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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 February 5, 2009, at 18:30:04
http://forum.mesomorphosis.com/mens-health-forum/ssri-hpta-disruption-134267207.html
Posted by Larry Hoover on February 5, 2009, at 20:14:44
In reply to SSRI Induced HPTA Disruption, posted by bulldog2 on February 5, 2009, at 18:30:04
Did you catch the obvious confound?
Groups 1 and 2 were not only using SSRIs, but they were also depressed. The comparison group had no psych diagnosis.
Lar
Posted by SLS on February 6, 2009, at 5:37:53
In reply to Re: SSRI Induced HPTA Disruption » bulldog2, posted by Larry Hoover on February 5, 2009, at 20:14:44
> Did you catch the obvious confound?
>
> Groups 1 and 2 were not only using SSRIs, but they were also depressed. The comparison group had no psych diagnosis.
>
> Lar
Thanks for pointing that out. I saw that immediately, but was too lazy to post about it.Silly.
Gotta pump them 'roids.
- Scott
Posted by linkadge on February 6, 2009, at 15:52:13
In reply to Re: SSRI Induced HPTA Disruption, posted by SLS on February 6, 2009, at 5:37:53
Yes, there is also the possibility that the SSRIs did infact act as a neuroendorine disruptor.
The neuroendocine effects of SSRI's have been noted in lab animals.
Linkadge
Posted by bulldog2 on February 6, 2009, at 17:00:09
In reply to SSRI Induced HPTA Disruption, posted by bulldog2 on February 5, 2009, at 18:30:04
There certainly is also anecdoctal evidence that ssris disrupt sexual function. Probably due to lowering of dopamine which is a key player in hormone production.
I read one study where a man on parnate actually had his dopamine and testosterone levels increase.
The question is would any of the dopamine agonists given with an ssri maintain dopamine function?
Posted by SLS on February 6, 2009, at 17:01:27
In reply to Re: SSRI Induced HPTA Disruption, posted by linkadge on February 6, 2009, at 15:52:13
> Yes, there is also the possibility that the SSRIs did infact act as a neuroendorine disruptor.
>
> The neuroendocine effects of SSRI's have been noted in lab animals.I don't doubt it. Do you recall which hormones were involved?
Thanks.
- Scott
Posted by SLS on February 6, 2009, at 17:49:39
In reply to Re: SSRI Induced HPTA Disruption, posted by bulldog2 on February 6, 2009, at 17:00:09
> There certainly is also anecdoctal evidence that ssris disrupt sexual function. Probably due to lowering of dopamine which is a key player in hormone production.
>
> I read one study where a man on parnate actually had his dopamine and testosterone levels increase.
>
> The question is would any of the dopamine agonists given with an ssri maintain dopamine function?I would like to know that, too. I hope some people who have tried it chime in. I think the problem with DA receptor agonists is that you get diminishing returns for depression over time. Perhaps this would not be true of sexual dysfunction. Apomorphine, a non-selective DA receptor agonist, almost got approved for erectile dysfunction.
I would think that Wellbutrin would be the first thing to try in combination with an SSRI to mitigate the reduction in dopaminergic neurotransmission. First and foremost, it does a good job to increase the probability of a robust antidepressant response. Secondly, for some people, it can completely reverse sexual dysfunction.
- Scott
Posted by bulldog2 on February 6, 2009, at 18:14:22
In reply to Re: SSRI Induced HPTA Disruption » bulldog2, posted by SLS on February 6, 2009, at 17:49:39
> > There certainly is also anecdoctal evidence that ssris disrupt sexual function. Probably due to lowering of dopamine which is a key player in hormone production.
> >
> > I read one study where a man on parnate actually had his dopamine and testosterone levels increase.
> >
> > The question is would any of the dopamine agonists given with an ssri maintain dopamine function?
>
> I would like to know that, too. I hope some people who have tried it chime in. I think the problem with DA receptor agonists is that you get diminishing returns for depression over time. Perhaps this would not be true of sexual dysfunction. Apomorphine, a non-selective DA receptor agonist, almost got approved for erectile dysfunction.
>
> I would think that Wellbutrin would be the first thing to try in combination with an SSRI to mitigate the reduction in dopaminergic neurotransmission. First and foremost, it does a good job to increase the probability of a robust antidepressant response. Secondly, for some people, it can completely reverse sexual dysfunction.
