Psycho-Babble Medication Thread 140745

Shown: posts 1 to 25 of 31. This is the beginning of the thread.

 

Transdermal Selegiline

Posted by djmmm on February 12, 2003, at 17:10:02

Transdermal Selegiline Avoids Adverse Effects of Oral Form


from The Brown University Psychopharmacology Update
Posted 02/03/2003

A new transdermal formulation of the monoamine oxidase inhibitor (MAOI) selegiline (Eldepryl) has proven effective in controlling depression without generating the serious side effects of oral MAOIs. The first placebo-controlled trial of transdermal selegiline reported a significantly greater improvement in symptoms of depression in patients taking transdermal selegiline as compared to patients taking placebo, with none of the dietary interactions associated with the oral formulation.

According to lead investigator J. Alexander Bodkin, M.D., many psychiatrists do not prescribe MAOIs any more due to fear of their side effects.

"The reason MAOIs aren't being used anymore is not because they aren't effective," Bodkin, Assistant Professor of Psychiatry, Harvard Medical School, and Associate Psychiatrist, McLean Hospital, Belmont, MA, told The Brown University Psychopharmacology Update. "They are supremely effective. But people who are on them can get killed as a result of eating the wrong food."

According to Bodkin, oral MAOIs currently available in the U.S., such as oral selegiline, inhibit the MAO-A enzymes in the gut, which detoxify dietary tyramine in fermented products such as cheese, red wine, soy sauce, beer on tap and air-cured sausage. Ingesting these fermented products while taking MAOIs can cause acute hypertension. Oral selegiline can also interact with medications such as over-the-counter cold remedies, as well as serotonergic antidepressants, causing hyperthermia.

Bodkin noted that although it is used off-label, oral selegiline is currently indicated for Parkinson's disease, not depression. At the lower doses used to treat Parkinson's disease, selegiline is selective for MAOB enzymes, which are not found in the gut. As a result, toxic interactions with dietary substances or other drugs are unlikely at such doses. At the higher doses needed to treat depression, MAO-B selectivity is lost.

Due to these interactions, MAOIs are used in treatment-resistant depression only, said Jonathan Cole, M.D., a senior consultant in psychopharmacology at McLean Hospital and a Professor of Psychiatry at Harvard Medical School. He added that, currently, few psychiatrists are even trained in how to use MAOIs.

Groundbreaking Study
This study, which was supported in part by the manufacturer of selegiline, randomly assigned 177 adult outpatients with major depressive disorder to six weeks of treatment with either 20 mg daily of transdermal selegiline applied by means of a patch (N=89), or placebo (N=88). Response to medication or placebo was measured by both the 17- and the 28-item versions of the Hamilton Depression Rating Scale, the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression (CGI) severity and improvement measures.

Patients taking transdermal selegiline improved more on all measures of depression than did patients taking placebo. Scores on the 17-item Hamilton Depression Rating Scale decreased by 8.73 from baseline to week six in the selegiline group, as compared to 6.10 over the same time period in the placebo group (p=0.01). The 28-item Hamilton Depression Rating Scale showed a decrease of 11.23 from baseline in the selegiline group, as compared to a 7.59 decrease from baseline in the placebo group over the six weeks of treatment (p=0.004). The MADRS, which according to Dr. Bodkin is a little bit more sensitive to changes due to medication, demonstrated a 9.77 point decrease from baseline in selegilinetreated patients and a 5.69 decrease from baseline in placebo-treated patients (p=0.005).

There was a statistically significant difference between the two groups on the 17-item Hamilton Depression Rating Scale (p=0.05), the 28-item Hamilton Depression Rating Scale (p=0.02) and the MADRS (p=0.01) as early as week one of treatment.

"It is quite unusual to find something that moves everything [all measures of depression] that rapidly," said Bodkin. Bodkin also noted that, although the first observation according to the study protocol was made at one week, several patients got well within a day of treatment.

The only statistically significant side effect of transdermal selegiline, according to Bodkin, was a skin rash, which occurred in 17 percent of the placebo group and 36 percent of the selegiline group (p=0.006). There were no significant differences between the two groups in side effects related to the body as a whole, or in the cardiovascular, nervous, digestive, respiratory, urogenital or musculoskeletal systems. There was no difference between the two groups in the rate of acute hypertension.

