Psycho-Babble Medication Thread 9748

Shown: posts 16 to 40 of 40. Go back in thread:

 

On behalf of Lucifer...

Posted by Zeke on December 13, 1999, at 7:52:39

In reply to Re: Parnate information wanted, posted by carole on November 29, 1999, at 21:49:24

> Much education is needed so that clinicians will not avoid trying patients on it when other meds just dont work. The benefits FAR outweigh the risks in many cases! We dont withhold the toxic cancer drugs from patients who need them as the only treatment available to extend life. Mental illness requires the same aggressive treatment sometimes.

Since it works for you witout severe untoward reaction, it's a wonderful drug.

No we don't withhold (some) toxic compounds in cancer therapy. But we are cautious about using them. We also withdrawl some drugs that have non fatal toxicities: thalidomide and fenfluramine.

I know you're venting, but just playing the devil's advocate...

Besides, have all other meds failed? Have all the SSRIs been tried? other newer antidepressants? Have they been augmented with Synthroid or pindilol or stimulants or... This may or may not be safer than an MAOI but sounds like it would cause less physician anxiety and hassle for you (in the long run).

 

Liz: Parnate: weight gain, & the literature

Posted by Zeke on December 13, 1999, at 8:28:53

In reply to Re: Parnate: sleep & weight, posted by Elizabeth on December 13, 1999, at 7:36:24

> > Re weight gain, the med may cause some weight gain but also by virtue of being an amphetamine-cogener also weight loss effects.
>
> AFAIK Parnate has *never* been reported to cause weight gain in the literature.

I beg to disagree -- see references. (I have to refrain from saying, "not in the literature, just in people.")

However since we're speaking of Parnate, note that the weight gain seems to occur much moreso with Nardil than Parnate. As Bernstein says, "...an amphetamine-like structure of tranylcypromine may explain its lesser ability to stimulate appetite and weight gain than the appetite and weight effects observed with phenelzine."

Bernstein JG
Induction of obesity by psychotropic drugs.
Ann N Y Acad Sci 1987;499:203-15
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2886102&form=6&db=m&Dopt=b

Remick RA, Froese C, Keller FD
Common side effects associated with monoamine oxidase inhibitors.
Prog Neuropsychopharmacol Biol Psychiatry 1989;13(3-4):497-504
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2748873&form=6&db=m&Dopt=b

Cantu TG, Korek JS
Monoamine oxidase inhibitors and weight gain.
Drug Intell Clin Pharm 1988 Oct;22(10):755-9
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3068037&form=6&db=m&Dopt=b

On the otherhand, some evidence exists for a weight loss effect from Parnate(tranylcypromine).

Dulloo AG, Miller DS
Thermogenic drugs for the treatment of obesity:
sympathetic stimulants in animal models.
Br J Nutr 1984 Sep;52(2):179-96
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6477859&form=6&db=m&Dopt=b

(Importantly, this article also rejects the common notion that stimulant type drugs reduce weight purely through reducing appetite.)

So its a mixed bag...

 

Re: Liz: Parnate: weight gain, & the literature

Posted by Adam on December 13, 1999, at 9:32:08

In reply to Liz: Parnate: weight gain, & the literature, posted by Zeke on December 13, 1999, at 8:28:53


> I have to refrain from saying, "not in the literature, just in people."

Why refrain? Individual responses to ADs can diverge quite dramatically from the average response.
'Not to say "the literature" has no value, it just doesn't account for everything.

 

Adam: My sarcasm missed!

Posted by Zeke on December 13, 1999, at 10:00:58

In reply to Re: Liz: Parnate: weight gain, & the literature, posted by Adam on December 13, 1999, at 9:32:08

> Why refrain? Individual responses to ADs can diverge quite dramatically from the average response.
> 'Not to say "the literature" has no value, it just doesn't account for everything.

I was being more sarcastic than literal. I didn't want to be hurtful to Elizabeth however. (Literally, weight gain is documented in (Parnate in) the medical journals.)

 

Re: Adam: My sarcasm missed!

Posted by Adam on December 13, 1999, at 10:53:49

In reply to Adam: My sarcasm missed!, posted by Zeke on December 13, 1999, at 10:00:58

I seem to have a special talent for failing to recognise sarcasm, or even mild irony. You didn't miss, I did.

> > Why refrain? Individual responses to ADs can diverge quite dramatically from the average response.
> > 'Not to say "the literature" has no value, it just doesn't account for everything.
>
> I was being more sarcastic than literal. I didn't want to be hurtful to Elizabeth however. (Literally, weight gain is documented in (Parnate in) the medical journals.)

 

Parnate: weight gain, & the literature - Zeke

Posted by Elizabeth on December 13, 1999, at 13:06:51

In reply to Liz: Parnate: weight gain, & the literature, posted by Zeke on December 13, 1999, at 8:28:53

> > AFAIK Parnate has *never* been reported to cause weight gain in the literature.
>
> I beg to disagree -- see references. (I have to refrain from saying, "not in the literature, just in people.")

:-) Well I *did* say "AFAIK." You can't argue that I knew of documented weight gain with Parnate! :-)

> However since we're speaking of Parnate, note that the weight gain seems to occur much moreso with Nardil than Parnate.

Tell me about it! (50 lbs - more than 40% of my original weight - on Nardil, none on Parnate.)

> As Bernstein says, "...an amphetamine-like structure of tranylcypromine may explain its lesser ability to stimulate appetite and weight gain than the appetite and weight effects observed with phenelzine."

I *really* wonder about the stimulant-like properties of Parnate (a psychopharm consultant first mentioned this to me in 1997 and I was intrigued).

> Bernstein JG
> Induction of obesity by psychotropic drugs.
> Ann N Y Acad Sci 1987;499:203-15
> http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2886102&form=6&db=m&Dopt=b

I can only view abstracts at this time, but I saw no reference to any specific case of Parnate-associated weight gain.

Also as an aside, remember there is a big confound in the claim that Parnate might "cause" weight gain: Parnate has been used, historically, mainly for atypical depression in which weight gain is already a feature of the depression!

> Remick RA, Froese C, Keller FD
> Common side effects associated with monoamine oxidase inhibitors.
> Prog Neuropsychopharmacol Biol Psychiatry 1989;13(3-4):497-504
> http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2748873&form=6&db=m&Dopt=b

Okay, here is a specific report. However, the abstract, at least, doesn't document the cases adequately to convince me the weight gain was *caused* by the Parnate (were they on other drugs? were they already gaining weight prior to taking the Parnate? etc.).

> Cantu TG, Korek JS
> Monoamine oxidase inhibitors and weight gain.
> Drug Intell Clin Pharm 1988 Oct;22(10):755-9
> http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3068037&form=6&db=m&Dopt=b

Uhh... "There are no cases of tranylcypromine-induced weight gain in the literature that are clearly associated with the drug." (This was after the drug had been approved in this country for nearly 30 years.)

> On the otherhand, some evidence exists for a weight loss effect from Parnate(tranylcypromine).
>
> Dulloo AG, Miller DS
> Thermogenic drugs for the treatment of obesity:
> sympathetic stimulants in animal models.
> Br J Nutr 1984 Sep;52(2):179-96
> http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6477859&form=6&db=m&Dopt=b
>
> (Importantly, this article also rejects the common notion that stimulant type drugs reduce weight purely through reducing appetite.)

