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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 11 of 11. This is the beginning of the thread.
Posted by trx resistant on October 30, 2007, at 17:16:33
Wondering if anyone has information about 9mg EMSAM raising risk of seizures. Had 7 seizures in five hours at the age of 49 (no prior history) caused by Wellbutrin(450mg) in combo with 30 mg Dexidrine taken for MDD. Tried SSRIs but were of no help, especially at lowest dose. Seizure free for nearly 5 years but when my Cymbalta was raised to 120mg had 1 suspected nocturnal seizure. Bristol Meyers said 6mg risk was less than 1 in a thousand. So I am a very nervous starting a new drug. This is my first experience with a MAOI. It does seem to work fast. Tried 6mg for 4 weeks but needed more activation. Just started 9mg and notice big difference. EMSAM is my last hope because it works on dopamine like Wellbutrin and none of the SSRIs were helpful. I am hoping I can tolerate it but do notice it is more activating at 9mg which I desparately need to get me up and out of the house and able to rejoin the world.
trx resistant
Posted by Phillipa on October 30, 2007, at 17:41:28
In reply to EMSAM and seizures, posted by trx resistant on October 30, 2007, at 17:16:33
So sorry about your history of seizures due to meds. Hoping the EMSAM is your med. Phillipa
Posted by trx resistant on October 31, 2007, at 13:14:12
In reply to Re: EMSAM and seizures » trx resistant, posted by Phillipa on October 30, 2007, at 17:41:28
Thanks for your support Phillipa. From reading your posts over the various boards it's people like you that can make all the difference in this world. I'll keep updating. I'm praying this works or I will end up being a bag lady if I can't get my act together to get a job.
trx resistant.
Posted by Phillipa on October 31, 2007, at 20:22:39
In reply to Re: EMSAM and seizures, posted by trx resistant on October 31, 2007, at 13:14:12
Thanks for the kind words but not good with neurotransmitters. Sure about dopamine with EMSAM? I guess I'll google it. Phillipa
Posted by Phillipa on October 31, 2007, at 20:34:36
In reply to Re: EMSAM and seizures, posted by trx resistant on October 31, 2007, at 13:14:12
Sure you've already read this but included it. Phillipa
transdermal system), the First Transdermal Patch for the Treatment of Major Depressive Disorder
Clinical Trials Showed Significant Improvement in Depressive Symptoms; No Tyramine Dietary Modifications Required at the Starting & Target Dose of 6 Milligram (mg)/24 hour (hr); Tyramine Dietary Modifications Required at 9 mg/24 hr and 12 mg/24 hr Doses
PRINCETON, N.J. and TAMPA, Fla., Feb. 28 /PRNewswire-FirstCall/ -- Bristol-Myers Squibb Company (NYSE: BMY) and Somerset Pharmaceuticals, Inc., a joint venture between Mylan Laboratories Inc. (NYSE: MYL) and Watson Pharmaceuticals, Inc., (NYSE: WPI), announced today that the U.S. Food and Drug Administration (FDA) approved EMSAM(R) (selegiline transdermal system), the first transdermal patch for the treatment of major depressive disorder (MDD) in adults. EMSAM, a transdermal delivery system manufactured by Mylan Technologies, Inc. for Somerset, is a monoamine oxidase inhibitor (MAOI) that has been shown to relieve depressive symptoms in patients with MDD."We are pleased to be able to provide this important treatment to people with major depressive disorder," said Peter R. Dolan, chief executive officer, Bristol-Myers Squibb Company. "We believe EMSAM will help physicians treat their patients living with this illness through a new and unique delivery system."
"Together with Bristol-Myers Squibb, we are excited to be able to utilize transdermal technology to administer EMSAM, belonging to the MAOI class of agents that have proven antidepressant efficacy," said Mel Sharoky, M.D., president and chief executive officer, Somerset Pharmaceuticals.
About Monoamine Oxidase Inhibitors (MAOIs)
Although their mechanisms of action are not fully understood, MAOIs, including EMSAM, are presumed to work through potentiation of monoamine neurotransmitter activity in the brain by inhibiting the MAO enzyme. In an in vivo animal model, EMSAM exhibited antidepressant properties only at doses that inhibited both MAO-A and MAO-B in the brain. In the brain, MAO-A and MAO- B play important roles in the breakdown of neurotransmitter amines such as norepinephrine, dopamine and serotonin.
