![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 25 of 25. This is the beginning of the thread.
Posted by bulldog2 on May 20, 2010, at 15:57:08
I found this on a forum. Does anyone care to chime in on wether this person's view on immipramine is based on sound science? Would these opinions apply to all the tcas as I am on clomipramine?
Posted by linkadge on May 20, 2010, at 18:05:53
In reply to Immipramine Causes Natural Endorphins to Drop, posted by bulldog2 on May 20, 2010, at 15:57:08
Not sure I follow, the study said that chronic treatment with the drug inhibited neutral endopeptidase. Nowhere does the study say this causes endorphins to drop.
It could be the other way around, perhaps increased opiate production is a consequence of remission, and that endopeptidase simply increases to metabolize the extra opiate production.
In this study, neutral endopeptidase actually lowers the levels of substance P. Substance P inhibitors have antidepressant potential. So perhaps the upregulation of neutral endopeptidase actually lowers upregulated levels of substance P in limbic regions.
http://gut.bmj.com/content/52/10/1457.abstract
Its complex and this guy is reading too much into things.
Linkadge
Posted by Laney on May 21, 2010, at 0:30:17
In reply to Re: Immipramine Causes Natural Endorphins to Drop, posted by linkadge on May 20, 2010, at 18:05:53
Bulldog,
How are you doing on the clomiprimine? How long have you been on it?
Thanks!
Laney
Posted by SLS on May 21, 2010, at 5:20:16
In reply to Re: Immipramine Causes Natural Endorphins to Drop, posted by linkadge on May 20, 2010, at 18:05:53
Thank you, Linkadge. I thought it was just me.
- Scott
> Not sure I follow, the study said that chronic treatment with the drug inhibited neutral endopeptidase. Nowhere does the study say this causes endorphins to drop.
>
> It could be the other way around, perhaps increased opiate production is a consequence of remission, and that endopeptidase simply increases to metabolize the extra opiate production.
>
> In this study, neutral endopeptidase actually lowers the levels of substance P. Substance P inhibitors have antidepressant potential. So perhaps the upregulation of neutral endopeptidase actually lowers upregulated levels of substance P in limbic regions.
>
> http://gut.bmj.com/content/52/10/1457.abstract
>
> Its complex and this guy is reading too much into things.
>
> Linkadge
>
>
>
>
>
Posted by linkadge on May 21, 2010, at 12:37:46
In reply to Re: Immipramine Causes Natural Endorphins to Drop, posted by SLS on May 21, 2010, at 5:20:16
I think the bottom line is whether the drug works or not.
If a patient's response to a drug is infact influenced by a study claiming good or bad effects, then it may not be a response at all.
Linkadge
Posted by bulldog2 on May 21, 2010, at 15:20:28
In reply to Re: Immipramine Causes Natural Endorphins to Drop, posted by linkadge on May 20, 2010, at 18:05:53
> Not sure I follow, the study said that chronic treatment with the drug inhibited neutral endopeptidase. Nowhere does the study say this causes endorphins to drop.
>
> It could be the other way around, perhaps increased opiate production is a consequence of remission, and that endopeptidase simply increases to metabolize the extra opiate production.
>
> In this study, neutral endopeptidase actually lowers the levels of substance P. Substance P inhibitors have antidepressant potential. So perhaps the upregulation of neutral endopeptidase actually lowers upregulated levels of substance P in limbic regions.
>
> http://gut.bmj.com/content/52/10/1457.abstract
>
> Its complex and this guy is reading too much into things.
>
> Linkadge
>
>
>
>
>LinkadgeThe guy makes the conclusions in the following paragraph. He does state the natural feel good transmitters would drop with immipramine. That was his conclusion from the study.
What is flawed in his logic? Here is paragraph.You state the opposite might actually be the case.
