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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 25. This is the beginning of the thread.
Posted by pat c. on November 3, 2001, at 20:44:47
This link says that Nardil (Phenelzine) elevates GABA.
It also says that MAO-B is the primary MAO that is inhibited by Nardil to cause this elevation of GABA.
What I'm not sure about is that the article says that Deprenyl (MAO-B inhibitor) was used to prove this theory. Since Deprenyl reduced the GABA-elevating action of rats that were on Nardil, this proves MAO-B is the real MAO in play here? How can two MAOIs counteract each other? And why would that prove MAO-B is the primary MAO to be inhibted in order to raise GABA.
Thanks.
Pat
Posted by JGalt on November 3, 2001, at 22:33:06
In reply to Inhibition of MAO-B Increases GABA, posted by pat c. on November 3, 2001, at 20:44:47
Interesting article...by the way, thats a fun website to read through from time to time, good to see I'm not the only one reading it...anyway, back to your questions...
"It also says that MAO-B is the primary MAO that is inhibited by Nardil to cause this elevation of GABA."
Right here is the source of your confusion, and I can easily see where you got what you did, I thought the same thing when I glanced it over.
What the article is actually saying is that Nardil, while it inhibits MAO-A and MAO-B is also metabolised by the MAO enzymes...basically its stopping those enzymes, and the enzymes are also responsible for stopping it (sudden thought, maybe this is why if Nardil is dosed beyond 80% MAO inhibition it can cause manic episodes, perhaps because the drug level doesn't go down anywhere near as fast thus causing a cumulative effect...anyway) . But when the MAO metabolizes (that isn't the right word but I'll go w/ it) the Nardil, a new compound is formed (undescribed in this article), which according to the article leads to higher GABA levels (this probably accounts for Nardil's generally greater effect than Parnate on social anxiety). K...now when they used selegiline to block MAO-B enzymes, the GABA levels didn't rise anywhere near as much when the subject was exposed to Nardil, but when they used a different drug to inhibit MAO-A enzymes GABA levels weren't effected as much. The selegiline isn't counteracting the Nardil, it is simply further reducing MAO-B levels, thus causing less of the metabolite of Nardil to be produced, thus leading to less increase of GABA. This leads to their conclusion that MAO-B is responsible for the conversion of Nardil to whatever metabolite it is that increases GABA.
Hope that made some sense without being excessively wordy.
JGalt
Posted by pat c. on November 4, 2001, at 8:33:04
In reply to Re: Inhibition of MAO-B Increases GABA, posted by JGalt on November 3, 2001, at 22:33:06
Well said. Thank you for the explanation.
Is there anything we can extrapolate from this?
Is MAO-B the primary MAO to be concerned about in aypical depression, or at least the social phobia aspect of it?
Is GABA a major player in atypical depression?
Does this say anything about the effectiveness or ineffectiveness of Seligine against atypical depression?
I'm curious whether low levels of GABA can cause depression. I took Nardil, but it kept pooping out. I was on 150mg at one point, if you can believe that. I was hypomanic as hell. But the symptoms of atypical depression kept coming back. I got off Nardil, and lost 50 pounds.
I was on 3.0 mg of Klonopin (a GABA agent), and I've gotten off most of that. I could really use the 3mg back. I wonder why Klonopin is so effective against atypical depression. It obviously solves the GAD, panic, and social phobia aspects of the disease. I'm also beginning to think Klonopin might have antidepressant action.
Currently, I'm on 0.25 of Klonopin (down from 0.5 mg last week) and 1600 of Neurontin (down from 4800 two months ago). I'm having a rough time getting off these two drugs. This week's 0.25 cut in Klonopin is hell. I'm ramping back up the Neurontin to counteract the Klonopin cut.
Lowering the levels of Neurontin (another GABA agent) has been quite difficult. I'm not sure whether Neurontin is just an augmenting agent, or whether it can be used by itself. I'll find out.
Meanwhile, the depression aspect on my atypical depression is getting worse.
Obviously, I'm looking for answers, so I'm persuing this GABA angle. It seems to be the common denominator between Nardil, Klonopin and Neurontin. I need a drug for atypical depression other than Nardil (made me too fat) and Klonopin (history of addiction).