No doubt the appetite reduction helps, though my appetite increased on Parnate (probably secondary to remission of depression!).

 

Re: Parnate: weight gain, & the literature - Liz

Posted by Zeke on December 14, 1999, at 1:39:09

In reply to Parnate: weight gain, & the literature - Zeke, posted by Elizabeth on December 13, 1999, at 13:06:51

> > > AFAIK Parnate has *never* been reported to cause weight gain in the literature.
> >
> > I beg to disagree -- see references. (I have to refrain from saying, "not in the literature, just in people.")
>
> :-) Well I *did* say "AFAIK." You can't argue that I knew of documented weight gain with Parnate! :-)
>

You're a tough sell -- probably from Missouri -- but I respect that!

General references like the PDR and the Merck Manual (and especially the watered down popular books) tend to generalize the MOAIs and use the same profile for all. What we can certainly agree on is that while Parnate and Nardil are similar, they have important differences. This is true of others, my pet peeve being the 'sameness' attributed to Ritalin and Dexedrine (the amphetamines in general). For example, there has been reluctance to treat epileptics with ADD because of Ritalin's proconvulsant effect, and this then is assumed for amphetamine. But the literature demonstrates an antiseizure property of amphetamines. But somehow this has been all but forgotten aboutand replace with the simple notion that amphetamines were used just to offset the sedative effects of phenobarbital. Fortunately, the therapeutic differences in stimulants is becomeing more appreciated by those who treat ADD.

> > However since we're speaking of Parnate, note that the weight gain seems to occur much moreso with Nardil than Parnate.
>
> Tell me about it! (50 lbs - more than 40% of my original weight - on Nardil, none on Parnate.)
>
> > As Bernstein says, "...an amphetamine-like structure of tranylcypromine may explain its lesser ability to stimulate appetite and weight gain than the appetite and weight effects observed with phenelzine."
>
> I *really* wonder about the stimulant-like properties of Parnate (a psychopharm consultant first mentioned this to me in 1997 and I was intrigued).

Well among other things, the DEA is keeping an eye on Parnate and its derivatives for abuse potential.
http://rhodium.lycaeum.org/chemistry/future_drugs.html
(Interestingly, is the Surgeon General's report documenting people not seeking help for psychiatric disorders. Gee guys, we take away the tools and what do you expect. We've already removed the promising application of MDMA in psychotherapy because of morally biased research.)

>
> > Bernstein JG
> > Induction of obesity by psychotropic drugs.
> > Ann N Y Acad Sci 1987;499:203-15
> > http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2886102&form=6&db=m&Dopt=b
>
> I can only view abstracts at this time, but I saw no reference to any specific case of Parnate-associated weight gain.
>
> Also as an aside, remember there is a big confound in the claim that Parnate might "cause" weight gain: Parnate has been used, historically, mainly for atypical depression in which weight gain is already a feature of the depression!

That's a good point. Further confounding is the fact that SSRIs are more frequently used in atypical depression with efficacy. Conversely here, weight loss is reported in the atypicals.

IMHO Parnate is also mainly for refractory depression:

"Tranylcypromine in high doses (20 to 30 mg po bid) is often effective for depression refractory to sequential trials of other antidepressants; it should be administered by physicians experienced in the use of MAOIs."
--The Merck Manual

>
> > Remick RA, Froese C, Keller FD
> > Common side effects associated with monoamine oxidase inhibitors.
> > Prog Neuropsychopharmacol Biol Psychiatry 1989;13(3-4):497-504
> > http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2748873&form=6&db=m&Dopt=b
>
> Okay, here is a specific report. However, the abstract, at least, doesn't document the cases adequately to convince me the weight gain was *caused* by the Parnate (were they on other drugs? were they already gaining weight prior to taking the Parnate? etc.).

Don't know - just pointing to evidence in the literature.

>
> > Cantu TG, Korek JS
> > Monoamine oxidase inhibitors and weight gain.
> > Drug Intell Clin Pharm 1988 Oct;22(10):755-9
> > http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3068037&form=6&db=m&Dopt=b
>
> Uhh... "There are no cases of tranylcypromine-induced weight gain in the literature that are clearly associated with the drug." (This was after the drug had been approved in this country for nearly 30 years.)

With emphasis on the word 'clearly.'


>
> > On the otherhand, some evidence exists for a weight loss effect from Parnate(tranylcypromine).
> >
> > Dulloo AG, Miller DS
> > Thermogenic drugs for the treatment of obesity:
> > sympathetic stimulants in animal models.
> > Br J Nutr 1984 Sep;52(2):179-96
> > http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6477859&form=6&db=m&Dopt=b
> >
> > (Importantly, this article also rejects the common notion that stimulant type drugs reduce weight purely through reducing appetite.)
>
> No doubt the appetite reduction helps, though my appetite increased on Parnate (probably secondary to remission of depression!).

Remember that increased appetite (especially carbo cravings) are a symptom of atypical depression, just as weight gain is!

You might find this one interesting

Richard J. Wurtman and Juidith J. Wurtman
Carbohydrates and Depression
SCIENTIFIC AMERICAN January 1989
http://www.sciam.com/0189issue/0189wurtman.html

 

Re: Parnate: weight gain, & the literature - Liz

Posted by Elizabeth on December 14, 1999, at 4:44:22

In reply to Re: Parnate: weight gain, & the literature - Liz, posted by Zeke on December 14, 1999, at 1:39:09

> > :-) Well I *did* say "AFAIK." You can't argue that I knew of documented weight gain with Parnate! :-)
> >
>
> You're a tough sell -- probably from Missouri -- but I respect that!

Not even close - Boston. :)

> General references like the PDR and the Merck Manual (and especially the watered down popular books) tend to generalize the MOAIs and use the same profile for all.

Yeah, I know. Among my many flames about such references. :)

> Well among other things, the DEA is keeping an eye on Parnate and its derivatives for abuse potential.

I guess they wonder about it too. There *have* been reports of that in the literature (and in people, too!).

> http://rhodium.lycaeum.org/chemistry/future_drugs.html

> (Interestingly, is the Surgeon General's report documenting people not seeking help for psychiatric disorders.

I can't find this...happen to have a URL?

>Gee guys, we take away the tools and what do you expect. We've already removed the promising application of MDMA in psychotherapy because of morally biased research.)

You know, I really don't think that opposing use oof certain types of drugs has anything to do with morality. Maybe that's just my own moral bias, though!

> IMHO Parnate is also mainly for refractory depression:
>
> "Tranylcypromine in high doses (20 to 30 mg po bid) is often effective for depression refractory to sequential trials of other antidepressants; it should be administered by physicians experienced in the use of MAOIs."
> --The Merck Manual

True, that's what I use MAOIs for (haven't given tricyclics an adequate trial due to side effects, though).

> > Uhh... "There are no cases of tranylcypromine-induced weight gain in the literature that are clearly associated with the drug." (This was after the drug had been approved in this country for nearly 30 years.)
>
> With emphasis on the word 'clearly.'