First, I would get off the imipramine as soon as possible. I was perplexed by your question and just did some considerable research on the effects of the drug. According to the following scientific study, for which I will post the link below, impramine significantly increases neutral endopeptidase activity in various parts of the brain, which is explained specifically in the article. The point here is that increased neutral endopeptidase activity increases the breakdown of the brain's natural painkillers, specifically enkephalins! No wonder you feel crappy! This is the opposite effect a recovering opiate addict would want, as our own endogenous, pain-killing enkephalins and endorphins have been already shut down by our opiate abuse. Further in another study I found, imipramine treatment in rats decreased tyrosine hydroxylase activity by 40% in the locus coreleus part of the brain. Tyrosine hydroxylase is the rate-limiting enzyme in the conversion of Tyrosine to the stimulatory neurotransmitters dopamine and norepinephrine,so basically the imipramine is significantly decreasing the levels of these "feel good" transmitters in your brain!
Posted by bulldog2 on May 21, 2010, at 15:43:10
In reply to Re: Immipramine Causes Natural Endorphins to Drop, posted by Laney on May 21, 2010, at 0:30:17
> Bulldog,
>
> How are you doing on the clomiprimine? How long have you been on it?
>
> Thanks!
>
> LaneyHi
I've been on clomipramine 50 mg a couple of months. I have to admidt that I feel good for such a low dose. I feel normal and I have used neurontin high dose or lyrica high dose for purpose of feeling sociable and relaxed. They also add to the ad response. It doesn't seem like any ad addresses sociability issues. I have generally gone to neurontin for that.Perhaps nardil would work better as an ad with pro social features.
The only down side is my prolactin has gone over the high range and my testosterone has gone to low normal. This is probably from the clomipramine and possibly the neurontin or lyrica. So I either have to dump the clomipramine or try a dopamine agonist such as miraprex or requip.It would be interesting to see if they work.
Posted by SLS on May 21, 2010, at 16:23:04
In reply to Re: Immipramine Causes Natural Endorphins to Drop, posted by bulldog2 on May 21, 2010, at 15:43:10
> > Bulldog,
> >
> > How are you doing on the clomiprimine? How long have you been on it?
> >
> > Thanks!
> >
> > Laney
>
> Hi
>
> I've been on clomipramine 50 mg a couple of months. I have to admidt that I feel good for such a low dose. I feel normal and I have used neurontin high dose or lyrica high dose for purpose of feeling sociable and relaxed. They also add to the ad response. It doesn't seem like any ad addresses sociability issues. I have generally gone to neurontin for that.Perhaps nardil would work better as an ad with pro social features.
> The only down side is my prolactin has gone over the high range and my testosterone has gone to low normal. This is probably from the clomipramine and possibly the neurontin or lyrica. So I either have to dump the clomipramine or try a dopamine agonist such as miraprex or requip.It would be interesting to see if they work.Why would you want to discontinue a drug that is working or introduce others unnecessarily? How do you know that you won't feel more social if you raise the dosage of clomipramine or give it more time to work? Is there any chance that the remaining social discomfort is psychological in origin?
What was your prolactin level when tested?
- Scott
Posted by bulldog2 on May 21, 2010, at 16:55:16
In reply to Re: Immipramine Causes Natural Endorphins to Drop » bulldog2, posted by SLS on May 21, 2010, at 16:23:04
> > > Bulldog,
> > >
> > > How are you doing on the clomiprimine? How long have you been on it?
> > >
> > > Thanks!
> > >
> > > Laney
> >
> > Hi
> >
> > I've been on clomipramine 50 mg a couple of months. I have to admidt that I feel good for such a low dose. I feel normal and I have used neurontin high dose or lyrica high dose for purpose of feeling sociable and relaxed. They also add to the ad response. It doesn't seem like any ad addresses sociability issues. I have generally gone to neurontin for that.Perhaps nardil would work better as an ad with pro social features.
> > The only down side is my prolactin has gone over the high range and my testosterone has gone to low normal. This is probably from the clomipramine and possibly the neurontin or lyrica. So I either have to dump the clomipramine or try a dopamine agonist such as miraprex or requip.It would be interesting to see if they work.
>
> Why would you want to discontinue a drug that is working or introduce others unnecessarily? How do you know that you won't feel more social if you raise the dosage of clomipramine or give it more time to work? Is there any chance that the remaining social discomfort is psychological in origin?
>
> What was your prolactin level when tested?
>
>
> - ScottInteresting point about giving the clomipramine more time to work or raising the dose. Never having been on an AD more than a couple months I guess I'm not familiar with the evolution of a complete remission. I know from using neurontin in the past about it's pro social attributes. So I threw it into the mix.
