![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 40 to 64 of 64. Go back in thread:
Posted by ggggg123 on October 27, 2010, at 0:47:31
In reply to Re: To Cheryl-Lynne Anhedonia » ggggg123, posted by Conundrum on October 26, 2010, at 9:18:04
I know what you mean about going back on the ssri, that does seem to help, but its not ideal i want to be free of this stuff forever!! lol,I think most people will recover from ssri induced apathy, I have been going through it for a few months now, since discontinuing citalopram, which I had taken for 9 months. I think it takes a long time and exercise can be helpful. da agonists could be helpful in providing us with motivation, which may help get the blood and dopamine flowing in our brains again, thats my theory. The reason da agonists could be useful is the fact they can be used longterm. I think we need a boost to get fully back into life then the body may take over. We need to keep a positive attitude any negativety only inhibits recovery, although I know it is hard though. Anyways I'm gonna give very low dose Bromocriptine a good go over a long period of time along with some good lifestyle choices and see if I get anywhere. Also hopefully a very low dose of a dopamine agonist should'nt be very stimulating like amphetamines, so it may help restore interest in life without causing anxiety and restlessness.
Posted by Conundrum on October 27, 2010, at 10:04:13
In reply to Re: To Cheryl-Lynne Anhedonia » Conundrum, posted by ggggg123 on October 27, 2010, at 0:47:31
Let us know how it goes. I've found drugs that work strongly increasing dopamine to be hard edged. They didn't seem to increase motivation the way a low dose of prozac dose, or sensation and color the way pristiq weakly did, before it stopped working.
Posted by ggggg123 on October 27, 2010, at 23:30:42
In reply to Re: To Cheryl-Lynne Anhedonia » ggggg123, posted by Conundrum on October 27, 2010, at 10:04:13
I will do, I've just started the bromo, feeling a bit strange, everything's abit dark lol, but I'm gonna stick with it long term to see if this clears. I've never tried prozac, but I have taken citalopram, I hear prozac has some affinity for norep and dop, where as citalopram has non, are you still taking the low dose prozac? do you think its a good long term strategy? one other option I was considering is using benztropine, although it is an anticholinergic and will have the dry mouth side effect, it is also a dopamine reuptake inhibitor, which maybe more beneficial than a direct agonist, but unfortunately I think it may have been withdrawn in the uk, but I think its still available online.
Posted by Conundrum on October 28, 2010, at 0:07:27
In reply to Re: To Cheryl-Lynne Anhedonia » Conundrum, posted by ggggg123 on October 27, 2010, at 23:30:42
I'm not on the low dose prozac now, but if I can't find anything that works better, I would consider taking it again. Its good for motivation and drive, but it didn't totally hit anhedonia at the core. I think Pristiq was starting to hit anhedonia, but it just stopped working and felt like an SSRI. I'd consider low dose prozac with an NRI in the future. I think it could be a good longterm strategy if it works, but once you're on it for a long time, don't stop it.
I'm skeptical about DA agonists helping with anhedonia, or drugs that are mainly dopaminergic in general. I'm sure they work for some, but there is more to the brain than low dopamine = anhedonia. Unfortunately there are too many sites that say dopamine is the pleasure chemical, but its not that simple. All the other neurotransmitters carry your emotions too. For example, mice unable to synthesize norepinephrine cannot distinguish between a pleasurable drug like cocaine from an unpleasant drug Lithium cloride. So without adequate norepinephrine, no drug reward, atleast for mice. The same is probably true with serotonin and endorphins.
Also people feel flat on drugs that increase dopamine strongly, like parnate and ritalin. Don't believe me? Look it up, tons of people saying they feel less creative on ritalin or people feeling flat on parnate.
Some people, with anhedonia, do better on drugs like nardil or even dexedrine that do increase dopamine but also have stronger effects on other neurotransmitters when compared to ritalin and parnate, respectively. Some don't.
There was one person on this board with anhedonia, who was taking selegine, adderall, DLPA and maybe one other dopaminergic and had no relief from anhedonia. I'm not trying to discourage you, but there is a reason DA agonists aren't marketed as antidepressants, so if it doesn't help, you may want to consider other options. As you might be able to tell, my anhedonia has not responded well to dopaminergic drugs. Some people do. I think a DA agonist would tell you whether you are on the right path or not. I mean what can tell you whether or not you need dopamine more, than a drug that acts directly on dopamine receptors and its effects are even more potent than the natural ligand.
I really look forward to hearing how you respond to it. I think it is interesting.
