![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 12 to 36 of 36. Go back in thread:
Posted by undopaminergic on April 18, 2008, at 11:47:19
In reply to Husbands Suggestion of Thread On Nardil for me, posted by Phillipa on April 17, 2008, at 12:55:07
There are many good articles in respected peer-reviewed medical and research journals on the effectiveness of MAOIs in certain types of depression. You may wish to order the full versions of some of these articles and show them to those who think MAOIs have no place in contemporary medicine.
As for the loss of taste and smell, I think only very few medications have been known to cause that, and even then, permanent loss is rare - not that it's much of a comfort for the unfortunate few who have fallen prey to it. A lot of medications and even minerals and supplements can cause temporary and reversible perversions of taste (not usually smell) - for example, I experienced that as a result of excessive magnesium.
Posted by Justherself54 on April 18, 2008, at 13:16:41
In reply to Re: Husbands Suggestion of Nardil for me » SLS, posted by Racer on April 18, 2008, at 10:12:42
I totally respect your position on MAOI's. Your reasons they are not an option for you should be recognized and respected.
I was one of the pro-Nardil posters. It was like a miracle drug at the beginning and my posts were full of yippees, this is the most amazing med! With my history I should have know better! I apologize if anything in my posts made you feel badly as I can relate to the self-blame and hopelessness of trying to cope with adverse effects from meds.
I know some think MAOI's should be first or second line of treatment as they are very powerful meds for treatment resistant depression. However, in my case so was Zoloft and Lexapro. Unfortunately they all poop out on me within a year, no matter what we've tried to boost them with. Depression and anxiety disorders run rampant in my family. Three family members have had continued success with Effexor. It made me a nervous wreck and I too was beating myself up wondering what the heck was wrong with me?? How come my immediate family can tolerate it and I can't? I've discontinued some meds after a short period of time, in one case one day, and I used to come down on myself for not sticking it out.
I've had friends ask (with one eyebrow raised) why are you going off this one..you seemed to be doing so well..they just don't get the poop out syndrome or intolerable side effects that crop up..and I don't expect them to..I usually just smile and say if you walked into my body right now you'd run out screaming..
After 25 years on this merry-go-round and another med failure due to side effects I refuse to do that anymore. Some may not agree with my rationale of what I'm prepared to tolerate with side effects from any med be it a SSRI, SNRI, TCA or mood stab, and that is if it shoots my anxiety sky high, nope, not going there. If it knocks me out for 12 hours after the first dose and leaves me feeling like I have the world's worse hangover without the booze, not going there either. If it leaves me unable to string a sentence together, not going there. With Nardil, I was vomiting in my sleep every night, can't go there, due to the obvious risk of that particular one. If it makes me gain a ton of weight to the point where I now have a fridge magnet that says "I'm not fat, I'm fluffy", not going there. Perhaps my attitude will come back to bite me in the bum but man oh man enough already..
I'm very happy for people who have lasting success with meds with minimal side effects. I am so not one of them. That is why MAOI's were the next step. My pdoc and I were simply hoping I could get some longevity from them. I knew there would be side effects but I sure wasn't prepared for the hurling in my sleep. I still go into each drug trial with hope. Next step for me is a retrial of Parnate. The first trial got muddied as it coincided with a surgery I had. Hypotension was its major side effect. I'll drop down on my hands and knees again for awhile, but if it doesn't abate within a reasonable amount of time or is severe enough that I'm afraid to walk down a flight of stairs with my grandchild in my arms, not going there.
I asked my pdoc what now if the MAOI's don't work? His answer was "I guess we're going to have to get really creative". Gotta love a pdoc that truly listens and understands my sensitivity to side effects but doesn't give up hope that some combination of something will work.
You are so right..what works for me may not work for you and vice versa..and I totally agree that all experiences are valid and worthy of respect.
I apologize if this post is a bit disjointed. Day one totally off Nardil and I've been having brain zaps continually since titrating down (3 weeks) and they are starting to wear me out.
Posted by Justherself54 on April 18, 2008, at 13:17:10
In reply to Re: Husbands Suggestion of Nardil for me » SLS, posted by Racer on April 18, 2008, at 10:12:42
I totally respect your position on MAOI's. Your reasons they are not an option for you should be recognized and respected.
I was one of the pro-Nardil posters. It was like a miracle drug at the beginning and my posts were full of yippees, this is the most amazing med! With my history I should have know better! I apologize if anything in my posts made you feel badly as I can relate to the self-blame and hopelessness of trying to cope with adverse effects from meds.
I know some think MAOI's should be first or second line of treatment as they are very powerful meds for treatment resistant depression. However, in my case so was Zoloft and Lexapro. Unfortunately they all poop out on me within a year, no matter what we've tried to boost them with. Depression and anxiety disorders run rampant in my family. Three family members have had continued success with Effexor. It made me a nervous wreck and I too was beating myself up wondering what the heck was wrong with me?? How come my immediate family can tolerate it and I can't? I've discontinued some meds after a short period of time, in one case one day, and I used to come down on myself for not sticking it out.
I've had friends ask (with one eyebrow raised) why are you going off this one..you seemed to be doing so well..they just don't get the poop out syndrome or intolerable side effects that crop up..and I don't expect them to..I usually just smile and say if you walked into my body right now you'd run out screaming..