Oral MAOI antidepressants pass through the digestive tract, thus inhibiting intestinal MAO-A, which is needed to break down tyramine,(1) a substance found in certain foods and beverages such as aged cheese and tap beer.(2) If a large amount of tyramine is absorbed systemically it can lead to a sudden and large increase in blood pressure called a hypertensive crisis, which is potentially life-threatening and requires immediate medical treatment. While most foods contain negligible amounts or no tyramine, a few food products may contain large amounts of tyramine that represent a potential risk for patients with significant inhibition of intestinal MAO-A resulting from administration of MAO inhibitors. As a result, patients taking oral MAOIs for MDD are required to avoid foods high in tyramine.(3)
About Transdermal Delivery of EMSAM
Through transdermal delivery, EMSAM is directly and continuously absorbed into the bloodstream over a 24-hour period. As a result, initial exposure of the drug to the digestive tract is minimized. As indicated in animal studies, the EMSAM 6 mg/24 hr patch allows for levels of medicine to inhibit MAO in the brain thought to be necessary for antidepressant effect while sufficiently preserving MAO-A in the digestive tract to break down tyramine. In its entirety, the data for EMSAM 6 mg/24 hr support the recommendation that tyramine dietary modifications are not needed. To reduce 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 relieving depressive symptoms was established in two double-blind, placebo-controlled studies of six- (N=176) and eight- (N=265) week durations that included adult outpatients ages 18- to 70-years- old with single and recurrent episodes of MDD. The antidepressant action of EMSAM in hospitalized depressed patients has not been studied.
The six-week trial showed that a 6 mg/24 hr dose of EMSAM was significantly more effective than placebo in improving depressive symptoms as determined 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 possible increases to 9 mg/24 hr or 12 mg/24 hr based on clinical response, showed significant improvement compared with placebo on the primary outcome measure, the 28-item HAM-D total score.
The benefit of maintaining patients with MDD on therapy with EMSAM after achieving a responder status for an average of 25 days was demonstrated in a controlled clinical trial. Three hundred twenty-two patients with major depressive disorder who had responded to EMSAM 6 mg/24 hr during an initial 10-week open-label treatment phase were randomized either to continuation of EMSAM 6 mg/24 hr (n=159), or to placebo (n=163) under double-blind conditions for observation of relapse. Approximately 52 percent of the EMSAM-treated patients as well as about 52 percent of the placebo-treated patients had discontinued treatment by week 12 of the double-blind phase. Patients continually receiving EMSAM experienced a significantly longer time to relapse.
"Using an innovative antidepressant delivery system, EMSAM provides significant relief of depressive symptoms with demonstrated safety 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 serious illness and not all treatments work equally well in all patients. The FDA approval of EMSAM is important because it adds another valuable treatment option to our armamentarium."
In clinical trials with EMSAM, application site reaction was the most commonly reported adverse event (EMSAM, 24 percent; placebo, 12 percent). Most were mild to moderate in severity with only two percent resulting in discontinuation. Overall, the rate of discontinuation due to adverse events was low (EMSAM 7.1 percent; placebo 3.6 percent). Additionally, EMSAM patients reported sexual dysfunction at a rate similar to placebo and experienced minimal weight change (mean weight change from baseline: EMSAM -1.2 lbs.; placebo +0.3 lbs.)
Dosing and Dietary Modifications
The recommended starting and target dose of EMSAM is one 6 mg/24 hr patch administered once daily without 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 assess if higher 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 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. Patients should be instructed to inform all of their healthcare professionals that they are using EMSAM, and not to stop or change treatment with EMSAM without consulting their healthcare professional.Important Safety Information
Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with major depressive disorder (MDD) and other psychiatric disorders. All pediatric patients being treated with antidepressants for any indication should be observed closely for clinical worsening, suicidality, or unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at time of dose changes, either increases or decreases. Families and caregivers should be advised for the need for close observation and communication with the prescriber. EMSAM is not approved for use 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), obsessive compulsive 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, twice the placebo risk of 2 percent. No suicides occurred 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 used with the following antidepressants: selective serotonin reuptake inhibitors (SSRIs), dual 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 stopping treatment with SSRIs, SNRIs, TCAs, MAOIs, mirtazapine, bupropion; meperidine and analgesics such as: tramadol, methadone, and propoxyphene; dextromethophan; St. John's wort; and buspirone, approximately 1 week (5 weeks for fluoxetine) should elapse before starting therapy with EMSAM. At least 2 weeks should elapse after stopping EMSAM before starting therapy with buspirone or a drug that is 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 cold products and weight-reducing preparations that contain vasoconstrictors (eg, pseudoephedrine, phenylephrine, phenylpropanolamine, and ephedrine).