Posted by ggggg123 on October 28, 2010, at 5:52:30
In reply to Re: To Cheryl-Lynne Anhedonia » ggggg123, posted by Conundrum on October 28, 2010, at 0:07:27
I agree with you that theres much more to it than dopamine, at least the dopamine that drugs provide, I think the only way is for the brain to normalize. But its very hard to succeed as drugs which increase one neurotransmitter often attenuate another, I think this is why we end up with anhedonia after taking ssri's. I agree that low dose should be the best policy in theory, still allowing the brain some natural input. Theres a new drug out here in the uk, called agomelatine, which indirectly increases norep and dop but not serotonin, also high dose venlafaxine is meant to have high affinity for norep and it is also dopaminergic (although I don't think going on a high dose ad is a great option), agomelatine might be useful though. I think norepinephrine and dopamine are very sensitive and respond to subtle changes, this is why stimulants and noradrenergic ad's don't make good ad's, as although it is well known they play a role in the aetiology of depression, these drugs can often increase dopamine and norep beyond normal levels, inducing mania and causing anxiety, basically theres a only a very thin line, between depression, feeling normal and mania. SSRI's can be beneficial as serotonin can be increased fairly substantially and the worst symptom you will experience is anhedonia,unlike dopaminergic drugs which are not ideal to dole out to the public as they could make you a threat to society or nervous wreck . There is virtually no ad's that increase dopaminergic output, just a few that have a slight disinhibiting affect and very slight reuptake inhibition.
My theory is to increase the brains dopamine very very slightly, hopefully acting as a probe to help initiate the flow of da and to also help motivate one back into an active life which inturn could prove very beneficial to the mind. I think its alot of trial and error to find something that helps, but I am positive that something will. I will keep you updated on the bromo and my progress. Cheers.
Posted by ggggg123 on October 29, 2010, at 9:45:46
In reply to Re: To Cheryl-Lynne Anhedonia » ggggg123, posted by Conundrum on October 28, 2010, at 0:07:27
day 3 of my new regime, I am taking 10/100mg carbidopa/levodopa and 1.25mg bromocriptine everyday, I am feeling slightly improved, more energy, more excited about life, it definitely affects my anhedonia, I do think for most people that dopamine is the main culprit in their anhedonia, its just many dopaminergic drugs don't pinpoint the pleasure centres, thats where exercise and being active comes in to help get some natural dopamine which is by far the best. But to beat anhedonia i do think dopaminergic medicine is the only method to speed up the process and help get back to life. I know you might say taking levodopa is'nt sustainable, but its very low dose just to give me a kick start and some people have taken it continuously for over 10 years. So basically after 3 days I am feeling alot better, I keep getting urges of excitement to go and get my life back. I hope the pattern continues and I see more improvement over the coming weeks.
Posted by Conundrum on October 29, 2010, at 11:47:37
In reply to Re: To Cheryl-Lynne Anhedonia, posted by ggggg123 on October 29, 2010, at 9:45:46
Wow that sounds great!
Like I had said, if one thing would tell you if dopamine would help, its a direct agonist. How did you manage to get a hold of those drugs?
Right now I'm trying tianeptine, which is a serotonin reuptake enhancer. One of the results of increasing serotonin reuptake is dopamine increases. But I doubt it is as strong as taking a direct agonist or supplementing with those forms of dopa.
Posted by ggggg123 on October 29, 2010, at 23:43:30
In reply to Re: To Cheryl-Lynne Anhedonia » ggggg123, posted by Conundrum on October 29, 2010, at 11:47:37
I got hold of the drugs over the internet theyre from india, one is made by sun pharmaceuticals a generic and the other is brand gsk, its not all plain sailing I'm feeling abit nauseous, not so good today, I found this on the internet:
When only 5-HTP is used in treatment, 5-HTP depletes dopamine, norepinephrine, and epinephrine levels. When dopamine levels drop low enough, 5-HTP becomes ineffective and the side effects of dopamine depletion occur. 5-HTP and dopa must be provided in proper balance to affect optimal serotonin dopamine balance. For years doctors have depleted serotonin levels in Parkinson's Disease patient by prescribing only levodopa
with no properly balance serotonin precursors. People taking 5-HTP never realize that when the 5-HTP does not work or quits working it is because the serotonin dopamine system is not in balance.I'm not sure whether to add a very low dose ssri. Sinemet (carbidopa/levodopa) is a very cheap drug you can get it off many websites, I think its making me feel abit sick though so not sure wether to continue taking it. But i think the bromo is quite good and can be taken longterm.
But overall I think its about getting the right serotonin norep and dopamine balance, maybe by taking something that regulates all of them long term, as ssri's only regulate one, it seems that for a subgroup of people this has a negative effect on dopamine and norepinephrine so aslong as we start raising the norep and dopamine we should be on to a winner, I am thinking of adding imipramine or reboxetine.
Which meds are you taking at the moment? are you taking remeron, I found remeron really good for the first few weeks then its stopped working and only worked 20% of the time.
Posted by Conundrum on October 29, 2010, at 23:52:24
In reply to Re: To Cheryl-Lynne Anhedonia, posted by ggggg123 on October 29, 2010, at 23:43:30
I found the same quick poopout with remeron as well. I'm probably gonna be coming off it. I just came off lamictal. I just started tianeptine today, which decreases serotonin and increases dopamine.