Is it a mistake to conclude after a couple of months that this is as good as it gets(drug wise? If you knew a drug was pro social are you saying you would not introduce it at this point with the clomipramine? Actually you do make a point about my being reclusive might have psychological origins. However after being this way for over 60 years I conclude I am pretty hard wired and not likely to change at this point. So I feel that I need a gaba drug in addition to any primary AD.
As for actually stopping clomipramine it is because of my high prolactin and clomipramine has a tendecy to raise it. High prolactin will kill libido. After starting the drug my libido dropped suddenly and that led me to test my prolactin.
prolactin range 2 to 18 and mine was 21. I would like to see it in the bottom half of the range. High prolactin lowers dopamine, testosterone and hgh.
So I have a choice as to dropping the drug or introducing a prolactin suppressing med which would be in the class of dopamine agonists.
Posted by SLS on May 21, 2010, at 18:01:26
In reply to Re: Immipramine Causes Natural Endorphins to Drop, posted by bulldog2 on May 21, 2010, at 16:55:16
Hi Bulldog2.
My best response to drug treatment took about three to four months to reach full remission. 50mg is a low dosage of clomipramine. I know you have some concerns regarding side effects. I wouldn't give up on clomipramine until you more fully explore its potential. See what you can tolerate. I don't know what to suggest regarding the prolactin. I was looking at the possibility of your adding mirtazapine to clomipramine to help with the prolactin and enhance the antidepressant effect. Too many drugs maybe.
- Scott
Posted by linkadge on May 21, 2010, at 18:45:11
In reply to Re: Immipramine Causes Natural Endorphins to Drop » linkadge, posted by bulldog2 on May 21, 2010, at 15:20:28
>The guy makes the conclusions in the following >paragraph. He does state the natural feel good >transmitters would drop with immipramine. That >was his conclusion from the study.
Yes, that was *his* conclusion from the study. This was not the conclusion of the study. There are likely other metabolic pathways for opiates. An alteration in one metabolic pathway does not really predict the actity of the substrate.
>What is flawed in his logic? Here is >paragraph.You state the opposite might actually >be the case.
Well you just can't conclude one thing from the other. Did the imipramine directly cause the endopeptidase to increase, or did the imipramine cause endorpins to rise which was compensated for by the increases in the endopeptidase. Even though one metabolic pathway for a neurotransmitter increases, does not necessarily mean that the neurotransmitter becomes depleted. It could simply be a result of enhanced opiate turnover. Perhaps opiate release that is enhanced by the imipramine with a corresponding increase in a metabolic pathway (i.e. increases functional activity of the opaites). If you take an SSRI, it has been shown that monoamine oxidase will increase. But, just because monoamine oxidase increases as a result of taking an SSRI, doesn't mean that serotonin levels are dropping as a result of taking an SSRI.
NRI's have an ability to prolong the activity of endorphins. So perhaps, the endopepidase is simply increasing as a homeostatic mechanism to correct for the inhibition a seperate metabolic pathway.
A seperate note. Some studies link *higher* opiate activity to depression! This study is entitled "overactive endorphin system linked to depression"
http://www.anxietyinsights.info/overactive_brain_endorphin_system_linked_to_depression.htm
So, perhaps the clinical effect is in part mediated by a decrease in endorphin levels.
The point I am trying to make, is the net effect is whether the drug works for you or not. Don't get all hung up on what brain chemical the drug tweaks, this is really inconsequential. Drugs tweak a lot of brain chemicals. What is the net effect for you?
Sure, if *you* feel crappy on the drug, then it is not right for you. Don't worry the shortsighted conlcusions that some nimrod comes to.
Linkadge
Posted by linkadge on May 21, 2010, at 18:53:12
In reply to Re: Immipramine Causes Natural Endorphins to Drop, posted by bulldog2 on May 21, 2010, at 16:55:16
I wouldn't just drop the clomipramine if its working for you. It sounds like you are getting pretty obsessed with the level of this chemical or that.
You could try dropping the clomipramine a little, but I wouldn't just drop it. You might try adding a dopamine agonist too as they can help certain forms of social phobia.