After 25 years on this merry-go-round and another med failure due to side effects I refuse to do that anymore. Some may not agree with my rationale of what I'm prepared to tolerate with side effects from any med be it a SSRI, SNRI, TCA or mood stab, and that is if it shoots my anxiety sky high, nope, not going there. If it knocks me out for 12 hours after the first dose and leaves me feeling like I have the world's worse hangover without the booze, not going there either. If it leaves me unable to string a sentence together, not going there. With Nardil, I was vomiting in my sleep every night, can't go there, due to the obvious risk of that particular one. If it makes me gain a ton of weight to the point where I now have a fridge magnet that says "I'm not fat, I'm fluffy", not going there. Perhaps my attitude will come back to bite me in the bum but man oh man enough already..
I'm very happy for people who have lasting success with meds with minimal side effects. I am so not one of them. That is why MAOI's were the next step. My pdoc and I were simply hoping I could get some longevity from them. I knew there would be side effects but I sure wasn't prepared for the hurling in my sleep. I still go into each drug trial with hope. Next step for me is a retrial of Parnate. The first trial got muddied as it coincided with a surgery I had. Hypotension was its major side effect. I'll drop down on my hands and knees again for awhile, but if it doesn't abate within a reasonable amount of time or is severe enough that I'm afraid to walk down a flight of stairs with my grandchild in my arms, not going there.
I asked my pdoc what now if the MAOI's don't work? His answer was "I guess we're going to have to get really creative". Gotta love a pdoc that truly listens and understands my sensitivity to side effects but doesn't give up hope that some combination of something will work.
You are so right..what works for me may not work for you and vice versa..and I totally agree that all experiences are valid and worthy of respect.
I apologize if this post is a bit disjointed. Day one totally off Nardil and I've been having brain zaps continually since titrating down (3 weeks) and they are starting to wear me out.
Posted by Justherself54 on April 18, 2008, at 13:18:33
In reply to Re: Husbands Suggestion of Nardil for me/racer, posted by Justherself54 on April 18, 2008, at 13:17:10
Posted by Phillipa on April 18, 2008, at 14:12:08
In reply to Re: Husbands Suggestion of Nardil for me/racer, posted by Justherself54 on April 18, 2008, at 13:17:10
Justherself thanks for getting the thread back on original topic somewhat and I also have experienced the same things as you and Racer and feel the same way. So many variables make us all unique. Maybe I should have worded the thread differently don't know but do know that some can take a course and then stop. Why who knows, situational, medical condition goes away or remission of it. I too have so many people who don't understand how hasimotos and other autoimmune diseases in family members make the success or unsuccess of a med be it for anxiety or depression. Oh I've taken meds for months on end and not had a single inprovement in anxiety. Cymbalta first time being one at 60mg and other only time on worked completely was the first ad paxil at l0mg with xanax and 4-6 beers a night which is supposed to cause an ad not to work. So why we don't know. Hope the parnate works well for you. And no falling down stairs with a grandchild. Love Phillipa
Posted by Sigismund on April 18, 2008, at 14:47:20
In reply to Re: Husbands Suggestion of Thread On Nardil for me, posted by undopaminergic on April 18, 2008, at 11:47:19
PJ, Nardil might help your anxiety, but it is unlikely to help you sleep better.
Posted by Phillipa on April 18, 2008, at 18:49:29
In reply to Phillipa, posted by Sigismund on April 18, 2008, at 14:47:20
Sigi whatcha got for sleep as didnt sleep last night as changing thyroid dosing and three docs fighting over it.? Very important organ. Love PJ
Posted by bleauberry on April 18, 2008, at 20:09:27
In reply to Husbands Suggestion of Thread On Nardil for me, posted by Phillipa on April 17, 2008, at 12:55:07
Ok. Population over 2 million? Cool. Guaranteed there is someone in there that will prescribe Nardil for you.
So, ask the pdoc who said no to Nardil, "refer me to someone who prescribes Nardil".
If he doesn't know of any, get out the phone book. Actually, you will have already gotten out the phone book, because you don't want to go back to the other pdoc who already said no, but you did get the book out to get his number and call him to ask for a referral...no need for another visit to do that. Easily done on the phone.
Call them all. Ask each one, "I am looking for pdoc to prescribe Nardil." If they say they don't, ask for a referral.
Keep calling down the phone list, and before letting them go after they say no, keep asking for referrals.
Have your husband do all this.
Total time maybe 1 to 5 hours over several days or weeks.
At google, type in the search box your city name and psychiatrist and nardil. If the hits don't bring desired results, modify the search words to towns around you and creative plays on other words.
Call all hospitals. Ask for the Head of Psychiatry. Tell them what you are looking for and ask politely if they could steer you in the right direction to a Nardil physician.
Any universities or research centers around? Do they have a psychiatric department or school? If so, ask them on the phone for referrals.
You WILL find someone, either through a "cold call" or through a referral.