The selegiline-treated patients also reported significantly improved sexual function compared with placebo-treated patients (p=0.03). This improvement in sexual functioning compares favourably with currently popular antidepressants as well as with oral MAOIs, both of which often cause sexual side effects, said Bodkin.

The rate of compliance in this particular study was virtually one hundred percent, quite unusual when compared with compliance rates of 65 percent in clinical trials and of 50 percent in the community, stated Bodkin.

Transdermal Delivery
In speaking about the benefits of the transdermal formulation Bodkin said it "gets into the blood stream immediately, you get much higher concentrations in a much more sustained way, you see the [parent] drug rather than the metabolites, and you avoid the effect on the gut."

Oral medications are metabolized almost immediately by the liver, explained Bodkin; therefore much of the drug is metabolized before it reaches the brain. Since transdermal delivery bypasses initial metabolism in the liver, more of the drug is available to enter the bloodstream.

It is believed that transdermal administration also results in slower metabolism of the drug, according to Cole, with more sustained concentrations. However, no studies have been done to test this hypothesis, he added.

Cole sees a role for transdermal selegiline in a significant subgroup of anxious depressed patients. Studies show MAOIs are better than placebo for a significant subgroup of anxious patients such as those with agoraphobia and social phobia, he said. With the transdermal delivery system addressing concerns about dietary interactions seen with the oral formulation, "maybe Eldepryl will help people who are now getting SSRIs" said Cole.

Bodkin added that transdermal selegiline might be a promising treatment for use in emergency situations, such as with depressed patients who are suicidal. Since it acts quickly, it might relieve depression more quickly than oral antidepressants, which take four to six days to take effect. Additionally, because the transdermal delivery system is always on the patient's body, it encourages compliance, especially in depressed individuals who can be unmotivated to take their medication, or the elderly, who forget to take oral medications. "It's really quite a compliance boon," he commented.

"The concern [with transdermal selegiline] is pretty much limited to the skin reaction," concluded Bodkin. "In people who had a bad skin reaction, it leaves a mark that lasts for two weeks. It's not the most discreet thing in the world."

"It will re-introduce American psychiatry to MAOIs," concluded Cole, commenting on the clinical implications of transdermal selegiline.

 

Anyone still finding benefits from Selegiline ?

Posted by hok on February 12, 2003, at 18:36:56

In reply to Transdermal Selegiline , posted by djmmm on February 12, 2003, at 17:10:02

On a similar note...

A few of you mentioned lately that you had tried or were still taking selegiline. Anybody still taking it for mood effects and finding it helpful for anhedonia and drive? It seems everybody has a go with it but no one sticks with it for long. Guess it's one of those drugs that looks great on paper, but no so hot in practice.

Back a couple of years ago, I tried a daily regimen, but from what I remember, I seem to notice the side effects of anxiety and tension more than anything else. Perhaps I need to have another go but with a lower dosage. I was fairly disappointed in the FDA's denial of the patch form. It seems like it would be an improvement on the side effects. Would love to know if anybody considers the oral dosage a viable therapy still.

Any details on the pros and cons of it will be very much apprecitated. Thanks

HK

 

Re: Transdermal Selegiline

Posted by jrbecker on February 12, 2003, at 18:38:51

In reply to Anyone still finding benefits from Selegiline ?, posted by hok on February 12, 2003, at 18:36:56

What's the news on this anyways? The latest I thought was that Somerset pharmaceutcals was dropping it due to escalating research costs since the FDA's non-approvable letter in 3/02.

 

Re: Anyone still finding benefits from Selegiline ? » hok

Posted by wingedcat on February 12, 2003, at 20:43:58

In reply to Anyone still finding benefits from Selegiline ?, posted by hok on February 12, 2003, at 18:36:56

See this post - http://www.dr-bob.org/babble/20030208/msgs/140749.html

It's great for anhedonia, drive, and mood. But yes, the anxiety is worse. My primary doctor refuses to work with me on it and tells me to consult a psychiatrist. A psychiatrist I saw got very angry with me for taking it and practically threw me out. I'm trying to find another psychiatrist and not having much luck at all.

I think a benzo + Selegiline would be perfect for me. But they won't treat me until I'm off the Selegiline. I guess they prefer me to be suicidal. I think that's really messed up.

The MAO-B shouldn't regenerate for a while anyway, so I'm praying I can get treatment before that happens.