Are you able to exercise? What about some caffiene?
I felt pretty damn good on 25mg of clomipramine and morning coffee. The coffee ofset the sexual problems.
The neurotonin and lyrica could be affecting the hormones too.
Linkadge
Posted by bulldog2 on May 22, 2010, at 9:08:55
In reply to Re: Immipramine Causes Natural Endorphins to Drop, posted by linkadge on May 21, 2010, at 18:53:12
> I wouldn't just drop the clomipramine if its working for you. It sounds like you are getting pretty obsessed with the level of this chemical or that.
>
> You could try dropping the clomipramine a little, but I wouldn't just drop it. You might try adding a dopamine agonist too as they can help certain forms of social phobia.
>
> Are you able to exercise? What about some caffiene?
>
> I felt pretty damn good on 25mg of clomipramine and morning coffee. The coffee ofset the sexual problems.
>
> The neurotonin and lyrica could be affecting the hormones too.
>
> Linkadge
>
>Thanks for your input. Some excellent alternative conclusions of what the study could prove. This guy had the nerve to tell the previous poster to dump the imipramine and play God with someone's life.
I think the p-doc had mentioned requip if the prolactin is high. That is one hormone you don't want to be high. It can seriously cause a lowering cascade of other hormones. Also on some painkillers for sciatica and they may also be players in this high prolactin mess. So let's see what a dopamine agonist can do.
Posted by ed_uk2010 on May 22, 2010, at 18:36:57
In reply to Re: Immipramine Causes Natural Endorphins to Drop » linkadge, posted by bulldog2 on May 22, 2010, at 9:08:55
>So let's see what a dopamine agonist can do.
Dopamine agonists can cause very considerable adverse effects in some cases, including psychiatric reactions. Give that you prolactin elevation is marginal at most, I would be concerned that the side effects of a dopamine agonist might be greater than the benefits (if indeed there were any benefits). Just a word of caution!
Posted by bulldog2 on May 23, 2010, at 9:11:29
In reply to Re: Immipramine Causes Natural Endorphins to Drop » bulldog2, posted by ed_uk2010 on May 22, 2010, at 18:36:57
> >So let's see what a dopamine agonist can do.
>
> Dopamine agonists can cause very considerable adverse effects in some cases, including psychiatric reactions. Give that you prolactin elevation is marginal at most, I would be concerned that the side effects of a dopamine agonist might be greater than the benefits (if indeed there were any benefits). Just a word of caution!
>
>
>Thank you for the words of caution. I am aware that all these meds have the potential for side effects and in some cases very severe ones.That is probably true for every med I'm on. That being written one must balance risk versus reward.
That being written I have to look at the high prolactin issue. What are my options? I can ignore it. I can drop my meds. I can try a medication to combat it. By the way low normal testosterone in addition.
In spite of it(prolactin) being only a little high I consider it a serious issue. Symptoms I was experiencing led me to ask for the blood test. I come from the school of thought that values body symtpoms over lab tests. Even high normal prolactin can lead to a host of hormonal issues in men. Contrary to popular thought declining testosterone and climbing estradial may be the culprit in prostate cancer. As prolactin climbs hgh, testosterone and other hormones decline and estradial climbs.
So ignoring high prolactin is not an option. So now I can ditch my clomipramine which is working for depression or try an agonist. So with med side effects as a possible outcome I chose to try a dopamine agonist.If the sides are bad or the outcome not good I will drop the agonist(s) and probably discontinue the clomipramine.
Posted by linkadge on May 23, 2010, at 12:29:24
In reply to Re: Immipramine Causes Natural Endorphins to Drop, posted by bulldog2 on May 23, 2010, at 9:11:29
I wouldn't necessarily associate the clomipramine with everything wrong. The lyrica could be to blame.
Linkadge
Posted by bulldog2 on May 23, 2010, at 14:39:22
In reply to Re: Immipramine Causes Natural Endorphins to Drop, posted by linkadge on May 23, 2010, at 12:29:24
> I wouldn't necessarily associate the clomipramine with everything wrong. The lyrica could be to blame.
