A double-blind, placebo-controlled study of selegiline transdermal system in depressed adolescents.

Objective: A randomized, double-blind, placebo-controlled flexible-dose, parallel group trial was conducted at 26 clinical investigational sites in the United States to examine the safety and efficacy of the selegiline transdermal system (STS) (EMSAM®) in adolescents (ages 12-17 years) meeting American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for moderate to severe major depressive disorder (MDD) without psychotic features.

Methods: Adolescents (n=308) with moderate to severe MDD were randomized to either STS (n=152) or placebo (n=156).

Lack of tyramine pressor response effect with oral CX157: A specific reversible MAOI.

This Phase 1, single-center, double-blind, placebo-controlled, three-period study assessed cardiovascular safety of CX157, a specific Reversible Inhibitor of Monoamine Oxidase A (RIMA), following the oral administration of tyramine. In Period 1, the sensitivity of each subject to orally administered tyramine was established by determining the dose of tyramine that elevates SBP ≥30 mmHg on ≥3 consecutive occasions (i.e.

Reversible inhibitors of monoamine oxidase-A (RIMAs): robust, reversible inhibition of human brain MAO-A by CX157.

Reversible inhibitors of monoamine oxidase-A (RIMA) inhibit the breakdown of three major neurotransmitters, serotonin, norepinephrine and dopamine, offering a multi-neurotransmitter strategy for the treatment of depression. CX157 (3-fluoro-7-(2,2,2-trifluoroethoxy)phenoxathiin-10,10-dioxide) is a RIMA, which is currently in development for the treatment of major depressive disorder. We examined the degree and reversibility of the inhibition of brain monoamine oxidase-A (MAO-A) and plasma CX157 levels at different times after oral dosing to establish a dosing paradigm for future clinical efficacy studies, and to determine whether plasma CX157 levels reflect the degree of brain MAO-A inhibition.

The selegiline transdermal system (emsam): a therapeutic option for the treatment of major depressive disorder.

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.

Treatment effects of selegiline transdermal system on symptoms of major depressive disorder: a meta-analysis of short-term, placebo-controlled, efficacy trials.

Objective: Selegiline transdermal system (STS) is efficacious for the treatment of major depressive disorder (MDD). This meta-analysis explores treatment effects of STS for individual symptoms of MDD derived from line-item analyses of the 28-item Hamilton Rating Scale for Depression (HAM-D28) and the Montgomery-Asberg Depression Rating Scale (MADRS).

Methods: Change in score from baseline to end of treatment for each item of the HAM-D28 and MADRS was assessed using a multilevel model for meta-analysis of continuous outcome data from all five short-term, randomized, placebo-controlled efficacy trials conducted during preapproval clinical development of STS for MDD.

Pharmacokinetics and absolute bioavailability of selegiline following treatment of healthy subjects with the selegiline transdermal system (6 mg/24 h): a comparison with oral selegiline capsules.

The selegiline transdermal system is a monoamine oxidase inhibitor that was recently approved by the US Food and Drug Administration for the treatment of major depressive disorder. The current study was conducted during the selegiline transdermal system development program to characterize the single-dose pharmacokinetics and absolute bioavailability of selegiline administered by the 6-mg/24-h selegiline transdermal system in healthy volunteers. Selegiline transdermal system results were compared with those obtained after a single 10-mg oral dose of selegiline HCl.

Evaluation of the potential for pharmacodynamic and pharmacokinetic drug interactions between selegiline transdermal system and two sympathomimetic agents (pseudoephedrine and phenylpropanolamine) in healthy volunteers.

Selegiline transdermal system is a recently approved monoamine oxidase inhibitor antidepressant. Medications that inhibit monoamine oxidase type A can augment the pressor effects of sympathomimetic amines, increasing the potential for hypertensive crisis. This study examined the potential for drug-drug interactions during treatment with selegiline transdermal system and pseudoephedrine or phenylpropanolamine.

Selegiline transdermal system: an examination of the potential for CYP450-dependent pharmacokinetic interactions with 3 psychotropic medications.

Selegiline transdermal system (STS) is a recently approved monoamine oxidase inhibitor antidepressant. This article reports results from 3 studies examining the potential for cytochrome P450-dependent pharmacokinetic interactions between STS and 3 psychotropic medications that might be coadministered. Three open-label, randomized, Latin square, 3-sequence crossover design studies were conducted with healthy volunteers to determine the pharmacokinetic parameters of STS 6 mg/24 h and test drug (alprazolam, olanzapine, or risperidone) when administered alone and concomitantly.

Effects of a tyramine-enriched meal on blood pressure response in healthy male volunteers treated with selegiline transdermal system 6 mg/24 hour.

Background: Monoamine oxidase inhibitors are well recognized as effective antidepressant agents but are rarely used due, in part, to the risk of hypertensive crisis following the ingestion of foods high in tyramine ("cheese reaction"). A selegiline transdermal system (STS) was developed to provide antidepressant concentrations of selegiline in the brain, while preserving the gastrointestinal monoamine oxidase A (MAO-A) barrier. The present study was conducted to determine the effect of the STS 6 mg/24 hour on cardiovascular safety following the ingestion of approximately 400 mg of tyramine consumed as a component of aged cheeses.

Tyramine pressor sensitivity during treatment with the selegiline transdermal system 6 mg/24 h in healthy subjects.

The oral tyramine pressor test was administered to healthy males during treatment with a selegiline transdermal system (STS; 6 mg/24 h). The tyramine sensitivity factor (TSF) was calculated from the ratio of baseline and on-treatment tyramine pressor doses. The tyramine sensitivity factor value following 9 days of treatment with the selegiline transdermal system was 1.

Tyramine pharmacokinetics and reduced bioavailability with food.

Tyramine challenge studies have demonstrated that it requires approximately twice the amount of tyramine administered with a meal compared to administration after a fast to elicit the same effect, suggesting a reduction in bioavailability of tyramine when administered with food. The pharmacokinetics of tyramine when administered in a fasted versus a fed state were studied. A single 200-mg dose of tyramine was administered orally to healthy subjects both after an overnight fast and during a meal.

Daily transdermal administration of selegiline to guinea-pigs preferentially inhibits monoamine oxidase activity in brain when compared with intestinal and hepatic tissues.

Selegiline has been formulated in an acrylic polymer adhesive mixture to be employed as a constant release topical patch for daily transdermal administration. Application of this selegiline transdermal system (STS) to guinea-pigs resulted in an average delivery of 1.185 mg selegiline/cm(2) patch/24 h.