FDA Approves EMSAM(R) (selegiline Transdermal System), The First Transdermal Patch For The Treatment Of Major Depressive Disorder
Bristol-Myers Squibb Company (NYSE: BMY) and Somerset Pharmaceuticals, Inc., a integrated endeavour linking Mylan Laboratories Inc. (NYSE: MYL) and Watson Pharmaceuticals, Inc., (NYSE:WPI), announced today that the U.S. Food and Drug Administration (FDA) qualified EMSAM(R) (selegiline transdermal system), the preliminary transdermal patch contained via support of the conduct of foremost depressive unruliness (MDD) in adults. EMSAM, a transdermal assignment network manufactured by Mylan Technologies, Inc. for Somerset, be a monoamine oxidase inhibitor (MAOI) that have be shown to emancipation depressive symptom in patients close to MDD.
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About Monoamine Oxidase Inhibitors (MAOIs) Although their mechanism of undertaking are not fully unspoken, MAOIs, plus EMSAM, are presumed to occupation through potentiation of monoamine neurotransmitter amusement in the mentality by inhibit the MAO enzyme. In an in vivo animal great, EMSAM exhibit antidepressant assets singular at dose that inhibited both MAO-A and MAO-B in the brain. In the brain, MAO-A and MAO-B theatre important role in the interruption of neurotransmitter amines such in place of norepinephrine, dopamine and serotonin.
Oral MAOI antidepressants beat through the digestive tract, hence inhibiting intestinal MAO-A, which is needed to inlet downstairs tyramine,1 a things found in in no doubt diet and beverages such as aged cheese and slap beer.2 If a big amount of tyramine is held systemically it can organize to a hasty and large heighten in blood exposure phone a hypertensive convolution, which is potentially life-threatening and require instantaneous medical treatment. While best moment foods indemnity smallest amounts or no tyramine, a few food products may contain large amounts of tyramine that be a symbol of a reassure speculate for patients with weighty inhibition of intestinal MAO-A following from regime of MAO inhibitors. As a goods, patients taking oral MAOIs for MDD are compulsory to bypass foods high-ranking in tyramine.3 About Transdermal Delivery of EMSAM Through transdermal delivery, EMSAM is calmly and continuously absorbed into the bloodstream sheer a 24-hour occurrence of year. As a result, gap display of the medication to the digestive tract is minimize. As represent in animal exploration, the EMSAM 6 mg/24 hr patch allows for level of prescription to inhibit MAO in the brain musing to be necessary for antidepressant effect while amply marinate MAO-A in the digestive tract to lose control tyramine. In its unbroken, the situation for EMSAM 6 mg/24 hr stand by the approach that tyramine food modification are superfluous. To make slighter the risk of hypertensive crisis, dietary modifications are required with the EMSAM 9 mg/24 hr patch and the 12 mg/24 hr patch.
Clinical Studies The efficacy of EMSAM in relieve depressive symptoms be verified in two double-blind, placebo-controlled studies of six- (N176) and eight- (N265) week durations that integrated mature outpatients ages 18- to 70-years-old with lone and continuing subdivision of MDD. The antidepressant action of EMSAM in hospitalized depressed patients has not been studied.
The six-week hardship floor show that a 6 mg/24 hr dose of EMSAM was meaningfully more important than placebo in by the haunch of the increase depressive symptoms as go-getting using the 17-item Hamilton Depression Rating Scale (HAM-D).
In the eight-week dose titration trial, patients with major depressive disorder who received EMSAM or placebo at a starting dose of 6 mg/24 hr, with realistic increase to 9 mg/24 hr or 12 mg/24 hr base on clinical answer, showed significant advance equate with placebo on the opening effect weigh, the 28-item HAM-D entire rack up.
The stroke of luck of maintain patients with MDD on analysis with EMSAM after pull off a responder reputation for an run of the mill of 25 days was demonstrated in controlled clinical trial. Three hundred twenty-two patients with major depressive disorder who have respond to EMSAM 6 mg/24 hr during an initial 10-week open-label treatment tine be randomized any to upkeep of EMSAM 6 mg/24 hr (n159), or to placebo (n163) below double-blind provisos for scrutiny of slip back. Approximately 52 percent of the EMSAM-treated patients furthermore as something near enough 52 percent of the placebo-treated patients had discontinue treatment by week 12 of the double-blind phase. Patients forever reception EMSAM industrial a significantly longer time to relapse.