Posted by ggggg123 on October 29, 2010, at 23:54:10
In reply to Re: To Cheryl-Lynne Anhedonia, posted by ggggg123 on October 29, 2010, at 23:43:30
sorry I misread your post, I see you are taking tianeptine not mirtazapine, did mirtazapine stop working? I wanted to try tianeptine,its got some good reviews, I really wanted to try amineptine, but its completely banned and the one source available is ridiculously expensive. I think I made the mistake of taking high dose ssri for a while, which seemed to cause this problem, I have heard on the tips part of this website of psychiatrists using ssri's with da agonist and having excellent results.
Posted by Conundrum on October 30, 2010, at 0:11:56
In reply to Re: To Cheryl-Lynne Anhedonia, posted by ggggg123 on October 29, 2010, at 23:54:10
> sorry I misread your post, I see you are taking tianeptine not mirtazapine, did mirtazapine stop working? I wanted to try tianeptine,its got some good reviews, I really wanted to try amineptine, but its completely banned and the one source available is ridiculously expensive. I think I made the mistake of taking high dose ssri for a while, which seemed to cause this problem, I have heard on the tips part of this website of psychiatrists using ssri's with da agonist and having excellent results.
I'm taking mirtazapine and tianeptine right now.
My anhedonia started after stopping prozac. Go figure. I felt great on it.
Posted by ggggg123 on October 30, 2010, at 13:01:16
In reply to Re: To Cheryl-Lynne Anhedonia, posted by Conundrum on October 30, 2010, at 0:11:56
heres an extract from dr bobs tips page:
From: MKomrad@aol.com
Date: Wed, 7 Feb 1996 21:32:19 -0800
Subject: Bromocriptine for SSRI poop outI have had a very similar experience. This is now spoken about in many psychopharm conferences as "poop out." In my experience it sometimes happens as late as 3 years into an SSRI (typically Prozac, since it's been around the longest), in as many as 20% of patients.
What is to be done? There is talk among "poop out" veterans of adding bromocriptine since there is speculation that this might be a dopaminergic depletion phenomenon. People have said this helps, but I haven't used it yet myself
--------------------------------------------------did you not poop out on prozac? maybe low dose prozac with a dopaminergic could be a good strategy. I think it is worse when withdrawaing from the drug. How was the aripiprazole, that is supposed to increase dopamine, did you feel any benefit? cheers
Posted by Conundrum on October 30, 2010, at 15:19:53
In reply to Re: To Cheryl-Lynne Anhedonia, posted by ggggg123 on October 30, 2010, at 13:01:16
> did you not poop out on prozac? maybe low dose prozac with a dopaminergic could be a good strategy. I think it is worse when withdrawaing from the drug. How was the aripiprazole, that is supposed to increase dopamine, did you feel any benefit? cheersHi again,
Well what happened with me and prozac was that I had been taking it successfully for years and while studying music in boston, I stopped taking it cuz I ran out. Being me, I didn't take the time to get it filled and, I remember my pdoc, saying because it has a long half life, you don't need to ween off of it. So after taking it for 4.5 years I stopped it abruptly. Akathesia, the feeling to constantly keep moving, anhedonia, and anxiety ensued. I saw a doctor in Boston and got a new script and when I went back on it I felt like I was in another world. I just felt awful, although I think the akathesia went away, the anhedonia stayed.
So if there is a moral to the story, its that if you find something that works, don't stop it, cuz it might not work again! AND don't stop psych drugs abruptly, even if its got a 2 week half life.
Now I can take a low dose, 5mg every other day, and get some motivation. I've tried adding ritalin to it, but it did not help. I would think ritalin would be one of the more powerful dopaminergics around. (Ritalin does help me if I'm really sad, not anhedonic. It has a very artificial rescue effect.)
Given that Pristiq added some "color" to my world, I tend to think I have a norepinephrine deficiency. Pristiq does not have the DRI effects that the parent drug, Effexor has.
Aripiprazole, hmm. At 2 mg I noticed a feeling that I had a lot of energy and wanted to get things done, similar to a cup of coffee, but this feeling lasted for a couple days. I noticed another boost at 2.5 mg, and then a fade. At 5mg I felt worse, it just made my head feel weird, I went back to 2.5 and felt that boost again, and then a fade.
I'm curious about taking that low dose of prozac with desipramine, or nortriptyline.
Right now I'm on tianeptine, so I won't be taking any SRI drug while I'm on it.
Since remeron felt like a stronger prozac, I wonder what combining remeron with an SNRI would be like. I think the 5 HT2A/C antagonism of remeron works better with SRI action, this is the mechanism by which low dose prozac increases norepinephrine and dopamine in the prefrontal cortex.
Oh also abilify, only increase dopamine in the prefrontal cortex, not in the striatum or nucleus accumbens, and at higher doses it decreases dopamine in the reward regions of the brain.
The motivation from remeron and low dose prozac felt more natural than abilify which seemed, kind of hyper and robotic.
