit only MAO-B do not affect gastrointestinal absorption of vasopressors.3,4 
A promising new treatment for patients with serious mental disorders delivers the benefits of MAOIs while minimizing the risks. The selegiline transdermal patch system (EMSAM®; Bristol-Myers Squibb Co, Princeton, NJ; Somerset Pharmaceuticals Inc, Tampa, Fla), approved by the US Food and Drug Administration (FDA) in February 2006,5 delivers the MAOI selegiline through the skin into the bloodstream. At its lowest strength (6 mg/d), transdermal selegiline offers safe and effective treatment for patients with major depressive disorder (MDD) without requiring the dietary restrictions associated with oral MAOIs.6 
Selegiline is both an MAOI1,3,4,6 and a dopamine reuptake inhibitor.4 Active metabolites of selegiline include L-amphetamine, L-desmethylselegiline (ie, N-propargylamphetamine), and L-methamphetamine.1,4 The extent of the clinical effects of these metabolites is controversial.1 A daily oral dose (eg, 5-10 mg) of selegiline requires no dietary restrictions and selectively and irreversibly inhibits MAO-B.1,4 Higher daily oral doses of selegiline have been used to treat patients with depression, but such doses inhibit MAO-A in the gastrointestinal tract.1,4 
The main advantage of using transdermal selegiline is that it bypasses metabolism in the gastrointestinal tract and liver, thereby permitting higher plasma levels without inhibiting gastrointestinal MAO-A. The higher selegiline patch dosages (9 mg/d, 12 mg/d) are FDA-approved for managing MDD, though these dosages carry dietary restrictions.5 Clinically, however, dietary concerns with the 9-mg and 12-mg selegiline patches may lack relevance unless the patient has a highly abnormal diet, such as consuming large quantities of aged cheeses or fermented wines.3 
In my practice as a clinical psychiatrist, I have successfully treated patients by using the selegiline transdermal patch system. One of my cases involved a middle-aged man who was formerly highly energetic and successful, but whose severe, long-term MDD left him bedridden, obese, unemployable, and pondering suicide. Extensive psychotherapy had failed to help this patient, as had intermittent psychopharmacologic management. After 6 months of treatment with transdermal selegiline (6 mg/d initially; 12 mg/d after 4 mo), the patient showed substantial increases in energy level and daily function. Although he is still obese, the patient is no longer bedridden or contemplating suicide, and he is now seeking to reestablish himself in the workplace. 
I urge physicians who have been reluctant in the past to prescribe MAOIs to consider my encouraging experiences with transdermal selegiline. The MAOIs can be effective in treating patients with MDD. They are relatively safe (particularly in transdermal form), and they can be a valuable tool for relieving the suffering of patients with serious mental disorders. 
 Editor's Note: Dr Tobe discloses that he has no conflicts of interest related to the topic of this letter to the editor.
 
Sadock BJ, Sadock VA, eds. Kaplan and Sadock's Comprehensive Textbook of Psychiatry. 8th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2005:2854-2860.
Depressive disorders: monoamine oxidase inhibitors (MAOIs); November 2005. Merck & Co Inc Web site. Available at: http://www.merck.com/mmpe/sec15/ch200/ch200b.html#sec15-ch200-ch200b-518. Accessed December 17, 2007.
Schatzberg AF, Cole JO, DeBattista C. Manual of Clinical Psychopharmacology. 5th ed. Washington, DC: American Psychiatric Publishing Inc; 2005:112-127.
Brunton L, Lazo J, Parker K. Goodman & Gilman's The Pharmacologic Basis of Therapeutics. 11th ed. New York, NY: McGraw-Hill Professional; 2006:442 .
US Food and Drug Administration approves EMSAM® (selegiline transdermal system), the first transdermal patch for the treatment of major depressive disorder. PRNewswire. February 28, 2006. Available at: http://www.selegiline.com/emsam/index.html. Accessed December 17, 2007.
Amsterdam JD. A double-blind, placebo-controlled trial of the safety and efficacy of selegiline transdermal system without dietary restrictions in patients with major depressive disorder. J Clin Psychiatry. 2003;64:208-214.