# SNRIs work for me but not SSRIs.. why?



## sadboy (Jan 29, 2010)

Hey,

I have tried 4 antidepressants:

Effexor XR @ 75 mg: Worked the 1st time, not the 2nd
Cymbalta @ 60 mg: I'm on it right now and it works
Paxil @ 40 mg: Didn't work
Celexa @ 40 mg: Didn't work but I didn't give it enough time

Is there a reason why only the SNRIs work for me or is it just a coincidence? Also they work pretty fast, I could see a difference the very first day I took them. I thought that maybe it's because they act on norepinephrine and dopamine too but then I realized that the Effexor XR only acts as a SSRI at 75 mg.


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## arth98 (Nov 30, 2009)

I think you have several mistakes but its normal for some ADs too work and some to not work for a person
as with all of us, the placebo effect from meds can be strong and its generally said that an AD working from day 1 must be from placebo effect only


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## Arisa1536 (Dec 8, 2009)

sadboy said:


> Hey,
> 
> I have tried 4 antidepressants:
> 
> ...


Well i have the same thing, exactly the same.
SNRI's work great for me whereas the SSRI's worked at the beginning but then they were pretty lethal for me, i was crying, eating, stressed and paxil and lexapro which i had in high doses did nothing for my anxiety, it got so bad i had serotonin overload due to being prescribed a higher dose.

A higher dose of effexor will not do this, in fact 300MG which i am on is really effective.

il tell you what my shrink told me, the good one when i started them in 2006 he said_ "SNRI's are for people who do not respond to standard SSRI antidepressants" "they are also a safer alternative to MAOI's and old school Tricyclics which have nasty side effects"_ :yes

there was no weight gain or fatigue on the effexor for me
with the SSRI's all of the ones i tried (lexapro, paxil and prozac/fluox) i had nausea, appetite changes and headaches, such bad headaches

SNRI's work for you, they work for me, they work for other people on this forum too, they are good. i recommend them :boogie


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## jim_morrison (Aug 17, 2008)

I agree, the SSRI's I tried had no positive effect on me, on paxil I had serotonin overload too and was constantly agitated (I suspect due to the fact that paxil is so potent for the serotonin transporter), lexapro was a bit more benign, for me it was just like a sugar pill albiet with sexual side effects.

However the SNRI effexor does work quite well for my depression. 
As far as 75 mg of effexor working better for you, most SRI's (SSRI's/SNRI's etc) have differing preferences for serotonin subtypes, common medical theory is that the 5HT1 subtype receptors mediate the best antidepressant/anxiolytic effect of the SSRI's, according to this study, effexor has been shown to act preferentially on 5-HT1A and 5-HT1B receptors, which may explain why it was working better for you even at a serotonin specific dose. 
http://www.ncbi.nlm.nih.gov/pubmed/...inkpos=4&log$=relatedreviews&logdbfrom=pubmed


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## sadboy (Jan 29, 2010)

jim_morrison said:


> I agree, the SSRI's I tried had no positive effect on me, on paxil I had serotonin overload too and was constantly agitated (I suspect due to the fact that paxil is so potent for the serotonin transporter), lexapro was a bit more benign, for me it was just like a sugar pill albiet with sexual side effects.
> 
> However the SNRI effexor does work quite well for my depression.
> As far as 75 mg of effexor working better for you, most SRI's (SSRI's/SNRI's etc) have differing preferences for serotonin subtypes, common medical theory is that the 5HT1 subtype receptors mediate the best antidepressant/anxiolytic effect of the SSRI's, according to this study, *effexor has been shown to act preferentially on 5-HT1A and 5-HT1B receptors, which may explain why it was working better for you even at a serotonin specific dose.*
> http://www.ncbi.nlm.nih.gov/pubmed/...inkpos=4&log$=relatedreviews&logdbfrom=pubmed


Interesting. Do you know other antidepressants that act on the 5-HT1A and 5-HT1B receptors? I will have to find another one if my insurance doesn't cover Cymbalta because it's too expensive.


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## meyaj (Sep 5, 2009)

Cymbalta is weaker than Effexor. Generally if Effexor doesn't work for some reason, Cymbalta probably won't either, it's usually a choice for people who can't tolerate the former. But perhaps you should try a higher dose of Effexor, 75mg is VERY low and I'm guessing that's why it doesn't seem to work anymore. You need a more substantial dose.

Because, personally I'd stay away from Cymbalta if you value your liver. It can do awful stuff. "Hepatitis that may progress to cirrhosis" sounds like a really pleasant side effect... not a really common one but it's indicative of liver toxicity. So is that fact that jaundice is a potential side effect. Oh, and a case of somebody dying from liver FAILURE linked to Cymbalta was reported post-marketing.

