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Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 23 of 23. This is the beginning of the thread.
Posted by Brainbeard on June 17, 2009, at 4:25:51
Sertraline (Zoloft) is a weak dopamine reuptake inhibitor (DRI). To get significant DRI, one would have to take high doses, possibly higher than the highest recommended dose (which is about 250mg). Since there are hardly any clean DRIs available, I was wondering if there is any way that sertraline's serotonin reuptake inhibition (SRI)could be countered or mitigated, so that one could take a higher dose of the drug without getting SRI overkill? The only thing I can think of is that perhaps tianeptine, which accelerates the reuptake of serotonin instead of inhibiting it, might work. But tianeptine doesn't grab the sert transporter, I guess, so perhaps the working mechanisms are too different. There has been a report of a woman on tianeptine who became depressed after adding paroxetine, but that doesn't tell us much.
Any ideas? Or might there be, more indirectly, (pharmacological) ways to mitigate the side-effects of serotonin receptor saturation?
All feedback appreciated, negative included.
Posted by desolationrower on June 20, 2009, at 1:43:13
In reply to Can serotonin reuptake inhibition be countered?, posted by Brainbeard on June 17, 2009, at 4:25:51
no
-d/r
Posted by desolationrower on June 20, 2009, at 1:43:50
In reply to Re: Can serotonin reuptake inhibition be countered?, posted by desolationrower on June 20, 2009, at 1:43:13
just get some ritalin
-d/r
Posted by Alexanderfromdenmark on June 20, 2009, at 12:33:21
In reply to Can serotonin reuptake inhibition be countered?, posted by Brainbeard on June 17, 2009, at 4:25:51
> Sertraline (Zoloft) is a weak dopamine reuptake inhibitor (DRI). To get significant DRI, one would have to take high doses, possibly higher than the highest recommended dose (which is about 250mg). Since there are hardly any clean DRIs available, I was wondering if there is any way that sertraline's serotonin reuptake inhibition (SRI)could be countered or mitigated, so that one could take a higher dose of the drug without getting SRI overkill? The only thing I can think of is that perhaps tianeptine, which accelerates the reuptake of serotonin instead of inhibiting it, might work. But tianeptine doesn't grab the sert transporter, I guess, so perhaps the working mechanisms are too different. There has been a report of a woman on tianeptine who became depressed after adding paroxetine, but that doesn't tell us much.
> Any ideas? Or might there be, more indirectly, (pharmacological) ways to mitigate the side-effects of serotonin receptor saturation?
> All feedback appreciated, negative included.Seems like a complicated way to get dopamine reuptake inhibition.
Posted by Brainbeard on June 21, 2009, at 7:24:50
In reply to Re: Can serotonin reuptake inhibition be countered?, posted by Alexanderfromdenmark on June 20, 2009, at 12:33:21
I was afraid already that 'No' would be the only right answer. Somebody had to give it, and thanks for doing that.
> Seems like a complicated way to get dopamine reuptake inhibition.
>
It is, I admit. I have once tried the cleanish dopamine reuptake inhibitor amineptine, but it cost me a fortune even before I could reach a therapeutic dose. I'll get back to it when I've become a millionaire.Ritalin.. Not really a clean DRI. A crude drug, a chemical peasant. Gives me terrible hangovers.
I would love to hate it, but can't get a prescription (yet) and it's too expensive over the internet.
Posted by Sigismund on June 22, 2009, at 2:45:01
In reply to Re: Can serotonin reuptake inhibition be countered?, posted by Brainbeard on June 21, 2009, at 7:24:50
Ritalin is not a lot of fun, is it?
What was amineptine like?
Too good to be legal?
Posted by Brainbeard on June 22, 2009, at 2:59:26
In reply to Re: Can serotonin reuptake inhibition be countered?, posted by Sigismund on June 22, 2009, at 2:45:01
>> What was amineptine like?
>
> Too good to be legal?No, I wouldn't day that. Well, in a way, yes, it is, since it's a pretty clean dopamine reuptake inhibitor with an excellent side-effects profile, which makes it a pretty unique drug. On the other hand, like its serotonergic cousin, tianeptine, it appears to be a rather mild drug; put differently, it may not be overwhelmingly effective. Like tianeptine, it has a very short half-life (something like 3 hours), although its effects last longer. One can only fantasize about a therapeutically available extended release version.
David Pearce, from the amazing http://www.biopsychiatry.com/, calls the euphoria that amineptine can induce 'extremely mild'.
It's funny that Ritalin can make me feel VERY euphoric, but always gives me a crude hangover in return.