I believe there are five possible reasons for my atypical depression (social phobia, anxiety attacks, and depression):
1) GABA (inhibiting neurotransmitter) level too low
2) Glutamate (excitatory neurotransmitter) level too high
3) Serotonin (inhibitor) level too low
4) Dopamine (excitatory) level too high
5) Norepinephrine (excitatory) level too highSerotonin reuptake inhibitors didn't help, so I'm writing off the Serotonin angle, although I'm curious about FDA testing of Gepirone, which is getting good reviews.
Lowering Glutamate with Lamactil caused major memory problems.
I've has some success in increasing GABA.
I get anxiety attacks from dopamine agents like Wellbutrin and Ritalin, which makes me think that I have too much Dopamine, and since norepinephrine is formed from Dopamine, perhaps I have too much norepinephrine.Any thoughts would be helpful.
Thank you for your time.
Pat
Posted by JGalt on November 4, 2001, at 10:32:02
In reply to Re: Inhibition of MAO-B Increases GABA » JGalt, posted by pat c. on November 4, 2001, at 8:33:04
What can we extapolate from this? Not much...
Basically this just tells us that MAO-B metabolizes Nardil in such a way that it produces a compound that increases GABA. As MAO-B inhibition helping atypical depression, well for me it seems to be the case that it does (though this article is really just discussing the metabolite from Nardil). Have you tried selegiline? That's a selective MAO-B inhibitor at doses 10mg and below. Combine it with some DL-Phenylaline or N-Acetyl-Tyrosine and it produces a very nice effect (for me). However, your symptoms are somewhat different from mine, as for me, the biggest prob is lack of energy/motivation and hypersomnia/overeating, whereas what i get from your post is that you seem to have the biggest prob with social phobia, so I'm not sure. I would still give it a try though, selegiline cures my minor social phobia provided I don't do something stupid (like take a bunch of caffeine+ephedrine on it).GABA is a major player in social problems, relaxation problems, anxiety problems, and similar.
The article's information doesn't really suggest anything about selegiline, it is only used to prove that MAO-B was responsible for breaking down Nardil into a substance that increased GABA.
Low levels of GABA could cause depression I suppose. Such depression would likely be a burnout type depression, wherein the thought of doing things causes way too much anxiety, leading one to want to just sit around (kinda similar to low serotonin, only with more anxiety symptoms, as opposed to serotonin which I imagine would also involve more lack of feelings towards others symptoms), as opposed to the atypical type which the person just wants to sit around primarily because of lack of motivation or feeling.
As for what you should choose for medication, I can't be of much help there. I'm not familiar with neurontin, but your theory about GABA seeming to be the common denominator between meds does look right.
As usual, a few years ago I would have recommended the previously legal GHB. For many people (inc. myself), it is an incredible drug for anxiety and depression if used correctly (in moderation) without hardly any of the side effects of present meds if used correctly (abuse it and its worse than present meds though). It may be soon (or maybe it already is) available for nacrolepsy under the name Xyrem. Good luck getting a script though and I hope you have real good insurance if you do (its roughly 100 times more expensive than it was OTC a few years ago).
Hoping someone else will chime in on this for you re: easier to get prescription meds that fit your description though.
JGalt
Posted by pat c. on November 4, 2001, at 13:01:57
In reply to Re: Inhibition of MAO-B Increases GABA, posted by JGalt on November 4, 2001, at 10:32:02
Thanks.
Does Seligine cause weight gain like the other MAOIs? I gained 50 pounds on Nardil. I looked like crap.
I heard the diet restrictions (i.e cheese causing high blood pressure) are not a factor with Seligine. Is this true?
Thank you for all your feeback.
Pat
Posted by JGalt on November 4, 2001, at 17:03:45
In reply to Re: Inhibition of MAO-B Increases GABA » JGalt, posted by pat c. on November 4, 2001, at 13:01:57
Actually I think Nardil is the only MAOi that many people complain about gaining weight on. I've heard of very few people gaining weight on Parnate (seems like more of the opposite). Selegiline, from my experience and others, is one that you either maintain or loose a little weight on (of course if your transferring from Nardil you may loose a lot of weight!).
No diet restrictions with 10mg (some say as high as 30mg but I wouldn't try it) or under of Selegiline. I've found that at that level most stimulants do need to have their dosages lowered (or else you're too wired...please note that the concept of being too wired was inconcievable to me until I tried 50mg ephedrine 10mg selegiline and 400mg caffeine one day), but that's no big deal. Some recreational or prescription drugs may act slightly differently but the chances of a full blown hypertensive or serotonin crisis are practically nil.