Posted by ggggg123 on October 31, 2010, at 11:06:06
In reply to Re: To Cheryl-Lynne Anhedonia, posted by Conundrum on October 30, 2010, at 15:19:53
I think remeron is a good drug when combined with other ad's, but not as a sole agent. I think as many of its ad properties consist of antagonism that synergistic use is the best policy. I have tried very briefly combining with venlafaxine, but i did'nt like the side effects of taking venlafaxine as it was making me feel sick, so I did'nt stick with it, although I know it is suppose to be very effective and they call it Californian rocket fuel, once the side effects have passed it could be a good combo. My theory on anhedonia is that norepinephrine and dopamine downregulaton must play a big part, i think to see any benefit one would have to take drugs to raise these for many many months to try and reverse the years of downregulations by the ssri, the tcas could be a good bet, exercise could also be very helpful, I'm pretty sure that once proper norep and dop functioning is restored one would feel normal again, although it could be a long process, I am definately feeling better taking the bromocriptine, but its not very strong, as I'm only taking low dose, so the effects are'nt amazing, but the only drugs I believe that could fully relieve the symptoms of anhedonia would be illegal and unsustainable, this is why it is inevitably a long process and all we can do is find other drugs which can provide a helping hand. Personally it annoys me that doctors dish out ssri's for any kind of mental disturbance, when everybodys depression is so unique, maybe if they understood mental health better then we would'nt be put in this mess!
I think the nortryptiline could be a good idea, I am also thinking about trying a noradrenergic tca, but I am unsure about the anticholinergic side effects and whether they would subside. Personally I don't think serotonin deficiency is the cause of depresson, it certainly was'nt the cause of mine, straight away I suffered side effects from citalopram, which included sexual dysfunction and blunted emotions, when a diabetic takes insuline they normally experience no side effects!!! now that is replacing a deficiency, now ssri's seem to produce side effects at even low dose, which would indicate a rise beyond normal levels. If you ask me, if you experience any side effects on an ad, which makes you feel very abnormal and are representative of a change in neurotransmitter level, such as apathy, anxiety, sexual dysfunction, loss of energy/motivation and the side effects persist then I would say to anybody that the ad is not for you and to find another rather than putting up with it for years and letting our doctors fool us into thinking its doing us some good.
I think recovering from anhedonia is one of lifes big challenges as it trys to prevent you from doing the things that will aid recovery.
Posted by Conundrum on October 31, 2010, at 16:34:26
In reply to Re: To Cheryl-Lynne Anhedonia, posted by ggggg123 on October 31, 2010, at 11:06:06
> I think remeron is a good drug when combined with other ad's, but not as a sole agent. I think as many of its ad properties consist of antagonism that synergistic use is the best policy.
I agree, I think this is the reason why low dose prozac works so well for me, but a higher dose does not. Prozac is a 5HT2A/C antagonist, most of the studies emphasize its actions as a 5HT2C antagonist more than its effect at the 2A receptor, so I think it may have a stronger effect on the 2C receptors. At a low dose there is an increase in motivation. At a higher dose there is the opposite effect. So i think that antagonism comes into play at the lower dose but the SRI effect isn't too strong. Its there believe, me, there is still sexual dysfunction, for me, even at that low dose. It seems like the antagonism needs an increase in serotonin to have an effect. Perhaps pure antagonism, creates an upregulation in receptors so the effect is lost, but with some agonism by serotonin the receptors are down regulated and some are blocked, leading to increase NE/DA release in the PFC.
My experience with low dose prozac and remeron, is that the subjective effect was EXACTLY THE SAME, except when remeron kicked in the effect was stronger, but short lived. I wonder what it would do in conjunction with pristiq or cymbalta.
My theory on anhedonia is that norepinephrine and dopamine downregulaton must play a big part, i think to see any benefit one would have to take drugs to raise these for many many months to try and reverse the years of downregulations by the ssri, the tcas could be a good bet, exercise could also be very helpful, I'm pretty sure that once proper norep and dop functioning is restored one would feel normal again, although it could be a long process.
Yes its important not to leave noradrenaline out of the process of treating anhedonia. Its not just the "energizing" neurotransmitter, it doesn't just increased blood pressure and heart rate, it actually has an effect on mood. The same is true with dopamine, its not just the feel good transmitter and if the other levels aren't right it won't work so good. Also dopamine and norepinephrine are administered in hospitals to stabalize low blood pressure, so dopamine does increase BP and energy as well.
> I think the nortryptiline could be a good idea, I am also thinking about trying a noradrenergic tca, but I am unsure about the anticholinergic side effects and whether they would subside. Personally I don't think serotonin deficiency is the cause of depresson, it certainly was'nt the cause of mine, straight away I suffered side effects from citalopram, which included sexual dysfunction and blunted emotions, when a diabetic takes insuline they normally experience no side effects!!! now that is replacing a deficiency, now ssri's seem to produce side effects at even low dose, which would indicate a rise beyond normal levels. If you ask me, if you experience any side effects on an ad, which makes you feel very abnormal and are representative of a change in neurotransmitter level, such as apathy, anxiety, sexual dysfunction, loss of energy/motivation and the side effects persist then I would say to anybody that the ad is not for you and to find another rather than putting up with it for years and letting our doctors fool us into thinking its doing us some good.