>
>
> - ScottI remember reading a book about ssris. Don't recall the title. The doc said that Wellbutrin doesn't do a good job reversing sexual problems.
Now the good thing is that he used buspar in conjunction with ssris and that in most cases restored sexual function. I believe that buspar acts as a block on one of the serotonin sites that causes the problem. Maybe I can find the book. But for him buspar and an ssri was the magic combo.
Posted by SLS on February 6, 2009, at 18:28:39
In reply to Re: SSRI Induced HPTA Disruption, posted by bulldog2 on February 6, 2009, at 18:14:22
> I remember reading a book about ssris. Don't recall the title. The doc said that Wellbutrin doesn't do a good job reversing sexual problems.
>
> Now the good thing is that he used buspar in conjunction with ssris and that in most cases restored sexual function. I believe that buspar acts as a block on one of the serotonin sites that causes the problem. Maybe I can find the book. But for him buspar and an ssri was the magic combo.I'd love to know which receptor that is. Is the combo good for the depressive disorder itself? Does Buspar make the antidepressant work better?
- Scott
Posted by bulldog2 on February 6, 2009, at 19:34:39
In reply to Re: SSRI Induced HPTA Disruption » bulldog2, posted by SLS on February 6, 2009, at 18:28:39
> > I remember reading a book about ssris. Don't recall the title. The doc said that Wellbutrin doesn't do a good job reversing sexual problems.
> >
> > Now the good thing is that he used buspar in conjunction with ssris and that in most cases restored sexual function. I believe that buspar acts as a block on one of the serotonin sites that causes the problem. Maybe I can find the book. But for him buspar and an ssri was the magic combo.
>
> I'd love to know which receptor that is. Is the combo good for the depressive disorder itself? Does Buspar make the antidepressant work better?
>
>
> - ScottHere's a link on buspar
http://en.wikipedia.org/wiki/Buspirone
The book is Beyond Prozac by Michael Norden
He claims
1. buspar augnments ad effect of prozac.
2. lessons side effect of prozac
3. lessons sexual sides in 70% of prozac usesProbably due to partial agonist effect...see wikipedia that blocks certain serotonin receptors that cause anxiety and sexual sides
Posted by bulldog2 on February 6, 2009, at 19:46:04
In reply to Re: SSRI Induced HPTA Disruption, posted by bulldog2 on February 6, 2009, at 19:34:39
> > > I remember reading a book about ssris. Don't recall the title. The doc said that Wellbutrin doesn't do a good job reversing sexual problems.
> > >
> > > Now the good thing is that he used buspar in conjunction with ssris and that in most cases restored sexual function. I believe that buspar acts as a block on one of the serotonin sites that causes the problem. Maybe I can find the book. But for him buspar and an ssri was the magic combo.
> >
> > I'd love to know which receptor that is. Is the combo good for the depressive disorder itself? Does Buspar make the antidepressant work better?
> >
> >
> > - Scott
>
> Here's a link on buspar
>
> http://en.wikipedia.org/wiki/Buspirone
>
> The book is Beyond Prozac by Michael Norden
>
> He claims
>
> 1. buspar augnments ad effect of prozac.
> 2. lessons side effect of prozac
> 3. lessons sexual sides in 70% of prozac uses
>
> Probably due to partial agonist effect...see wikipedia that blocks certain serotonin receptors that cause anxiety and sexual sidesDon't know if it can be taken with an maoi
Posted by SLS on February 6, 2009, at 20:11:14
In reply to Re: SSRI Induced HPTA Disruption, posted by bulldog2 on February 6, 2009, at 19:34:39
> Here's a link on buspar
>
> http://en.wikipedia.org/wiki/Buspirone
>
> The book is Beyond Prozac by Michael Norden
>
> He claims
>
> 1. buspar augnments ad effect of prozac.
> 2. lessons side effect of prozac
> 3. lessons sexual sides in 70% of prozac uses
>
> Probably due to partial agonist effect...see wikipedia that blocks certain serotonin receptors that cause anxiety and sexual sides
One thing often overlooked with buspirone is that its metabolite, 1PP, is a potent NE alpha-2 antagonist - just like Remeron. I can't imagine that this wouldn't add to the augmenting utility of this drug.Thanks for the link, by the way.
