Pharmacy & Therapeutics - April 2008 - (Page 212) DRUG FORECAST The Selegiline Transdermal System (Emsam) A Therapeutic Option for the Treatment Of Major Depressive Disorder Lois Jessen, MS, PharmD, Lawrence J. Kovalick, PharmD, and Albert J. Azzaro, PhD ABSTRACT Although monoamine oxidase inhibitors (MAOIs) at one time represented the mainstay of therapy for major depressive disorder (MDD), the risk of acute hypertensive reactions following the ingestion of tyramine-rich foods and the consequent need to restrict dietary tyramine represent a barrier to their use. In this article, we present an overview of the efficacy and safety of a transdermal formulation of the MAOI selegiline for the treatment of MDD. Transdermal delivery of selegiline at the effective dose of 6 mg every 24 hours eliminates the need for a tyramine-restricted diet. Our emphasis on potential drug–drug interactions and contraindications should be useful to prescribers who counsel patients with MDD. INTRODUCTION Despite the wide availability of clinically efficacious therapies for depression, as many as 50% of patients who begin treatment do not respond to it, and up to 30% do not gain benefits from a range of therapy regimens.1 Reflecting their established efficacy, safety, and widespread clinical use, oral monoamine oxidase inhibitors (MAOIs) were the mainstay of major depressive disorder (MDD) therapy during the 1950s. However, reports of serious adverse events, including acute hypertensive reactions following ingestion of tyramine-rich foods such Dr. Jessen is Director of Medical Information at Bristol-Myers Squibb in Plainsboro, New Jersey. Dr. Kovalick is Director of Global Medical Writing at Amgen. Dr. Azzaro is President of AJA PharmaServices in Tarpon Springs, California. Drug Forecast is a regular column coordinated by Alan Caspi, PhD, PharmD, MBA, President of Caspi & Associates in New York, New York. as aged cheese,2 and the subsequent need to restrict dietary intake of tyramine with MAOI therapy led to a decline in the use of these agents. Despite these barriers, many psychiatrists believe that MAOIs are currently underused in clinical practice,3,4 particularly given their proven efficacy in atypical depression,5–9 psychotic depression, 10,11 dysthymic disorder,12 treatment-resistant depression,13–17 and bipolar depression.14,18,19 As a result, considerable efforts have been made to develop an MAOI antidepressant that can overcome these limitations. Transdermal selegiline (Emsam, Somerset/Bristol-Myers Squibb) is the first therapeutic option of its kind to be approved by the Food and Drug Administration (FDA) for the treatment of MDD. Given the primary role of pharmacists and physicians in advising patients on the use of concomitant medications, we outline the efficacy, safety, potential interactions, and contraindications of the selegiline transdermal system (STS). ticularly those relating to dietary constraints. Monoamine oxidase (MAO) in the gastrointestinal (GI) tract (predominantly the MAO-A isoenzyme) is a key enzyme in tyramine metabolism. When MAO-A in the GI tract is sufficiently inhibited, tyramine cannot be metabolized; it enters the systemic circulation, resulting in an elevation of blood pressure and potentially leading to a hypertensive crisis.2,20 The pharmacokinetic and pharmacodynamic properties of the STS permit the inhibition of MAO-A and MAO-B in the central nervous system (CNS) while limiting MAO-A inhibition in the intestinal mucosa and liver. At the effective selegiline dose of 6 mg every 24 hours, the system’s dermal application enables targeted inhibition of MAO enzymes in the CNS without significantly increasing sensitivity to dietary tyramine, thus eliminating the need for dietary modifications of foods containing tyramine at this dose.21 A NOVEL DELIVERY SYSTEM The STS has a unique delivery system that was designed to overcome the limitations associated with oral MAOIs, parDisclosure: Funding was provided by Bristol-Myers Squibb. Dr. Jessen is an employee and stockholder of Bristol-Myers Squibb; she previously served as a consultant to McNeil Pediatrics and has been a member of the speaker’s bureau for Novartis. At the time of this manuscript preparation, Dr. Kovalick was an employee and stockholder of BristolMyers Squibb; he is currently an employee of Amgen. At the time of this manuscript preparation, Dr. Azzaro was an employee and Chief Scientific Officer at Somerset Pharmaceuticals, Inc., in Tampa, Florida; he is currently a consultant in the pharmaceutical industry and is President of AJA PharmaServices in Tarpon Springs, Florida. EFFICACY AND SAFETY Efficacy The efficacy and tolerability of the STS at a dose of 6 mg every 24 hours in MDD has been demonstrated in several shortterm and long-term placebo-controlled clinical trials. It was also assessed in a flexible-dose study. Bodkin and Amsterdam22 In a short-term, randomized, doubleblind study of six weeks’ duration (n = 177), patients with moderate-to-severe depression received either the STS (6 mg/24 hours) or placebo once daily. Because this was the first large study of the STS for MDD, subjects followed a tyramine-restricted diet. At the study’s endpoint, the STS showed significantly greater efficacy, compared with placebo, according to: 212 P&T® • April 2008 • Vol. 33 No. 4
For optimal viewing of this digital publication, please enable JavaScript and then refresh the page. If you would like to try to load the digital publication without using Flash Player detection, please click here.