Transdermal selegiline: The new generation of monoamine oxidase inhibitors
Duke University, Durham, North Carolina, United States CNS spectrums
(Impact Factor: 2.71).
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.
Available from: pratikkumar A Patel
- "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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ABSTRACT: The objective was to investigate the anodal iontophoresis of the MAO-B inhibitors rasagiline (RAS) and selegiline (SEL) across porcine and human skin in vitro. Passive delivery of RAS and SEL from aqueous solution was minimal; however, increasing current density from 0.1 to 0.3 and 0.5mA/cm(2) produced a linear increase in steady-state iontophoretic flux (J(ss,RAS)=49.1i(d)+27.9 (r(2)=0.96) and J(ss,SEL)=27.8i(d)+25.8 (r(2)=0.98)). In the absence of background electrolyte, a four-fold change in donor concentration (10, 20 and 40mM) did not produce a statistically significant increase in cumulative permeation of either drug after iontophoresis at 0.5mA/cm(2) for 7h. Co-iontophoresis of acetaminophen confirmed that electromigration was the dominant transport mechanism for both drugs (∼90%). Total iontophoretic delivery of RAS and SEL across porcine and human skin in vitro was statistically equivalent (RAS: 1512.7±163.7 and 1523.6±195.9μg/cm(2), respectively, and SEL: 1268.7±231.2 and 1298.3±253.3μg/cm(2), respectively). Transport efficiencies for RAS and SEL were good (ranged from 6.81 to 8.50 and 2.86 to 3.61%, respectively). Furthermore, the delivery efficiency, i.e., the fraction of the drug in the formulation that was delivered was very high (>56% at 0.5mA/cm(2)). Cumulative permeation of RAS and SEL from carbopol gels, potential drug reservoirs for iontophoretic systems, was 891.5±148.3 and 626.6±162.4μg/cm(2), respectively; this was less than from solution and was tentatively attributed to either different partitioning or slower drug diffusion in the gel matrix. The results demonstrated that therapeutic amounts of rasagiline and selegiline could be easily delivered by transdermal iontophoresis with simple gel patches of modest surface area.
Available from: etd.auburn.edu
Available from: Cara T Hoepner
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ABSTRACT: Every clinician faces the daily question of which antidepressant is best for a particular depressed patient. Double-blind studies submitted for U.S. Federal Drug Administration marketing approval include only the "purest" population of patients, and the American Psychiatric Association and other treatment guidelines often do not adequately address the complexities of developmental, family history, psychosocial, medical, and psychiatric comorbidity, and treatment-refractory issues that are seen in routine clinical practice. Long-term trends in depression treatment include ever-expanding choices among drugs, highly specific psychotherapies, and attempts to treat chronic and/or mild cases, with the goal of remission for all patients. We performed literature reviews and attempted to synthesize factors that may be useful in the application of evidence-based medicine in office-based psychiatric practice. We have found that factors influencing antidepressant selection include drug factors (including tolerability, interactions, and cost), depression subtype, psychiatric and medical comorbidity, and stage of life. In addition, patient preference for avoiding certain side effects and personal and family history of treatment response are helpful information. Most patients in the community would not fit strict antidepressant study criteria. Biologic markers predicting treatment response are not yet widely available, so the optimal choice of medication must be guided by detailed history.
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