# prozac vs zoloft



## RockiNToM (Jun 15, 2009)

I'm just wondering if anyone knows which of these has the most Dopamine activity. I know Zoloft has negligible DRI activity at certain doses (200mg?) and Prozac gets some DRI activity via 5-HT2C.

What I'm trying to determine is which of these has the most stimulation for motivation in depression, least cognitive impairment, least dose induced anhedonia and fatigue.

My memories are a little fuzzy since I last used these two drugs and I would like to know people's experiences with each of these for the above reasons. I've only ever tried Prozac once, for a brief period. In that period it gave me extreme nausea and GI upset, but gave me a great an extremely good stimulating mood enhancement, that I can still remember - if only brief. I couldn't get past the side-effects, and I believe I was only on it for 2-3 weeks. With Zoloft it gave me less fatigue and side-effects than some of the other SSRIs but I couldn't take more than 50mg without getting a really bad migraine. It also on and off kept giving me bad anhedonia, whilst still being stimulating.

I'm thinking of giving each of these another go, but I just need to weigh up first which of these is going to provide me the most benefit. Prozac is something I'd like to give another try and Zoloft I would like to explore the higher doses if I can tolerate it. Before I do anything, I need to get more specific facts and experiences on each of these, thus the reason for this thread.


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## Iwillovercomeanxiety1 (Aug 23, 2010)

I've been on Zoloft for a couple years now. I tested out Prozac, but I believe it gave me anxiety or didn't help much in that department. I didn't know that Prozac had actions on Dopamine. I definitely know Zoloft works on dopamine and I think that is reason for it's effectiveness in social anxiety as compared to other SSRI's. From my personal experience, Zoloft has been far superior to Prozac.


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## RockiNToM (Jun 15, 2009)

I thanks for your response.

I was on Zoloft too for over a year, and has been the only AD second to Paxil that I've been on the most. I've wanted to give antidepressants another go for some time, since coming off them for a long time, as my depression is affecting my life too much. I couldn't decide if Zoloft was worth giving another go at higher doses for the DRI effect or to try something I only explored very brief (Prozac). I feel inclined to try Prozac because it's largely unexplored for me, and has some positives that make me interested in trying it. _Some_ people have said Prozac has very little inhibition on their creativity and cognition - similarly can be said for Zoloft too, although I have come across more people supporting these claims with Prozac. I just need to gather more data on the pros and cons for each, and if there are any particularly bad aspects I need to know/remind myself of for each.


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## riptide991 (Feb 1, 2012)

I never had much luck with SSRI's on their own. Both actually have an effect on dopamine. I think prozac does but not 100% sure, I know Zoloft does for sure from studies I read. But yah I liked Zoloft with Remeron and now I'm on Zoloft with Wellbutrin XL. I find that this combo is amazing, at least so far.


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## CD700 (Apr 22, 2010)

kehcorpz said:


> I never had much luck with SSRI's on their own. Both actually have an effect on dopamine. I think prozac does but not 100% sure, I know Zoloft does for sure from studies I read. But yah I liked Zoloft with Remeron and now I'm on Zoloft with Wellbutrin XL. I find that this combo is amazing, at least so far.


At what dose does it effect Dopamine ?


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## ourwater (Jun 2, 2012)

Zoloft. Prozac is the only FDA approved drug for treating children.


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## Spungo (Jul 30, 2012)

RockiNToM said:


> I'm just wondering if anyone knows which of these has the most Dopamine activity. I know Zoloft has negligible DRI activity at certain doses (200mg?) and Prozac gets some DRI activity via 5-HT2C.


The reason they're both called "selective" serotonin drugs is that the effect on serotonin is >10x stronger than the next closest neurotransmitter. That means your only hope of getting any dopamine activity is by blocking the 5-HT2c receptor. Sertraline (Zoloft) might have the highest affinity blocking dopamine pumps, but it doesn't really mean anything because the effect on serotonin is still more than 10x stronger. You'll get serotonin syndrome before you get any meaningful dopamine re-uptake inhibition.



> What I'm trying to determine is which of these has the most stimulation for motivation in depression, least cognitive impairment, least dose induced anhedonia and fatigue.