Maybe it's just me because my liver isn't in the greatest shape to begin with, but when you're taking medication, your liver is absolutely invaluable but often susceptible to damage. It's also usually critical to the proper function of the medications. I'd be concerned with making sure I protect it. Nardil is another antidepressant that's not particularly nice on the liver but Cymbalta really takes the cake, and many experts believe that it shouldn't even have a place in a psychiatrist's pharmacologic toolbelt because there are more similar and much more effective drugs on the market that AREN'T so hepatotoxic. It's filling a need that isn't really there... well, except for Big Pharma's bottom line.

If you want to try an *ahem* real SNRI, the tricyclics can be great and, while not perfect in terms of side effects, I can tell you I tolerated it MUCH better than (Side-)Effexor.

But probably the best idea is to try Effexr again, with at LEAST double the dose, and probably take it with Remeron as well, just by looking at the way they bind to each receptor, it's clear the two drugs have synergy. You get SNRI action and hit like a dozen receptors in *just* the right way. Remeron also indirectly increases activity at the 5HT1A receptor, generally the MAIN target of many if not most antidepressants, and so should enhance Effexor's 5HT1A agonism. 5HT1A increases the release of dopamine, so with these 2 drugs combined, you should get decent dopamine effects as well.

There is a very good reason they call this drug combination "California Rocket Fuel!" It does just about everything, even sigma-1 agonism which I can find preliminary studies about being just another one of Effexor's effects.


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## jim_morrison (Aug 17, 2008)

sadboy said:


> Interesting. Do you know other antidepressants that act on the 5-HT1A and 5-HT1B receptors? I will have to find another one if my insurance doesn't cover Cymbalta because it's too expensive.


I'd say go for effexor at a higher dose preferably 150 - 300 mg. Compared to cymbalta, effexor is stronger, safer, has less drug-drug interactions and is also available in generic so it would be cheaper too so your insurance company may cover it.


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## Arisa1536 (Dec 8, 2009)

jim_morrison said:


> I'd say go for effexor at a higher dose preferably 150 - 300 mg. Compared to cymbalta, effexor is stronger, safer, has less drug-drug interactions and is also available in generic so it would be cheaper too so your insurance company may cover it.


Definitely the better option 
Give them time to work and as jim said anything over 150MG is preferable and i have not found them harmful to my liver, well i have had regular tests since i was a bit abusive with pain killers a few months ago which inflamed my liver, but the effexor' seems relatively safe on the liver so thats always a plus :yes


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## sadboy (Jan 29, 2010)

meyaj said:


> Cymbalta is weaker than Effexor. Generally if Effexor doesn't work for some reason, Cymbalta probably won't either, it's usually a choice for people who can't tolerate the former. But perhaps you should try a higher dose of Effexor, 75mg is VERY low and I'm guessing that's why it doesn't seem to work anymore. You need a more substantial dose.
> 
> Because, personally I'd stay away from Cymbalta if you value your liver. It can do awful stuff. "Hepatitis that may progress to cirrhosis" sounds like a really pleasant side effect... not a really common one but it's indicative of liver toxicity. So is that fact that jaundice is a potential side effect. Oh, and a case of somebody dying from liver FAILURE linked to Cymbalta was reported post-marketing.
> 
> ...


I'm very tempted to try that but wouldn't that combination increase the risk of serotonin syndrome?


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## meyaj (Sep 5, 2009)

sadboy said:


> I'm very tempted to try that but wouldn't that combination increase the risk of serotonin syndrome?


Nope, Remeron is quite commonly used to augment SSRIs/SNRIs. Most of its action is based on BLOCKING certain receptors, as far as I'm aware it doesn't really elevate levels of serotonin.


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## sadboy (Jan 29, 2010)

meyaj said:


> Nope, Remeron is quite commonly used to augment SSRIs/SNRIs. Most of its action is based on BLOCKING certain receptors, as far as I'm aware it doesn't really elevate levels of serotonin.


Alright thanks! I will probably ask my doctor to try that next if my insurance doesn't cover Cymbalta.


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## meyaj (Sep 5, 2009)

sadboy said:


> Alright thanks! I will probably ask my doctor to try that next if my insurance doesn't cover Cymbalta.


I personally would be taking that stuff at all, it can be so harsh on the liver. At a proper dose, Effexor should be able to do everything Cymbalta does and more, it's from what happened to you originally with Effexor, and the fact the the WEAKER Cymbalta IS helping you, that there's an extremely high probability of a proper dose of Effexor working better you anyways... and adding Remeron on top of it can have VERY powerful effects if one can tolerate it, if you even need it.


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## jim_morrison (Aug 17, 2008)

sadboy said:


> I'm very tempted to try that but wouldn't that combination increase the risk of serotonin syndrome?