- Scott
Posted by linkadge on February 7, 2009, at 7:23:17
In reply to Re: SSRI Induced HPTA Disruption » bulldog2, posted by SLS on February 6, 2009, at 17:49:39
>I think the problem with DA receptor agonists is >that you get diminishing returns for depression >over time
I think that might be more true for people using DA agonist as monotherapy. I know of two people augmenting SSRI's with a DA agonist and both have had long term sucess. I know thats not proof but..
Linkadge
Posted by linkadge on February 7, 2009, at 7:30:39
In reply to Re: SSRI Induced HPTA Disruption, posted by bulldog2 on February 6, 2009, at 18:14:22
I think that buspar has a better track record of treating female sexual dysfunction. Apparently 5-ht1a agonists are aphrodesiacs for women.
Being essentially bisexual myself, I have noticed that some drugs significantly enhance my desire for one gender or the other. The SSRI's definately make me more prefer males while dopaminergics the opposite.
Not that I want to get into details, but I can't help but think that I have intiated some of this by my adolecent use of psychiatric medications and possible hormone disruptions that may have caused.
Linkadge
Posted by SLS on February 7, 2009, at 8:28:35
In reply to Re: SSRI Induced HPTA Disruption, posted by linkadge on February 7, 2009, at 7:23:17
> >I think the problem with DA receptor agonists is >that you get diminishing returns for depression >over time
>
> I think that might be more true for people using DA agonist as monotherapy. I know of two people augmenting SSRI's with a DA agonist and both have had long term sucess. I know thats not proof but..I always take anecdotal stuff seriously, depending on the source. This is actually big news as far as I'm concerned.
Do you recall which drugs, and at what dosages.
- Scott
Posted by bulldog2 on February 7, 2009, at 9:11:20
In reply to Re: SSRI Induced HPTA Disruption » linkadge, posted by SLS on February 7, 2009, at 8:28:35
> > >I think the problem with DA receptor agonists is >that you get diminishing returns for depression >over time
> >
> > I think that might be more true for people using DA agonist as monotherapy. I know of two people augmenting SSRI's with a DA agonist and both have had long term sucess. I know thats not proof but..
>
> I always take anecdotal stuff seriously, depending on the source. This is actually big news as far as I'm concerned.
>
> Do you recall which drugs, and at what dosages.
>
>
> - ScottScott are you contemplating a change to an ssri from parnate?
Posted by SLS on February 7, 2009, at 13:16:05
In reply to Re: SSRI Induced HPTA Disruption, posted by bulldog2 on February 7, 2009, at 9:11:20
> > > >I think the problem with DA receptor agonists is >that you get diminishing returns for depression >over time
> > >
> > > I think that might be more true for people using DA agonist as monotherapy. I know of two people augmenting SSRI's with a DA agonist and both have had long term sucess. I know thats not proof but..
> >
> > I always take anecdotal stuff seriously, depending on the source. This is actually big news as far as I'm concerned.
> >
> > Do you recall which drugs, and at what dosages.
> >
> >
> > - Scott
>
> Scott are you contemplating a change to an ssri from parnate?
LOL No friggin' way!:-)
But seriously, at this point, the Parnate seems to be doing its job. It's just that my doctor is playing it very conservatively with our titration of desipramine. I am still significantly underdosed, so I am having a difficult time with things.
Thanks for asking Bulldog.
Obviously, I have nothing against SSRIs unless they have something against me (tolerability issues). I have been lucky that they all were tolerable, just not effective.
- Scott
Posted by linkadge on February 7, 2009, at 13:23:35
In reply to Re: SSRI Induced HPTA Disruption » linkadge, posted by SLS on February 7, 2009, at 8:28:35
Yes one is a middle aged man on sertraline and mirapex and the other is younger lady on paroxetine CR and mirapex. The man was originally on TCA's but had to change because of a cardiac issue.
In both cases, the SSRI alone was not controlling depression. Both the man and women stopped the SSRI because the mirapex produced such a rapid improvement. After relapsing, the SSRI was reinitiated and both are (apparently) doing well. They have been doing well for over a year.
The psychiatrist in my hometown is into using DA agonists for augmentation.
One study showed that the SSRI fluoextine can prevent tollerance to morphine. I am wondering if the SSRI's can act as anti-tollerance agents towards dopaminergics.
Linkadge
Posted by bulldog2 on February 7, 2009, at 13:28:38
In reply to Re: SSRI Induced HPTA Disruption, posted by linkadge on February 7, 2009, at 13:23:35
> Yes one is a middle aged man on sertraline and mirapex and the other is younger lady on paroxetine CR and mirapex. The man was originally on TCA's but had to change because of a cardiac issue.