>
>
> Linkadge
So far I've found that opiates raise prolactin and I'm on them for sciatica and hip pain. Also ssris raise prolactin because of elevated serotonin. Apparently anything that raises serotonin depresses dopamine which raises prolactin. Googled lyrica and neurontin and nothing about prolactin. Anyhow p-doc wants to try requip and apparently it has some action on opiate receptors also. He wants me on 75 mg of clomipramine with a target of 100 mg. Tried 75mg last night and felt a big boost today. Hopefully will maintain it. Of all the tcas I've been on this is the easiest to tolerate.I would like to see big pharmaceutical firms work on the raised prolactin issue with ssris. Find a med to maintain dopamine levels and use that with ssris and other drugs that elevate serotonin. In the meantime educate doctors about the possible use of dopamine agonists for sexual problems.
I find it amazing that no one could forsee that ssris being so selective would not create some imbalance in the human body.
Posted by ed_uk2010 on May 23, 2010, at 15:01:56
In reply to Re: Immipramine Causes Natural Endorphins to Drop, posted by bulldog2 on May 23, 2010, at 9:11:29
>Symptoms I was experiencing led me to ask for the blood test.
I understand. Are you hoping that the dopamine agonist would help with sexual dysfunction?
Posted by bulldog2 on May 23, 2010, at 15:45:30
In reply to Re: Immipramine Causes Natural Endorphins to Drop » bulldog2, posted by ed_uk2010 on May 23, 2010, at 15:01:56
> >Symptoms I was experiencing led me to ask for the blood test.
>
> I understand. Are you hoping that the dopamine agonist would help with sexual dysfunction?
>
>
>Not dysfunction but rather lack of libido. I believe that agonists help stimulate libido.
Posted by ed_uk2010 on May 23, 2010, at 15:53:52
In reply to Re: Immipramine Causes Natural Endorphins to Drop, posted by bulldog2 on May 23, 2010, at 15:45:30
>I believe that agonists help stimulate libido.
Hypersexuality has been reported as a side effect of dopamine agonists when used to treat Parkinson's Disease.
You may find this interesting (but disturbing), if you have not read it already....
J Clin Psychopharmacol 2008
Evaluation of endocrine profile and hypothalamic-pituitary-testis axis in selective serotonin reuptake inhibitor-induced male sexual dysfunction.
PURPOSE: To evaluate endocrine profile and hypothalamic-pituitary-testis (HPT) axis in male depressed patients with selective serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction (SDF).
MATERIALS AND METHODS: Eighty-six fertile depressed male patients with SSRI-induced SDF, aged 18 to 50 years, were enrolled in the study (group 1). Sixty-two age-matched depressed fertile patients who currently receive one of the SSRIs but without SDF (group 2), and 68 age-matched healthy fertile men who had never received a psychiatric diagnosis (group 3) served as controls. Pretreatment evaluation included history and physical examination and International Index of Erectile Function. Two blood samples were drawn from each subject at 20-minute intervals for the determination of the resting levels of the following hormones: luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, prolactin, and estradiol. The HPT axis was also assessed using the gonadotropin-releasing hormone test.
RESULTS: The prevalence of hormonal abnormalities in groups 1, 2, and 3 were 83.7% (72), 51.6% (32), and 11.8% (7), respectively (P = 0.001 vs group 1 and 0.007 vs group 2). Compared with normal controls, the subjects taking SSRIs had significantly lower serum levels of LH, FSH, and testosterone. In addition, there were significantly decreased LH and FSH responses to gonadotropin-releasing hormone test in groups 1 and 2 compared with normal controls. Of patients in groups 1 and 2, 68 (79.1%) and 27 (43.5%) had elevated serum levels of prolactin (P = 0.0001 vs group 1 and 0.001 vs group 2).
CONCLUSIONS: Most depressed subjects taking SSRIs with and without SDF had diminished HPT axis function. This should be replicated in further studies.
Posted by bulldog2 on May 23, 2010, at 16:28:32
In reply to Re: Immipramine Causes Natural Endorphins to Drop » bulldog2, posted by ed_uk2010 on May 23, 2010, at 15:53:52
> >I believe that agonists help stimulate libido.