If the klonopin is helping you that much I'd stay on it if you decide to go for selegiline.
JGalt
Posted by Rick on November 4, 2001, at 21:11:43
In reply to Re: Inhibition of MAO-B Increases GABA » JGalt, posted by pat c. on November 4, 2001, at 13:01:57
Some personal experience relating to the discussions here...
My treatment has been soley for non-depressive social anxiety (although I also have mild OCD tendencies, which my very-effective social anxiety "cocktail" doesn't help at all).
The first psychotropic med I ever tried was Nardil, with as-needed Xanax. The Nardil pooped out quickly. Ironically, it didn't cause weight gain at all. In fact, I began my first real dieting attempt concurrently, and it was very successful.
After going through several other meds, I found that Klonopin was a godsend for my social anxiety. But even though I had cut the dose back fom 3 mg. to 2 mg. (it actually worked better for me at the lower dose), I still had some midday lethargy much of the time. So my pdoc agreed to let me add back some of the selegiline (which we had earlier tried very unsuccessfully as a Nardil replacement) for added wakefulness and alertness (selegiline had done nothing but make me MORE anxious when taken solo). It was a good combo, even though the seligiline detracted a bit from Klonopin's anxiety benefits even as it added the desired concentration and alertness. I've since found that 10 mg Provigil provides a similar alertness benefits, plus anxiety *reduction* and increased confidence and sociability. (Current cocktail: mainstay Klonopin 1 mg; Serzone 300 mg; Provigil 100 mg -- all first thing in a.m. at this point.)
A few more points:
-- Wellbutrin (in tandem with Klonopin) added back as much anxiety as the selegiline did, but with less in the way of cognitive benefits and alertess.
-- In the selegiline+Klonopin combo, the selegiline was really asserting itself despite that fact that I was taking only 2.5 mg/day (trying to split those pills is "loads" of fun, even with a splitter!). In retrospect, I read that people can get plenty of activation from 2.5 mg of seligiline just two or three days a week, and I believe it! Selegiline efects *really* stay with you (even the sexual enhancement, although I didn't need help in that area post-Nardil)! So if you DO take a Klonopin-selegiline combo (as I *believe* JGalt suggested -- sorry if I'm misquoting), and also experience added anxiety, keep in mind that after you've reached steady state you may be able to retain the seligiline benefits without possible anxiety side effects through minimal every-other-day dosing.
-- Since I'm always redundant, let me again point out that solo seligiline was a disaster for anxiety. I sure wouldn't recommend it as a primary AD for anyone with prominent anxiety.
-- Again, someone may have mentioned this already, but selegiline shouldn't cause weight gain.
> Thanks.
>
> Does Seligine cause weight gain like the other MAOIs? I gained 50 pounds on Nardil. I looked like crap.
>
> I heard the diet restrictions (i.e cheese causing high blood pressure) are not a factor with Seligine. Is this true?
>
> Thank you for all your feeback.
>
> Pat
Posted by Rick on November 5, 2001, at 2:15:29
In reply to Re: Inhibition of MAO-B Increases GABA » JGalt, posted by pat c. on November 4, 2001, at 8:33:04
>I wonder why Klonopin is so effective against atypical depression. It obviously solves the GAD, panic, and social phobia aspects of the disease. I'm also beginning to think Klonopin might have antidepressant action.
Funny how Klonopin -- unlike Xanax -- has a reputation for often *causing* depression. In fact, many medical reviews list this as one of the main risks of Klonopin use, as if it's been clinically proven. I was warned by a user, "it WILL hit you at some point", but it's now 2+ years and counting. Beats me. I guess what some Klonopin users experience is either classic YMMV, or breakthrough depression unrelated to the Klonopin but incorrectly attributed to it.
I did a Medline search on clonazepam and depression, and the only study-based correlations I saw showed Klonopin exerting *anti*-depressant effects -- even when taken alone. There were several references to Klonopin's pro-serotonergic properties, although its pro-GABA effects are probably the most relevant.
Rick
Posted by pat c. on November 6, 2001, at 0:52:26
In reply to Re: Inhibition of MAO-B Increases GABA » pat c., posted by Rick on November 4, 2001, at 21:11:43
Thank you.
Excellent feedback.