I don't speak for everybody, but I found that:
-fluoxetine (Prozac) makes me more motivated
-sertraline has far less cognitive impairment
-sertraline has less anhedonia
-neither of them make me tired

I like fluoxetine a lot more than the other antidepressants because it lasts longer. Drugs like sertraline and citalopram work great, but they seem to wear off extremely fast. I could take sertraline in the morning and I would almost feel like crying before supper. I think the half-life posted on wikipedia is BS. There's no way it's anywhere close to 26 hours. The effect is completely gone within 12 hours.



> I've only ever tried Prozac once, for a brief period. In that period it gave me extreme nausea and GI upset


You could always try taking it at a different time. I find that taking Prozac in the morning makes me very sick at work. Taking it after work is fine. Taking it before bed is fine. Taking it once after work then once before bed is fine too, so the dosage itself is less important than the time of day.

You might want to check out SNRI drugs and bupropion. Dopamine can be moved around by both dopamine and noradrenaline transporters. Blocking noradrenaline transporters also blocks dopamine reuptake. SNRI drugs only block the noradrenaline transporters, but bupropion blocks both dopamine and noradrenaline transporters.


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## riptide991 (Feb 1, 2012)

blakeyz said:


> At what dose does it effect Dopamine ?


It is really dependent on the individual because of bioavailability and saturation rate of SERT as well as conversion to different metabolites. The average saturation rate of SERT was 80% at 50mg in the tests carried out by Pfizer. So you would want to at least double that to 100mg. I find that most people start noticing it at around 150-300mg. Zoloft binds to Dopamine Transporters more so than Wellbutrin or other dopamine agonists, but the problem is it has a strong affinity for SERT. So if you can saturate those receptors then its next target should be DAT.

I noticed increased vigilance at 200mg. I basically had great focus and alertness.

A lot of studies have been done on rats too because it's tough to do thorough tests on humans and rats have a similar brain to us. Here's one in particular:



> *Sertraline increases extracellular levels not only of serotonin, but also of dopamine in the nucleus accumbens and striatum of rats.*
> 
> Kitaichi Y, Inoue T, Nakagawa S, Boku S, Kakuta A, Izumi T, Koyama T.
> *Source*
> ...


I don't have the full text so I can't really say what doses they used but it is very promising none the less.


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## riptide991 (Feb 1, 2012)

Spungo said:


> You'll get serotonin syndrome before you get any meaningful dopamine re-uptake inhibition.


That's just silly. You can't honestly believe that? You can block SERT at 100% and not get serotonin syndrome. Your body downregulates production of SERT at axon terminals. This is why quitting an SSRI cold turkey usually produces withdrawal effects. You would have to take something that produces serotonin or a MAOI to get serotonin syndrome. Serotonin syndrome is very rare too. The problem is doctors warn about it due to all the different drug combinations that people combine.



Spungo said:


> You'll get serotonin syndrome before you get any meaningful dopamine re-uptake inhibition.
> -sertraline has far less cognitive impairment
> -sertraline has less anhedonia


That's because it has the greatest impact on Dopamine levels of the 2. Having a strong affinity for a receptor also does not mean it will not bind to other receptors. The way these drugs circulate through the brain is also a factor. It's not going to ignore other receptors because its looking for SERT. A lot of drugs like Prozac will bind to other receptor sites, they just don't create a statistically significant changes. What makes zoloft unique is that its affinity for DAT is so strong that it is more likely to bind to these receptors if it comes across them. The human brain is so complex that we cannot really make these assumptions, even Stahl brings up that sertraline does have a higher SERT affinity and most of it will go to SERT but in some people a big chunk can go to DAT. In fact, there are people who get really anxious on Zoloft as a result of this. But Zoloft has a pretty high effect in very specific brain regions when it comes to Dopamine as these areas are over saturated with these receptors and a drug does not get bound/metabolized on first pass. The study posted above shows the regions I'm talking about.


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## Cletis (Oct 10, 2011)

I've read that Zoloft affects dopamine more than any other SSRI. 

But this is a question for your doctor and/or pharmacist.


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