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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 20 of 20. This is the beginning of the thread.
Posted by Morhoun on November 24, 2006, at 10:19:29
So do SSRIs decrease dopamine in the long run or increase it? I've read things saying both.
Posted by Phillipa on November 24, 2006, at 11:50:39
In reply to SSRIs and Dopamine, whats the verdict?, posted by Morhoun on November 24, 2006, at 10:19:29
I thought they only increased serotonin? Love Phillipa
Posted by tensor on November 24, 2006, at 13:12:25
In reply to SSRIs and Dopamine, whats the verdict?, posted by Morhoun on November 24, 2006, at 10:19:29
>I've read things saying both.
That's probably the answer.
/Mattias
Posted by Racer on November 24, 2006, at 15:24:00
In reply to SSRIs and Dopamine, whats the verdict?, posted by Morhoun on November 24, 2006, at 10:19:29
The total amount of neurotransmitters isn't necessarily the most important question. In fact, there's a certain amount of evidence that SSRIs owe their success to their indirect effect on the dopamine system. (By the same token, the paradoxical calming effects of Ritalin, etc, are most likely due to their downregulation of the 5HT2c receptor, rather than to the increased availability of dopamine per se.)
Also, dopamine doesn't necessarily act in one way -- some dopamine receptor types are inhibitory, others excitory, so increasing dopamine transmission isn't necessarily going to have a predictable effect.
My understanding, though, based on what I've read, is that SSRIs tend to increase dopamine. Hope that helps.
Posted by blueberry on November 24, 2006, at 17:37:55
In reply to SSRIs and Dopamine, whats the verdict?, posted by Morhoun on November 24, 2006, at 10:19:29
I think they all affect the dopamine system in one way or another, either negatively or positively. But the way all the systems interact is too complicated to understand it as far as I can tell.
Of the ssris, zoloft has the strongest dopamine reuptake inhibition. Prozac is slight. Not sure about paxil or lexapro. They both felt like pure serotonin to me. I could feel dopamine in zoloft or prozac.
Posted by ace on November 24, 2006, at 20:19:14
In reply to SSRIs and Dopamine, whats the verdict?, posted by Morhoun on November 24, 2006, at 10:19:29
> So do SSRIs decrease dopamine in the long run or increase it? I've read things saying both.
Withoubt a doubt they DECREASE it. It is an indirect was, as opposed to the mechanisms of the antipsychotics.
This is hypothesised to lead to great problems, by certain clinicians. I personally agree with the clinicians after reflection and study. However, nothing is proven conclusively. Many would beg to differ.However, many clinicians believe that long term Benzo use leads to atrophy of the brain (Shrinkage of certain parts)
I vehemently oppose this.
Posted by linkadge on November 24, 2006, at 20:45:15
In reply to Re: SSRIs and Dopamine, whats the verdict? » Morhoun, posted by ace on November 24, 2006, at 20:19:14
I would tend to agree with ACE. There is a substantial amount of literatue supporting the theory that SSRI's supress many normal dopaminergically mediated processes. From drive to sexual function. For certain types of depression, SSRI therapy often makes the situation worse.
There are some exceptions being prozac and zoloft which which *may* posess additional dopamine preserving properties. In the end though, the effect of serotonin reuptake likely supercedes this to a certain extent, and produces an overall damepning of dopamienrgic function.
I've never seen an literature which shows that SSRI's increase dopamine to any significant extent, except fluoxetine. Even the dopaminergic effects of fluoxetine however are restricted to the frontal cortex.
Linkadge
Posted by Robert35 on November 25, 2006, at 4:18:12
In reply to Re: SSRIs and Dopamine, whats the verdict? » Morhoun, posted by linkadge on November 24, 2006, at 20:45:15
> I've never seen an literature which shows that SSRI's increase dopamine to any significant extent, except fluoxetine. Even the dopaminergic effects of fluoxetine however are restricted to the frontal cortex.
>
>
>
> Linkadge
>Hi Linkadge,
We are talking about ssri's here but is anything known about Effexor in regards of dopamine downregulation ?
I don't want to steal this thread but don't see much links to this in the current longwinding Effexor thread but if so I will ask there ... (I am sorry for inconveniences I may cause).
I was puzzled by a remark of my paindoc who prescribed me Effexor (+ tramadol I already used next to ad's); he claimed that small dosages of Eff. (75 to 112,5 mg a day) already had painkilling properties and would apparently hitting nor-adrenaline.
Maybe the same could be true about the dopaminergic action of Effexor (supposedly at high dosages of 300 mg a day).
Does anyone know perhaps ?
Thanks in advance,Robert
Posted by linkadge on November 25, 2006, at 9:06:07
In reply to Re: SSRIs and Dopamine, whats the verdict? » linkadge, posted by Robert35 on November 25, 2006, at 4:18:12
Effexor affects the reuptake of the three in descending order of potency, ser/nor/dopamine.