 

Re: Anyone still finding benefits from Selegiline ? » wingedcat

Posted by hok on February 12, 2003, at 22:54:44

In reply to Re: Anyone still finding benefits from Selegiline ? » hok, posted by wingedcat on February 12, 2003, at 20:43:58

That's too bad you have to quit what works for you, but it sounds like it's only making your anxiety worse.

I suffer only mildly from anxiety (in counjunction with my depression). So I'm wondering if I might find a low dose that might work for me. Couple of questions, if you don't mind:

Have you had success on Wellbutrin or any of the other stims? The only one I've been able to tolerate without irritability/tension has been methylphenidate.

Also, can I inquire as to what dosage of deprenyl you were taking?

I swear, if I can't find something to replace the smoking I think I'm just going to keep it up for the rest of my life. It's the only thing that seems to work for anhedonia!!!

> See this post - http://www.dr-bob.org/babble/20030208/msgs/140749.html
>
> It's great for anhedonia, drive, and mood. But yes, the anxiety is worse. My primary doctor refuses to work with me on it and tells me to consult a psychiatrist. A psychiatrist I saw got very angry with me for taking it and practically threw me out. I'm trying to find another psychiatrist and not having much luck at all.
>
> I think a benzo + Selegiline would be perfect for me. But they won't treat me until I'm off the Selegiline. I guess they prefer me to be suicidal. I think that's really messed up.
>
> The MAO-B shouldn't regenerate for a while anyway, so I'm praying I can get treatment before that happens.

 

Re: Transdermal Selegiline » jrbecker

Posted by not exactly on February 13, 2003, at 5:50:17

In reply to Re: Transdermal Selegiline, posted by jrbecker on February 12, 2003, at 18:38:51

Dr. Bodkin told me that Somerset is reapplying for FDA approval, and he expects that this time they will succeed.

- Bob

 

Re: Transdermal Selegiline » not exactly

Posted by jrbecker on February 13, 2003, at 10:15:34

In reply to Re: Transdermal Selegiline » jrbecker, posted by not exactly on February 13, 2003, at 5:50:17

Right on!! Did he hint at any timeline for re-application?

Thanks for all the detective work.

JB

> Dr. Bodkin told me that Somerset is reapplying for FDA approval, and he expects that this time they will succeed.
>
> - Bob

 

Re: Anyone still finding benefits from Selegiline ? » hok

Posted by wingedcat on February 13, 2003, at 14:03:20

In reply to Re: Anyone still finding benefits from Selegiline ? » wingedcat, posted by hok on February 12, 2003, at 22:54:44

Wellbutrin SR worked very well for me for about 2 years. Then all of a sudden it seemed to give out completely. But 2 years is quite a long time. I was never a smoker, but it stopped cravings for other drugs. Any caffeine on Wellbutrin will give you twitches and diarrhea, just a word of warning ;)

I was taking 5 mg of Deprenyl a day with 400 mg of DL-phenylalanine. Yeah, I think it does make my anxiety worse. But it did work well as far as that anhedonia goes, and I'd rather be anxious than suicidal. It looks like it may get approved in the form of a patch after all, I'll be happy when that day comes and I can take it without arguing with my doctors.

 

Re: Anyone still finding benefits from Selegiline ? » wingedcat

Posted by hok on February 13, 2003, at 14:35:22

In reply to Re: Anyone still finding benefits from Selegiline ? » hok, posted by wingedcat on February 13, 2003, at 14:03:20

Wingedcat-

the issues that your doctor has with it put aside for a moment and you were hypothetically going to still stay on it...

how 'bout lowering the dose of the the DL-phenylalanine augmentor, or just not taking it at all. Would that make the dperenyl-induced anxiety more manageable or does it dilute the effectiveness of the deprenyl to a point for you where it's not worth taking it?

 

Benefits from Selegiline ? » wingedcat

Posted by Jack Smith on February 13, 2003, at 16:27:00

In reply to Re: Anyone still finding benefits from Selegiline ? » hok, posted by wingedcat on February 12, 2003, at 20:43:58

Screw those doctors, stay on the selegeline if you can and go see a doctor to get a benzo, you don't have to tell him you are on selegeline. Also, you could go through the yellow pages looking for a doctor who is a little more openminded. Doctors can be such schmucks, sorry Dr. Bob but it's true. If it is helping you why would anyone tell you to get off it?? It is certainly as safe as TCA's or other MAOI's.