>
> In both cases, the SSRI alone was not controlling depression. Both the man and women stopped the SSRI because the mirapex produced such a rapid improvement. After relapsing, the SSRI was reinitiated and both are (apparently) doing well. They have been doing well for over a year.
>
> The psychiatrist in my hometown is into using DA agonists for augmentation.
>
> One study showed that the SSRI fluoextine can prevent tollerance to morphine. I am wondering if the SSRI's can act as anti-tollerance agents towards dopaminergics.
>
> Linkadge
>
>
>
>How about an ssri plus ritalin?
Posted by SLS on February 7, 2009, at 13:31:58
In reply to Re: SSRI Induced HPTA Disruption, posted by linkadge on February 7, 2009, at 13:23:35
> Yes one is a middle aged man on sertraline and mirapex and the other is younger lady on paroxetine CR and mirapex. The man was originally on TCA's but had to change because of a cardiac issue.
>
> In both cases, the SSRI alone was not controlling depression. Both the man and women stopped the SSRI because the mirapex produced such a rapid improvement. After relapsing, the SSRI was reinitiated and both are (apparently) doing well. They have been doing well for over a year.
>
> The psychiatrist in my hometown is into using DA agonists for augmentation.
>
> One study showed that the SSRI fluoextine can prevent tollerance to morphine. I am wondering if the SSRI's can act as anti-tollerance agents towards dopaminergics.
>
> Linkadge
>
>
>
>
Hmm. Interesting thought. Perhaps the SSRI is DA sparing (inhibition of release) and prevents a saturation of receptors, so there isn't as much downregulation from DA agonist exposure.The more I think about it, the more I think you might have something here.
- Scott
Posted by linkadge on February 7, 2009, at 17:43:27
In reply to Re: SSRI Induced HPTA Disruption, posted by SLS on February 7, 2009, at 13:31:58
SSRI's tend to increase the respsivness of dopamine d3 receptors. 3 week treatemtns with SSRI's, TCA's and ECT increase d3 receptor mRNA in certain limbic brain regions. Whether this is (as some suggest) a common target of antidepressive agents or simply an upregulation in responce to decrease dopaminergic function is unknown.
If the d3 receptors are a common target of AD agents, then perhaps mirapex's AD effect is a result of its potent d3 receptor agonism. It may be, as you suggest, that repeated exposure leads to desensiziaton and thus loss of clinical effect. Perhaps SSRI's can compensate by upregulating the receptors. BDNF is known to regulate the expression of the d3 receptors. Injections of BDNF may exert their AD effect by increaseing the responsivity of the d3 receptors. There is also the possibility that AD's increase d3 receptor expression by increasing BDNF levels and not by a dopamine supersensitivity responce to a serotonin boost.
A futher point of interest is this. As I mentioned in a previous post, certain AD agents (such as NMDA antagonists) don't increase BDNF levels. But it is interesting to note that NMDA antagonists work to functionally agonize d3 receptors. Infact, all of the behavioral effects of high dose NDMA antagonists can be blocked selectively by d3 receptor antagonists.
In other words, NMDA antagonists might exert their rapid acting AD effects by directly activating d3 receptor systems, wherease conventional AD agnets work by upregulating d3 receptor expression via BDNF enhancement.
Certain NMDA antagonists like zinc, also increase BDNF. Adding zinc to subtheraputic doses of TCA's produces AD effects in animals.
Linkadge
Posted by garnet71 on February 7, 2009, at 19:58:19
In reply to Re: SSRI Induced HPTA Disruption, posted by linkadge on February 7, 2009, at 17:43:27
Geez.how do you know all this stuff???
Posted by bulldog2 on February 8, 2009, at 7:45:33
In reply to Re: SSRI Induced HPTA Disruption, posted by linkadge on February 7, 2009, at 17:43:27
> SSRI's tend to increase the respsivness of dopamine d3 receptors. 3 week treatemtns with SSRI's, TCA's and ECT increase d3 receptor mRNA in certain limbic brain regions. Whether this is (as some suggest) a common target of antidepressive agents or simply an upregulation in responce to decrease dopaminergic function is unknown.