I think that's what I'd require to consider it real evidence that Parnate "causes" or "induces" weight gain.

> > No doubt the appetite reduction helps, though my appetite increased on Parnate (probably secondary to remission of depression!).
>
> Remember that increased appetite (especially carbo cravings) are a symptom of atypical depression, just as weight gain is!

Well yeah, I thought that was where the weight gain came from! Eating junk food, especially at night.

> You might find this one interesting
>
> Richard J. Wurtman and Juidith J. Wurtman
> Carbohydrates and Depression
> SCIENTIFIC AMERICAN January 1989
> http://www.sciam.com/0189issue/0189wurtman.html

Oh god, not the Wurtmans!

 

Re: Parnate: weight gain, & the literature - Liz

Posted by Zeke on December 14, 1999, at 11:25:55

In reply to Re: Parnate: weight gain, & the literature - Liz, posted by Elizabeth on December 14, 1999, at 4:44:22

> > (Interestingly, is the Surgeon General's report documenting people not seeking help for psychiatric disorders.
>
> I can't find this...happen to have a URL?
>

http://www.nytimes.com/library/politics/121399mental-health.html


> >Gee guys, we take away the tools and what do you expect. We've already removed the promising application of MDMA in psychotherapy because of morally biased research.)
>
> You know, I really don't think that opposing use oof certain types of drugs has anything to do with morality. Maybe that's just my own moral bias, though!
>

I'm not talking about people taking ecstasy every weekend at the local rave -- though that's the reason it's schedule 1. I'm talking about limited clinical use to augment therapy just as pindolol augments Prozac. When I say morality, I mean the government passing along research that supports its view and withholding research that doesn't, or even preventing research in the first place. I get upset when they rant that 'MDMA destroys serotonin neurons," but never mention that administration of an SSRI four hours later will block the uptake and damage. I'm sorry, I just get upset when moral prejudice strongarms block scientific discovery. And remember that many of these folks would like to cast all psych meds in to the sea -- ' and by God, you should just pull yourself up by your bootstraps!'

> > IMHO Parnate is also mainly for refractory depression:
> >
> > "Tranylcypromine in high doses (20 to 30 mg po bid) is often effective for depression refractory to sequential trials of other antidepressants; it should be administered by physicians experienced in the use of MAOIs."
> > --The Merck Manual
>
> True, that's what I use MAOIs for (haven't given tricyclics an adequate trial due to side effects, though).

Despite all the bliss, I think the side effects of SSRIs cause many to drop those too. I can't deal with higher doses of Luvox but use a lower dose and pindolol.
>
> > > Uhh... "There are no cases of tranylcypromine-induced weight gain in the literature that are clearly associated with the drug." (This was after the drug had been approved in this country for nearly 30 years.)
> >
> > With emphasis on the word 'clearly.'
>
> I think that's what I'd require to consider it real evidence that Parnate "causes" or "induces" weight gain.
>

OK, with emphasis on no case being clear to this particular researcher.

> > > No doubt the appetite reduction helps, though my appetite increased on Parnate (probably secondary to remission of depression!).
> >
> > Remember that increased appetite (especially carbo cravings) are a symptom of atypical depression, just as weight gain is!
>
> Well yeah, I thought that was where the weight gain came from! Eating junk food, especially at night.
>
> > You might find this one interesting
> >
> > Richard J. Wurtman and Juidith J. Wurtman
> > Carbohydrates and Depression
> > SCIENTIFIC AMERICAN January 1989
> > http://www.sciam.com/0189issue/0189wurtman.html
>
> Oh god, not the Wurtmans!

If I'd only know you were from Boston! (Besides, RW's a good guy -- Now if I'd have said John Mack... Beam me up Scotty!)

 

Re: Parnate: weight gain, & the literature - Liz

Posted by Adam on December 14, 1999, at 22:06:45

In reply to Re: Parnate: weight gain, & the literature - Liz, posted by Zeke on December 14, 1999, at 11:25:55

>
> I'm not talking about people taking ecstasy every weekend at the local rave -- though that's the reason it's schedule 1. I'm talking about limited clinical use to augment therapy just as pindolol augments Prozac. When I say morality, I mean the government passing along research that supports its view and withholding research that doesn't, or even preventing research in the first place. I get upset when they rant that 'MDMA destroys serotonin neurons," but never mention that administration of an SSRI four hours later will block the uptake and damage. I'm sorry, I just get upset when moral prejudice strongarms block scientific discovery. And remember that many of these folks would like to cast all psych meds in to the sea -- ' and by God, you should just pull yourself up by your bootstraps!'
>
I had the opportunity to take MDMA not too long ago which I thankfully declined. Anyway, what I read lead me to believe that it takes very high doses of MDMA or chronic use to kill
brain cells. However, axonal damage might still be a problem at lower doses, and even though axons can grow back, it's tough to know how they will grow back, and in the mean time
the cell is out of comission. MDMA also stimulates excessive dopamine release, and reactive oxygen species produced during metabolism of dopamine by MAO have been implicated in
neurotoxicity. Addition of an SSRI might offer some protection, but its difficult to know how much and what neurons.

This may all be really nitpicky, though. I've become very casually aquainted with a couple fairly regular users, and it's hard to tell if "Adam" (gotta love _that_ nickname) is doing
them any real harm or not.

> > > IMHO Parnate is also mainly for refractory depression:
> > >
> > > "Tranylcypromine in high doses (20 to 30 mg po bid) is often effective for depression refractory to sequential trials of other antidepressants; it should be administered by physicians experienced in the use of MAOIs."
> > > --The Merck Manual
> >
> > True, that's what I use MAOIs for (haven't given tricyclics an adequate trial due to side effects, though).

I wonder what it takes before some people decide you are "refractory" enough and insist you consider an MAOI. I had one doctor keep me on Serzone for more than two months even though
I knew it wasn't working and started rapidly spiraling the drain while on it. I guess a quivering, weeping, suicidal state of frenzy is "refractory."

>
> Despite all the bliss, I think the side effects of SSRIs cause many to drop those too. I can't deal with higher doses of Luvox but use a lower dose and pindolol.
> >

I never got anywhere near bliss on an SSRI, but had a couple fun side effects for my troubles: a spare tire around the waist, anorgasmia, and loss of libido. Perhaps if I had
tried Prozac I could have been thin, asexual, and depressed. Will MAOIs never be a first or even second-line treatment again?

 

MAOIs - Adam

Posted by Elizabeth on December 15, 1999, at 10:06:46

In reply to Re: Parnate: weight gain, & the literature - Liz, posted by Adam on December 14, 1999, at 22:06:45

> I wonder what it takes before some people decide you are "refractory" enough and insist you consider an MAOI. I had one doctor keep me on Serzone for more than two months even though
> I knew it wasn't working and started rapidly spiraling the drain while on it. I guess a quivering, weeping, suicidal state of frenzy is "refractory."

Actually I think it's just "nonresponse to other stuff." :-)

> I never got anywhere near bliss on an SSRI, but had a couple fun side effects for my troubles: a spare tire around the waist, anorgasmia, and loss of libido. Perhaps if I had
> tried Prozac I could have been thin, asexual, and depressed. Will MAOIs never be a first or even second-line treatment again?

