Transdermal Selegiline: New Opportunity for Managing Depression
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Edward H. Tobe
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.
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Editor's Note: Dr Tobe discloses that he has no conflicts of interest related to the topic of this letter to the editor.
1 Sadock BJ, Sadock VA, eds. Kaplan and Sadock's Comprehensive Textbook of Psychiatry. 8th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2005:2854-2860.Search in Google Scholar
2 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.Search in Google Scholar
3 Schatzberg AF, Cole JO, DeBattista C. Manual of Clinical Psychopharmacology. 5th ed. Washington, DC: American Psychiatric Publishing Inc; 2005:112-127.Search in Google Scholar
4 Brunton L, Lazo J, Parker K. Goodman & Gilman's The Pharmacologic Basis of Therapeutics. 11th ed. New York, NY: McGraw-Hill Professional; 2006:442 .Search in Google Scholar
5 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.Search in Google Scholar
6 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;64:208-214.10.4088/JCP.v64n0216Search in Google Scholar
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Articles in the same Issue
- AOA COMMUNICATIONS (REPRINT)
- History Bureau's Essay Competition Now Targets Five Core Principles
- LETTERS
- Miller Fisher Variant of Guillain-Barré Syndrome: A Report of Case
- Time to Respond to In-Store Clinics
- Debt Control for Young DOs
- ORIGINAL CONTRIBUTIONS
- Kinematic Measures to Objectify Head and Neck Motions in Palpatory Diagnosis: A Pilot Study
- CLINICAL PRACTICE
- Reducing Patient Risk for Human Papillomavirus Infection and Cervical Cancer
- SPECIAL COMMUNICATIONS
- Revisiting Castlio and Ferris-Swift's Experiments on Direct Splenic Stimulation in Patients With Acute Infectious Disease
- LETTERS
- Electronic Medical Records: What Are You Waiting For?
- Thirteen Guidelines for Better Public Healthcare
- Retraining Our Sights: From Tobacco Use to Obesity Awareness
- Ignorance in High Places
- Transdermal Selegiline: New Opportunity for Managing Depression
- Unknown Risks of Pharmacy-Compounded Drugs
- OMM Education vs “Real World” Medicine
- Colleges of Osteopathic McMedicine?