Posted by Phillipa on April 18, 2008, at 20:22:02
In reply to Re: Husbands Suggestion of Thread On Nardil for me » Phillipa, posted by bleauberry on April 18, 2008, at 20:09:27
I don't want nardil. No. Love Phillipa
Posted by Racer on April 18, 2008, at 20:59:52
In reply to Re: Husbands Suggestion of Nardil for me/racer, posted by Justherself54 on April 18, 2008, at 13:16:41
>
> I was one of the pro-Nardil posters. I apologize if anything in my posts made you feel badly as I can relate to the self-blame and hopelessness of trying to cope with adverse effects from meds.
>No, no, no! I wasn't referring to people who were happy that the medications were working for them and posting about it. What I was thinking of were a few posts which were written in reply to some posts of mine asking about specific medications. Even in the posts where I specifically stated that I was looking specifically for information regarding these specific drugs, and specifically stated that MAOIs were not options, and I really didn't want to hear that I should take one, some responses still said that I should take an MAOI. Some of those posts said I should find another doctor, if mine wouldn't prescribe Nardil. Others said that I should "give up" my eating disorder in order to take Nardil -- that's one of the reasons it's not an option, but it's because you don't prescribe dietary restrictions to someone with an eating disorder. The idea is to STOP restrictions. And, of course, there are physical issues as well, having to do with cardiovascular health.
Sorry -- my little rant.
The end result of that sort of post was that I kinda felt rejected, abandoned, unsupported, and unheard. I'm sure that wasn't anyone's intent -- but it was my feeling. So, that's what I had in mind when I posted what I did above...
Thanks for the apology, but it certainly wasn't necessary. We're good, right? ;-)
Posted by undopaminergic on April 18, 2008, at 21:57:18
In reply to Husbands Suggestion of Nardil for me » Phillipa » Racer, posted by SLS on April 18, 2008, at 6:00:43
> Hi Racer.
>
> IMHO, Nardil is the second most efficacious drug on the planet. Clorgyline is the first. Both of these drugs are potent inhibitors of MAO-A.
>I read an article today concluding that trimipramine wss more effective than MAOIs (phenelzine and isocarboxazid) in most cases. As is well known, of course, in certain subgroups TCAs are ineffective while MAOIs work great.
Targeting MAO-A makes sense if you're more interested in boosting serotonin and noradrenaline. For extracellular dopamine, it is more logical to target MAO-B (and COMT, in theory), with MAO-A as a secondary target. Inhibition of intracellular MAO-A (*) is associated with downregulation of tyrosine hydroxylase activity, which to a considerable extent defeats the effects of MAO inhibition. (* there is very little intracellular MAO-B.)
>
> I find the MAOIs to be generally tolerable. ... I am surprised that these drugs should be regarded as poorly tolerated.
>There is much mythology surrounding MAOIs, and unfounded beliefs that are constantly repeated without questioning. That said, however, phenelzine in particular seems to be quite a challenge to tolerate for many people. Even if most of the side effects eventually subside, which isn't guaranteed, the initial phase must be endured before significant antidepressant efficacy to develops. This makes Nardil one of the lasts resorts. Personally, I'm not even ready to resort to tranylcypromine (or high-dose selegiline/rasagiline) yet.
>
> As far as Jan is concerned, I am frustrated and angry. I am aware of her treatment history, and things that are "first-line" drugs have already been tried. I agree with her that it would be beneficial to attack the endocrine system at this point. However, for recalcitrant anxiety, Nardil is a great drug. Marplan would be another consideration in place of Nardil, as it is more tolerable and easier on the liver.
>I just found this, which may be of particular interest in the case of Phillipa:
http://www.ithyroid.com/mao_and_tsh.htmAnyway, I agree that the hydrazine MAOIs (phenelzine, isocarboxazid) probably would be the most suitable MAOIs for Phillipa due to their GABAergic (and hence anxiolytic) properties, which are not shared by other MAOIs (tranylcypromine, selegiline, etc.).
I didn't know Marplan was easier on the liver; I thought it was the other way around, as the prescribing info (PI) for it expresses some concern about hepatoxicity. Similar prominence is not give to these concerns in the case of Nardil. If I'm not mistaken, hepatoxicity was the primary reason for the discontinuation of iproniazid, the original MAOI.
Posted by Justherself54 on April 18, 2008, at 22:39:19
In reply to Oh, dear, no! » Justherself54, posted by Racer on April 18, 2008, at 20:59:52
> > We are good..:-)
> > I was one of the pro-Nardil posters. I apologize if anything in my posts made you feel badly as I can relate to the self-blame and hopelessness of trying to cope with adverse effects from meds.
> >
>
> No, no, no! I wasn't referring to people who were happy that the medications were working for them and posting about it. What I was thinking of were a few posts which were written in reply to some posts of mine asking about specific medications. Even in the posts where I specifically stated that I was looking specifically for information regarding these specific drugs, and specifically stated that MAOIs were not options, and I really didn't want to hear that I should take one, some responses still said that I should take an MAOI. Some of those posts said I should find another doctor, if mine wouldn't prescribe Nardil. Others said that I should "give up" my eating disorder in order to take Nardil -- that's one of the reasons it's not an option, but it's because you don't prescribe dietary restrictions to someone with an eating disorder. The idea is to STOP restrictions. And, of course, there are physical issues as well, having to do with cardiovascular health.
>
> Sorry -- my little rant.