I guess I'm going to stay away
from seligiline.I don't need more anxiety,
although I need an antidepressant
that fights atypical depression
(social phobia/depression/anxiety attacks).I don't want to do Nardil again (weight gain),
and I'd like to live without Klonopin (history of addiction), even though Klonopin is, like you said, a Godsend. I think it does have some antidepressant qualities. I don't know, but it sure helps my atypical depression.I don't know what to take.
Thanks.
Pat
Posted by pat c. on November 6, 2001, at 0:59:44
In reply to Re: Klonopin and Depression » pat c., posted by Rick on November 5, 2001, at 2:15:29
Yeh, I definitely need to pursue the possibility Klonopin acts as an antidepressant.
I'd love to live life without it, but I
can't be a hero. I'm tired of suffering.Klonopin works great with me (big-time atypical
depressant).I'd be interested in reading some of the references, that you mentioned, that indicate
that Klonopin works on Serotonin, as well as
GABA.Thanks.
Pat
Posted by SLS on November 6, 2001, at 12:04:08
In reply to Re: Klonopin and Depression » Rick, posted by pat c. on November 6, 2001, at 0:59:44
> Yeh, I definitely need to pursue the possibility Klonopin acts as an antidepressant.
>
> I'd love to live life without it, but I
> can't be a hero. I'm tired of suffering.
>
> Klonopin works great with me (big-time atypical
> depressant).
>
> I'd be interested in reading some of the references, that you mentioned, that indicate
> that Klonopin works on Serotonin, as well as
> GABA.
>
> Thanks.
>
> Pat
Hi Pat.For me, Klonopin definitely has the ability to make me feel more depressed.
Klonopin has been attributed pro-serotonergic properties for quite a few years. I remember this being the case as early as 1988. I believe you will find sufficient references on Medline.
How sure are you that Klonopin is acting as an antidepressant for you, and why? I have no reason to think otherwise, but I am curious. I think Rick's perspective on the use of benzodiazepines is applicable, and I would not think of Klonopin as being some kind of demon if it is working for you. If it somehow leaves you more vulnerable to abusing other substances, that would be a different story.
While we're on the subject, have you ever tried buspirone?
Did Nardil poop-out on you, or did you discontinue it only because of weight-gain? I gained 40lbs. when I took Nardil as monotherapy. However, I experienced some weight loss when it was combined with desipramine. I believe that there is some reduction of appetite. Also, for me, there is a noticeable increase in basal metabolism as is evidenced by lipolysis, thermogenesis, and weight-loss when I experience a significant remission of depression. Although I have bipolar disorder, my depression is predominantly atypical with respect to vegetative features. However, there is no mood-reactivity.
Do you experience mood-reactivity?
- Scott
Posted by Elizabeth on November 6, 2001, at 15:59:09
In reply to Inhibition of MAO-B Increases GABA, posted by pat c. on November 3, 2001, at 20:44:47
Phenelzine, or one of its metabolites, inhibits GABA-transaminase.
-elizabeth
Posted by pat c. on November 6, 2001, at 16:35:43
In reply to Re: Nardil and GABA, posted by Elizabeth on November 6, 2001, at 15:59:09
I think it's the metabolite.
PC
Posted by Rick on November 6, 2001, at 21:03:48
In reply to Re: Klonopin and Depression » pat c., posted by SLS on November 6, 2001, at 12:04:08
While I see many recent reveiews that allude to Klonopin's beneficial serotonergic properties (though far outnumbered by reviews that warn of depression risk), recent sudies are few and far between -- for obvious economic and bias reasons. And as Scott personally attested, Klonopin really *does* seem to increase depression for some people even as it may help alleviate it for others. (Of course, I like to point out that if you look at the complete adverse effects list for any antidepressant, you'll always see depression!)
While there are several recent Medline abstracts suggestive of Klonopin antidepressant effects based on small open trials (the most recent studies were on individuals with chronic physical illnesses), the lab analyses of serotonergic effects were indeed older. And to the extent I can understand them, there wasn't exactly a consensus. Below are a few exmples. (First, though, is a small 1988 study of Klonopin for refractory depression.)
Rick
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3279721&dopt=Abstract
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2415867&dopt=Abstract
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2580249&dopt=Abstract
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2418653&dopt=Abstract
> > Yeh, I definitely need to pursue the possibility Klonopin acts as an antidepressant.
> >
> > I'd love to live life without it, but I
> > can't be a hero. I'm tired of suffering.
> >
> > Klonopin works great with me (big-time atypical
> > depressant).
