Pharmacology Update

Selegiline Transdermal System (Emsam®)

By William T. Elliott, MD, FACP, and James Chan, PhD, PharmD, Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationships to this field of study.

The first transdermal patch has been approved for the treatment of depression. Selegiline is an irreversible monoamine oxidase inhibitor (MAOI), which, because of the transdermal delivery system, avoids some of the dietary restrictions associated with oral MAOIs. It is marketed by Bristol-Myers Squibb and Somerset Pharmaceuticals as Emsam®.

Indications

Selegiline patch is indicated for the treatment of major depressive disorder.1

Dosage

The recommended initial dose is 6 mg/24 hours (one patch). The dose may be increased by 3 mg/24 hour (at no less than 2 week interval) to a 9 mg/24 hour patch and to a maximum of 12 mg/24 hours. Tyramine-rich food or beverages should be avoided with the first dose of the 9 mg/24 hour patch and should continue until 2 weeks after a dose reduction to 6 mg/24 hour. The patch should be applied to dry intact skin on the upper torso (between the neck and waist) or the upper thigh or the outer surface of the upper arm.1

Selegiline patch is supplied as 6 mg/24 hours, 9 mg/24 hours, and 12 mg/24 hours.

Potential Advantages

Selegiline transdermal provides an alternative delivery system of MAOIs to the central nervous system without extensive inhibition of MAO-A in the gastrointestinal system.2 Typical side effects associated with MAOI are not seen with the patch.3 Avoidance of tyramine-rich food and beverage is not required for the initial recommended dose (6 mg/24 hrs).4 There is also less exposure to the metabolites of selegiline, l-amphetamine and l-methamphetamine, which are the less active isomers of amphetamine and methamphetamine.5,6

Potential Disadvantages

As with oral MAOIs, concomitant use of other anti-depressants are contraindicated with selegiline the patch including SSRIs, SNRIs (eg, venlafaxine), and tricyclic antidepressants. Carbamazepine, oxcarbazepine, and sympathomimetic amines are also contraindicated. Selegiline patch should be discontinued 10 days before elective surgery. If not possible, benzodiazepine, neuromuscular blockers (eg, mivacurium), fetanyl, morphine, and codeine should be used with caution.1

Comments

Selegiline is an inhibitor of MAO-A and MAO-B isoenzymes. Transdermal delivery of selegiline provides sufficient drug concentration to inhibit MAO activity in the central nervous system while minimizing inhibition of MAO activity in the liver and intestines. Tyramine dietary restriction is not required for the initial dose (6 mg/24hrs). The efficacy of the transdermal patch was shown in placebo-controlled, 6- or 8-week studies.1,3,4 Selegiline was found to be more effective than placebo based on standard assessment methods such as the Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scales (HAM-D 17, HAM-D 28), and Clinical Global Impression. Greater improvement was seen with selegiline, although one study characterized the benefit of a fixed dose of 6 mg/24 hour as modest.4 In 2 fixed-dosed studies (6 mg/24 hr), a 50% or greater reduction in MADRS total score was achieved in 33.1% for selegiline patients compared to 20.8% for placebo patients in one study (n = 289). In the other (n = 177), a 50% reduction in HAM-D total score of 37.5% and 22.7% were achieved respectively.3,4 The patch is generally well tolerated with 30-40% experiencing application site reactions.3,4 Sixteen percent (16%) of patients required symptomatic treatment with topical corticosteroid or an oral antihistamine.3 Sexual side effects were not significantly different from placebo. The wholesale cost of selegiline patch is $385.50 for 30 days.

Clinical Implications

The American Psychiatry Association Guidelines indicate that MAO inhibitors are useful in atypical major depressive symptoms, anger, hostility, and impulsivity in patients with borderline personality disorder.7 Oral MAO inhibitors have limited use due to adverse events and need for diet restriction. The transdermal system provides delivery of a MAO inhibitor with less restrictive diet requirement and better tolerance compared to oral agents.

References

1. Emsam® Product Information. Bristol-Myers Squibb, February 2006.

2. Wecker L, et al. Biol Psychiatry. 2003;54:1099-1104.

3. Bodkin JA, Amsterdam JD. Am J Psychiatry. 2002;159:1869-1875.

4. Amsterdam JD. J Clin Psychiatry. 2003;64:208-214.

5. Rohatagi S, et al. Biopharm Drug Dispos. 1997;18:567-84.

6. Schindler CW, et al. Drug Alcohol Depend. 2003;72:133-139.

7. www.aapel.org/bdp/BLpharmacotherapyUS.html. Accessed 4/10/06.