Well there is also desipramine, which is supposed to have less anticholinergic effects. I think many people reporting these effects going away with time, probably similar to Remeron poop out, since the anticholonergic effects are due to muscarinic antagonism.
>
> I think recovering from anhedonia is one of lifes big challenges as it trys to prevent you from doing the things that will aid recovery.Thats so true. Sometimes I'll go and exercise and feel good about it. The next day I could go to exercise and not like it and be fighting the whole time. Usually I just don't exercise. I try to walk, because anhedonia hasn't me me so lazy I can't do that.
I think I find stablon a bit relaxing but its too soon to say.
Posted by ggggg123 on October 31, 2010, at 17:22:55
In reply to Re: To Cheryl-Lynne Anhedonia » ggggg123, posted by Conundrum on October 31, 2010, at 16:34:26
>------I agree, I think this is the reason why low dose prozac works so well for me, but a higher dose does not. Prozac is a 5HT2A/C antagonist, most of the studies emphasize its actions as a 5HT2C antagonist more than its effect at the 2A receptor, so I think it may have a stronger effect on the 2C receptors. At a low dose there is an increase in motivation. At a higher dose there is the opposite effect. So i think that antagonism comes into play at the lower dose but the SRI effect isn't too strong. Its there believe, me, there is still sexual dysfunction, for me, even at that low dose. It seems like the antagonism needs an increase in serotonin to have an effect. Perhaps pure antagonism, creates an upregulation in receptors so the effect is lost, but with some agonism by serotonin the receptors are down regulated and some are blocked, leading to increase NE/DA release in the PFC
Maybe the upregulation is the reason why we experience worse symptoms when off the drug, as when we go back on the drugs they antagonize the receptors but when we come off they are upregulated, causing anhedonia, maybe a long term strategy using a 5ht2c and a agonist might help return receptor functioning to pre ssri levels. we need a drug that is the opposite to an ssri lol
lol just a thought, but there seems to be some reason why symptoms are even worse off the drug.
Posted by Conundrum on October 31, 2010, at 17:32:20
In reply to Re: To Cheryl-Lynne Anhedonia, posted by ggggg123 on October 31, 2010, at 17:22:55
> >------I agree, I think this is the reason why low dose prozac works so well for me, but a higher dose does not. Prozac is a 5HT2A/C antagonist, most of the studies emphasize its actions as a 5HT2C antagonist more than its effect at the 2A receptor, so I think it may have a stronger effect on the 2C receptors. At a low dose there is an increase in motivation. At a higher dose there is the opposite effect. So i think that antagonism comes into play at the lower dose but the SRI effect isn't too strong. Its there believe, me, there is still sexual dysfunction, for me, even at that low dose. It seems like the antagonism needs an increase in serotonin to have an effect. Perhaps pure antagonism, creates an upregulation in receptors so the effect is lost, but with some agonism by serotonin the receptors are down regulated and some are blocked, leading to increase NE/DA release in the PFC
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> Maybe the upregulation is the reason why we experience worse symptoms when off the drug, as when we go back on the drugs they antagonize the receptors but when we come off they are upregulated, causing anhedonia, maybe a long term strategy using a 5ht2c and a agonist might help return receptor functioning to pre ssri levels. we need a drug that is the opposite to an ssri lol
>
> lol just a thought, but there seems to be some reason why symptoms are even worse off the drug.Well I just started taking tianeptine, which is a serotonin reuptake enhancer, so it is an indirect serotonergic antagonist. In the end it may not make a different. Taking an SSRI decreases the number of transporters that bring serotonin back into the cell, tianeptine does the same thing, which would seem to limit its effectiveness overtime. I'm not convinced there is a way to get the brain to function the way it once had. I've been off prozac for 7 years. For of those years I took no drugs, save ginkgo biloba, which is supposed to help the brain. I also took choline precursors and fish oil. My brain never went back to the way it was. I'm not convinced that it is possible. Some people do get back to their previous state, but I'm just not that lucky.
Perhaps I would have ended up in this state without the drugs? Idk.
Posted by ggggg123 on October 31, 2010, at 17:49:11
In reply to Re: To Cheryl-Lynne Anhedonia, posted by Conundrum on October 31, 2010, at 17:32:20
Many GPCRs downregulate in response to agonists for the receptor, and upregulate in response to antagonists. The 5-HT2A and 5-HT2C receptors appear to downregulate in response to both antagonists and agonists. Chronic treatment with antipsychotic drugs, which possess 5-HT2 antagonist activity, results in downregulation of both 5-HT2A and 5-HT2C, as does chronic treatment with SSRIs and other 5-HT agonists.[12] However, chronic SSRI treatment may increase 5-HT2C expression, specifically in the choroid plexus.