> >
> > I'd be interested in reading some of the references, that you mentioned, that indicate
> > that Klonopin works on Serotonin, as well as
> > GABA.
> >
> > Thanks.
> >
> > Pat
>
>
> Hi Pat.
>
> For me, Klonopin definitely has the ability to make me feel more depressed.
>
> Klonopin has been attributed pro-serotonergic properties for quite a few years. I remember this being the case as early as 1988. I believe you will find sufficient references on Medline.
>
> How sure are you that Klonopin is acting as an antidepressant for you, and why? I have no reason to think otherwise, but I am curious. I think Rick's perspective on the use of benzodiazepines is applicable, and I would not think of Klonopin as being some kind of demon if it is working for you. If it somehow leaves you more vulnerable to abusing other substances, that would be a different story.
>
> While we're on the subject, have you ever tried buspirone?
>
> Did Nardil poop-out on you, or did you discontinue it only because of weight-gain? I gained 40lbs. when I took Nardil as monotherapy. However, I experienced some weight loss when it was combined with desipramine. I believe that there is some reduction of appetite. Also, for me, there is a noticeable increase in basal metabolism as is evidenced by lipolysis, thermogenesis, and weight-loss when I experience a significant remission of depression. Although I have bipolar disorder, my depression is predominantly atypical with respect to vegetative features. However, there is no mood-reactivity.
>
> Do you experience mood-reactivity?
>
>
> - Scott
Posted by Elizabeth on November 7, 2001, at 11:58:04
In reply to Re: Nardil and GABA » Elizabeth, posted by pat c. on November 6, 2001, at 16:35:43
> I think it's the metabolite.
>
> PCMe too.
-e
Posted by gilbert on November 7, 2001, at 12:28:34
In reply to Re: Nardil and GABA » pat c., posted by Elizabeth on November 7, 2001, at 11:58:04
I read somewhere and I think it was the medline research archives that klonopin had aa affinity for the the 5ht1 and 5ht2 recepter sites and downregulated the processing of srotonin at these sites. This would certainly explain why klonopin out of all the benzos seems to have some sexual side effects especially in males. I have a running script for klonopin and xanax both my pdoc wants me settle in on one. On the one hand with the xanax at theraputic doses...I over sleep and have some slight delay in orgasm, with the klnopin I seem to jump right out of bed but have more distinguishable sexual dysfunction which again brings me back to seratonin......Any drug I have ever taken that effects serotonin has dulled my sex life significantly.........could ALL JUST BE CONJECTURE BUT IF THE SHOE FITS....?
gIL
Posted by Thrud on November 8, 2001, at 0:22:48
In reply to Re: klonopin and serotonin, posted by gilbert on November 7, 2001, at 12:28:34
Gil,
I understand your problem *perfectly*....
Tried Ativan???
I haven't, but it is one of the 'big three' benzos so it might be worth a shot. I am tempted to give it a try. I am on Xanax. After your posting I am not keen at all to try Klonopin; I can do without *another* disappointment. I MUST escape sexual dysfunction soon or I am afraid it will make me so angry I will turn to the 'dark side' of the force and use my powers for evil rather than for good!Best of luck to you.
Thrud
Posted by Rick on November 8, 2001, at 1:20:51
In reply to Re: klonopin and serotonin Gil, posted by Thrud on November 8, 2001, at 0:22:48
Klonopin has always increased my libido, but that may be less common than the sexual dysfunction -- not that either one is real common at typical doses for anxiety. I do seem to recall that during the period I was on 3.0 mg of Klonopin that Mr. Willy would do his job but would sometimes refuse to stand at attention as long as before.
I definitely had the pop-out-of-bed feeling with Klonopin when I was taking it by itself, in combo with BuSpar, and in combo with selegiline. That was a very pleasant surprise for me, a 180 degree turn. Since I started taking Serzone and Provigil along with the Klonopin, that situation has completely reversed big-time. I actually have two LOUD alarm clocks by my bed, and have slept through BOTH a few times. Once I'm up for 15 minutes, though, I'm ready to go.
> Gil,
>
> I understand your problem *perfectly*....
> Tried Ativan???
> I haven't, but it is one of the 'big three' benzos so it might be worth a shot. I am tempted to give it a try. I am on Xanax. After your posting I am not keen at all to try Klonopin; I can do without *another* disappointment. I MUST escape sexual dysfunction soon or I am afraid it will make me so angry I will turn to the 'dark side' of the force and use my powers for evil rather than for good!