Also, you can find benzos if you need them without going to a doctor--it's not the greatest thing to do but that is what the doctors are forcing you to do.

JACK

 

Re: Transdermal Selegiline » not exactly

Posted by Jack Smith on February 13, 2003, at 16:32:39

In reply to Re: Transdermal Selegiline » jrbecker, posted by not exactly on February 13, 2003, at 5:50:17

> Dr. Bodkin told me that Somerset is reapplying for FDA approval, and he expects that this time they will succeed.
>
> - Bob

This is great news. Did he give you ANY idea why the FDA did not approve it. I tend not to believe the great conspiracy theories that the SSRI manufacturers blocked it but who knows? Any news as to WHEN it will be available. When did you talk to him? Keep us informed.

JACK

 

Re: Transdermal Selegiline

Posted by not exactly on February 13, 2003, at 18:34:24

In reply to Re: Transdermal Selegiline » not exactly, posted by Jack Smith on February 13, 2003, at 16:32:39

The stated reason for the FDA rejection was insufficient efficacy data [see http://www.selegiline.com/somerset.html]. I remember that Dr. Bodkin had been very disappointed by the 'non-approval letter', since he truly believed that transdermal selegiline was a breakthrough in depression treatment. However, he was not bitter about it and never hinted of any competition conspiracies. Mostly he was frustrated by the FDA's insistence on viewing depression as a single condition, which means that a treatment that is effective for only a subset of the overall depressed population has an unfair statistical hurdle.

For the sake of argument, let's say that one-third of all depressed people are in a category (some have labelled it "atypical", "anhedonic", "anergic", or "low-dopamine" depression) which tends to respond much better to dopaminergic antidepressants than to serotonergic ones. Then imagine a medication which has a 90% (!) success rate for treating this subclass, but shows no benefit whatsoever for other types of depression. A clinical trial of this medication, when given to a random sample of depressed subjects, would therefore show an overall success rate of only 30%. But this is the kind of success rate normally seen with placebo. So the FDA concludes that the med is no better than placebo, and is therefore deemed "ineffective".

There's also the "sample bias" problem. Subjects for AD clinical trials are usually obtained by advertising for volunteers. "Typical" depressives who feel "I am miserable, I'll try anything to get well" are likely to volunteer, but "atypical" depressives who feel "why bother, what good would it do" are obviously going to be under-represented.

These are the same problems that spoiled Mirapex's chances for approval as an antidepressant (fortunately it was approved for Parkinson's treatment, so it is available).

As of last week, Dr. Bodkin either did not know, or was unwilling to divulge, a timeframe for the reapproval process. He merely stated that Somerset is now able to present the confirming data that the FDA requested, and advised me to "stay tuned" for further developments. I would guess that we'll need to wait several more months. But the good news is that the effort has not been abandoned, and appears to be going well.

BTW, there's very little official word from Somerset on this matter. The only mention of the patch on their website [http://www.somersetpharm.com/corporate/profile.html] is the brief statement: "Somerset is currently engaged in the clinical development of a selegiline transdermal system for the treatment of several indications, including Alzheimer's Disease, Depression and Parkinson's Disease."

I'll post an update if/when I learn more.

- Bob

 

Current Selegiline options: oral or sublingual?

Posted by hok on February 13, 2003, at 20:33:02

In reply to Re: Transdermal Selegiline, posted by not exactly on February 13, 2003, at 18:34:24

which version is 1) more effective and 2) associated with less side effects?

I'm assuming there is less side effects from the sublingual form. Would love some feedback from people who've tried both. Planning to try one in the upcoming month but need some advice before I do so. Thanks.

HK

 

Re: Current Selegiline options: oral or sublingual?