Posted by morganpmiller on June 27, 2009, at 2:31:49
In reply to Re: Can serotonin reuptake inhibition be countered?, posted by Brainbeard on June 22, 2009, at 2:59:26
Are you currently trying zoloft? I was on zoloft for years at 100mgs and I swear I noticed a fairly significant dopamine boost. There is a lot of anecdotal evidence and experiences suggesting that some may get noticeable dopamine reuptake inhibition at fairly low doses. You never know until you try I guess
Posted by Brainbeard on June 27, 2009, at 5:24:38
In reply to Re: Can serotonin reuptake inhibition be countered?, posted by morganpmiller on June 27, 2009, at 2:31:49
Indeed, the anecdotal evidence certainly points to pro-dopaminergic action of sertraline even at moderate doses. Sertraline has shown to improve cognitive and psychomotor function in older parkinson patients. But technically, this can hardly be due to sertraline's extremely weak dopamine reuptake inhibition at such doses. Check the 'Is sertraline an inhibitor of dopamine uptake?' section of this column by Dr. Preskorn: http://www.preskorn.com/columns/9909.html
So I wonder if sertraline might have some other, yet unknown dopaminergic mechanism.By the way, I found a partial answer to my own question: the main side-effect of over-saturated serotonin receptors, namely diarrhea, can be countered by adding a constipating TCA (preferably a non-SRI...).
Posted by morganpmiller on June 27, 2009, at 5:38:23
In reply to Re: Can serotonin reuptake inhibition be countered?, posted by Brainbeard on June 27, 2009, at 5:24:38
Nice
Posted by garnet71 on June 29, 2009, at 22:31:26
In reply to Can serotonin reuptake inhibition be countered?, posted by Brainbeard on June 17, 2009, at 4:25:51
despite what all/any research has to say, Zoloft has an extrmee adverse affect on me-it makes me depressed, takes away my motiviation, I don't enjoy music adn other normal things. However, it works great for my anxiety. I'm not a depressive; my symptoms are anxiety only; yet when I take zoloft, it's a protracted, negative reaction that realizes w/in 2 months--I am immobilized with amotivation. I understand its complicated, beyond what I understand, but zoloft really does, imo, have an adverse effect on dopamine for me.
Posted by morganpmiller on June 30, 2009, at 6:36:37
In reply to Re: Can serotonin reuptake inhibition be countered?, posted by garnet71 on June 29, 2009, at 22:31:26
> despite what all/any research has to say, Zoloft has an extrmee adverse affect on me-it makes me depressed, takes away my motiviation, I don't enjoy music adn other normal things. However, it works great for my anxiety. I'm not a depressive; my symptoms are anxiety only; yet when I take zoloft, it's a protracted, negative reaction that realizes w/in 2 months--I am immobilized with amotivation. I understand its complicated, beyond what I understand, but zoloft really does, imo, have an adverse effect on dopamine for me.
I totally believe you..Just curious to know what dosages you tried..50,100,150,200?
Isn't it crazy how each individual can react so differently to the same medication.
Posted by Brainbeard on June 30, 2009, at 9:54:54
In reply to Re: Can serotonin reuptake inhibition be countered?, posted by garnet71 on June 29, 2009, at 22:31:26
> I understand its complicated, beyond what I understand, but zoloft really does, imo, have an adverse effect on dopamine for me.
Of course Zoloft has adverse effects on dopamine: it's a strong SSRI, and any strong SRI has strong anti-dopaminergic effects, manifesting in loss of libido most prominently and possibly lethargy and apathy. Any strong SRI will raise prolactin levels, which is a sign of anti-dopaminergic action. Zoloft can raise prolactin levels wildly.
The dosage question is key, since the anti-dopaminergic effects of Zoloft are bound to be dose-related. That's why I'm hoping to avoid them myself with a low dose of Zoloft. Low definitely means <50mg, since at 50mg sertraline (Zoloft) already occupies 80% of serotonin transporters, which comes down to full SRI in a therapeutic sense.
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Current meds: imipramine 12.5mg + amitriptyline 6mg at bedtime; sertraline 12.5mg + ondansetron 2mg + modafinil 50mg in the morning'Some of the Magic Syrup was Preserved'
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Posted by garnet71 on June 30, 2009, at 18:46:27
In reply to Re: Can serotonin reuptake inhibition be countered?, posted by Brainbeard on June 30, 2009, at 9:54:54
I wish I could remember the dosage of Zoloft I took.