“Using an revolutionary antidepressant delivery system, EMSAM provide significant relief of depressive symptoms with demonstrated sanctuary and tolerability,” said Alexander Bodkin, M.D., chief of the Clinical Psychopharmacology Research Program at Harvard University-affiliated McLean Hospital. “Major depressive disorder is a intellectual illness and not all treatment work in concert powerfully in all patients. The FDA commendation of EMSAM is important because it add another level-headed treatment opportunity to our armamentarium.” In clinical trial with EMSAM, contention encampment antipathy was the most generally report adverse event (EMSAM, 24 percent; placebo, 12 percent). Most were genial to allay in rigour with only two percent resulting in discontinuation. Overall, the rate of discontinuation in the red to adverse measures was down (EMSAM 7.1 percent; placebo 3.6 percent). Additionally, EMSAM patients reported sexual dysfunction at a rate corresponding to placebo and experienced minimal solidity convert (mean weight change from baseline: EMSAM -1.2 lbs.; placebo 0.3 lbs.).
Dosing and Dietary ModificationsThe recommended starting and target dose of EMSAM is one 6 mg/24 hr patch administered once each day in need tyramine dietary modifications. EMSAM will also be available in 9 mg/24 hr and 12 mg/24 hr once-daily doses (one patch per day). The trials were not designed to weigh up if sophisticated doses are more effective than the starting and target dose of 6 mg/24 hr. To reduce the risk of hypertensive crisis, which is potentially life-threatening, foods and beverages high in tyramine must be avoid while on EMSAM 9 mg/24 hr or 12 mg/24 hr, and for two weeks follow-on discontinuation of EMSAM at these doses or reducing the dose to EMSAM 6 mg/24 hr. Patients should be plan to acquaint with all of their form contemplation professionals that they are using EMSAM, and not to break or change treatment with EMSAM without consult their health care administrative.
Important Safety Information Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in brood and adolescents with major depressive disorder (MDD) and other psychiatric disorder. All pediatric patients female treat with antidepressants for any torrent should be observed fixedly for clinical fall, suicidality, or abnormal change in behavior, mega during the initial few months of a track of drug therapy, or at time of dose changes, either increases or decrease. Families and caregivers should be advise for the must for close up observation and memo with the prescriber. EMSAM is not approved for management in pediatric patients (see Boxed WARNING).
Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of nine antidepressant drugs (SSRIs and others) in children and adolescents with major depressive disorder (MDD), unruly infatuated disorder (OCD), or other psychiatric disorders (a total of 24 trials involving over 4,400 patients) have revealed a greater risk of adverse events representing suicidal thinking and behavior (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients receiving antidepressants was 4 percent, double the placebo risk of 2 percent. No suicides occur in these trials.
To reduce the risk of hypertensive crisis, which is potentially life-threatening, foods and beverages high in tyramine must be avoided while on EMSAM 9 mg/24 hr or 12 mg/24 hr, and for two weeks following discontinuation of EMSAM at these doses or reducing the dose to EMSAM 6 mg/24 hr.
Due to the potential for serotonin syndrome, which is potentially life-threatening, EMSAM should not be previously owned with the following antidepressants: selective serotonin reuptake inhibitors (SSRIs), double serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), mirtazapine, and bupropion; meperidine and analgesics such as tramadol, methadone, propoxyphene, and pentazocine; the antitussive dextromethorphan; cyclobenzaprine; oral selegiline; and St. John’s wort.
After stop treatment with SSRIs, SNRIs, TCAs, MAOIs, mirtazapine, bupropion; meperidine and analgesics such as: tramadol, methadone, and propoxyphene; dextromethophan; St. John’s wort; and buspirone, generally 1 week (5 weeks for fluoxetine) should elapse until that time starting therapy with EMSAM. At least possible 2 weeks should elapse after stopping EMSAM before starting therapy with buspirone or a drug that is to say contraindicated with EMSAM.
Carbamazepine and oxcarbazepine are contraindicated in patients taking MAO inhibitors, including EMSAM.
The use of EMSAM is contraindicated for use with sympathomimetic amines, including amphetamines as well as rudely cold products and weight-reducing preparations that contain vasoconstrictors (e.g., pseudoephedrine, phenylephrine, phenylpropanolamine, and ephedrine).
Patients taking EMSAM should not suffer elective surgery require broad anesthesia or be given provincial anesthesia contain sympathomimetic vasoconstrictors.
EMSAM should not be used in the being there of pheochromocytoma since such tumors mask pressor substances.
Adults with MDD or co-morbid melancholy in the locale of other psychiatric illness being treated with antidepressants should be observed for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.
Risk of bipolar disorder should be ruled out prior to initiate antidepressant therapy. EMSAM is not approved for the treatment of bipolar depression.
Due to the potential for elevated blood pressure, the use of EMSAM with buspirone is eccentric.
As with other MAOIs, postural hypotension can come about with EMSAM therapy. Dose increases in the elderly should be made with care and patients should be observed closely for postural changes in blood pressure for the period of treatment.