Posted by not exactly on February 13, 2003, at 23:51:43

In reply to Current Selegiline options: oral or sublingual? , posted by hok on February 13, 2003, at 20:33:02

The advantages of the transdermal delivery method are 1) negligible impact on MAO-A in the digestive system (freedom from "cheese effect"), 2) no first-pass gut metabolism (which produces active metabolites responsible for some of the side effects), 3) greater bioavailability (higher plasma concentration for the same amount), and 4) gradual continuous administration. I would think that the sublingual form would be almost as good as transdermal with respect to the first three advantages (the fourth advantage can be approximated with multiple divided doses). Oral is the least desirable route for high-dose (AD levels) selegiline (although obviously the most convenient).
- Bob

 

Re: Quick question for hok (off topic of thread) » hok

Posted by Ron Hill on February 15, 2003, at 1:26:46

In reply to Current Selegiline options: oral or sublingual? , posted by hok on February 13, 2003, at 20:33:02

HK,
Please forgive me for asking a couple quick questions off topic of this thread. I see that you plan to do a trial of Selegiline. Are you still taking ENADA NADH? If yes, is it helping you? If not, what prompted you to quit?

-- Ron

------------------------------------
> which version is 1) more effective and 2) associated with less side effects?
>
> I'm assuming there is less side effects from the sublingual form. Would love some feedback from people who've tried both. Planning to try one in the upcoming month but need some advice before I do so. Thanks.
>
> HK
>

 

Re: Benefits from Selegiline ? » Jack Smith

Posted by wingedcat on February 15, 2003, at 17:39:41

In reply to Benefits from Selegiline ? » wingedcat, posted by Jack Smith on February 13, 2003, at 16:27:00

> Screw those doctors, stay on the selegeline if you can and go see a doctor to get a benzo, you don't have to tell him you are on selegeline. Also, you could go through the yellow pages looking for a doctor who is a little more openminded. Doctors can be such schmucks, sorry Dr. Bob but it's true. If it is helping you why would anyone tell you to get off it?? It is certainly as safe as TCA's or other MAOI's.

hahaha, thanks for the message. truthful stuff. yes, they weren't giving me any help and that is why I found selegiline on my own. they were quizzing me on where I got it and getting all mad at me. well if they refuse to help me, I either help myself or I live with the suicidal thoughts. is that what they prefer? all the doctors I've seen so far have been such tools of the pharm industry, if it's not approved they don't want any part of it. I will see a new one on tuesday and I'm hoping he's more open minded. my psychologist recommended a benzo. I may get back on selegiline if/when it gets approved.

 

Re: Anyone still finding benefits from Selegiline ? » wingedcat

Posted by Craig Allen on February 15, 2003, at 19:08:38

In reply to Re: Anyone still finding benefits from Selegiline ? » hok, posted by wingedcat on February 13, 2003, at 14:03:20

hello. i'm thinking about a trial on selegeline, if my doctor will go for it. can you tell me about DL-phenylalanine? i saw that you were augmenting the selegeline with it. i'm not familiar with this item. what is it, what does it do? thanks.

 

Re: Quick question for hok (off topic of thread)

Posted by hok on February 15, 2003, at 19:48:54

In reply to Re: Quick question for hok (off topic of thread) » hok, posted by Ron Hill on February 15, 2003, at 1:26:46

Ron-

It's funny you should ask. I remember reading your post from a couple of days ago about your update on NADH on how you were experienced a little tolerance at the 10mg dose and that it tends to give you a little irritability by the end of the day. Ditto.

I'm back down to 5mg myself after about a week at 10mg. It ended up making me feel really irritable and also tired during some parts of the day. 5mg is an acceptale lift for me at this point, although it's nowhere as good as the first day I tried it. Sometimes I add 500mg of tyrosine, which gives me an added lift as well. But this can also get me a little too excited.

God I miss those cigarettes. There's nothing like the smooth administration it gives you throughout the day. Maybe I should try the patch and see if it gives me anything similar to the NADH.

On a similar note, I just ordered sublingual selegiline. Last time I tried Selegiline was a couple of years ago and I didn't really have a great response to it (made me irritable and overly-excited). I'm hoping I can give it a fairer shot this time by starting low and waiting it out a little longer. I'm also hoping the sublingual version will cause less side effects.
Maybe it will be a good replacement for smoking afterall, since there's been some good research lately that says it's fairly useful. Not really getting my hopes up though. Perhaps the patch form will be better in the end, but that looks like a year or two off.

Still avoiding the eventual Nardil trial until I've exploited the rest of my options. My fear is that most MAO-A inihbitors are going to make me into a zombie. In the end, this might just be my saving grace though. This anhedonia is really getting to me.

I've enjoyed all the chatter on the board about the anhedonia issue though. It seems there's a lot more anhedonic/atypicals out there than I thought. Think we should keep the ideas coming and try and help each other out.