I think meyaj has already covered most of this, but it's very unlikely that the combo would cause serotonin syndrome, infact it would possibly even lower the chances of it, since remeron is a potent 5HT2 antagonist. 
However remeron can have alot of side effects, so it is usually used as a second line agent when treating depression. 
So your best bet would be to try a higher dose of effexor alone first, preferably in the 150-300 mg range. If that's still not working then you could try adding the 5HT1A agonist Buspar, while Buspar is usually pretty useless when taken on its own, it has been used to augment SSRI/SNRI's with some success.
If all that is still failing, then it may be time to think about the effexor + mirtazapine combo.


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## sadboy (Jan 29, 2010)

Thanks guys. I've checked and my insurance covers Cymbalta. Without insurance it costs 140$ CAN for 1 month of 60 mg pills and 280$ CAN for someone that needs 120 mg! That's some crazy shizzle.

I'll ask my doctor to switch me to Effexor XR because even with insurance it's gonna cost me a lot if I have to increase the dosage to 90 mg or 120 mg.


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## csrpj (Feb 24, 2010)

speaking of SNRIs, anybody with experience with milnacipran (or ixel, or savella)? it has a 3:1 N to S ratio (versus efflexor's 1:30 N:S).


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## Arisa1536 (Dec 8, 2009)

sadboy said:


> Thanks guys. I've checked and my insurance covers Cymbalta. Without insurance it costs 140$ CAN for 1 month of 60 mg pills and 280$ CAN for someone that needs 120 mg! That's some crazy shizzle.
> 
> I'll ask my doctor to switch me to Effexor XR because even with insurance it's gonna cost me a lot if I have to increase the dosage to 90 mg or 120 mg.


Hey there yeah i agree with meyaj that cymbalta can be dangerous on the liver and there is no proof that it is stronger or more effective than efexor for treating depression and anxiety

SSRI's are selective serotonin re uptake inhibitors meaning they only work on serotonin receptors.
SNRI's are Serotonin-norepinephrine reuptake inhibitors meaning they affect both serotonin and norepinephrine receptors and that would be why u feel the benefits because the norepinephrine levels are in need of a boost, if u have a chemical imbalance that is, if not the norepinephrine mixed with serotonin is still getting an increase rather drastically and its doing you good :d

personally at first i found efexor wonderful and for a good year to year and half they worked on everything from my eating disorder to my anxiety and phobias but the depression was always a battle and make sure that if u start to experience major depression more than once over the next two years that you do not leave it like i did  well i did tell the docs but they said i have tried every other medication, not true off course but again doctors nowadays like SSRI and SNRI promotion. I hope they do work for you because you will avoid having to withdraw from them and try other pills.

Augmentation with remeron is a good idea 
it seems to be safer than withdrawal from Efexor and has been effective in people on other forums, also u may want to see the reviews form people on revolutionhealth.com who have reviewed efexor and remeron taken together for depression


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## broflovski (Feb 1, 2011)

jim_morrison said:


> However the SNRI effexor does work quite well for my depression.
> As far as 75 mg of effexor working better for you, most SRI's (SSRI's/SNRI's etc) have differing preferences for serotonin subtypes, common medical theory is that the 5HT1 subtype receptors mediate the best antidepressant/anxiolytic effect of the SSRI's, according to this study, effexor has been shown to act preferentially on 5-HT1A and 5-HT1B receptors, which may explain why it was working better for you even at a serotonin specific dose.
> http://www.ncbi.nlm.nih.gov/pubmed/...inkpos=4&log$=relatedreviews&logdbfrom=pubmed


I still can't understand how any SRI may be preferential for some definite 5HT receptor subtype, unless it acts as a direct agonist in it (as vilazodone for 5HT1a) or, indirectly, as antagonist in others (like fluoxetine in 5ht2c/2a, so activation with serotonin, overall increased by reuptake inhibition, does not effect blocked receptors, "preferentially" activating unblocked ones). Such agonism/antagonism is not shown for Effexor, as I know (while activation of opioid receptors is demonstrated for this close relative of tramadol - it may have some contribution to the antidepressant effect as to the severity of withdrawal).


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## foxy (Jul 3, 2010)

meyaj said:


> Nope, Remeron is quite commonly used to augment SSRIs/SNRIs. Most of its action is based on BLOCKING certain receptors, as far as I'm aware it doesn't really elevate levels of serotonin.


 no it just makes you fatter than a pig


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## foxy (Jul 3, 2010)

*ssri snri*

i carnt take snri,s where ssri,s are cool for me. effexor near on nuked me. an if your on 300 mg an decide its not the med for you, then get ready for the biggest withdrawl ever. its not pretty, cymbalta is used now for pain relief as well as people on the med found a lot of aches an pains were cool on cymbalta.Did nothing for my depression but my jiont,s felt magic :bash


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