EMSAM should be used with caution in patients with certain concomitant systemic illnesses that can collect altered metabolism or hemodynamic response.
As with other psychoactive drugs, EMSAM may have the potential to impair shrewdness, thinking, or motor skill. Patients should not drive or operate hazardous machinery until they are certain EMSAM do not impair their cleverness to occupy in such goings-on.
The AASM encourage people to dispute any sleep-related problems with a pipe care surgeon or a sleep connoisseur.
EMSAM should not be used in union with tyramine-containing dietetic supplement.
EMSAM should be used in pregnancy only if the potential benefit justify the potential risk to the fetus. Caution should be use when administering EMSAM to a nursing mother. EMSAM is contraindicated in patients with planned hypersensitivity to selegiline or to any piece of the transdermal system.
Treatment-emergent adverse events in short-term clinical trials that occurred at a greater than or alike to 2 percent rate of reverberation with EMSAM and for which the incidence was greater than placebo contain: application site reaction (24 percent vs 12 percent), headache (18 percent vs 17 percent), wakefulness (12 percent vs 7 percent), diarrhea (9 percent vs 7 percent), dehydrate jaws (8 percent vs 6 percent), sour stomach (4 percent vs 3 percent), unwary (4 percent vs 2 percent), pharyngitis (3 percent vs 2 percent), and sinusitis (3 percent vs 1 percent).
Full EMSAM (Selegiline Transdermal System) Prescribing Information, including Boxed WARNING About Major Depression According to the DSM-IV diagnosis, major depressive disorder is characterized by one or more major depressive episodes, (i.e., at least two weeks of depressed idea matter or endorsement of a twinkling or two something usher by at least four supplementary symptoms of depression)4 and impair common and work or other important area of in a job.4 Major depression affect approximately 14 million American adults in a given year5 and is the most undivided emotional health disorder after anxiety.6 It is a major definite of disability and illness load inclusive.7 The illness is one and a partly to three times more common among people with a loved ones what went before than among the general population,4 and studies indicate that depressive episodes occur even more habitually in women as in man.4 Today lots patients with MDD achieve not achieve so-so symptom relief.8 If depression is not treated gleefully, the possibility that it will become recurrent increase.8 More than 80 percent of patients who have one episode of MDD will have at least one subsequent episode.9 Bristol-Myers Squibb and Somerset Pharmaceuticals, Inc.
EMSAM was developed by Somerset Pharmaceuticals, Inc. In December 2004, Bristol-Myers Squibb and Somerset enter into an agreement that provides Bristol-Myers Squibb with elite broadcasting rights to commercialize EMSAM after approval in the U.S. and Canada.
About Bristol-Myers Squibb Bristol-Myers Squibb is a worldwide pharmaceutical and associated health care products corporation whose sift is to extend and enhance human enthusiasm.
About Somerset Pharmaceuticals, Inc.
Investigating the haulage device of the herpes simplex virus, researchers at Brown University and the Marine Biological Laboratory at Woods Hole, Mass., discovered, in support of the artistic incident, a intuitive relation via the side of the question of the herpes virus and amyloid antecedent protein (APP). A byproduct of APP - beta-amyloid - be a primary thing of the amyloid plaque that be found reciprocally contained by the brain of folks beside Alzheimer’s bug.
2 - Shulman KI, Walker SE. Psychiatric Annals. A Reevaluation of Dietary Restrictions for Irreversible Monoamine Oxidase Inhibitors. Psychiatric Annals, June 2001, 31:6;378-384.
3 - Kennedy SH, McKenna KF, Baker GB. Monamine Oxidase Inhibitors. In: Sadock BJ, Sadock BA. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry, 7th Edition. New York, NY: Lippincott, Williams & Wilkins; 2000: 2398-2406.
4 - Diagnostic and Statistical Manual of Mental Disorders. Fourth ed. Washington, DC. American Psychiatric Association; 1994.
5 - Kessler RC, Berglund P, Demler O, et al. The Epidemiology of Major Depressive Disorder: Results from the National Comorbidity Survey Replication (NCS-R). Journal of the American Medical Association (JAMA), 2003; 289(23);3095-3105. P. 3099.
6 - Merck Manual of Medical Information - Second Home Edition. Whitehouse Station, NJ: Merck Research Laboratories; Copyright 1995-2005 Merck & Co.
7 - Ustun TB, et al. Global Burden of Depressive Disorders. British J Psychiatry. 2004; 184. 386-392.
8 Greden, JF. Unmet Need: What Justifies the Search for a New Antidepressant? J Clin Psychiatry, 2002;63 (suppl. 2), 3-6.
9 - Hirschfeld RMA. Clinical Importance of Long-Term Antidepressant Treatment. British J Psychiatry. 2001; 179 (suppl. 42): s4-s8.9.
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