Transdermal selegiline: The new generation of monoamine oxidase inhibitors

Duke University, Durham, North Carolina, United States
CNS spectrums (Impact Factor: 2.71). 06/2006; 11(5):363-75.
Source: PubMed


The clinical use of monoamine oxidase inhibitors (MAOIs) has declined due to concerns about food and drug interactions and waning physician experience. Evidence indicates that MAOIs are effective in depressive disorders, in particular depression with atypical features. Efforts to address safety issues have led to the development of more selective and reversible MAOIs, such as moclobemide. Selegiline, a selective monoamine oxidase B inhibitor, has been approved for the adjunctive treatment of Parkinson's disease at low doses. At higher doses, oral selegiline is also effective in major depressive disorder (MDD) but loses its selectivity and has the potential for tyramine interactions. To overcome these problems, a transdermal formulation of selegiline, the selegiline transdermal system (STS), was developed with novel pharmacokinetic and pharmacodynamic properties. Compared with oral administration, transdermal selegiline leads to sustained plasma concentrations of the parent compound, increasing the amount of drug delivered to the brain and decreasing metabolite production. In addition, STS allows targeted inhibition of central nervous system monoamine A (MAO-A) and monoamine B isoenzymes with minimal effects on MAO-A in the gastrointestinal and hepatic systems, thereby reducing the risk of interactions with tyramine-rich foods (the "cheese-reaction"). Clinical trials have found 6 mg/24 hours of STS to be effective in MDD without the need for dietary restrictions. The efficacy and safety profile of STS supports its use in MDD. It is possible that STS may demonstrate benefit in MDD with atypical features or MDD resistant to other antidepressants. However, more research is needed. Clinicians should familiarize themselves with the properties and indications for the new generation of MAOIs.

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    • "Hence, therapy would not depend on the patient's condition and capacity to follow the treatment; this would obviously help to improve compliance, efficacy and clinical outcome. Although a passive transdermal patch for SEL has been approved for the treatment of MDD, there are reports of skin reactions (Bodkin and Amsterdam, 2002; Patkar et al., 2006); these were described as rash, itching, redness or irritation (36% of patients receiving the selegiline patch cf. 17% of those receiving placebo) (Bodkin and Amsterdam, 2002). "
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