Patients taking EMSAM should not undergo elective surgery requiring general anesthesia or be given local anesthesia containing sympathomimetic vasoconstrictors.
EMSAM should not be used in the presence of pheochromocytoma since such tumors secrete pressor substances.
Adults with MDD or co-morbid depression in the setting 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 initiating 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 not recommended.
As with other MAOIs, postural hypotension can occur with EMSAM therapy. Dose increases in the elderly should be made with caution and patients should be observed closely for postural changes in blood pressure throughout treatment.
EMSAM should be used with caution in patients with certain concomitant systemic illnesses that can produce altered metabolism or hemodynamic responses.
As with other psychoactive drugs, EMSAM may have the potential to impair judgment, thinking, or motor skills. Patients should not drive or operate hazardous machinery until they are certain EMSAM does not impair their ability to engage in such activities.
The use of alcohol is not recommended while taking EMSAM. EMSAM should not be used in combination with tyramine-containing nutritional supplements.
EMSAM should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Caution should be exercised when administering EMSAM to a nursing mother.
EMSAM is contraindicated in patients with known hypersensitivity to selegiline or to any component of the transdermal system.
Treatment-emergent adverse events in short-term clinical trials that occurred at a greater than or equal to 2 percent incidence with EMSAM and for which the incidence was greater than placebo include: application site reaction (24% vs 12%), headache (18% vs 17%), insomnia (12% vs 7%), diarrhea (9% vs 7%), dry mouth (8% vs 6%), dyspepsia (4% vs 3%), rash (4% vs 2%), pharyngitis (3% vs 2%), and sinusitis (3% vs 1%).
Posted by Larry Hoover on November 1, 2007, at 11:51:06
In reply to EMSAM and seizures, posted by trx resistant on October 30, 2007, at 17:16:33
> Wondering if anyone has information about 9mg EMSAM raising risk of seizures. Had 7 seizures in five hours at the age of 49 (no prior history) caused by Wellbutrin(450mg) in combo with 30 mg Dexidrine taken for MDD. Tried SSRIs but were of no help, especially at lowest dose. Seizure free for nearly 5 years but when my Cymbalta was raised to 120mg had 1 suspected nocturnal seizure. Bristol Meyers said 6mg risk was less than 1 in a thousand. So I am a very nervous starting a new drug. This is my first experience with a MAOI. It does seem to work fast. Tried 6mg for 4 weeks but needed more activation. Just started 9mg and notice big difference. EMSAM is my last hope because it works on dopamine like Wellbutrin and none of the SSRIs were helpful. I am hoping I can tolerate it but do notice it is more activating at 9mg which I desparately need to get me up and out of the house and able to rejoin the world.
> trx resistantI've reviewed all the literature I can find, and I cannot find any correlation between Emsam exposure and seizure incidence. There is nothing whatsoever in the product monograph, so I'd presume that any seizure activity noted in the clinical trials was at the baseline level of the population at large. In other words, coincidental to Emsam exposure.
In contrast, Wellbutrin is known to lower the seizure threshold. In fact, the upper dose recommendation was dropped from 600 mg/day to 450 mg/day, to reduce seizure risk to an acceptable level. It is quite possible that concurrent exposure to amphetamine might have increased the risk of seizure further. This risk does not transfer to Emsam, as far as I can tell.
Lar
Posted by Astounder on November 2, 2007, at 15:18:25
In reply to Re: EMSAM and seizures » trx resistant, posted by Larry Hoover on November 1, 2007, at 11:51:06
> > Wondering if anyone has information about 9mg EMSAM raising risk of seizures. Had 7 seizures in five hours at the age of 49 (no prior history) caused by Wellbutrin(450mg) in combo with 30 mg Dexidrine taken for MDD. Tried SSRIs but were of no help, especially at lowest dose. Seizure free for nearly 5 years but when my Cymbalta was raised to 120mg had 1 suspected nocturnal seizure. Bristol Meyers said 6mg risk was less than 1 in a thousand. So I am a very nervous starting a new drug. This is my first experience with a MAOI. It does seem to work fast. Tried 6mg for 4 weeks but needed more activation. Just started 9mg and notice big difference. EMSAM is my last hope because it works on dopamine like Wellbutrin and none of the SSRIs were helpful. I am hoping I can tolerate it but do notice it is more activating at 9mg which I desparately need to get me up and out of the house and able to rejoin the world.
