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Am Fam Physician. 2008;77(4):505-506

Author disclosure: Nothing to disclose.

Selegiline (Eldepryl) is an irreversible monoamine oxidase (MAO)-B inhibitor used at low doses for the adjunctive treatment of Parkinson's disease. The selegiline transdermal patch (Emsam) delivers higher, more sustained blood levels to the brain and is labeled for the treatment of major depression in adults.1,2

NameStarting dosageDose formApproximate monthly cost*
Selegiline transdermal patch (Emsam)Patch with a dose of 6 mg per 24 hours applied each day; may increase dosage by 3 mg per 24 hours at two-week intervals to a maximal dosage of 12 mg per 24 hoursPatches with a dose of 6, 9, or 12 mg per 24 hours$493

SAFETY

Unlike oral MAO inhibitors, transdermal selegiline delivers antidepressant drug concentrations to the central nervous system without substantially impairing gastrointestinal MAO-A activity. At the target dose of 6 mg per 24 hours, tyramine dietary restrictions are not needed.2

Transdermal selegiline is contraindicated in patients taking selective serotonin reuptake inhibitors; dual serotonin and norepinephrine reuptake inhibitors; tricyclic antidepressants; bupropion (Wellbutrin); mirtazapine (Remeron); buspirone (Buspar); and certain analgesics, vasoconstrictors, sympathomimetics, and anticonvulsants. Administration of these drugs with transdermal selegiline may cause serotonin syndrome or hypertensive crisis. After discontinuation of any of these agents (except fluoxetine [Prozac]), at least four to five half-lives of the drug or active metabolite (approximately one to two weeks) should elapse before initiating therapy with transdermal selegiline.2 At least five weeks should elapse between discontinuation of fluoxetine and beginning treatment with transdermal selegiline because of the long half-life of fluoxetine and its active metabolite. When switching from transdermal selegiline to another antidepressant or contraindicated drug, a washout period of two weeks is recommended.2

As with most other antidepressants, transdermal selegiline is not labeled for use in children. Its effectiveness in children has not been demonstrated, and there is an increased risk of suicidal thoughts and behaviors associated with antidepressants in this population.2 Transdermal selegiline is U.S. Food and Drug Administration pregnancy category C.2

TOLERABILITY

Insomnia, dry mouth, dizziness, nervousness, and abnormal dreams occur in about 8 to 18 percent of patients on transdermal selegiline. In clinical trials, approximately twice as many patients on transdermal selegiline (7 percent) discontinued treatment because of adverse effects compared with patients taking placebo. Localized skin reactions will occur in about one third of patients and will result in 2 percent of patients discontinuing therapy. Skin reactions can be minimized by proper application of the patch; persistent reactions can be treated with local corticosteroids or oral antihistamines. Sexual dysfunction and orthostatic hypotension, which are common side effects of oral MAO inhibitors, are uncommon with transdermal selegiline.26

EFFECTIVENESS

Transdermal selegiline is modestly effective in treating major depression. In clinical trials, approximately 33 to 40 percent of patients responded to treatment compared with 22 to 30 percent who took placebo; results in actual practice will likely be lower.36 Typical rates of response to other antidepressants are 70 percent in clinical trials and 30 percent in practice. Transdermal selegiline will prevent relapse over one year to a greater extent than placebo; however, one in six patients will still experience a relapse.6 Transdermal selegiline has not been directly compared with any other antidepressant.

PRICE

A one-month supply of transdermal selegiline will cost approximately $493 for any strength. First-line antidepressants, such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine, paroxetine (Paxil), and sertraline (Zoloft), cost between $15 and $149 per month.

SIMPLICITY

The starting and target dose of transdermal selegiline is an extended-release 6-mg/24-hour patch applied once daily. If necessary, the dosage may be increased by 3 mg per 24 hours at two-week intervals up to a maximal dosage of 12 mg per 24 hours.2

Patients should be informed that tyraminerich foods and beverages (e.g., aged cheeses; tap and nonpasteurized beers; nonfresh meat, fish, and poultry; concentrated yeast products; protein extracts) should be avoided during use and for two weeks after discontinuation of the 9-mg and 12-mg patches.2 The recommended dosage for patients 65 years or older is 6 mg per 24 hours.2

Bottom Line

Transdermal selegiline is an expensive treatment option for patients with major depressive disorder who have not responded to other antidepressants or who cannot swallow or take oral medications. Based on guidelines from the American Psychiatric Association, MAO inhibitor pharmacotherapy should be reserved for patients with atypical and treatment-resistant depression. Patient education is very important with this product because of potentially serious food and drug interactions.

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