Hmm. I recently read about prolactin too and want to get mine tested. The problem is, I think the zoloft has had some kind of long-term affect on my dopamine. though I quit taking it last Dec., my motivation never came back 100%; it improved greatly, but I'm still only about 50%?
Since seratonin agents work for anxiety in my case, do you think this means I will always have to take something for dopamine simulataneously? I've been thinking about the TCAs and klonopin, but am not sure what to do at this point. Wellbutrin no longer works for me, which was once great to counteract this effect. My current PDoc, while new and just refilling my scripts from last doctor, said he could get wellbutrin to work again w/a small dose of Prozac (5 mgs?). I'm wondering if he was just thinking of that as a placebo though, since I couldn't find any research on that combo.
I chose buspirone because of this issue, but it's no longer holding up with all the environmental stressors. I'm afraid I'm not going to make it through school.
Posted by garnet71 on June 30, 2009, at 18:49:53
In reply to Can serotonin reuptake inhibition be countered?, posted by Brainbeard on June 17, 2009, at 4:25:51
Oh, Brainbeard--dextroamphetamine helps me a lot (10 mg x 2). But i was taking dextrat/tablets and new PDoc gave me dexadrine/capsules.
I got no side effects from dextrat, but dexadrine does not seem to work for me very well. Maybe I still have to get used to it, but it doesn't seem to be affecting motivation and mental sharpness like dextrat. Still, it's a temporary fix only. The day you quit taking it is the day your motivation goes back to the way it was the day before.
Posted by morganpmiller on July 1, 2009, at 2:28:58
In reply to Re: Can serotonin reuptake inhibition be countered?, posted by Brainbeard on June 30, 2009, at 9:54:54
It's so weird how I keep hearing about these things that Zoloft can do to you. I was on it for 8 years and always felt strong like and ox, super energized, very motivated, and never once had an issue with sexual side effects. I know many others that have felt the way I did on Zoloft. I believe that some people can experience the negative side effects discussed hear. I just think it is funny that these side effects are talked about in a way that most that take a drug like Zoloft are doomed to suffer them.
Like I mentioned before, I seriously doubt that it takes up to 300 mgs of Zoloft to get a significant boost in dopamine. I can't prove this, but there are plenty of people out there that can testify to feeling dopamine-like effects when taking Zoloft at 100mgs or more.
> I understand its complicated, beyond what I understand, but zoloft really does, imo, have an adverse effect on dopamine for me.
>
> Of course Zoloft has adverse effects on dopamine: it's a strong SSRI, and any strong SRI has strong anti-dopaminergic effects, manifesting in loss of libido most prominently and possibly lethargy and apathy. Any strong SRI will raise prolactin levels, which is a sign of anti-dopaminergic action. Zoloft can raise prolactin levels wildly.
>
> The dosage question is key, since the anti-dopaminergic effects of Zoloft are bound to be dose-related. That's why I'm hoping to avoid them myself with a low dose of Zoloft. Low definitely means <50mg, since at 50mg sertraline (Zoloft) already occupies 80% of serotonin transporters, which comes down to full SRI in a therapeutic sense.
>
> --------------------------------------------------------------------------------------------------------------
> Current meds: imipramine 12.5mg + amitriptyline 6mg at bedtime; sertraline 12.5mg + ondansetron 2mg + modafinil 50mg in the morning
>
> 'Some of the Magic Syrup was Preserved'
> --------------------------------------------------------------------------------------------------------------
>
>
Posted by SLS on July 1, 2009, at 4:49:52
In reply to Re: Can serotonin reuptake inhibition be countered?, posted by morganpmiller on July 1, 2009, at 2:28:58
I think Psycho-Babble attracts both people whom are treatment resistant and people who are idiosyncratically sensitive to the side effects of psychotropic medication. It might be that the two go together. I don't know. It would seem so.
- Scott
Posted by Brainbeard on July 1, 2009, at 5:06:58
In reply to Re: Can serotonin reuptake inhibition be countered? » Brainbeard, posted by garnet71 on June 30, 2009, at 18:46:27
>The problem is, I think the zoloft has had some kind of long-term affect on my dopamine. though I quit taking it last Dec., my motivation never came back 100%; it improved greatly, but I'm still only about 50%?
The SSRIs cause brain changes that take time to be reversed after withdrawal; anecdotal evidence delivered by the hypersensitive (I am among them) points to at least six months for a more or less full recovery. More or less, because further anecdotal evidence - and this time I'm talking about myself only - points to some more permanent changes after long-term SSRI therapy. For instance, my sense of hunger has never returned to normal after years of Paxil. I used to be very hungry before a meal, but after Paxil I often have to look at the clock to see if it's time to eat. Also, I suspect that my motivational problems have permanently gotten worse after Paxil.