>
> The end result of that sort of post was that I kinda felt rejected, abandoned, unsupported, and unheard. I'm sure that wasn't anyone's intent -- but it was my feeling. So, that's what I had in mind when I posted what I did above...
>
> Thanks for the apology, but it certainly wasn't necessary. We're good, right? ;-)
Posted by SLS on April 19, 2008, at 5:25:39
In reply to Re: Husbands Suggestion of Nardil for me, posted by undopaminergic on April 18, 2008, at 21:57:18
> > Hi Racer.
> >
> > IMHO, Nardil is the second most efficacious drug on the planet. Clorgyline is the first. Both of these drugs are potent inhibitors of MAO-A.
> >
>
> I read an article today concluding that trimipramine wss more effective than MAOIs (phenelzine and isocarboxazid) in most cases.Nope. I hope you take into consideration more than one article to conclude for yourself what was indicated by the authors of that paper.
> Targeting MAO-A makes sense if you're more interested in boosting serotonin and noradrenaline. For extracellular dopamine, it is more logical to target MAO-B (and COMT, in theory), with MAO-A as a secondary target. Inhibition of intracellular MAO-A (*) is associated with downregulation of tyrosine hydroxylase activity, which to a considerable extent defeats the effects of MAO inhibition. (* there is very little intracellular MAO-B.)
By the way, there is a significant amount of DA that acts as a substrate for MAO-A. It is regionally selective, though. I think some is located at levels higher than the basal ganglia.
The only truly effective MAOIs are potent inhibitors of MAO-A. Of this I am certain.
- Scott
Posted by cumulative on April 19, 2008, at 8:07:45
In reply to Re: Husbands Suggestion of Nardil for me, posted by undopaminergic on April 18, 2008, at 21:57:18
I'm pretty convinced that a great deal of Nardil's effects probably stem from:
1) metabolism to beta-phenethylamine (which, I suspect, is allowed to reach significant blood levels due to MAOI) -- a stimulant effect. Might underlie the hyperthymic reactions some people get.
2) GABAnergic stimulationMaybe even moreso than the MAO-inhibition.
Posted by cumulative on April 19, 2008, at 8:10:18
In reply to Oh, dear, no! » Justherself54, posted by Racer on April 18, 2008, at 20:59:52
That sucks. You shouldn't have been treated that way.
Posted by SLS on April 19, 2008, at 8:12:12
In reply to Re: undopaminergic, nardil's effects, posted by cumulative on April 19, 2008, at 8:07:45
> I'm pretty convinced that a great deal of Nardil's effects probably stem from:
>
> 1) metabolism to beta-phenethylamine (which, I suspect, is allowed to reach significant blood levels due to MAOI) -- a stimulant effect. Might underlie the hyperthymic reactions some people get.
> 2) GABAnergic stimulation
>
> Maybe even moreso than the MAO-inhibition.Wow! I think you're right about everything.
Thanks for sharing your knowledge.
- Scott
Posted by Racer on April 19, 2008, at 8:52:35
In reply to Sorry about that, Racer., posted by cumulative on April 19, 2008, at 8:10:18
Thank you. As I said, I don't think anyone meant to hurt -- I'm sure everyone who posted that way meant to help. The end result was still pain for me, but I would never believe it was intentional.
But thank you. When I read your post, I felt very supported and heard. I appreciate that.
Posted by undopaminergic on April 20, 2008, at 0:06:30
In reply to Re: Husbands Suggestion of Nardil for me/racer, posted by Justherself54 on April 18, 2008, at 13:16:41
>
> After 25 years on this merry-go-round and another med failure due to side effects I refuse to do that anymore. Some may not agree with my rationale of what I'm prepared to tolerate with side effects from any med be it a SSRI, SNRI, TCA or mood stab, and that is if it shoots my anxiety sky high, nope, not going there. If it knocks me out for 12 hours after the first dose and leaves me feeling like I have the world's worse hangover without the booze, not going there either. If it leaves me unable to string a sentence together, not going there. With Nardil, I was vomiting in my sleep every night, can't go there, due to the obvious risk of that particular one. If it makes me gain a ton of weight to the point where I now have a fridge magnet that says "I'm not fat, I'm fluffy", not going there. Perhaps my attitude will come back to bite me in the bum but man oh man enough already..
>
> I'm very happy for people who have lasting success with meds with minimal side effects. I am so not one of them. That is why MAOI's were the next step. My pdoc and I were simply hoping I could get some longevity from them. I knew there would be side effects but I sure wasn't prepared for the hurling in my sleep. I still go into each drug trial with hope. Next step for me is a retrial of Parnate. The first trial got muddied as it coincided with a surgery I had. Hypotension was its major side effect. I'll drop down on my hands and knees again for awhile, but if it doesn't abate within a reasonable amount of time or is severe enough that I'm afraid to walk down a flight of stairs with my grandchild in my arms, not going there.
>
> I asked my pdoc what now if the MAOI's don't work? His answer was "I guess we're going to have to get really creative".
>I think creativity is indeed what you need more of. Many of the side effects you mentioned can be treated, if they don't go away by themselves in a reasonable period of time. Treating the adverse effects is particularly worthwhile if the drug is otherwise effective, as in the case of Nardil, for example.