I think they should be put ahead of tricyclics in some cases actually, at least.

 

Re: Parnate: weight gain, & the literature - Liz

Posted by Elizabeth on December 15, 1999, at 10:24:21

In reply to Re: Parnate: weight gain, & the literature - Liz, posted by Zeke on December 14, 1999, at 11:25:55

> I'm not talking about people taking ecstasy every weekend at the local rave -- though that's the reason it's schedule 1. I'm talking about limited clinical use to augment therapy just as pindolol augments Prozac.

Yes, I know what you're talking about, although I really don't see *either* use as being morally wrong.

> When I say morality, I mean the government passing along research that supports its view and withholding research that doesn't, or even preventing research in the first place.

Now *that's* morally wrong. God I hate the War on Some Drugs!

> I'm sorry, I just get upset when moral prejudice strongarms block scientific discovery.

Nothing to be sorry about!

> And remember that many of these folks would like to cast all psych meds in to the sea -- ' and by God, you should just pull yourself up by your bootstraps!'

The government (NIDA etc.), or just random anti-med people?

> Despite all the bliss, I think the side effects of SSRIs cause many to drop those too. I can't deal with higher doses of Luvox but use a lower dose and pindolol.

How is pindolol for you? I'm using it with Marplan - had a fast response, now have really low BP and insomnia! (Like, even more insomnia than I had before. Which is a lot.)

> OK, with emphasis on no case being clear to this particular researcher.

We'd have to comb through the literature for ourselves to make a real decision, of course.

> If I'd only know you were from Boston!

I'm not just from Boston...I went to MIT!

> (Besides, RW's a good guy -- Now if I'd have said John Mack... Beam me up Scotty!)

:-)

 

Re: Parnate: weight gain, & the literature - Adam

Posted by Zeke on December 15, 1999, at 10:26:36

In reply to Re: Parnate: weight gain, & the literature - Liz, posted by Adam on December 14, 1999, at 22:06:45

> >
> > I'm not talking about people taking ecstasy every weekend at the local rave -- though that's the reason it's schedule 1. I'm talking about limited clinical use to augment therapy just as pindolol augments Prozac. When I say morality, I mean the government passing along research that supports its view and withholding research that doesn't, or even preventing research in the first place. I get upset when they rant that 'MDMA destroys serotonin neurons," but never mention that administration of an SSRI four hours later will block the uptake and damage. I'm sorry, I just get upset when moral prejudice strongarms block scientific discovery. And remember that many of these folks would like to cast all psych meds in to the sea -- ' and by God, you should just pull yourself up by your bootstraps!'
> >
> I had the opportunity to take MDMA not too long ago which I thankfully declined. Anyway, what I read lead me to believe that it takes very high doses of MDMA or chronic use to kill
> brain cells. However, axonal damage might still be a problem at lower doses, and even though axons can grow back, it's tough to know how they will grow back, and in the mean time
> the cell is out of comission.

I don't want to beat this subject to death but one more ecstatic respone!

I am referring to limited, controlled use of entactogens (eg, MDMA) in psychotherapy, in persons where fear and anxiety are roadblocks to insight and expression. I think two factors must be considered:

1. A protocol of giving the entactogen and several hours later giving an SSRI (and perhaps deprenyl) would aloow for the beneficial effects but minimize possible neurotoxicity. Use of the levo isomer of MDMA appears safer as it excludes delayed damage -- loss of uptake sites. SSRIs may offer no protection from this toxicity, but again is is stereospicific.

2. Lack of effective treatment (often) allows for high levels of glucocorticoids (eg, cortisol) which also have documented neurotoxicity. This toxicity however, has been more clearly linked with behavioral deficits and abnormalities.


> MDMA also stimulates excessive dopamine release, and reactive oxygen species produced during metabolism of dopamine by MAO have been implicated in
> neurotoxicity.

(And you're taking deprenyl right?!!!)

Yet I think you'd agree that the significant toxicity is to 5HT processes, and this seems to occur when MDMA is carried inside the neuron, and thus the protective effect of an SSRI. I susbect that MDMA competes with 5HT for entry so initially there is very little MDMA uptake and damage.

As for free radical damage, there are MAOis but also other central antioxidants.

> Addition of an SSRI might offer some protection, but its difficult to know how much and what neurons.

I agree it is complex and damage may occur at different times. But documentation of the damage (immediate vs. delayed) suggests that testing SSRI interactions whould be one of the next steps.


> This may all be really nitpicky, though. I've become very casually aquainted with a couple fairly regular users, and it's hard to tell if "Adam" (gotta love _that_ nickname) is doing
> them any real harm or not.

Not nitpicky at all, and this observation is typical. Correlation between reported damage and obvious behavioral changes have been the exception, to my knowledge.

>
> > > > IMHO Parnate is also mainly for refractory depression:
> > > >
> > > > "Tranylcypromine in high doses (20 to 30 mg po bid) is often effective for depression refractory to sequential trials of other antidepressants; it should be administered by physicians experienced in the use of MAOIs."
> > > > --The Merck Manual
> > >
> > > True, that's what I use MAOIs for (haven't given tricyclics an adequate trial due to side effects, though).
>
> I wonder what it takes before some people decide you are "refractory" enough and insist you consider an MAOI. I had one doctor keep me on Serzone for more than two months even though
> I knew it wasn't working and started rapidly spiraling the drain while on it. I guess a quivering, weeping, suicidal state of frenzy is "refractory."
>

But who knows what else may have worked in you.
> >
> > Despite all the bliss, I think the side effects of SSRIs cause many to drop those too. I can't deal with higher doses of Luvox but use a lower dose and pindolol.
> > >
>
> I never got anywhere near bliss on an SSRI, but had a couple fun side effects for my troubles: a spare tire around the waist, anorgasmia, and loss of libido. Perhaps if I had
> tried Prozac I could have been thin, asexual, and depressed. Will MAOIs never be a first or even second-line treatment again?

I meant the bliss ABOUT them, not from them! But I hear you. A spare tire from an SSRI --- really?

I think selective MAO inhibitors will be their resurrection. Side effects and interactions are few(er) and rare, and efficacy in depression is being demonstrated. What do you think?

 

Re: Parnate: weight gain, & the literature - Adam

Posted by Adam on December 15, 1999, at 11:45:04

In reply to Re: Parnate: weight gain, & the literature - Adam, posted by Zeke on December 15, 1999, at 10:26:36

> I am referring to limited, controlled use of entactogens (eg, MDMA) in psychotherapy, in persons where fear and anxiety are roadblocks to insight and expression.

I understand that. I was acting as one of those minions of Satan you referred to above, mostly. This is, I believe, one of the early clinical uses of MDMA (after it lost favor as an appetite supressant), yes?

I think two factors must be considered:
>
> 1. A protocol of giving the entactogen and several hours later giving an SSRI (and perhaps deprenyl) would aloow for the beneficial effects but minimize possible neurotoxicity. Use of the levo isomer of MDMA appears safer as it excludes delayed damage -- loss of uptake sites. SSRIs may offer no protection from this toxicity, but again is is stereospicific.
>
> 2. Lack of effective treatment (often) allows for high levels of glucocorticoids (eg, cortisol) which also have documented neurotoxicity. This toxicity however, has been more clearly linked with behavioral deficits and abnormalities.
>

There are probably all kinds of potential sources of neurotoxicity associated with use of MDMA, and from what I can see, the subject is still open to debate. That significant neurotoxicity even occurs from recreational use is a point of debate, it appears.