Stay in touch,

HK


 

Re: Anyone still finding benefits from Selegiline ? » Craig Allen

Posted by wingedcat on February 16, 2003, at 18:12:46

In reply to Re: Anyone still finding benefits from Selegiline ? » wingedcat, posted by Craig Allen on February 15, 2003, at 19:08:38

> hello. i'm thinking about a trial on selegeline, if my doctor will go for it. can you tell me about DL-phenylalanine? i saw that you were augmenting the selegeline with it. i'm not familiar with this item. what is it, what does it do? thanks.

It is the precursor to some neurotransmitters, including phenylethylamine and dopamine. Because selegiline increases the level of these two in the brain (mostly by taking away the enzyme which destroys them), DLpa speeds up the buildup of them. It lets you take a lower dose of selegiline. You should take the DLpa on an empty stomach, and then take the selegiline with food. 5mg a day was enough for me with 400 mg DLpa.

Like I said, it did make me more anxious, that is why I am stopping it now, until I can get on something for the anxiety. BUT... it has helped concentration, get rid of anhedonia(lack of pleasure) and banishing the suicidal thoughts faster and better than Wellbutrin, Paxil, or Buspar did for me. Also, I had faster orgasms while I was on selegiline than any other time in my life!!!


Deprenyl plus L-phenylalanine in the treatment of depression.
Birkmayer W, Riederer P, Linauer W, Knoll J.

The antidepressive efficacy of 1-deprenyl (5-10 mg daily) plus 1-phenylalanine (250 mg/day) has been evaluated in 155 unipolar depressed patients. Both oral and intravenous administration showed beneficial effects in 90% of outpatients and 80.5% of inpatients. It is concluded that this combined treatment has a potent antidepressive action based on the accumulation of 1-phenylethylamine in the brain.

------
Sustained antidepressant effect of PEA replacement.
Sabelli H, Fink P, Fawcett J, Tom C.
Rush University and the Center for Creative Development, Chicago, Illinois, USA.

Phenylethylamine (PEA), an endogenous neuroamine, increases attention and activity in animals and has been shown to relieve depression in 60% of depressed patients. It has been proposed that PEA deficit may be the cause of a common form of depressive illness. Fourteen patients with major depressive episodes that responded to PEA treatment (10-60 mg orally per day, with 10 mg/day selegiline to prevent rapid PEA destruction) were reexamined 20 to 50 weeks later. The antidepressant response had been maintained in 12 patients. Effective dosage did not change with time. There were no apparent side effects. PEA produces sustained relief of depression in a significant number of patients, including some unresponsive to the standard treatments. PEA improves mood as rapidly as amphetamine but does not produce tolerance.
-----
History of deprenyl--the first selective inhibitor of monoamine oxidase type B
Knoll J.

(-)Deprenyl (Selegiline, Jumex, Eldepryl, Movergan), a close structural relative of phenylethylamine (PEA), is a drug with a unique pharmacological spectrum. Whereas PEA and its long-lasting variants, the amphetamines, are mixed-acting stimulants of the sympathetic system in the brain, they primarily enhance the impulse propagation generated release of catecholamines (catecholamine activity enhancer, CAE, effect) and displace catecholamines in higher concentration (catecholamine releasing effect). (-)Deprenyl is the first CAE substance in clinical use devoid of catecholamine releasing activity. (-)Deprenyl is a highly potent and selective, irreversible inhibitor of B-type monoamine oxidase (MAO), a predominantly glial enzyme in the brain. The activity of this enzyme significantly increases with age. (-)Deprenyl, the first selective inhibitor of MAO-B described in the literature, has become a universally used research tool for selectively blocking B-type MAO and is still the only selective MAO-B inhibitor in world wide clinical use. In contrast to MAO inhibitors which strongly potentiate the catecholamine releasing effect of tyramine, (-)deprenyl inhibits it and is free of the 'cheese effect', which makes it a safe drug. Because its lack of the catecholamine releasing activity (-)deprenyl is devoid of amphetamine like dependence capacity.
-----
Are metabolites of l-deprenyl (selegiline) useful or harmful?
Yasar S, Goldberg JP, Goldberg SR
Department of Anesthesiology
and Critical Care Medicine,
Johns Hopkins University,
Medical School, Baltimore, MD, USA.

