The selegiline transdermal system in major depressive disorder: A systematic review of safety and tolerability☆
Received 19 December 2006; received in revised form 4 April 2007; accepted 24 April 2007.
Abstract
Background
Monoamine oxidase inhibitors (MAOIs) are highly efficacious antidepressants, but safety concerns have limited their broad use.
Methods
We reviewed key safety and tolerability data from all clinical trials of patients with major depressive disorder (MDD) accrued during the clinical development of the selegiline transdermal system (STS), as reported to the Food and Drug Administration. This review includes data from both controlled and uncontrolled clinical trials involving STS-treated (n=2036) and placebo-treated (n=668) patients.
Results
Except for the initial trial, subsequent trials, which involved STS doses ranging from 3 mg/24 h to 12 mg/24 h, lacked tyramine restrictions, and no acute hypertensive reactions occurred during study treatment. Safety experience with STS 6 mg/24 h supports this therapeutic dose without tyramine dietary modifications, but until more data are available for STS doses 9 mg/24 h and 12 mg/24 h, foods that are rich sources of tyramine should be avoided. The principal side effects of STS therapy were local dermal reactions and insomnia, both of which were dose-related. Side effects associated with MAOI treatment, such as sexual dysfunction and excessive weight gain, were uncommon.
Conclusions
A comprehensive review of safety from the clinical development program suggests that the STS is safe and well tolerated, with an improved safety margin compared with orally administered MAOIs.
aWorldwide Drug Development, 102 East Avenue, Burlington, VT 05401, United States
bDepression Research Unit, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, United States
Corresponding author. Tel.: +1 802 658 2961.
☆ Role of funding source: Data in this report were derived from research studies sponsored and funded by Somerset Pharmaceuticals, Inc. (Tampa, FL). Preparation of the report was partially funded by Bristol-Myers Squibb (Princeton, NJ) and The Jack Warsaw Endowment for Research in Biological Psychiatry of the University of Pennsylvania Medical Center (Dr. Amsterdam). Conflict of interest: Dr. Robinson has served as consultant to Bristol-Myers Squibb, Somerset Pharmaceuticals, Epix, Genaissance, Medicinova, and Ono Pharmaceuticals. Dr. Amsterdam has served as scientific consultant to Bristol-Myers Squibb and Somerset Pharmaceuticals. Contributors: Dr. Robinson analyzed and reviewed safety data in the selegiline transdermal system NDA submitted to the Food and Drug Administration by Somerset Pharmaceuticals, Inc. Dr. Robinson wrote the first draft of the manuscript. Both authors were involved with literature review, preparation, and final approval of the report.
ABSTRACT