> (And you're taking deprenyl right?!!!)

Yes. Um, I'm not sure what this statement means. Perhaps you are referring to this: taking deprenyl means exposure to l-methamphetamine (some similarities to MDMA) and l-amphetamine. To be honest, I find it rather difficult to understand why people, especially on high oral doses of selegiline, don't have more problems than they do. Serotonin syndrome and spontaneous hypertension seem like obvious potential problems, and yet nobody gets these things with high-dose selegiline monotherapy. I read about selegiline, and it seems like the magic molecule. It protects against oxidative stress by upregulating expression of things like superoxide dismutase. It has antipressor properties that not only protect against its own sympathomimetic metabolites, but even other pressor stimuli like tyramine (IF you take it in small doses). People say it enhances memory and sex drive. What doesn't deprenyl do?

> Yet I think you'd agree that the significant toxicity is to 5HT processes, and this seems to occur when MDMA is carried inside the neuron, and thus the protective effect of an SSRI. I susbect that MDMA competes with 5HT for entry so initially there is very little MDMA uptake and damage.
>
> As for free radical damage, there are MAOis but also other central antioxidants.
>
I am frankly a bit confused by the things I read about MDMA and how it causes neuron damage. Excitotoxicity? Oxidative stress? Neither, both, other things?

I've seen references to use of deprenyl and SSRIs in protecting against MDMA-induced neurotoxicity. In the clinical setting, use of deprenyl at any dose within the time frame needed to give this supposed protective effect would be a tough sell indeed. Not to say you're wrong. I honestly don't know.


> I think selective MAO inhibitors will be their resurrection. Side effects and interactions are few(er) and rare, and efficacy in depression is being demonstrated. What do you think?

I'm sure they are efficacious. I don't think they will replace the old, non-selective MAOIs, though. The doctors I am working with right now seem rather unimpressed with the RIMAs, and that appears to be the consensus, in this country at least. What excites me is the transdermal delivery system. It gives the benefits of an MAOI with fewer side effects and no dietary restrictions. I'm not certain why this approach isn't being explored with other MAOIs besides selegiline. I think the head of the study I am participating in mentioned something about Parnate, at least, being a little "too toxic" for this, but I'm not sure what that means (skin irritation?) Maybe its just money, since the patents ran out on the big three a long time ago. But other MAOIs could conceivably be developed, maybe some that are more tolerable in general than the older ones, for transdermal delivery too. This is way, way cool if you ask me.

 

Adam: dangling threads from Parnate

Posted by Zeke on December 15, 1999, at 20:53:30

In reply to Re: Parnate: weight gain, & the literature - Adam, posted by Adam on December 15, 1999, at 11:45:04


> > (And you're taking deprenyl right?!!!)
>
> Yes. Um, I'm not sure what this statement means. Perhaps you are referring to this: taking deprenyl means exposure to l-methamphetamine (some similarities to MDMA) and l-amphetamine. To be honest, I find it rather difficult to understand why people, especially on high oral doses of selegiline, don't have more problems than they do. Serotonin syndrome and spontaneous hypertension seem like obvious potential problems, and yet nobody gets these things with high-dose selegiline monotherapy. I read about selegiline, and it seems like the magic molecule. It protects against oxidative stress by upregulating expression of things like superoxide dismutase. It has antipressor properties that not only protect against its own sympathomimetic metabolites, but even other pressor stimuli like tyramine (IF you take it in small doses). People say it enhances memory and sex drive. What doesn't deprenyl do?
>

You were referring to MDMA increasing dopamine & dopamine metabolism and in turn which free radicals toxic to the dopamine neurons. And it came to mind that you are taking deprenyl, which of course is an antioxiant specific to dopamine! (Coincidence perhaps but also suggests in part your knowledge in this area.)

I'm glad you responded and said what you did. In sannning MedLine this morning about the 5HT axon damage issue, I learned that this occurs in part because 5HT uptake pumps occur not just at terminals, but all along the axon as well. I guess some reading this will say so what, but I think you will appreciate how this contrasts with what we were taught. It's like recent findings about neurogenesis, about electrical transmission without chemical transmitters, and about the greater importance of the cerebellum. (Actually Robert Heath alluded to this but he has been discounted because of his 'mad science' -- putting active electrodes in human subjects.)


> > Yet I think you'd agree that the significant toxicity is to 5HT processes, and this seems to occur when MDMA is carried inside the neuron, and thus the protective effect of an SSRI. I susbect that MDMA competes with 5HT for entry so initially there is very little MDMA uptake and damage.
> >
> > As for free radical damage, there are MAOis but also other central antioxidants.
> >
> I am frankly a bit confused by the things I read about MDMA and how it causes neuron damage. Excitotoxicity? Oxidative stress? Neither, both, other things?
>
> I've seen references to use of deprenyl and SSRIs in protecting against MDMA-induced neurotoxicity. In the clinical setting, use of deprenyl at any dose within the time frame needed to give this supposed protective effect would be a tough sell indeed. Not to say you're wrong. I honestly don't know.
>
>

The thing that jumped out at me, is that both +MDMA and -MDMA are entactogens, but -MDMA lacks the delayed damage of +MDMA, and the immediate damage is what can be blocked (to whatever degree) by SSRIs and deprenyl.

The one thing that I don't see mentioned re MDMA is an effect on endogenous opioids (ie, enkephalins) which are intermediate between 5HT and dopamine neurons. And the flood of dopamine you mention is supposedly caused by the massive release of 5HT.

> > I think selective MAO inhibitors will be their resurrection. Side effects and interactions are few(er) and rare, and efficacy in depression is being demonstrated. What do you think?
>
> I'm sure they are efficacious. I don't think they will replace the old, non-selective MAOIs, though. The doctors I am working with right now seem rather unimpressed with the RIMAs,

is RIMA: Reversible Inhibitors of MonoAmine oxidase? or what???

> and that appears to be the consensus, in this country at least.

I'm glad you said "in this country at least" as European researchers seem to be way out in front on the possibilities (eg, derivatives of deprenyl with even more specific properties and applications.)

> What excites me is the transdermal delivery system. It gives the benefits of an MAOI with fewer side effects and no dietary restrictions. I'm not certain why this approach isn't being explored with other MAOIs besides selegiline. I think the head of the study I am participating in mentioned something about Parnate, at least, being a little "too toxic" for this, but I'm not sure what that means (skin irritation?) Maybe its just money, since the patents ran out on the big three a long time ago. But other MAOIs could conceivably be developed, maybe some that are more tolerable in general than the older ones, for transdermal delivery too. This is way, way cool if you ask me.

You know, my mother died of Alzheimer's last year. I unsucessfully tried to get the doctors to try deprenyl -- the last one seemed fearful of psychotic reactions. (They seemed to like the idea of neurolepticss widespite the toxicity of those drugs. BTW she had much less than typical agitation and positive symptoms.) Anyway, you mention transdermals and I think that one other possibility we considered was the nicotine patches used for smoking cessation.