This is an extract from wikipedia, its a little bit ambiguous and contradictory, but in the end it points out that ssri's may increase 5ht2c expression, which could play a major factor I think in post ssri apathy. If any receptor is responsible for anhedonia it would be this one, this is the one that stops our dopamine and norepinephrine from working. Basically the cure should be a drug which reduces 5ht2c expression or causes downregulation. Maybe a tca or 5htp supplement could be beneficial? or maybe an anti psychotic taken for a long period? how long did you take aripiprazole for?
Posted by Conundrum on October 31, 2010, at 18:01:40
In reply to Re: To Cheryl-Lynne Anhedonia, posted by ggggg123 on October 31, 2010, at 17:49:11
> Many GPCRs downregulate in response to agonists for the receptor, and upregulate in response to antagonists. The 5-HT2A and 5-HT2C receptors appear to downregulate in response to both antagonists and agonists. Chronic treatment with antipsychotic drugs, which possess 5-HT2 antagonist activity, results in downregulation of both 5-HT2A and 5-HT2C, as does chronic treatment with SSRIs and other 5-HT agonists.[12] However, chronic SSRI treatment may increase 5-HT2C expression, specifically in the choroid plexus.
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> This is an extract from wikipedia, its a little bit ambiguous and contradictory, but in the end it points out that ssri's may increase 5ht2c expression, which could play a major factor I think in post ssri apathy. If any receptor is responsible for anhedonia it would be this one, this is the one that stops our dopamine and norepinephrine from working. Basically the cure should be a drug which reduces 5ht2c expression or causes downregulation. Maybe a tca or 5htp supplement could be beneficial? or maybe an anti psychotic taken for a long period? how long did you take aripiprazole for?Perhaps, I assume the reason that low dose prozac can increase motivation without pooping out(when i first took prozac, I took the normal 20mg dose) and remeron poops out has to do with an increase in serotonin due to reuptake inhibition. Hmm I have buspar, perhaps adding it to remeron would increase dopamine release. IDK. I don't think there is enough knowledge on the 17 varieties of serotonergic receptors to be sure what does what.
The TCAs amitriptyline and nortriptyline would be good for antagonizing these receptors, the drugs from Imipramine would be less so. I was only on Abilify for 3 weeks, I had samples just to see if it worked. Its very expensive. I wouldn't want to be on an antipsychotic longterm, they cause a whole host of problems due to D2 antagonism. Zyprexa would probably be the most potent drug AP for blocking the 5 HT2C receptor.
It might make more sense to do what you said and take a dopamine agonist with an adrenergic TCA.
One thing I've noticed about SSRIs, is that they prevent me from having bad dreams, so maybe I have some deficiency there, and it just needs to be properly balanced with excitatory neurotransmitters.
Posted by ggggg123 on November 2, 2010, at 6:34:46
In reply to Re: To Cheryl-Lynne Anhedonia, posted by Conundrum on October 31, 2010, at 18:01:40
I am definately starting to feel alot better, taking the 1.25mg of bromo and I've been taking a little bit of bupropion, defo seems to be a norep and dopa thing, today I have a doctors appointment and I'm going to ask to start reboxetine, as its an nri and bupropion is'nt available over here. I am thinking nri low dose combined with small amount of bromo and exercise/getting out and about, today I feel like going out for the first time in a while, which is how I used to feel before I went into hibernation.
I'm not going to try to antagonize the 5ht2c receptor as, when i took mirt all i wanted to do was eat and sleep, I believe you are right about the nor and dop drugs, my problem really seems to be a pure norep and dop deficiency, basically a depression, which could stem from the original symptoms prior to using an ssri and have later been attenuated by the serotonergic properties of the drug. Also most tca's are serotonergic aswell, which I really do want to avoid, its is said that norep increases serotonin indirectly, pesonally I think it increases both serotonin and dopamine, and can be very useful, where as serotonin seems to diminsh the other neurotransmitters. I know I have a norepinephrine deficiency, because I no longer get nervous or excited, I used to be fairly nervous and felt quite alot of emotion, since my anhedonia I have felt non. I think long term nri therapy at a reasonably low dose could be the best strategy for a subgroup of people wo do not improve after ssri therapy. Adding a small amount of a dopamine agonist may also be very useful. Theres a section on the good drug guide at biopsychiatry . c o m which talks about reboxetine, I don't know how it will compare to bupropion as its also twice a day dosing. But honestly I am feeling so much better now I can feel some norepinephrine and dopamine in my brain, it makes you feel content and almost half way to happy.
Posted by Conundrum on November 2, 2010, at 12:58:00
In reply to Re: To Cheryl-Lynne Anhedonia, posted by ggggg123 on November 2, 2010, at 6:34:46
> I am definately starting to feel alot better, taking the 1.25mg of bromo and I've been taking a little bit of bupropion, defo seems to be a norep and dopa thing, today I have a doctors appointment and I'm going to ask to start reboxetine, as its an nri and bupropion is'nt available over here. I am thinking nri low dose combined with small amount of bromo and exercise/getting out and about, today I feel like going out for the first time in a while, which is how I used to feel before I went into hibernation.
