Out Of The Pipeline

Transdermal selegiline

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MAO-inhibiting antidepressant in a patch



Many psychiatrists do not prescribe monoamine oxidase inhibitors (MAOIs) for fear of causing a potentially fatal hypertensive reaction, even though restricting foods high in the amino acid tyramine usually prevents this effect.1 Consequently, most depressed patients who might respond well to MAOIs do not receive them.2,3

Transdermal selegiline, FDA-approved for treating major depressive disorder (MDD) (Table 1), offers the clinical efficacy of an MAOI but without adverse interactions with food at the 6-mg strength. Transdermal selegiline may inhibit too much gastrointestinal MAO-A at 9 mg/d and 12 mg/d to clear tyramine from foods, so tyramine-rich foods must be restricted at these dosages (Table 2).

Table 1

Transdermal selegiline: Fast facts

Brand name: EMSAM
Class: Monoamine oxidase inhibitor
FDA-approved indication: Major depressive disorder
Manufacturer: Somerset Pharmaceuticals (marketed by Bristol-Myers Squibb Co.)
Dosing forms: 6-, 9-, and 12-mg patches
Recommended dosage: One 6-mg patch every 24 hours, worn on the chest, back, or stomach. Increase dosage after 2 to 3 months if clinical response is inadequate

Table 2

Restrict these foods when prescribing transdermal selegiline at 9 or 12 mg/d

Food/beverage classFoods to avoid
BeveragesTap beer
Beer that has not been pasteurized*
Red wines
DairyAged cheeses
Meat, poultry, fishAir-dried, aged, and fermented meats, sausages, and salamis (including cacciatore and mortadella)
Pickled herring
Spoiled or improperly stored fish, meat, poultry, or animal livers (check for mold, discoloration, or odor)
VegetablesBroad bean pods (fava beans)
MiscellaneousConcentrated yeast extract (such as Marmite)
Fermented soybean products (including soy sauce)
Over-the-counter supplements containing tyramine
*Bottled and canned beer and white wine contain little or no tyramine, but more than moderate alcohol use while taking selegiline is not recommended.
Source: Shulman KI, Walker SE. A reevaluation of dietary restrictions for irreversible monoamine oxidase inhibitors. Psychiatr Ann 2001;31:378-84.

How it works

MAO enzyme subtypes A and B metabolize CNS monoamines, but primarily MAO-A metabolizes tyramine in the gut before the amino acid enters systemic circulation. At low concentrations, selegiline selectively inhibits MAO-B.4

Oral selegiline, approved as a adjunct to levodopa/carbidopa for patients with Parkinson’s disease,5 has been shown to be effective for treating depression at ≥30 mg/d.6 Because the drug does not selectively inhibit MAOB at ≥20 mg/d, dietary tyramine must be restricted when oral selegiline is used off-label at therapeutic dosages for depression. Otherwise, selegiline has been well-tolerated up to 60 mg/d.7

The 6-mg “patch” delivers more selegiline to the bloodstream than does low-dose oral selegiline but without inhibiting gut MAO-A. This provides the brain MAO-A and MAO-B inhibition necessary for an antidepressant effect while eliminating the need for dietary restrictions at this lowest dosage.

Clinical implications

Transdermal selegiline offers an MAOI antidepressant option that might help:

  • patients whose depression has not responded satisfactorily to selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs)
  • adults and children with chronic depression marked by atypical features, including reactive mood, rejection sensitivity, anergia, and reversed vegetative symptoms—such as oversleeping, overeating, and psychomotor retardation. Although transdermal selegiline’s efficacy against these features has not been studied, patients with this depressive subtype tend to respond preferentially to MAOIs.


Transdermal selegiline achieves therapeutic blood levels and reaches sustained concentration within 4 to 8 hours of administration. Compared with oral selegiline, transdermal delivery results in higher plasma selegiline concentrations (1,500 pg/mL with the 6-mg patch) with much lower exposure to metabolites.8 The concentration is maintained with successive doses.

Transdermal selegiline clears rapidly upon discontinuation but MAO inhibition persists for 2 weeks, so wait 2 weeks after the last dose before starting a new antidepressant or stopping food restrictions with the 9-mg and 12-mg patches.


In two randomized, double-blind clinical trials,9,10 a total of 466 adults ages 18 to 65 who met DSM-IV-TR criteria for MDD received transdermal selegiline, 6 mg/d, or placebo for 6 to 8 weeks. Participants had 17-item Hamilton Rating Scale for Depression (HAM-D-17) scores ≥20 at baseline.

In the 6-week study,9 transdermal selegiline produced a 46% greater reduction in HAM-D-17 scores, a 52% greater decrease in HAM-D-28 scores, and a 79% greater drop in Montgomery-Asburg Depression Rating Scale (MADRS) scores compared with placebo. In the 8-week trial,10 HAM-D-28 and MADRS scores among the treatment group were significantly improved at endpoint compared with placebo, but HAM-D-17 scores were not.

In a 1-year, double-blind study,11 322 subjects with MDD—who had been rated as responders in a 10-week, open-label transdermal selegiline trial—received the 6-mg patch or placebo. At 6 months and 1 year, relapse was much less frequent among the treatment group compared with placebo. Relapse was defined as:

  • HAM-D-17 ≥14
  • Clinical Global Impressions of Severity score ≥3 with a ≥2-point increase from baseline
  • and meeting DSM-IV criteria for MDD on two consecutive visits ≥11 days apart.

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