The brain is a plastic thing, but plastic doesn't mean elastic - and even a rubber band can break..> Since seratonin agents work for anxiety in my case, do you think this means I will always have to take something for dopamine simulataneously?
You mean something that works AGAINST dopamine? Not necessarily. The connection between the serotonin and the dopamine system is too complex for that. Only with schizofrenia and psychosis it seems that anti-dopaminergic meds are (for many) a necessity.
In my case, pro-dopaminergic meds can help with anxiety short-term, but when the pendulum swings to the other side, they worsen it.The TCA's are very effective drugs, but their side-effects can suck very bad. They do tend to be more or less cognitively debilitating, which is not good for school, depending on how much IQ it would leave you with. Nortriptyline might be an option: it's anxiolytic because of its 5HT2A-antagonism, but it's also stimulating because it's an NRI. And as a secondary amine TCA it's not very debilitating cognition-wise. You might need to add some SRI to it though, if you have the OCD kind of anxiety.
>My current PDoc, while new and just refilling my scripts from last doctor, said he could get wellbutrin to work again w/a small dose of Prozac (5 mgs?). I'm wondering if he was just thinking of that as a placebo though, since I couldn't find any research on that combo.
Low dose Prozac raises noradrenaline and dopamine levels in certain parts of the brain more than inhibiting serotonin reuptake. Even a 2.5mg dose would be enough. Some people got good results with even less. Buspar, perhaps unexpectedly, when taken in combination with Prozac, helps to raise DA and NA levels even more. So your doc might be right. The thing is that this stimulation is not very likely to help with anxiety in the long run.
I was on such a low dose of Prozac + Buspar myself for a while. I gained weight on it very fast though. And I didn't like the 2D6-inhibition, which meant there were many drugs I couldn't take, at least not in normal doses.
Posted by Brainbeard on July 1, 2009, at 5:12:05
In reply to Re: Can serotonin reuptake inhibition be countered? » morganpmiller, posted by SLS on July 1, 2009, at 4:49:52
> I think Psycho-Babble attracts both people whom are treatment resistant and people who are idiosyncratically sensitive to the side effects of psychotropic medication. It might be that the two go together. I don't know. It would seem so.
Interesting thought.
The treatment resistant phenomenon isn't very unique though, if you consider that most antidepressants are only slightly more effective than placebo. Besides that, it is also very normal for a placebo control group to experience side-effects..
Posted by garnet71 on July 1, 2009, at 8:45:25
In reply to Re: Can serotonin reuptake inhibition be countered?, posted by morganpmiller on July 1, 2009, at 2:28:58
Re: zoloft problems
In my experience, it's because hormones and nutrition are not considered in psychiatric treatment; yet they are so important to brain function.
My pronounced negative effects to Zoloft were ignored by the doctors; the doctors I was seeing did not use much besides xxRIs. I felt there was something wrong w/my hormones, went to an endo-got lots of tests and found out I'm hypothyroid, severely deficient in Vit. E (though lots of people in this region have some deficiency), and cortisol tests indicated a problem and the doctor wanted me to get all kind of cortisol tests. I never followed up because I lost my health insurance for 6 months, though I'm going to follow up soon.
I asked the endo if she knew of any hormonal effects caused by xxRIs and she said she knew of nothing. She didn't want to test me for anything (people w/severe anxiety are sometimes considered hypochondriacs, and I admit I am a bit of one sometimes.). There's plenty of research out there that indicates long-term use of some of these meds cause hypothyroidism and low prolactin. ANyone who has been on these seratonin meds long term should be checked for such imbalances if they are having unfavorable reactions, imo.
Despite feeling amotivational and lack of concentration, my mood has been good and stable since about January-when I took the script of vitamin E and started busipirone. Don't know which has changed this, but I have felt no depression a couple weeks after starting those, until just recently when I had a strong emotional expeirence resulting from psychoanalytic therapy.
Perosnally, I'd like to go to a dietician for more nutrient? tests, and go to a psychoneuroendochronologist for further testing, inlcuding prolactin, in addition to taking care of my thyroid problem.
Chronic stress affects your cortisol, and people with PTSD anxiety like me tend to have cortisol issues. Psychotropic meds affect cortisol, I've read positively in some cases, but after having too much cortisol in your system for so long, you can get adrenal burnout, not the medical term endos use..I haven't taken the time to learn enough to be able to explain it, but the bottom line is that hormonal issues are often ignored in psychopharmaceutical management, at least I know this from my personal case.