> > trx resistant
>
> I've reviewed all the literature I can find, and I cannot find any correlation between Emsam exposure and seizure incidence. There is nothing whatsoever in the product monograph, so I'd presume that any seizure activity noted in the clinical trials was at the baseline level of the population at large. In other words, coincidental to Emsam exposure.
>
> In contrast, Wellbutrin is known to lower the seizure threshold. In fact, the upper dose recommendation was dropped from 600 mg/day to 450 mg/day, to reduce seizure risk to an acceptable level. It is quite possible that concurrent exposure to amphetamine might have increased the risk of seizure further. This risk does not transfer to Emsam, as far as I can tell.
>
> LarEMSAM reverses and prevents seizure in animal models of epilepsy, an effect synergistic with diazepam (Valium) and phenytoin (Dilantin). Amphetamines only very mildly decrease the seizure threshold, unlike cocaine & bupropion (Wellbutrin).
MAOIs in general are not epileptogenic. Chronic use of the full MAOI phenelzine (Nardil) is strongly antiepileptogenic in animal models by virtue of its active metabolite phenylethylidenehydrazine (PEH): PEH markedly increases CNS GABA levels by inhibiting its catabolizm by GABA-transaminase (GABA-T), an action shared by the valproates and vigabatrin (Sabril), which are used treat epilepsy. There is also some evidence the reversible inhibitor of MAO-A (RIMA) moclobemide increases the seizure threshold.
Posted by trx resistant on November 12, 2007, at 2:43:50
In reply to Re: EMSAM and seizures » trx resistant, posted by Larry Hoover on November 1, 2007, at 11:51:06
Thanks so much for doing the research for me. I thought my dr. told me in the past that MAIOs' generally were safer since I now have permenantly lowered threshold cause by the Wellbutrin. But now he denies he said that. He claims all anti-depressants lower seizure threshold and I'm still at risk, but lower risk than with Wellbutrin/Dexidrine combo. I guess once you had a seizure, you are forever at risk. Lack of sleep seems to trigger seizures as well. The last one I had was nocturnal and I bit my tongue so severely I couldn't speak for 2-3 weeks without severe pain. But your info is reassuring.
Posted by trx resistant on November 12, 2007, at 2:55:05
In reply to Re: EMSAM and seizures, posted by Astounder on November 2, 2007, at 15:18:25
Wow, Astounder! I wish I could nominate you for a Nobel prize. I can't tell you how much relief and hope this gives me. You have an amazing future ahead. I agree with Phillipa you should really consider what a treasure you could be to those of us that can't seem to get this information from our own treating physicians. I have decided to change doctors because all mine does each week is listen to what you have shared on this board and then I decide what I'm going to do. He won't read the clinical papers and explain how and at what rate this medication is absorbed. He just says I will be his guinea pig!
Posted by rskontos on November 18, 2007, at 12:56:23
In reply to Re: EMSAM and seizures » Astounder, posted by trx resistant on November 12, 2007, at 2:55:05
Hey trxresistant, I have had seizures in the past and see a neuro. She says that all AD can cause seizures but that certain ones have a less tendency to do so. due to my family history of them she said had I seen her first there would have been certain ones that she would not have recommended due to their propensity to cause them in individuals with history. Now you seem not to have a history so that is tricky. However, now that you have had one you are right you are more at risk. I do remember that my neuro said that wellbutrin was out for me as well as zoloft. I could always call her and ask which ones I cant take and give you that information if you would feel better. I don't think asking for a referral to a neuro is ever a bad idea since you had 7 of them. Cymbalta did cause me to have partial seizures and quite a few. I was even on a Anti convulsant at the time but it wasn't high enough to combat the cymbalta. I would not want to be guinea pig either. My T and I decide I would continue to seeing the neuro for meds since she knows them and seizures and while she is knowledge about it all and wants to help why not. Hey she even listens and gives me options. Good luck with the change. I hope you find one that listens like I have. Rk
Posted by trx resistant on November 19, 2007, at 16:17:03
In reply to Re: EMSAM and seizures, posted by rskontos on November 18, 2007, at 12:56:23
Thanks for your info and suggestions. I'm keeping my fingers crossed but I think found something truly helpful, EMSAM. It gives me the stimulation I need that only Wellbutrin gave but it seems much safer. Thanks to the wonderful information I received from Larry Hoover (my hero) and Astounder (my hero or herione?) they found literature that suggests it might actually raise seizure treshold and protect me. Consider EMSAM. It may have saved my life! Good luck!
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