Its effects on noradrenaline might indireclty preserve dopamine, as agents affecting noradrenaline release can promote dopamine release too.
Anhedonia and apathy are generally seen less with effexor as compared to the SSRI's. It still happens just a little less.
Linkadge
Posted by madeline on November 26, 2006, at 7:08:14
In reply to SSRIs and Dopamine, whats the verdict?, posted by Morhoun on November 24, 2006, at 10:19:29
Hand waving occurs when scientists have an experimental finding, yet have NO IDEA how to explain it so they basically start speculating as to the cause.
It not a literal term. If it were, most research would cease as most scientists would spend their days flailing about wildly in their laboratories.
Hand waving is rampant in psychopharmacology. Very few people are actually honest enough to say "hey guys, we are clueless here, but give us a few decades and we will come back with an answer".
At present there are too many variables to say what drug does what in a particular brain on a given day.
I'm sorry, but that's pretty close to the truth -at least the way I see it.
Posted by lukeds on November 26, 2006, at 8:31:05
In reply to It's all hand waving anyway., posted by madeline on November 26, 2006, at 7:08:14
I have been taken paxil since early 1998 to March of 2006, and do you know why I left it?
SEXUAL ANHEDONIA.I couldn't experience absolutely nothing pleasure in sex, and the dopamine is the neurotransmitter of the pure pleasure, so I don't know of other SSRIs, but this one without a doubt decrease the dopamine.
lukeds.
Posted by Nezirov on November 26, 2006, at 12:17:01
In reply to Experience from 8 years on paxil., posted by lukeds on November 26, 2006, at 8:31:05
Did the sexual side effects reverse when you quit it?
Nezirov
> I have been taken paxil since early 1998 to March of 2006, and do you know why I left it?
> SEXUAL ANHEDONIA.
>
> I couldn't experience absolutely nothing pleasure in sex, and the dopamine is the neurotransmitter of the pure pleasure, so I don't know of other SSRIs, but this one without a doubt decrease the dopamine.
>
> lukeds.
>
>
Posted by Morhoun on November 26, 2006, at 12:53:15
In reply to SSRIs and Dopamine, whats the verdict?, posted by Morhoun on November 24, 2006, at 10:19:29
SSRI antidepressants involve dopamine as well as serotonin signaling
07.04.2005Researchers have discovered that antidepressant drugs such as Prozac not only affect levels of the neurotransmitter serotonin in the brain, but also "hijack" dopamine signaling as well--causing it to launch serotonin signals. Their findings offer new insight into how Prozac and other "selective serotonin uptake inhibitors" (SSRIs) work and how they might cause problems in patients taking them.
SSRIs perform their antidepressant function by increasing the concentration of serotonin in the signaling junctions, called synapses, between neurons. This increase alleviates the deficiency of serotonin that causes depression.
As their name indicates, SSRIs prevent uptake of the serotonin after it has performed its task as a chemical messenger that enables one neuron to trigger a nerve impulse in a neighbor. SSRIs prevent this uptake by inhibiting the action of the molecular cargo carriers called transporters that recycle serotonin back to the neuronal storage sacs called vesicles.
Now, however, Fu-Ming Zhou (presently at the University of Tennessee) and colleagues at Baylor College of Medicine have revealed that SSRIs can have more complex effects on neurotransmitter traffic in the brain than just altering serotonin levels. They found that higher serotonin concentrations caused by SSRIs can "trick" transporters of another key neurotransmitter, dopamine, into retrieving serotonin into dopamine vesicles. Dopamine transporters have a low affinity for serotonin, but the higher serotonin levels result in its uptake by the dopamine transporters, found the scientists.
As a result, the normal dopamine-triggered firing from such neurons, in essence, launches two different types of neuronal ammunition, causing "cosignaling."
The researchers were led to study the role of dopamine signaling in SSRI action by previous evidence that dopamine was involved in depression and in the function of antidepressants in the brain. They studied the nature and machinery of serotonin and dopamine signaling by treating mouse brain slices with fluoxetine (Prozac) and other chemicals, and analyzing the effects on the dopamine-signaling machinery.
The relatively inefficient, slow process of "hijacking" of dopamine transporters by serotonin during SSRI treatment could explain why it takes many days of treatment before antianxiety effects are seen, suggested the researchers.
Also, they wrote that their findings may explain why treatment of children with fluoxetine can induce depressive symptoms in adulthood. The researchers wrote that, since serotonin plays a vital role in neuronal development, disruption by fluoxetine of the normal serotonin levels during development could be responsible for such behavioral abnormalities.
They also theorized that such corelease of dopamine and serotonin caused by SSRIs could explain cases of a "potentially life-threatening serotonin syndrome" caused by such situations as dietary overload of serotonin precursors in people taking SSRIs.