For vomiting, there are a number of anti-emetic drugs. For example, the -setron serotonin 5-HT3-receptor antagonists (granisetron, tropisetron, ondansetron, etc.). Another major class of antiemetics are dopamine antagonists (domperidone, sulpiride, metoclopramide, chlorpromazine, etc.). There are also anticholinergics (scopolamine, atropine, etc.) and anticholinergic antihistamines (cyclizine, diphenhydramine, promethazine, etc.). Last, but possibly not least, cannabinoids (dronabinol, nabilone) may be effective.
For sedation, stimulants (modafinil, methylphenidate, amphetamines) are usually effective.
For hypotension, some stimulants (methylphenidate, amphetamines) and noradrenergic agents (ephedrine, pseudoephedrine, phenylephrine, etc.) are usually effective. While stimulants are typically contraindicated with MAOIs, when you're suffering from severe hypotension, the risk of hypertensive crisis from the introduction of a stimulant is minimal.
For weight gain, metformin, stimulants, and beta2-adrenergic agonists (clenbuterol, salbutamol, etc.) may be worth trying.
For anxiety, benzodiazepines are often useful.
Posted by Justherself54 on April 20, 2008, at 1:21:16
In reply to Re: Husbands Suggestion of Nardil for me/racer, posted by undopaminergic on April 20, 2008, at 0:06:30
> Thanks for the advice. I do appreciate it but I'm not talking about waking up and vomiting..I'm talking about vomiting during a dead sleep, and choking on it. The last episode was very frightening as I was gasping for air and choking while it was shooting out my mouth and nose (sorry to be so graphic)...the risk of aspiration into my lungs was too great and I'm just not willing to try an anti-emetic in case is doesn't work...the next time, especially with that kind of severity, I may not have been so lucky. I think 7 months is a reasonable amount of time to determine whether you feel safe on a medication. There were many other side effects which I haven't discussed, and with all combined my pdoc and I made a decision that I must go off it. I trust his judgment and I believe if he felt that trying to treat the vomiting was worth a try he would have suggested that. In his opinion and mine it was just too dangerous.
I'm very happy when Nardil works well for someone. It is a wonderful AD. Initially it was like a miracle and then side effect after side effect started to crop up..and I couldn't tolerate them. I must admit I feel a bit angry right now. When someone has a failed Nardil trial I wish there would be more support for the decision they've reached with their doctors.
I don't mean to sound harsh but I am very irritable and feel unwell due to the continual brain zaps I've been experiencing ever since the first titration and if I sound a little ratty, it's because right now I am! Four weeks of intense zaps are driving me up the wall and they aren't getting any better. To those that it has worked for, I am so happy for them...but for those who have given it a fair trial but can't tolerate the side effects and have to come off it, I hope they can simply accept that Nardil is not for everyone and be at peace with their decision.
> I think creativity is indeed what you need more of. Many of the side effects you mentioned can be treated, if they don't go away by themselves in a reasonable period of time. Treating the adverse effects is particularly worthwhile if the drug is otherwise effective, as in the case of Nardil, for example.
>
> For vomiting, there are a number of anti-emetic drugs. For example, the -setron serotonin 5-HT3-receptor antagonists (granisetron, tropisetron, ondansetron, etc.). Another major class of antiemetics are dopamine antagonists (domperidone, sulpiride, metoclopramide, chlorpromazine, etc.). There are also anticholinergics (scopolamine, atropine, etc.) and anticholinergic antihistamines (cyclizine, diphenhydramine, promethazine, etc.). Last, but possibly not least, cannabinoids (dronabinol, nabilone) may be effective.
>
> For sedation, stimulants (modafinil, methylphenidate, amphetamines) are usually effective.
>
> For hypotension, some stimulants (methylphenidate, amphetamines) and noradrenergic agents (ephedrine, pseudoephedrine, phenylephrine, etc.) are usually effective. While stimulants are typically contraindicated with MAOIs, when you're suffering from severe hypotension, the risk of hypertensive crisis from the introduction of a stimulant is minimal.
>
> For weight gain, metformin, stimulants, and beta2-adrenergic agonists (clenbuterol, salbutamol, etc.) may be worth trying.
>
> For anxiety, benzodiazepines are often useful.
Posted by undopaminergic on April 20, 2008, at 19:26:55
In reply to Re: Husbands Suggestion of Nardil for me, posted by SLS on April 19, 2008, at 5:25:39
> > > Hi Racer.
> > >
> > > IMHO, Nardil is the second most efficacious drug on the planet. Clorgyline is the first. Both of these drugs are potent inhibitors of MAO-A.
> > >
> >
> > I read an article today concluding that trimipramine wss more effective than MAOIs (phenelzine and isocarboxazid) in most cases.
>
> Nope. I hope you take into consideration more than one article to conclude for yourself what was indicated by the authors of that paper.
>Quote: "The results show a clear superiority for the tricyclic antidepressant trimipramine over MAOIs and the combination of trimipramine plus MAOIs in this large but unselected group of depressed outpatients, most of whom also received diazepam."