>
> I'm not going to try to antagonize the 5ht2c receptor as, when i took mirt all i wanted to do was eat and sleep, I believe you are right about the nor and dop drugs, my problem really seems to be a pure norep and dop deficiency, basically a depression, which could stem from the original symptoms prior to using an ssri and have later been attenuated by the serotonergic properties of the drug. Also most tca's are serotonergic aswell, which I really do want to avoid, its is said that norep increases serotonin indirectly, pesonally I think it increases both serotonin and dopamine, and can be very useful, where as serotonin seems to diminsh the other neurotransmitters. I know I have a norepinephrine deficiency, because I no longer get nervous or excited, I used to be fairly nervous and felt quite alot of emotion, since my anhedonia I have felt non. I think long term nri therapy at a reasonably low dose could be the best strategy for a subgroup of people wo do not improve after ssri therapy. Adding a small amount of a dopamine agonist may also be very useful. Theres a section on the good drug guide at biopsychiatry . c o m which talks about reboxetine, I don't know how it will compare to bupropion as its also twice a day dosing. But honestly I am feeling so much better now I can feel some norepinephrine and dopamine in my brain, it makes you feel content and almost half way to happy.I'm glad you are feeling better. Its nice to see that my ideas on norepinephrine an anhedonia have helped lead to someone else feeling better. I felt like I was a voice in the wilderness, crying anhedonia is not just low dopamine!
Bupropion is an interesting drug. It's effects can be added to or subtracted from by changing the effects of nitric oxide synthase.
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T1J-4NN0WF3-2&_user=10&_coverDate=07/30/2007&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_searchStrId=1524325290&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=4abec21ba9b5583faa206e51d4b10822&searchtype=aIt also works on nicotonergic receptors.
Its effect on norepinephrine is fairly weak compared to reboxetine.My point is, that reboxetine may not have the same effect that bupropion does. How ever if you need more NE than bupropion can offer you than it might be a good drug. Bupropion is stronger on dopamine and then norepinephrine.
I'm glad you are feeling better and are getting out.
Is there any reason you chose bromo as the DA agonist and not another one like mirapex?
Posted by ggggg123 on November 2, 2010, at 14:21:54
In reply to Re: To Cheryl-Lynne Anhedonia, posted by Conundrum on November 2, 2010, at 12:58:00
Hi, cheers for the info. The only reason I choose bromocriptine was cost, its cheap I would rather buy miraplex. I haven't started the Reboxetine and probably won't get it for at least a week or two, as the doctor said only a psych can prescribe it. My experience with bupropion after using it irregularly for many months, I would say it is relativcely weak, I am hoping the strength of reboxetine can provide a more stable sustained flow of NE, but as with bupropion it is dosed BID. After you mentioned about ne it made a whole lot of sense, as bromo is not anywhere near sufficient alone, but is good when combined with bupropion, plus dopamine makes you tired.
NE is what gives you the fight of flight response, it keeps you on your toes, it makes you want to do things, it makes you want to move forward with time, rather than backwards. It gives you emotion and passion, where as I believe dopamine allows you to experience pleasure from these activities, overall I thoroughly agree that NE is of major importance in anhedonia, I also believe that raising ne will indirectly increase dopamine and some serotonin. If you suffer anhedonia without much anxiety, as I do, just a complete horrible flat apathetic zombie type feeling, which you can tell is biological, then i think the main building block will be norepinephrine, obviously if you have anxiety a small amount of serotonin maybe needed.Personally I think its best to get shut of the ssri, and try and adopt new habits when taking a more NE based med, like getting lots of exercise, good sleeping habits and healthy eating habits. all this will boost serotonin, the problem is with ssri's is one does not feel like exercising or being very active, including mental activity, which is absolutely crucial. When I was 16 I has severe depression, but my docs gave me nothing, and over a period of a year I made a full recovery, I then went to college and then started university, in my second year at university I got severely stressed out and fell into depression and anxiety again, this time it was in the severe range, where as before it was moderate. this time I felt I needed treatment, So I was prescribed citalopram, which is very common practice in the uk. But my depression was very severe, I went upto 60mg of citalopram and was told its the best drug and to keep taking it, so I took it for 7 months after this time I was so sick of having no kind of sexuality and feeling so dissociated from life, that I decided I wanted to quit, I slowly tapered, still experienced terrible headaches, what I was left with after the side effects cleared was anhedonia, in the purest biological form. I have rarely experienced despair in my life, as I always try to be positive, but.... I found myself in a state of despair day after day after day, all because of my anhedonia, the way I was feeling and the worry of ever improving. People talk about permanent problems, which scared me, but deep down I don't believe they are permanent because I am able to look at the situation as a whole and each symptom, including sexual dysfunction, loss of drive, emotional blunting, over sleeping etc all indicate a lack of NE and DA, if you think about it, the fight or flight response is also affected as: you don't feel as excitable or as nervous, you don't feel the adrenaline pumping that makes you feel alive, basically you have lost the ability to experience thrill, if you work from the top it becomes obvious that all the symptoms tie together and can easily be linked to the simple mental symptoms, which are certainly a loss of adrenaline and a drop in dopamine. How effective ad therapy is for raising these neurotransmitters still remains to be seen for myself, but it should'nt be too difficult and within a year I imagine the adrenal system will kick back into action and life will be just as we once knew it.