>
> If the d3 receptors are a common target of AD agents, then perhaps mirapex's AD effect is a result of its potent d3 receptor agonism. It may be, as you suggest, that repeated exposure leads to desensiziaton and thus loss of clinical effect. Perhaps SSRI's can compensate by upregulating the receptors. BDNF is known to regulate the expression of the d3 receptors. Injections of BDNF may exert their AD effect by increaseing the responsivity of the d3 receptors. There is also the possibility that AD's increase d3 receptor expression by increasing BDNF levels and not by a dopamine supersensitivity responce to a serotonin boost.
>
> A futher point of interest is this. As I mentioned in a previous post, certain AD agents (such as NMDA antagonists) don't increase BDNF levels. But it is interesting to note that NMDA antagonists work to functionally agonize d3 receptors. Infact, all of the behavioral effects of high dose NDMA antagonists can be blocked selectively by d3 receptor antagonists.
>
> In other words, NMDA antagonists might exert their rapid acting AD effects by directly activating d3 receptor systems, wherease conventional AD agnets work by upregulating d3 receptor expression via BDNF enhancement.
>
> Certain NMDA antagonists like zinc, also increase BDNF. Adding zinc to subtheraputic doses of TCA's produces AD effects in animals.
>
>
> Linkadge
>
>
>
>
>
>So do you believe the addition of a dopamine agonist to a ssri would prevent hormonal disruption.
Posted by SLS on February 8, 2009, at 8:56:19
In reply to Re: SSRI Induced HPTA Disruption, posted by linkadge on February 7, 2009, at 17:43:27
> SSRI's tend to increase the respsivness of dopamine d3 receptors. 3 week treatemtns with SSRI's, TCA's and ECT increase d3 receptor mRNA in certain limbic brain regions. Whether this is (as some suggest) a common target of antidepressive agents or simply an upregulation in responce to decrease dopaminergic function is unknown.
If desipramine, which is practically specific for NET, were to produce the same upregulation of D3 receptors, then I would say that there is something going on there other than compensations for changes in synaptic concentrations of ligand. Apparantly, it does. So, I think your inclinations to ascribe a persistent augmentative boost to Mirapex when combined with many different antidepressants are well supported.
This is probably an abstract that you have already come across:
- Scott-------------------------------------------------
1: Mol Psychiatry. 2000 Jul;5(4):378-88.Links
Selective increase of dopamine D3 receptor gene expression as a common effect of chronic antidepressant treatments.
Lammers CH, Diaz J, Schwartz JC, Sokoloff P.Laboratoire de Physiologie, Université René Descartes, 4 Avenue de l'Observatoire, 75006 Paris, France.
The mesolimbic dopaminergic system is a neuroanatomical key structure for reward and motivation upon which previous studies indicated that antidepressant drugs exert a stimulatory influence, via still unknown neurobiological mechanisms. Here we examined the effects of chronic administration of antidepressants of several classes (amitriptyline, desipramine, imipramine, fluoxetine and tranylcypromine) and repeated electroconvulsive shock treatments (ECT) on dopamine D3 receptor expression in the shell of the nucleus accumbens, a major projection area of the mesolimbic dopaminergic system. Short-term drug treatments had variable effects on D3 receptor mRNA expression. In contrast, treatments for 21 days (with all drugs except fluoxetine) significantly increased D3 receptor mRNA expression in the shell of nucleus accumbens; D3 receptor binding was also significantly increased by amitriptyline or fluoxetine after a 42-day treatment. ECT for 10 days increased D3 receptor mRNA and binding in the shell of nucleus accumbens. D1 receptor and D2 receptor mRNAs were increased by imipramine and amitriptyline, but not by the other treatments. The time-course of altered D3 receptor expression, in line with the delayed clinical efficiency of antidepressant treatment, and the fact that various antidepressant drugs and ECT treatments eventually produced the same effects, suggest that increased expression of the D3 receptor in the shell of nucleus accumbens is a common neurobiological mechanism of antidepressant treatments, resulting in enhanced responsiveness to the mesolimbic dopaminergic system.
Posted by linkadge on February 8, 2009, at 17:08:29
In reply to Re: SSRI Induced HPTA Disruption, posted by bulldog2 on February 8, 2009, at 7:45:33
>So do you believe the addition of a dopamine >agonist to a ssri would prevent hormonal >disruption
Oh yeah, thats what we're talking about. I don't have a clue.
Linkadge
This is the end of the thread.
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