>
> Hypersexuality has been reported as a side effect of dopamine agonists when used to treat Parkinson's Disease.
>
> You may find this interesting (but disturbing), if you have not read it already....
>
> J Clin Psychopharmacol 2008
>
> Evaluation of endocrine profile and hypothalamic-pituitary-testis axis in selective serotonin reuptake inhibitor-induced male sexual dysfunction.
>
> PURPOSE: To evaluate endocrine profile and hypothalamic-pituitary-testis (HPT) axis in male depressed patients with selective serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction (SDF).
> MATERIALS AND METHODS: Eighty-six fertile depressed male patients with SSRI-induced SDF, aged 18 to 50 years, were enrolled in the study (group 1). Sixty-two age-matched depressed fertile patients who currently receive one of the SSRIs but without SDF (group 2), and 68 age-matched healthy fertile men who had never received a psychiatric diagnosis (group 3) served as controls. Pretreatment evaluation included history and physical examination and International Index of Erectile Function. Two blood samples were drawn from each subject at 20-minute intervals for the determination of the resting levels of the following hormones: luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, prolactin, and estradiol. The HPT axis was also assessed using the gonadotropin-releasing hormone test.
> RESULTS: The prevalence of hormonal abnormalities in groups 1, 2, and 3 were 83.7% (72), 51.6% (32), and 11.8% (7), respectively (P = 0.001 vs group 1 and 0.007 vs group 2). Compared with normal controls, the subjects taking SSRIs had significantly lower serum levels of LH, FSH, and testosterone. In addition, there were significantly decreased LH and FSH responses to gonadotropin-releasing hormone test in groups 1 and 2 compared with normal controls. Of patients in groups 1 and 2, 68 (79.1%) and 27 (43.5%) had elevated serum levels of prolactin (P = 0.0001 vs group 1 and 0.001 vs group 2).
> CONCLUSIONS: Most depressed subjects taking SSRIs with and without SDF had diminished HPT axis function. This should be replicated in further studies.
>
>Did not read that study but I'm more than aware of what ssris can do and why I don't like them. Apparently any ad that raises serotonin can have the same effect because clomipramine does raise prolactin. I've seen some studies that dopamine agonists can reverse ssri sexual disfunction and libido issues. We shall see.
Posted by linkadge on May 23, 2010, at 20:44:58
In reply to Re: Immipramine Causes Natural Endorphins to Drop » bulldog2, posted by ed_uk2010 on May 23, 2010, at 15:53:52
This is interesting *BUT*, a number of these hormonal alterations have been demonstrated in the depressed population in general.
They should have compared these patients to patients on SSRI's who did not experience significant sexual dysfunction, those on medications with other mechanisms, and depressed controlls not on medications.
Posted by linkadge on May 23, 2010, at 20:46:48
In reply to Re: Immipramine Causes Natural Endorphins to Drop, posted by bulldog2 on May 23, 2010, at 16:28:32
I have read studies where depressed patients not on medications have decreased prolactin - possibly due to serotonergic deficiancy.
This is why I just recomend lowering (not eliminating) the medication. You could also try augmenting with something like SAMe.
Linkadge
Posted by ed_uk2010 on May 24, 2010, at 14:58:45
In reply to Re: Immipramine Causes Natural Endorphins to Drop » ed_uk2010, posted by linkadge on May 23, 2010, at 20:44:58
>They should have compared these patients to.............those on medications with other mechanisms, and depressed controls not on medication.
Excellent point. The study certainly suggests that SSRIs affect sex hormones, but it doesn't prove anything. Would be interesting to compare levels of prolactin, LH and testosterone in unmedicated depressed men versus unmedicated non-depressed men. Annoyingly, because depression is such a 'broad' diagnosis, this type of study often doesn't come up with anything useful.
Posted by ed_uk2010 on May 24, 2010, at 14:59:49
In reply to Re: Immipramine Causes Natural Endorphins to Drop, posted by bulldog2 on May 23, 2010, at 16:28:32
>I've seen some studies that dopamine agonists can reverse ssri sexual disfunction and libido issues. We shall see.
Let us know. I will be very interested to hear how you do.
This is the end of the thread.
Psycho-Babble Medication | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
[email protected]
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.