>
> Best of luck to you.
>
> Thrud
>
Posted by gilbert on November 8, 2001, at 11:13:41
In reply to Re: klonopin and serotonin Gil, posted by Rick on November 8, 2001, at 1:20:51
Thrud,
Don't rule out the klonopin.....Rick is right on lower doses the sexual effect is much less. I may even try it agin at 1-2mg per day. The up and downs of the xanax get old. It is weird I would get right out of bed on the klonopin monotherapy as well. The xanax I have to wrestle to get out of bed....I just love to sleep on xanax.....not depressed just sleppy.
Gil
Posted by PaulB on November 11, 2001, at 3:02:57
In reply to Re: klonopin......Thrud, posted by gilbert on November 8, 2001, at 11:13:41
The themes written about in the posts on depression and Klonopin are issues that I have looked into in the past. I thought they were interesting to read and would add that Klonopin, I think, is different from Ativan, and other typical benzodiazepines with pro-GABA effects only because it is also an anticonvulsant, with marked sodium cannel blocking properties. This for a start can help to alleviate or worsen depression. In fact in the UK, Clonazepam is marketed almost exclusively as an anticonvulsant under the trade name Rivotril. Klonopin's seroternergic properies stem from its metabolite mCPP which is an agonist at the 5-HT2c receptors. This metabolite is metabolised by the CYP2D6 isoenzyme so Im sure it doesnt take long for the liver to metabolise it too quickly to have any effect. The only other reason I can think that Klonopin is likely to cause or worsen depression, more so than the other benzodiazepines is because of its high-potency. It very tightly binds to the bz receptors to exert its anti-anxiety action. This may cause a more severe dampening of the monoamines in the brain.
PaulB
Posted by Thrud on November 11, 2001, at 4:33:16
In reply to Re: klonopin......Thrud, posted by PaulB on November 11, 2001, at 3:02:57
> The themes written about in the posts on depression and Klonopin are issues that I have looked into in the past. I thought they were interesting to read and would add that Klonopin, I think, is different from Ativan, and other typical benzodiazepines with pro-GABA effects only because it is also an anticonvulsant, with marked sodium cannel blocking properties. This for a start can help to alleviate or worsen depression. In fact in the UK, Clonazepam is marketed almost exclusively as an anticonvulsant under the trade name Rivotril. Klonopin's seroternergic properies stem from its metabolite mCPP which is an agonist at the 5-HT2c receptors. This metabolite is metabolised by the CYP2D6 isoenzyme so Im sure it doesnt take long for the liver to metabolise it too quickly to have any effect. The only other reason I can think that Klonopin is likely to cause or worsen depression, more so than the other benzodiazepines is because of its high-potency. It very tightly binds to the bz receptors to exert its anti-anxiety action. This may cause a more severe dampening of the monoamines in the brain.
> PaulBHi Paul,
That's pretty interesting. How does Xanax differ in its mode of operation compared to Klonopin (Rivotril)? Xanax is supposed to be somewhat of an antidepressant: I presume it interacts with seratonin receptors somehow as well?
With regards to Klonopin being an anticonvulsant, I happen to be taking Lamictal as well as Xanax...but for its AD, not AC properties, so I doubt I could simply trade my Lamictal+Xanax combo in for Klonopin alone.BTW I read somewhere that Xanax is not available in the UK? If that is true you are missing out on a very effective anxiolytic (if very short acting).
Thanks.
Thrud
Posted by Dinah on November 11, 2001, at 8:34:24
In reply to Re: klonopin......PaulB, posted by Thrud on November 11, 2001, at 4:33:16
I hate to be over-simplistic, but I have found Klonopin to "cause" depression in me. However, I don't really think it causes it. I just think it unmasks it by removing the covering anxiety. Severe anxiety can keep you from realizing you are depressed.
Posted by Rick on November 11, 2001, at 16:27:25
In reply to Re: klonopin......PaulB Thrud, posted by Dinah on November 11, 2001, at 8:34:24
> I hate to be over-simplistic, but I have found Klonopin to "cause" depression in me. However, I don't really think it causes it. I just think it unmasks it by removing the covering anxiety. Severe anxiety can keep you from realizing you are depressed.
Dinah -
Interesting thought. It's usually believed that unrelenting anxiety, like chronic illnesses, can lead to depression -- especially in genetically predisposed individuals.