 

Re: Parnate: weight gain, & the literature - Zeke

Posted by Elizabeth on December 15, 1999, at 21:10:30

In reply to Re: Parnate: weight gain, & the literature - Adam, posted by Zeke on December 15, 1999, at 10:26:36

> 1. A protocol of giving the entactogen and several hours later giving an SSRI (and perhaps deprenyl) would aloow for the beneficial effects but minimize possible neurotoxicity. Use of the levo isomer of MDMA appears safer as it excludes delayed damage -- loss of uptake sites. SSRIs may offer no protection from this toxicity, but again is is stereospicific.

Even excluding the slight problem of illegality of MDMA (yes I am opposed to this, but it is a difficulty nevertheless!) I think you would have a nigh-impossible time convincing most pdocs to do this, between the speculative uses of SSRI and selegiline, and the mixing of the three. Indeed, I believe more research needs to be done before this is done clinically, and the patient would have to be very well monitored.

That said, though, interesting idea. Can you explain (on a psychological level) the mechanisms whereby MDMA might aid with this kind of "blocking?" Never experienced the stuff myself.

> As for free radical damage, there are MAOis but also other central antioxidants.

I hope you just mean selegiline (you *do* know what happens when you take a nonselective MAOI with MDMA, right? do we actually know this won't happen with selegiline? especially with an SSRI too?).

> I think selective MAO inhibitors will be their resurrection. Side effects and interactions are few(er) and rare, and efficacy in depression is being demonstrated. What do you think?

Not that you asked :), but I thought selegiline was much more difficult to tolerate than the nonselective MAOIs (I took it at high (nonselective) doses, though). It also did not work - doh. As for moclobemide, it has a rep in countries where it's used for not being particularly effective in the people who would be trying the irreversible MAOIs (those who've already tried a lot of other stuff). I also don't think, based on the stories I've heard from patients who've tried it, that it's really all that much more tolerable than the irreversible MAOIs.

Does anyone know what happened to clorgyline, though? Was it ever marketed for clinical use?

But anyway, I think it's more likely that the nonselective MAOIs will be resurrected as the "stigma" surrounding them (re the dietary restrictions, which it turns out have been overblown) vanishes.

 

Re: dangling threads from Parnate

Posted by Elizabeth on December 15, 1999, at 21:24:31

In reply to Adam: dangling threads from Parnate, posted by Zeke on December 15, 1999, at 20:53:30

(this subject: line makes it sound like the dangling threads were a side effect of Parnate!)

> is RIMA: Reversible Inhibitors of MonoAmine oxidase? or what???

Exactly.

> You know, my mother died of Alzheimer's last year. I unsucessfully tried to get the doctors to try deprenyl -- the last one seemed fearful of psychotic reactions. (They seemed to like the idea of neurolepticss widespite the toxicity of those drugs. BTW she had much less than typical agitation and positive symptoms.)

ARGH!!!!! I'm very sorry to hear this. (Misuse of neuroleptics in demented elderly patients is a big pet peeve of mine.)

> Anyway, you mention transdermals and I think that one other possibility we considered was the nicotine patches used for smoking cessation.

*Very* jittery for a nonsmoker!

 

Re: Hanging from a thread - E, Z...

Posted by Adam on December 15, 1999, at 22:44:55

In reply to Re: Parnate: weight gain, & the literature - Zeke, posted by Elizabeth on December 15, 1999, at 21:10:30

> I hope you just mean selegiline (you *do* know what happens when you take a nonselective MAOI with MDMA, right? do we actually know this won't happen with selegiline? especially with an SSRI too?).

Here's a review that addresses some of those issues:

Drug Saf 1998 Jul;19(1):11-22

Safety of selegiline (deprenyl) in the treatment of Parkinson's disease.

Heinonen EH, Myllyla V
Orion Pharma, CNS Drugs, Turku, Finland.

Selegiline (deprenyl), a selective, irreversible inhibitor of monoamine oxidase type B (MAO-B) is widely used in the treatment of Parkinson's disease. As the first MAO-B inhibitor approved for the treatment of Parkinson's disease, concerns were raised about the safety of the drug based on the adverse effect profiles of older, nonselective MAO inhibitors. Unlike the nonselective MAO inhibitors, selegiline does not significantly potentiate tyramine-induced hypertension (the 'cheese effect') at the dosages (5 to 10 mg daily) used for the treatment of Parkinson's disease. Selegiline has been well tolerated when given alone. The most frequent adverse events seen during monotherapy have been insomnia, nausea, benign cardiac arrhythmias, dizziness and headache. When combined with levodopa, selegiline can potentiate the typical adverse effects of levodopa, if the dose of levodopa is not reduced sufficiently. Thus, the most common adverse effects associated with this combination are nausea, dizziness, fatigue, constipation and insomnia. At the later stages of Parkinson's disease when fluctuations in disability occur, peak dose dyskinesias, psychiatric complications like hallucinations and insomnia, and orthostatic hypotension are further potentiated by selegiline. Mortality was recently reported to be increased when selegiline and levodopa were given together in comparison with treatment with levodopa alone, but a large meta-analysis of 5 long term studies and 4 separate studies did not support this conclusion. Selegiline seems to be generally well tolerated in combination with other drugs. However, when pethidine (meperidine) has been given to patients who are receiving selegiline therapy, severe adverse effects have been reported. Thus, the concomitant use of these drugs is not recommended. A low tyramine diet is recommended if selegiline is used together with nonselective MAO inhibitors or the selective, reversible MAO-A inhibitor, moclobemide. Several adverse effects have been reported when fluoxetine and selegiline have been used together. A recent survey revealed that the incidence of a true serotonin syndrome is, however, very low with this combination. Concomitant use of selegiline and other selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) like citalopram, which have generally less interactions than fluoxetine, seems to be well tolerated. Nevertheless, caution is advised when combining a SSRI or a tricyclic antidepressant and selegiline.


It seems like a lot of this talk about combining low-dose selegiline with MAOIs, RIMAs, SSRIs, etc., comes out of Finland. Maybe the habit of sitting in a 50+ deg. C sauna for as long as one can stand it, then jumping naked into a snow bank heightens their overall sense of adventure. Anyway, one particularly bad drug interaction that I've come across here and a couple other places is with meperidine (Demerol). I don't know if MDMA-induced 5-HT release is of the order caused by meperidine, but I get the feeling that even low-dose selegiline+MDMA could be unacceptably risky. I can't find any specific cases to support this, though. I don't imagine there are very many Parkinson's sufferer's doing E.

 

Elizabeth: MAOI threads

Posted by Zeke on December 16, 1999, at 2:03:22

In reply to Re: Parnate: weight gain, & the literature - Zeke, posted by Elizabeth on December 15, 1999, at 21:10:30

> > 1. A protocol of giving the entactogen and several hours later giving an SSRI (and perhaps deprenyl) would aloow for the beneficial effects but minimize possible neurotoxicity. Use of the levo isomer of MDMA appears safer as it excludes delayed damage -- loss of uptake sites. SSRIs may offer no protection from this toxicity, but again is is stereospicific.
>
> Even excluding the slight problem of illegality of MDMA (yes I am opposed to this, but it is a difficulty nevertheless!)