There were limitations of this particular study. They used a maximum of 60 mg of phenelzine and little more than 30 mg isocarboxazid, which may have been insufficient, and furthermore, the duration of the trial was only 6 weeks, which may also have been insufficient. Nevertheless, it illustrates the reasons why MAOIs are not first-line agents.
>
> > Targeting MAO-A makes sense if you're more interested in boosting serotonin and noradrenaline. For extracellular dopamine, it is more logical to target MAO-B (and COMT, in theory), with MAO-A as a secondary target. Inhibition of intracellular MAO-A (*) is associated with downregulation of tyrosine hydroxylase activity, which to a considerable extent defeats the effects of MAO inhibition. (* there is very little intracellular MAO-B.)
>
> By the way, there is a significant amount of DA that acts as a substrate for MAO-A. It is regionally selective, though. I think some is located at levels higher than the basal ganglia.
>There are differences betwen regions and between species. The details are complex, but as an example, clorgyline at a MAO-A selective dose, reduces DA metabolites in the rat nucleus accumbens (NAc), but fails to alter basal extracellular DA levels or cocaine-induced increases thereof. Selegiline, on the other hand, at MAO-B selective doses, doesn't reduce metabolites, but clearly potentiates the effects of cocaine on extracellular DA. This illustrates 1) the dominant role of MAO-A in DA metabolism in the rat NAc under normal conditions, 2) the downregulation of DA synthesis (no change in DA levels, despite reduced metabolism) in response to MAO-A inhbition, and 3) the role of MAO-B in extracellular DA metabolism under conditions of elevated DA concentration (as produced by reuptake inhibition by cocaine).
MAO-B is of much greater significance in primates than in rats. Nevertheless, chronic selegiline treatment actually attenuates the subjective effects of cocaine in humans. This may reflect desensitation of DA receptors following prolonged elevation of extracellular DA levels by selegiline treatment.
> The only truly effective MAOIs are potent inhibitors of MAO-A. Of this I am certain.
>All known potent MAOIs are capable of potent inhibition of MAO-A, depending on dose. However, I see no reason for choosing a MAOI that preferentially inhibits MAO-A and hence introduces the risk of cheese reaction and serotonin syndrome even at subtherapeutic doses, while provoking downregulation of neurotransmitter synthesis on top of it. Why not start with a noradrenaline+dopamine reuptake inhibitor (e.g. methylphenidate) that blocks (or slows) tyramine uptake into sympathetic nerve terminals and produces an elevation of synaptic concentrations of these neurotransmitters without any enzyme inhibition at all, and then introduce a MAO-B-preferring inhibitor at increasing doses until the desired effect is achieved? In most treatment-resistant cases, a considerable degree of MAO-A inhibition will be required in addition to the catecholamine reuptake blockade and the near-total MAO-B inhibition. Another potential advantage of this protocol is the likely alleviation of MAOI-induced hypotension.
Posted by undopaminergic on April 20, 2008, at 19:51:14
In reply to Re: Husbands Suggestion of Nardil for me, posted by Justherself54 on April 20, 2008, at 1:21:16
No-one quits Nardil with impunity. The brain-zaps are God's punishment for your sin of giving up on the Divine Nardil. (And by the way, everyone who chokes on their Nardil-elicited vomit is guaranteed a place in Heaven!)
(Just kidding.)
Posted by 4WD on April 22, 2008, at 18:33:47
In reply to Re: Husbands Suggestion of Nardil for me, posted by SLS on April 19, 2008, at 5:25:39
Scott,
What is clorgyline? I've never heard of it by the generic name. I know it's not Parnate. If it's more effective than Nardil, why aren't you taking it?
Marsha
Posted by Phillipa on April 22, 2008, at 19:38:13
In reply to Re: Husbands Suggestion of Nardil for me » SLS, posted by 4WD on April 22, 2008, at 18:33:47
Marsha well this is interesting. Love Phillipa.
MONOAMINE OXIDASE (MAO) AND THYROID STIMULATING HORMONE (TSH)I've run across some studies indicating that monoamine oxidase inhibitors (MAOIs) which are used as antidepressant drugs can suppress TSH levels in a fairly high percentage of patients. Monoamine oxidase (MAO) seems depressed in many cases of hyperthyroidism and at an excess in manic depression. I intend to accumulate studies here dealing with these issues in an attempt to figure out what is going on between MAO and TSH.
Psychiatry Clin Neurosci 1995 Aug;49(4):231-6
Effects of antidepressants on thyroid stimulating hormone release in rats under ether stress.Kadono Y, Kaneda H, Maeda K
Department of Psychiatry, Kobe University Medical School, Japan.
We found inhibitory effects of antidepressants (clomipramine, maprotyline, mianserin and zimelidine) and 5-hydroxytryptophan (5-HTP) on thyroid stimulating hormone (TSH) release induced by ether stress in freely moving rats. We confirmed that ether stress suppressed the plasma TSH levels after 30 min. We then injected intravenously 250 ng thyrotropin releasing hormone (TRH), 0.1 mg/kg clomipramine, 2.5 mg/kg maprotyline, 2.5 mg/kg mianserin, 0.5 mg/kg zimelidine and 25 mg/kg 5-HTP simultaneously. These materials blocked the influences on plasma TSH levels by the ether stress. Serotonergic antidepressants (clomipramine, zimelidine) and 5-HTP (precursor of serotonin) had a higher potency against the ether stress. These results suggest that antagonizing effects against the ether stress may involve the serotonergic system in the pituitary gland.