A frequent topic of controversy has been whether metabolism of l-deprenyl (selegiline) to active metabolites is a detriment to clinical use. This paper reviews possible roles of the metabolites of l-deprenyl in producing unwanted adverse side effects or in augmenting or mediating its clinically useful actions. Levels of l-amphetamine and l-methamphetamine likely to be reached, even with excessive intake of l-deprenyl, would be unlikely to produce neurotoxicity and there is no preclinical or clinical evidence of abuse liability of l-deprenyl. In contrast, there is evidence that l-amphetamine and l-methamphetamine have some qualitatively different actions than their d-isomer counterparts on EEG and cognitive functioning which might result in beneficial clinical effects and complement beneficial clinical actions of l-deprenyl itself.
-----
Metabolism of deprenyl to amphetamine and methamphetamine may be responsible for deprenyl's therapeutic benefit: a biochemical assessment.
Karoum F, Chuang LW, Eisler T, Calne DB, Liebowitz MR, Quitkin FM, Klein DF, Wyatt RJ.

The urinary excretion of some important phenylethylamines, catecholamines, their metabolites, amphetamine, and methamphetamine were measured in parkinsonian patients on Sinemet (L-dopa plus carbidopa, a peripheral dopadecarboxylase inhibitor) and depressed patients after chronic (-) deprenyl treatment. Deprenyl was efficiently metabolized to amphetamine and methamphetamine. It increased the excretion of phenylethylamine and of m- and p-tyramine, and reduced the output of norepinephrine metabolites, but failed to alter the excretion of dopamine-deaminated metabolites. These changes were attributed more to amphetamine and methamphetamine than to inhibition of monoamine oxidase type B. Sinemet treatment alone increased the excretion of dopamine, 3-methoxytyramine, and their respective deaminated metabolites, 3, 4-dihydroxyphenylacetic acid and homovanillic acid. It is concluded that conversion of deprenyl to amphetamine and methamphetamine may contribute to some of the therapeutic benefits of deprenyl.
---
Selegiline-Transdermal - Somerset: Emsam.

Adis CommentsSomerset Pharmaceuticals, a 50/50 joint venture between Watson Pharmaceuticals and Mylan Laboratories, is developing a transdermal formulation of the monoamine oxidase type B inhibitor selegiline [Emsam] for the treatment of depression, Alzheimer's disease and Parkinson's disease. Somerset have filed an NDA with the US FDA for the use of the transdermal formulation of selegiline in depression. However, the FDA has deemed the application 'not approvable' and is requesting additional efficacy data. The product is also undergoing phase III development in the US for Alzheimer's disease and Parkinson's disease. However, initial results in Alzheimer's disease have not been promising. Somerset Pharmaceuticals is also investigating the utility of the selegiline transdermal formulation in patients with attention-deficit hyperactivity disorder (ADHD) and has conducted an 8-week fixed-dose study in adolescent patients in the US.
---
Selegiline transdermal system Somerset.

Mahmood I.

Division of Clinical Trial Design and Analysis, Center for Biologics Evaluation and Research, Food & Drug Administration, MD 20852, USA. Mahmoodi@CBER.fda.gov

Somerset is developing a selegiline transdermal system (STS) for potential use in the treatment of depression. It has also been developed for Alzheimer's disease (AD), Parkinson's disease and attention-deficit hyperactivity disorder (ADHD) [182121], although no development has been reported for AD or ADHD in recent years. Somerset claims the transdermal system could be more effective than the oral formulation of selegiline already marketed [250573]. In May 2001, Somerset filed an NDA with the US FDA for STS for the treatment of depression [410848], however, in March 2002, the company received a 'non-approvable' letter from the FDA requesting additional efficacy data. At this time, Somerset had scheduled a meeting with the FDA to review and clarify their comments [456735]. Selegiline will be co-promoted in the US by Watson, under the terms of a previous agreement [275389].
---


 

Re: Selegiline: best brands and form ?

Posted by hok on February 17, 2003, at 13:39:40

In reply to Re: Anyone still finding benefits from Selegiline ? » Craig Allen, posted by wingedcat on February 16, 2003, at 18:12:46

Has anyone tried the sublingual liquid form with any success yet?

I'd like to know what form (e.g., tablets or sublingual form) as well what brand is best recommended. Would love to know before I order some. Thanks.

