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A case report of high-dose transdermal selegiline in the treatment of major depressive disorder

Adam Keller Ashton, MD

Clinical Professor of Psychiatry, State University of New York at Buffalo, School of Medical Sciences, Suburban Psychiatric Associates, Amherst, NY, USA

KEYWORDS: selegiline transdermal patch, topical, depression, high dose, off-label dosing



The selegiline transdermal patch is the newest FDA–approved antidepressant available in the United States.1 It is approved for up to 12 mg topically to treat major depressive disorder. Until now, there have been no reports of its use above 12 mg and no preclinical research on use of a higher dose in humans, according to the manufacturer (personal communication, Bristol-Myers Squibb, December 22, 2007). This is the first report of treatment with the selegiline transdermal system at a high dose in a patient, as well as its apparent success in obtaining remission of her major depression.

Mrs. M. is a 37-year-old, Caucasian woman with a past psychiatric history significant for major depressive disorder. She did not respond to therapeutic trials of fluoxetine 20 mg once daily, sertraline 100 mg once daily, citalopram 60 mg once daily, lamotrigine 300 mg bid, venlafaxine 300 mg once daily, nefazodone 400 mg once daily, mixed amphetamine salt augmentation up to 60 mg once daily, duloxetine 120 mg once daily, olanzapine/fluoxetine combination 6 mg/25 mg once daily, or clomipramine 75 mg once daily. She had a partial response to bupropion XL 450 mg once daily over several years, but this was suboptimal even in combination with most of the above-mentioned agents.

Mrs. M. began using the selegiline patch topically in December 2006 and titrated up over many months to 18 mg topically once daily. Each time she increased the dose, her mood improved further, without side effects. A dose of 15 mg was skipped, as it would have required 2 different patch sizes and, therefore, 2 copayments. For several months, she has felt optimal—with depression in remission—at this dose as monotherapy, without any adverse events. Her only other medications (clonazepam, omeprazole, ibuprofen, and acyclovir) were taken as needed.

This is the first report of treatment with the selegiline patch above 12 mg for any use—not limited to depression, whether successful or not. Limitations of this report include small sample size and the possibility that this is a placebo response, despite the failures of numerous antidepressants prior to treatment with selegiline. The patient’s sustained remission makes a placebo response less likely. It is not clear why this individual needed such a high dose, but some patients may require higher-than-customary doses of the selegiline patch for optimal results. In this patient’s other antidepressant trials, the agents were pushed to the highest tolerated dose. It is possible that orally absorbed medications caused metabolic problems, since some of the antidepressants were not maximized because of tolerability problems. Perhaps this limitation was bypassed by a topical agent. The transdermal system for selegiline avoids first-pass metabolism by the gut and liver, which may have contributed to its efficacy. This also may reduce the potential risk from dietary tyramine interactions that may occur with other monoamine oxidase inhibitors. Although all MAO inhibitors carry this risk, it appears only as a listed warning of the selegiline patch at high doses.

Further research in this area may help clinicians in their decision making in terms of selecting a high-dose strategy for patients with refractory depression. Occasionally, psychiatrists elect to attempt higher-than-approved doses of medication for select patients. Reports such as this that describe how high an antidepressant has been dosed in clinical practice may help clinicians factor such information into their own decisions regarding off-label dosing of a medication for individual patients.


Dr. Ashton receives grants/research support from Cyberonics and is on the speaker’s bureau for Eli Lilly and Company, Pfizer Inc., Bristol-Myers Squibb, Takeda, Wyeth Pharmaceuticals, sanofi-aventis, Glaxo-SmithKline, Sepacor Inc., and AstraZeneca.


  1.  Emsam [package insert]. Princeton, NJ: Bristol-Myers Squibb; 2008. http://packageinserts.bms.com/pi/pi_emsam.pdf. Accessed October 30, 2008.

CORRESPONDENCE: Adam Keller Ashton, MD, State University of New York at Buffalo, School of Medical Sciences, Suburban Psychiatric Associates, 85 Bryant Woods South, Amherst, NY 14228. E-MAIL: aashton@suburbanpsych.org