Endocrinol 1994 Nov;143(2):303-8
Thyroid iodide transport is reduced by administration of monoamine oxidase A inhibitors to rats.Cabanillas AM, Masini-Repiso AM, Costamagna ME, Pellizas C, Coleoni AH
Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Argentina.
The present work was addressed to study a possible relationship between monoamine oxidase (MAO) and the thyroid iodide transport mechanism. Normal rats treated with clorgyline (a selective MAO-A inhibitor) or tranylcypromine (a non-selective MAO inhibitor) showed a significantly diminished thyroid MAO activity, while deprenyl and pargyline (MAO-B inhibitors) did not modify the thyroidal enzyme activity with respect to the control group. Under these conditions, in vivo iodide transport was reduced both by clorgyline and tranylcypromine administration whereas it remained unchanged after treatment with MAO-B inhibitors. The effect of MAO inhibitors on thyroid MAO activity and in vivo iodide transport was also evaluated in rats treated with exogenous thyrotrophin (TSH) after endogenous TSH secretion blockade produced by T4 administration. In this condition, thyroid MAO activity was significantly lowered by clorgyline and was not modified by deprenyl. In contrast to the results observed in normal rats, in vivo iodide transport in TSH-treated rats remained unaltered after treatment either with clorgyline or deprenyl. MAO activity evaluated in bovine thyroid follicles in primary culture was highly sensitive to low concentrations of clorgyline (< 10 nmol/l) and relatively insensitive to deprenyl, a finding that indicates a predominance of the MAO-A isoform in the follicular cells in culture. When clorgyline (0.1 and 1 mumol/l) or deprenyl (1 mumol/l) were added to the culture medium, no modifications in the active transport of iodide were observed. These results indicate the absence of a direct linkage between thyroid MAO activity and the active iodide transport.
J Endocrinol 1991 Oct;131(1):25-31
Rat thyroid monoamine oxidase (MAO) is regulated by thyrotrophin: evidence that the main form of the enzyme (MAO-A) is not directly involved in iodide organification.Cabanillas AM, Masini-Repiso AM, Coleoni AH
Catedra de Quimica Clinica I, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Argentina.
The characteristics and regulation of monoamine oxidase (MAO) were studied in rat thyroid tissue. A measured Michaelis constant (Km) value of 102 mumol/l was similar to the Km values found in other tissues. Maximal velocity (Vmax) was 1.028 nmol/mg protein per min. It is known that MAO is present as two isoenzymes, A and B, which are sensitive to clorgyline and deprenyl respectively. The in-vitro effect of graded concentrations of these selective MAO inhibitors was used to estimate the relative proportion of A and B isoenzymes. Clorgyline strongly decreased thyroid MAO activity at concentrations as low as 1 pmol/l while the effect of deprenyl was observed only at concentrations higher than 10 mumol/l. These results indicated that MAO-A is the main form of the enzyme in the rat thyroid. In-vivo administration of L-thyroxine (5.6-224 nmol/kg) significantly reduced thyroid MAO activity at doses equal to or greater than those which have been reported to inhibit iodine output from the thyroid. Increased TSH levels, induced either by exogenous TSH or methimazole administration, resulted in a significant increase in thyroid MAO activity. Theophylline, a phosphodiesterase inhibitor and dibutyryl cyclic AMP were also able to stimulate MAO activity when administered in vivo. Iodide organification (protein-bound 131I) in vivo as well as the relative proportion of the different thyroid iodo-compounds were not affected in animals with reduced or increased thyroid MAO activity induced by clorgyline or theophylline respectively. It was concluded that rat thyroid MAO activity is under the influence of TSH.
Br J Pharmacol 1989 Feb;96(2):465-9
Monoamine oxidase activity and triiodothyronine biosynthesis in human cultured thyroid cells.Kraiem Z, Sadeh O, Youdim MB
Endocrine Research Unit, Carmel Hospital, Haifa, Israel.
1. The proposal that monoamine oxidase (MAO) is a source of peroxide in thyroid hormone biosynthesis has been examined by use of isolated cultured human thyroid cells which retain the ability to secrete triiodothyronine (T3) in response to thyroid stimulating hormone (TSH). 2. The results demonstrated the presence of MAO A and B in human thyroid cells which oxidized 5-hydroxytryptamine and 2-phenylethylamine, respectively, and were selectively inhibited by the MAO inhibitors clorgyline and (-)-deprenyl. 3. Addition of propylthiouracil to the culture system induced a 61% reduction in TSH-stimulated T3 secretion, indicating that the bulk of such secretion apparently derives from de novo iodothyronine synthesis. 4. The MAO A and B substrate, tyramine, was ineffective in stimulating T3 secretion. 5. The selective MAO inhibitors, clorgyline and (-)-deprenyl, alone and in combination, and in the presence and absence of tyramine, failed to inhibit basal as well as TSH-stimulated T3 secretion in cultured human thyrocytes. 6. It is therefore apparent that even though thyroid MAO A and B enzyme reactions result in the generation of H2O2, this H2O2 does not seem to play a significant role in T3 biosynthesis.