HK

 

Selegiline patch: Bodkin says 1 year til market

Posted by hok on February 26, 2003, at 16:42:09

In reply to Transdermal Selegiline , posted by djmmm on February 12, 2003, at 17:10:02

I had a brief email exchange with Dr. Bodkin today regarding the current status of Somerset Pharmaceuticals and whether they'll ever be getting the go-ahead for the trasdermal patch. In his own words, he states, "come next year at around this time I bet it will be at your local pharmacy, FDA willing."

So that's his prediction. Maybe we can call this good news.

HK

 

Re: Selegiline patch: Bodkin says 1 year til market » hok

Posted by Jumpy on February 26, 2003, at 17:09:11

In reply to Selegiline patch: Bodkin says 1 year til market , posted by hok on February 26, 2003, at 16:42:09

> I had a brief email exchange with Dr. Bodkin today regarding the current status of Somerset Pharmaceuticals and whether they'll ever be getting the go-ahead for the trasdermal patch. In his own words, he states, "come next year at around this time I bet it will be at your local pharmacy, FDA willing."
>
> So that's his prediction. Maybe we can call this good news.
>
> HK

Finally! Selegiline is going to make a huge impact for so many people (my personal guess). Thanks for the update.

Jumpy

 

Re: Selegiline patch: Bodkin says 1 year til market » Jumpy

Posted by SLS on February 26, 2003, at 20:01:32

In reply to Re: Selegiline patch: Bodkin says 1 year til market » hok, posted by Jumpy on February 26, 2003, at 17:09:11

> > I had a brief email exchange with Dr. Bodkin today regarding the current status of Somerset Pharmaceuticals and whether they'll ever be getting the go-ahead for the trasdermal patch. In his own words, he states, "come next year at around this time I bet it will be at your local pharmacy, FDA willing."


> Finally! Selegiline is going to make a huge impact for so many people (my personal guess). Thanks for the update.


Hi Jumpy.

I would not necessarily disagree with you. However, I would like to know what it is about selegiline that makes you feel this way?

Thanks.

- Scott

 

Re: Selegiline patch: Bodkin says 1 year til market » SLS

Posted by Jumpy on February 27, 2003, at 1:42:01

In reply to Re: Selegiline patch: Bodkin says 1 year til market » Jumpy, posted by SLS on February 26, 2003, at 20:01:32

> > > I had a brief email exchange with Dr. Bodkin today regarding the current status of Somerset Pharmaceuticals and whether they'll ever be getting the go-ahead for the trasdermal patch. In his own words, he states, "come next year at around this time I bet it will be at your local pharmacy, FDA willing."
>
>
> > Finally! Selegiline is going to make a huge impact for so many people (my personal guess). Thanks for the update.
>
>
> Hi Jumpy.
>
> I would not necessarily disagree with you. However, I would like to know what it is about selegiline that makes you feel this way?
>
> Thanks.
>
> - Scott

Hey Scott,

I feel like the patch will make a big impact just because many doctors have told me that MAOIs are some of the most effective medications for moderate to severe depression.

Jumpy

 

Possible Positive Impact of Selegiline Patch

Posted by Jack Smith on February 27, 2003, at 12:24:50

In reply to Re: Selegiline patch: Bodkin says 1 year til market » SLS, posted by Jumpy on February 27, 2003, at 1:42:01

I agree with Jumpy but for different reasons. I think that the selegiline patch will have positive effects because if successful it could spur some new developments in antidepressant pharmaceuticals.

1. It will revive MAOI's to a degree and this could help new research into creating new, possibly "safer" MAOI's with less side effects.

2. Patch technology. This is a creative way to deliver antidepressant meds and I think that it could spur a lot of research into such a delivery system for other drugs.

I am, however, a little skeptical that the patch will come out and, if it does, it will be that successful. I hope Somerset can get a good ad campaign going and can pressure the FDA to get the thing approved.

JACK


> Hey Scott,
>
> I feel like the patch will make a big impact just because many doctors have told me that MAOIs are some of the most effective medications for moderate to severe depression.
>
> Jumpy


Go forward in thread:


Show another thread

URL of post in thread:


Psycho-Babble Medication | Extras | FAQ


[dr. bob] Dr. Bob is Robert Hsiung, MD, bob@dr-bob.org

Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.