In a case which follows the pattern you described, the conclusion would seem to be that Klonopin should be continued because of its potent anti-anxiety properties, while an AD should be used for depression. The exception would be if you're one of those people whose anxiety responds markedly to an AD, in which case the Klonopin would be superfluous.
Rick
Posted by Rick on November 12, 2001, at 2:11:31
In reply to Re: klonopin......Thrud, posted by PaulB on November 11, 2001, at 3:02:57
Interesting perspective.
In the U.S. Klonopin/clonazepam's two formal indications are epilepsy (certain types) and panic disorder. Even though it was introduced as an anti-epileptic here years before the PD indication was added, I'd wager that PD and many off-label uses account for the lion's share of Klonopin scripts. This is because it's such a versatile and effective med, and also because there are so many new anti-convulsants which may hold some advantages in that arena.
As you may know, some of the many uses of Klonopin include several forms of anxiety (besides PD, it's especially effective for social anxiety, as I can personally attest), a sweeping variety of movement disorders, as an adjunctive med in unipolar and especially bipolar depression, as an adjunctive med for OCD (I have my doubts about efficacy there), and for pain management.
I was personally introduced to Klonopin's versatility in a quite unexpected way. Shortly before I started taking Klonopin for social anxiety in summer 1999, I had been planning to finally see a TMJ speciaist about the frequent facial and jaw pain that I had been suffering through for about ten years. (Over-the-counter pain medications had provided me zero benefit. My sister was treated for bruxism-induced TMJ with a bedtime splint, and my boss was treated for TMJ with three surgeries.) As time passed I realized that the unsually long facial-pain-free period that started about the time I began taking Klonopin for social anxiety seemed to have become permanent. Later I did a Medline search on TMJ and clonazepam, and sure enough there was a study that discussed how Klonopin effectively treated TMJ pain. Now that was certainly a very pleasant and unexpected "side effect"! I still have virtually no problem with facial pain, even though I'm only taking 1 mg/day of Klonopin.
BTW, apparently many benzos are used as anticonvulsants, but none of the other meds in this class seem to be as effective as Klonopin.
Rick
> The themes written about in the posts on depression and Klonopin are issues that I have looked into in the past. I thought they were interesting to read and would add that Klonopin, I think, is different from Ativan, and other typical benzodiazepines with pro-GABA effects only because it is also an anticonvulsant, with marked sodium cannel blocking properties. This for a start can help to alleviate or worsen depression. In fact in the UK, Clonazepam is marketed almost exclusively as an anticonvulsant under the trade name Rivotril. Klonopin's seroternergic properies stem from its metabolite mCPP which is an agonist at the 5-HT2c receptors. This metabolite is metabolised by the CYP2D6 isoenzyme so Im sure it doesnt take long for the liver to metabolise it too quickly to have any effect. The only other reason I can think that Klonopin is likely to cause or worsen depression, more so than the other benzodiazepines is because of its high-potency. It very tightly binds to the bz receptors to exert its anti-anxiety action. This may cause a more severe dampening of the monoamines in the brain.
> PaulB
Posted by PaulB on November 12, 2001, at 12:43:53
In reply to Re: klonopin......PaulB, posted by Thrud on November 11, 2001, at 4:33:16
>Hi Paul,
>
> That's pretty interesting. How does Xanax differ in its mode of operation compared to Klonopin (Rivotril)? Xanax is supposed to be somewhat of an antidepressant: I presume it interacts with seratonin receptors somehow as well?
> With regards to Klonopin being an anticonvulsant, I happen to be taking Lamictal as well as Xanax...but for its AD, not AC properties, so I doubt I could simply trade my Lamictal+Xanax combo in for Klonopin alone.
>
> BTW I read somewhere that Xanax is not available in the UK? If that is true you are missing out on a very effective anxiolytic (if very short acting).
>
> Thanks.
>
> ThrudXanax is very similar to Klonopin, the major difference being the longer half-life with the former. Xanax may exert ad effects by stimulating the release of norepinephrine indirectly because of its agonism at the bz site,i.e. it may decrease serotonin firing but consequently increase norepinephrine firing rate and turnover.
Perhaps Klonopin and Lamictal is worth a try. You would get a longer duration of anxiety relief with Klonopin and you could still use Lamictal for its AD effect if there were no known drug-drug interactions beytween the two.
PaulB
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