I noticed most most endos around here specialize in diabetes, and know little about psychoneuroendo dynamics, and maybe my psychiatrists were not trained to look at these issues, or don't read current research. I can't say I have the answers, but this is my experience and I'm glad I recently decided to take charge of researching my health issues.
Posted by garnet71 on July 1, 2009, at 8:48:20
In reply to Re: Can serotonin reuptake inhibition be countered?, posted by Brainbeard on July 1, 2009, at 5:06:58
Hey thanks for the information...Are there any articles you can point me to that discuss this further?
________________________________Low dose Prozac raises noradrenaline and dopamine levels in certain parts of the brain more than inhibiting serotonin reuptake. Even a 2.5mg dose would be enough. Some people got good results with even less. Buspar, perhaps unexpectedly, when taken in combination with Prozac, helps to raise DA and NA levels even more. So your doc might be right. The thing is that this stimulation is not very likely to help with anxiety in the long run.
I was on such a low dose of Prozac + Buspar myself for a while. I gained weight on it very fast though.
Posted by Brainbeard on July 2, 2009, at 8:13:31
In reply to Re: Can serotonin reuptake inhibition be countered? » Brainbeard, posted by garnet71 on July 1, 2009, at 8:48:20
> Hey thanks for the information...Are there any articles you can point me to that discuss this further?
> ________________________________
>
> Low dose Prozac raises noradrenaline and dopamine levels in certain parts of the brain more than inhibiting serotonin reuptake. Even a 2.5mg dose would be enough. Some people got good results with even less. Buspar, perhaps unexpectedly, when taken in combination with Prozac, helps to raise DA and NA levels even more. So your doc might be right. The thing is that this stimulation is not very likely to help with anxiety in the long run.
> I was on such a low dose of Prozac + Buspar myself for a while. I gained weight on it very fast though.
>Yeah: 'Low dose Prozac raises noradrenaline and dopamine levels in certain parts of the brain more than inhibiting serotonin reuptake': first of all, check this link: http://www.lef.org/protocols/prtcl-165a.htm and scroll down to the 'Listening to Prozac'. There you'll find some evidence for even very low doses of Prozac to have an antidepressant effect. Stahl's Essential Pharmacology Online briefly summarizes the probable cause for this in the following link http://stahlonline.cambridge.org/prescribers_drug.jsf?page=0521683505c32_p183-188.html.therapeutics&name=Fluoxetine&title=Therapeutics as follows: 'Fluoxetine also has antagonist properties at 5HT2C receptors, which could increase norepinephrine and dopamine neurotransmission'. Elsewhere he expresses himself more strongly, but that was a presentation I gained acces to yesterday but thah I couldn't bookmark since it appears to be a subscription page. This is the link: http://cme.medscape.com/viewarticle/484929 Anyway, on low doses, Prozac doesn't do much SRI yet, but it's a strong 5HT2C-antagonist. 5HT2C-receptors inhibit dopamine and noradrenaline release, so blocking them 'disinhibits' DA and NA.
STahl in mentioned presentation (I could gain access through google): 'Have you ever given a dose of fluoxetine (Prozac) to a patient and had them have an activation? Fluoxetine is the only other drug that has powerful 5HT2C antagonist properties [not true; Zyprexa is a stronger 5HT2C-antagonist; sertindole is even stronger; and the newer AD agomelatine is also a (strong?) 5HT2C-antagonist - but that's a very recent drug (BB)] in fact, fluoxetine has more powerful antagonist properties than reuptake blocking properties.''Buspar, perhaps unexpectedly, when taken in combination with Prozac, helps to raise DA and NA levels even more': http://cat.inist.fr/?aModele=afficheN&cpsidt=2585906
The reason I gained weight rapidly on a low dose of Prozac must precisely be because it's a potent 5HT2C-antagonist: http://jop.sagepub.com/cgi/content/abstract/20/4_suppl/15. I hadn't expected this, since I didn't know about the 5HT2C-antagonism (only that Prozac raised DA and NA) and thought that without significant SRI, it wouldn't make me gain weight.
Posted by creepy on November 2, 2009, at 13:39:57
In reply to Can serotonin reuptake inhibition be countered?, posted by Brainbeard on June 17, 2009, at 4:25:51
I just wish theyd bring tianeptine here in the US.
This is the end of the thread.
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Dr. Bob is Robert Hsiung, MD,
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