IMHO the illegality issue is relative. Amphetamine and methylpheniate are illegal substances -- schedule II controlled substances -- but they are used legally in ADHD and narcolepsy and to a lesser degree in affective disorders. Research of methampletamine(Desoxyn) demonstrates somewhat lesser but very similar neurotoxic effects as MDMA by virtue of acting on 5-HT neurons. But it is an amphetamine and is used in the previously mentioned disorders. It often provides relief when the others fail.

Or a better example is ibogaine -- a schedule I controlled substance like MDMA -- that is being actively considered here in the US for treatment of addiction (opiate dependence). On Nov. 5 & 6 a conference was held at the New York University School of Medicine, to discuss and plan applications and possible trials. The audience was not hippies or or new age pot heads, but physicians, neuroscientists, NIDA officials and social scientists. 'A single oral dose on the order of 20mg./kg. is given Individuals undergoing ibogaine treatment for the objective of "addiction interruption" ' So illegal status need not be an absolute barrier to a therapeutic application.

see: http://www.med.nyu.edu/Psych/ibogaineconf/objectives.html
see also: ibogaine in the treatment of chemical dependence disorders: clinical perspectives
http://www.maps.org/news-letters/v05n3/05316ibo.html


> I think you would have a nigh-impossible time convincing most pdocs to do this, between the speculative uses of SSRI and selegiline, and the mixing of the three. Indeed, I believe more research needs to be done before this is done clinically, and the patient would have to be very well monitored.

I totally agree Elizabeth. It won't be available to the average psychiatrist at this point. And like the limited licenses to despense methadone for heroin addict, ibogaine isn't likely to be a among the psychopharmacy of the average psychiatrist in the future.

Note that ibogaine would not be an ongoing medication but would be administered once (or perhaps twice) early in treatment. This is the same protocol as MDMA. And BTW, MDMA was in the 60s and 70s already used by therapists. I'm not just making a novel proposal!

Re coadministration consider the treatment of Parkinson's syndrome: L-Dopa is frequently given with carbidopa, a peripheral decarboxylase inhibitor, to lessen periferal dopamine side effects. And drugs such as tolcapone -- Catechol O-methyltransferase (COMT) inhibitors -- and deprenyl -- the selective MAO inhibitor -- as likewise coadministered with L-Dopa to increase central dopamine and thus allow lower doses of L-Dopa. This in turn decreases tolerance to L-Dopa which is a common problem as the disease progresses. So the protocol is not novel inestablished medicine. see: http://www.merck.com/pubs/mmanual/section14/chapter179/179e.htm


> That said, though, interesting idea. Can you explain (on a psychological level) the mechanisms whereby MDMA might aid with this kind of "blocking?" Never experienced the stuff myself.

Let me quote from Alexander Shulgin:


"Here is a drug that has the unusual property of, more often than not, freeing a patient in psychotherapy from the anxiety and lack of trust that often prevents the emotionally fragile person from expressing his feelings to another. And, as has been attested to by many therapists and patients, MDMA allows a personal perspective, which is called "insight," with a minimum amount of fear and self-censoring. All of this without any loss of self-control or rationality... I am completely convinced that this is the type of tool that must be developed and explored as a possible adjunct to psychotherapy."

But he also says:

"However, since it came to administrative attention at the same time that the Fentanyl analogs became notorious, it was labeled a designer drug, and condemned as an abuse drug that had no virtue. The DEA holds that it is a hallucinogen, which is simply untrue. MDMA is not a hallucinogen."

see: Barriers to Research, Alexander & Ann Shulgin, Yearbook for Ethnomedicine and the Study of Consciousness,, Issue 2, 1993, pp9-20.
http://www.psychedelic-library.org/shulgin.htm

> > As for free radical damage, there are MAOis but also other central antioxidants.
>
> I hope you just mean selegiline (you *do* know what happens when you take a nonselective MAOI with MDMA, right?

The would be a great danger of the serotonin syndrome IMHO.

> do we actually know this won't happen with selegiline? especially with an SSRI too?).

Well that's what the research says. Deprenyl(selegiline) is specific for MAO-B which effects dopamine. MAO-A effects serotonin and tyramine, and deprenyl doesn't inhibit MAO-A. This is why deprenyl is free of the so called 'cheese effect' (at clinical doses).
>
> > I think selective MAO inhibitors will be their resurrection. Side effects and interactions are few(er) and rare, and efficacy in depression is being demonstrated. What do you think?
>
> Not that you asked :), but I thought selegiline was much more difficult to tolerate than the nonselective MAOIs (I took it at high (nonselective) doses, though). It also did not work - doh.

I believe just the opposite is true -- by not inhibiting MAO-A it is free of the side effects of MAO-A inhibition so is better tolerated that nonselectives like Nardil or Parnate. At higher does however, deprenyl may begin to inhibit MAO-A and share the side effect profile of the older nonselective MAOIs.

> As for moclobemide, it has a rep in countries where it's used for not being particularly effective in the people who would be trying the irreversible MAOIs (those who've already tried a lot of other stuff). I also don't think, based on the stories I've heard from patients who've tried it, that it's really all that much more tolerable than the irreversible MAOIs.

I admit present ignorance about this.

> Does anyone know what happened to clorgyline, though? Was it ever marketed for clinical use?
>
Clorgyline is irreversibe has been supplanted by moclobemide and toloxatone, which are reversible, and theoretically safer re the serotonin syndrome and tyramine crises. All are effective antidepressants, but the latter are safer re hypertensive crises.

BTW deprenyl is an IRREVERSIBLE inhibitor of MAO-B.


> But anyway, I think it's more likely that the nonselective MAOIs will be resurrected as the "stigma" surrounding them (re the dietary restrictions, which it turns out have been overblown) vanishes.

Perhaps overblown -- but they're real; I wouldn't chuck down a chunk of aged cheese if I were you! The selective and reversible MAOIs are indeed safer. This is similar to the preference of lorazepam over diazepam, where lorazepam(Ativan) lacks active metabolites but diazepam(Valium) doesn't.

I want you to know that I do respect your thoughts about this and enjoy the dialog.

BTW, you are lucky to be in Boston because of the avant guard medical community there. You have so many more options than those of us out here in the sticks!

Is your doc associated with one of the Harvard clinics/hospitals there?

 

Re: dangling threads from Parnate

Posted by Zeke on December 16, 1999, at 2:41:00

In reply to Re: dangling threads from Parnate, posted by Elizabeth on December 15, 1999, at 21:24:31

> (this subject: line makes it sound like the dangling threads were a side effect of Parnate!)
>
> > is RIMA: Reversible Inhibitors of MonoAmine oxidase? or what???
>
> Exactly.

OK, but deprenyl(selegiline) is irreversible. (Always starting trouble, aren't I!)