Horm Metab Res 1983 Apr;15(4):191-3
Effect of hypophysectomy and administration of TSH on the activity of monoamine oxidase in the thyroid gland of rats.Knopp J, Torda T
The thyroid monoamine oxidase (MAO) activity was measured in rats after hypophysectomy and TSH treatment to find out whether the thyroid MAO activity can be modified with TSH. Hypophysectomy decreased MAO activity in the thyroid gland of rats. The administration of TSH (2.5 U kg-1 daily for 5 days) to hypophysectomized rats increased MAO activity and fully compensated the absence of the pituitary. These data suggest that the thyroid gland MAO activity is under the regulatory influence of TSH.
Posted by Questionmark on April 27, 2008, at 1:37:08
In reply to Re: Husbands Suggestion of Nardil for me/racer, posted by undopaminergic on April 20, 2008, at 0:06:30
Good point(s) undopaminergic. There are definitely things you can do to combat most of Nardil's side effects, especially the vomiting (and especially if that was the only or main thing preventing you/her from staying on Nardil). But i must disagree with the following:
"... and noradrenergic agents (ephedrine, pseudoephedrine, phenylephrine, etc.) are usually effective. While stimulants are typically contraindicated with MAOIs, when you're suffering from severe hypotension, the risk of hypertensive crisis from the introduction of a stimulant is minimal."
Stimulants are sometimes ok, yes-- methylphenidate in particular at least. But noradrenergic agents are VERY dangerous to mess with while on an MAOI. I mean it would seem like you're right, but just a tad too much and you could be propelled into the heart of a hypertensive crisis-- even if you're normally quite hypotensive with the MAOI.
> > After 25 years on this merry-go-round and another med failure due to side effects I refuse to do that anymore. Some may not agree with my rationale of what I'm prepared to tolerate with side effects from any med be it a SSRI, SNRI, TCA or mood stab, and that is if it shoots my anxiety sky high, nope, not going there. If it knocks me out for 12 hours after the first dose and leaves me feeling like I have the world's worse hangover without the booze, not going there either. If it leaves me unable to string a sentence together, not going there. With Nardil, I was vomiting in my sleep every night, can't go there, due to the obvious risk of that particular one. If it makes me gain a ton of weight to the point where I now have a fridge magnet that says "I'm not fat, I'm fluffy", not going there. Perhaps my attitude will come back to bite me in the bum but man oh man enough already..
> >
> > I'm very happy for people who have lasting success with meds with minimal side effects. I am so not one of them. That is why MAOI's were the next step. My pdoc and I were simply hoping I could get some longevity from them. I knew there would be side effects but I sure wasn't prepared for the hurling in my sleep. I still go into each drug trial with hope. Next step for me is a retrial of Parnate. The first trial got muddied as it coincided with a surgery I had. Hypotension was its major side effect. I'll drop down on my hands and knees again for awhile, but if it doesn't abate within a reasonable amount of time or is severe enough that I'm afraid to walk down a flight of stairs with my grandchild in my arms, not going there.
> >
> > I asked my pdoc what now if the MAOI's don't work? His answer was "I guess we're going to have to get really creative".
> >
>
> I think creativity is indeed what you need more of. Many of the side effects you mentioned can be treated, if they don't go away by themselves in a reasonable period of time. Treating the adverse effects is particularly worthwhile if the drug is otherwise effective, as in the case of Nardil, for example.
>
> For vomiting, there are a number of anti-emetic drugs. For example, the -setron serotonin 5-HT3-receptor antagonists (granisetron, tropisetron, ondansetron, etc.). Another major class of antiemetics are dopamine antagonists (domperidone, sulpiride, metoclopramide, chlorpromazine, etc.). There are also anticholinergics (scopolamine, atropine, etc.) and anticholinergic antihistamines (cyclizine, diphenhydramine, promethazine, etc.). Last, but possibly not least, cannabinoids (dronabinol, nabilone) may be effective.
>
> For sedation, stimulants (modafinil, methylphenidate, amphetamines) are usually effective.
>
> For hypotension, some stimulants (methylphenidate, amphetamines) and noradrenergic agents (ephedrine, pseudoephedrine, phenylephrine, etc.) are usually effective. While stimulants are typically contraindicated with MAOIs, when you're suffering from severe hypotension, the risk of hypertensive crisis from the introduction of a stimulant is minimal.
>
> For weight gain, metformin, stimulants, and beta2-adrenergic agonists (clenbuterol, salbutamol, etc.) may be worth trying.
>
> For anxiety, benzodiazepines are often useful.
Posted by undopaminergic on April 27, 2008, at 2:55:41
In reply to Re: Husbands Suggestion of Nardil for me/racer » undopaminergic, posted by Questionmark on April 27, 2008, at 1:37:08
True if you take too large a dose, but that is entirely avoidable if proper care is taken. You can also have a fast-acting anti-hypertensive agent at hand (nitro would seem the most rapid-acting, but nifepidine seems a more popular choice). Furthermore, if you're really worried, you can introduce the potentially dangerous drug while under medical supervision, such as at a hospital.
This is the end of the thread.
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