The researchers wrote that the relationship between dopamine and serotonin signaling "is likely vital for normal behavior and for the pathology that can be treated with SSRIs." The brain area involved, the ventral striatum, "is critically involved in the neuronal processes of reward and emotional functions." Thus, they wrote, enhanced participation of the striatal dopamine system in serotonin signaling during treatment with SSRIs "may contribute to the therapeutic efficacy of SSRIs."
Posted by lukeds on November 26, 2006, at 13:28:26
In reply to Re: Experience from 8 years on paxil., posted by Nezirov on November 26, 2006, at 12:17:01
> Did the sexual side effects reverse when you quit it?
>
> Nezirov
>When I left Paxil, the next day I begun to take Anafranil, and I still had sexual side effects but with Anafranil they were weakest, I passed from a total anhedonia to a pseudo anhedonia.
20 days later I quitted Anafranil for 14 days, and during that 14 days I still had sexual side effects but too much weakest. Then I tried Nardil for 6 weeks but It wasn't well. Maybe too many time taking Paxil has altered my sexuality forever, I don't know.
lukeds.
Posted by linkadge on November 26, 2006, at 13:44:49
In reply to Re: SSRIs and Dopamine, whats the verdict?, posted by Morhoun on November 26, 2006, at 12:53:15
This doesn't say that SSRI's increase dopamine at all. At it says is that when you artificilly increase serotonin with SSRI's, the brain start to try and look for other ways to metabolize the unnaturally high levels of the neurotransmitter.
>Dopamine transporters have a low affinity for >serotonin, but the higher serotonin levels >result in its uptake by the dopamine >transporters, found the scientists.
In this case, the dopamine transporter starts to work to mop up serotonin. Ie to try and counteract the SSRI.
>As a result, the normal dopamine-triggered >firing from such neurons, in essence, launches >two different types of neuronal ammunition, >causing "cosignaling."
This doesn't mean that the drug triggers dopamine signalling, it means that now normal dopaminergic responces result in serotonergic responces as well.
This kind of research just points to the havoc that SSRI's cause.
Linkadge
Posted by linkadge on November 26, 2006, at 13:47:31
In reply to Re: SSRIs and Dopamine, whats the verdict? » Morhoun, posted by linkadge on November 26, 2006, at 13:44:49
And, of course, the fact that people like me who were force fed prozac growing up, are screwed.
I had never seen a study actually admit that SSRI use in childhood can lead to adult depression, but its true.
Linkadge
Posted by Nezirov on November 26, 2006, at 23:05:39
In reply to Re: SSRIs and Dopamine, whats the verdict?, posted by linkadge on November 26, 2006, at 13:47:31
It has been very well-documented in animal (rodent) studies.
Nezirov
> And, of course, the fact that people like me who were force fed prozac growing up, are screwed.
>
> I had never seen a study actually admit that SSRI use in childhood can lead to adult depression, but its true.
>
> Linkadge
>
Posted by Morhoun on November 27, 2006, at 14:45:34
In reply to Re: SSRIs and Dopamine, whats the verdict? » Morhoun, posted by linkadge on November 26, 2006, at 13:44:49
> This doesn't say that SSRI's increase dopamine at all. At it says is that when you artificilly increase serotonin with SSRI's, the brain start to try and look for other ways to metabolize the unnaturally high levels of the neurotransmitter.
Yah, I wasn't really making a claim one way or the other, I just thought it was an interesting article.
> >Dopamine transporters have a low affinity for >serotonin, but the higher serotonin levels >result in its uptake by the dopamine >transporters, found the scientists.
>
> In this case, the dopamine transporter starts to work to mop up serotonin. Ie to try and counteract the SSRI.
>
>
>
> >As a result, the normal dopamine-triggered >firing from such neurons, in essence, launches >two different types of neuronal ammunition, >causing "cosignaling."
>
> This doesn't mean that the drug triggers dopamine signalling, it means that now normal dopaminergic responces result in serotonergic responces as well.
>
> This kind of research just points to the havoc that SSRI's cause.Or the havoc that meds in general cause. After 7 months of hell trying to find an AD that helps and having them only make things worse, I'm gonna try med free for a while and see how I do. I'm real guns hy about trying anything else but I'm afraid that I will have to.
Posted by elanor roosevelt on November 28, 2006, at 10:36:36
In reply to Re: SSRIs and Dopamine, whats the verdict?, posted by Morhoun on November 27, 2006, at 14:45:34
i think the pharm comapanies have great PR and want to sell ssri's
Posted by FredPotter on November 29, 2006, at 1:52:53
In reply to It's all hand waving anyway., posted by madeline on November 26, 2006, at 7:08:14
I asked a pdoc if taking SSRIs over a long period messed up the dopamine system. Talk about hand-waving - he looked like he was bringing in a jumbo jet
This is the end of the thread.
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