Do not give up or despair, there is absolutely no reason any of us can't make a full recovery, trust me the brain and body recovers from depression, I've been there, but honestly I can't stress enough how important activity is, today I have been out and about and I feel much better. In my last depression I had no meds, but I had to go to college, then over a period of about 6 months I had improved massively, as I had to concentrate on making friends, studying etc, I actually became excited and the depression disappeared, but my depression was moderate, I know if I had'nt had NE I would never of got better as I became so active, playing soccer, going on nights out, studying, exams etc, all the behaviours that led to my full recovery, these are the behaviours that make you well, they are not achievable without NE and some DA. Serotonin will make you a functioning zombie, but when you come off you will be a non functioning zombie, the drug that suits you best will cause you no bad side effects once the initiation problems have subsided.
The brain loves exercise, who takes an ssri and feels like going out and doing a marathon? I am ssri free for 6 months and starting to feel better and better. NE is very important, but one only needs a small amount, if you feel the prozac does you some good a low dose might be ok combined with a NRI, but in my view its better to adopt the lifestyle habits and drop the ssri, they are bad news, man needs every bit of sexuality he can get, its part of who we are, plus we need to feel love and passion, I don't even watch my favourite soccer team who I have supported all my life. Maybe amintepine with an nri? I think low dose NRI is important and as I said people need to understand how important being active is, its like magic!!! nothing in this world will give you the all round well being. I have never felt normal taking even 5mg citalopram, serotonin is definitely to the answer for a lot of people. We are just tricked by our doctors that it is, but we need to learn about our own body and make our own decisions.
Posted by ggggg123 on November 2, 2010, at 14:48:10
In reply to Re: To Cheryl-Lynne Anhedonia, posted by ggggg123 on November 2, 2010, at 14:21:54
Sorry one last thing I need to get off my chest.
I don't think ssri's are beneficial to people with clinical depression, I think they are beneficial to people with ocd, social phobia and emotional disorders. If your neurotransmitters are fully functioning, but you feel abit anxious and hyper emotional or hysterical, an ssri will calm you down, make you feel more calm and less emotional, it will reduce your obsessive thinking, as ssri's reduce frontal lobe activity, slowing rate of thoughts and affecting your memory.
People with actual clinical depression, where their neurotransmitter functioning is severely diminished, often do not respond well to ssri's and why would they: for a start they are already suffering from a drop in NE and DE activity, but I think the main point is a clinically depressed brain is much more manipulable than a non clinically depressed persons brain, since their are no tests to determine clinical depression, many people with emotional disorders and problems, including many psychological problems as opposed to neuropsychiatric problems, are treated using ssri's maybe it is these people who benefit, as their NE and DA are not manipulated, and they are left with a pleasant reduction in their hurting emotions.
Posted by ggggg123 on November 2, 2010, at 14:52:38
In reply to Re: To Cheryl-Lynne Anhedonia, posted by ggggg123 on November 2, 2010, at 14:48:10
sorry my spelling was'nt great in the last posts, Mirapex** and DA** not DE lol
Posted by ggggg123 on November 3, 2010, at 19:40:33
In reply to Re: To Cheryl-Lynne Anhedonia, posted by ggggg123 on November 2, 2010, at 14:52:38
It has been proven that reduced activity in the prefrontal cortex contributes to anhedonia, this is definately true in my case, as before I had anhedonia I used to have quite bad ocd, since my anhedonia I have no ocd ( ocd is caused by a high level of activity in the prefrontal cortex). SSRI's treat ocd, they reduce the activity in the prefrontal cortex and they therefore induce anhedonia, excitorary neurochemicals and lots of exercise are probably good strategies to try and regain that frontal lobe actvity. Basically anhedonia represents a frontal lobe syndrome, which is a common complaint of psychiatric meds and it would seem ssri's do play a big part in causing these symptoms and are not in anyway and advancement in psychopharmacology, only when an agent that restores normality, producing few side effects is released can we truly say that psychopharmacology has advanced, if anything its getting worse. If you have memory problems after taking an ssri, this is typical of the frontal lobe symptoms, people say ect is bad for memory, but at least you do not have the whole other array of side effects like the wonderfully brilliant ssri's.
Unfortunately by depleting NE/DA one will develop frontal lobe syndrome type symptoms and anhedonia, as neuronal activity is vastly reduced, it is inevitable. These chemicals fuel frontal lobe activity, without them sadly we become dawn of the dead extras.
This is the end of the thread.
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