>
> > You know, my mother died of Alzheimer's last year. I unsucessfully tried to get the doctors to try deprenyl -- the last one seemed fearful of psychotic reactions. (They seemed to like the idea of neurolepticss widespite the toxicity of those drugs. BTW she had much less than typical agitation and positive symptoms.)
>
> ARGH!!!!! I'm very sorry to hear this. (Misuse of neuroleptics in demented elderly patients is a big pet peeve of mine.)

What I didn't mention was the estrogen connection -- which is beconing clear thanks to folks like Bruce McEwen etal. (For example, the majority of folks with Alzheimers are post menopausal women. In men testosterone levels don't drop so much and T is converted to estrogen in the brain.) Estrogen also is reported to improve mood and has applications in treating depression, but this isn't realized in the US (though it is in countries like Australia).

My Mom was post menapausal and because of breast cancer was given the estrogen blocker tamoxifen(Nolvadex). Then some (male) gynaecologist cut out her overies. Within months memory problems presented. I read and read about Alzheimer's and discovered the protective and therapeutic effect of estrogen in Alzheimers. I pushed and pushed for estrogen replacement. (This was 5+ years after the cancer so contraindication wer not a big risk factor then. Besides, the risk of having Mom fewer years but with her mind seemed a better option than living longer but deep in dementia. That's what I'd want for me in such a situation.) But I was told by one emminent neurologist that estrogen receptors don't exist in the brain! WRONG!!! Eventually we got her on estrogen, but by then she had progressed deep into Alzheimers -- her mind had regressed to that of an infant. It was hard for me or my Dad to tell if it helped though other family members said they saw a difference.

(Excuse me, but I wouldn't lose sleep if someone took that gynaecologist and similarly whopped off his testicles. I wholly agree with women that feel that gynaecologists should be women! Again, excuse my outburst.)

As I'd mentioned the doc also rejected deprenyl, which benefits folks with Alzheimers. In the end, they kept pushing the nasty neuroleptics, but we finally got someone to replace it with Ativan, which calmed her without shutting down her frontal lobes and all the neuroleptic toxicities. I guess some of thse docs never took the Hippocratic oath.


> > Anyway, you mention transdermals and I think that one other possibility we considered was the nicotine patches used for smoking cessation.
>
> *Very* jittery for a nonsmoker!

I'm not sure how you mean that but compare nicotine to the other ACh stimulants for Alzheimers (that she was given) like tacrine(Cognex) and all the nasty side effects like severe nausea. And as Adam said, the transdermals provide smoother pharmacokinetics. (thanks Adam for mentioning this!)

 

Adam: Hanging from a thread - E, Z...

Posted by Zeke on December 16, 1999, at 3:23:43

In reply to Re: Hanging from a thread - E, Z..., posted by Adam on December 15, 1999, at 22:44:55

But as it mentions, and I mentioned, coadministration of deprenyl allows the dose of L-Dopa to be decreased without decrease in desired effect. Likewise it slows the tolerance of L-Dopa. I suspect when psychotic features present the deprenyl can be dropped and L-Dopa therapy agressively increased. I think this protocol would still allow a longer course of effective treatment than just L-Dopa.

Re MDMA + deprenyl + SSRI, remember this would be only be done once or twice. Its not an ongoing thing as typical antidepressant treatment. A single experience (or two) should be enough to precipitate self discovery, approach of traumatic events, insight, etc... Subjective reports of MDMA experiences in people include seeing people in an objective fashion ("as you've never see/perceived them before") and often verbalizing true deep thoughts we protect from awareness. It reminds me of the situation where all your friends say, "Why are you going out with that shmuck, what do you see in him/her" Except you can see it as others do -- without all the psychological baggage that are our rose colored spectacles, and let us really mess up our lives and miss the important things.)

Better stop psycho-babbling!

PS, meperidine was also one of the drugs given Libby Zion who died of serotonin syndrome. The MAOI phenelzine(Nardil) was the other.

 

Re: Parnate: weight gain, & the literature - Zeke

Posted by Scott L. Schofield on December 18, 1999, at 18:32:51

In reply to Re: Parnate: weight gain, & the literature - Zeke, posted by Elizabeth on December 15, 1999, at 21:10:30


> Does anyone know what happened to clorgyline, though? Was it ever marketed for clinical use?

Clorgyline is suppose to be the most "potent" MAOI in the world according to NIH clinicians. I was there. It was considered to be their "ace-in-the-hole" when it came to treatment-resistant depressions - bipolar or unipolar. It was also looked at for ADHD, with some success. Clorgyline is a specific, irreversible MAO-A inhibitor. It has been used for many years as a biological probe and is considered a paradigm for MAO-A investigations.

I have heard nothing regarding the marketing of clorgyline. It was provided to the NIH by the chemical company who manufactured it. As of 1993, there had been a handful of people who had been depression-free for up to ten years on clorgyline. Of all the MAO-inhibitors that I have tried, clorgyline provided me with the most relief. Unfortunately, the FDA protocol did not allow for the combining of any other drugs, with the exception of lithium. Also, moclobemide produced an improvement early on that felt very much like clorgyline before it severely exacerbated my depression. It is noteworthy to emphasize that both clorgyline and moclobemide are selective for the MAO-A enzyme. MAO-A inhibition is thought to be the mechanism by which these drugs exert their antidepressant effects. In a conversation I had with William Z. Potter, he stated that he believed the concomitant inhibition of MAO-B was actually counterproductive.

I don't believe you will ever see clorgyline marketed anywhere in the world. This is a shame because so many people would benefit from it who have been unresponsive to anything else. Perhaps a drug company might entertain the idea if enough people were to petition them for it. I do think it would have a market at least as big as Parnate or Nardil, especially since these drugs now seem to be used more often.


- Scott

 

clorgyline - Zeke

Posted by Elizabeth on December 19, 1999, at 10:07:23

In reply to Re: Parnate: weight gain, & the literature - Zeke, posted by Scott L. Schofield on December 18, 1999, at 18:32:51

The obvious next question is, "Do you know of anywhere on the internet I can order it from?"

:)

 

Re: Parnate: sleep & weight

Posted by Scott L. Schofield on December 23, 1999, at 20:15:20

In reply to Re: Parnate: sleep & weight, posted by Elizabeth on December 13, 1999, at 7:36:24

> > Re weight gain, the med may cause some weight gain but also by virtue of being an amphetamine-cogener also weight loss effects.
>
> AFAIK Parnate has *never* been reported to cause weight gain in the literature.


I wonder if some people eat more during a Parnate-induced remission simply due to the fact that food will taste better and thus be more enjoyable to eat, regardless of appetite satiation. Perhaps appetite is decreased while satiety is blunted.


- Scott

 

Re: Parnate: sleep & weight

Posted by Elizabeth on December 24, 1999, at 0:14:09

In reply to Re: Parnate: sleep & weight, posted by Scott L. Schofield on December 23, 1999, at 20:15:20

> I wonder if some people eat more during a Parnate-induced remission simply due to the fact that food will taste better and thus be more enjoyable to eat, regardless of appetite satiation. Perhaps appetite is decreased while satiety is blunted.

I do, but that's probably because I hardly eat at all while depressed! I never gained weight past my original weight this way, though some people might (but probably not much before plateauing).

No, decreased satiety happens with the hydrazines but not with Parnate, at least not to any significant extent.


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