Misc Effexor (Venlafaxine) - Neurotransmitter levels question

[optimuswind]

I currently take 150mg Venlafaxine (Effexor) on prescription. I have only been on it about 3 months.

I plan to get off it sooner rather than later, I have some questions regarding what happens to the built up Serotonin / Norepinephrine in the brain after stopping.

The drug prevents the re-uptake of S/N, so my brain has an excess of S/N right now, correct? When I stop, my brain will be able to re-uptake the neurotransmitters again (Presumably the drug doesn't completely stop the re-uptake, just slows it down a lot, because if it stopped it completely then you would get serotonin syndrome and die, right?).

How soon after stopping will my serotonin/nore levels return to normal, is my main question really.

Edit: Oh, also, I take diazepam also which I plan to come off of aswell, will it help to stay on the diazepam while withdrawing from the Venlafaxine to reduce any symptoms, and then come off the diazepam? (I've come off diazepam once before and it wasn't that rough, just a week of, well, feeling rough, but I read that coming off Effexor is really bad and might be worse for me, but saying that, in the past I have quit Citalopram cold turkey after taking it for 2 years and felt nothing, so maybe i'll get lucky with this too, I haven't been on it very long either. Anyway thanks in advance.)

 

[Swimmingdancer]

This is a tough question to answer, because it's still not fully understood exactly how SSRIs/SNRIs even work and exactly what goes on in the brain when you stop taking them.

Basically my understanding, in laymen's terms is this: In the brain, messages are passed between two nerve cells via a chemical synapse, a small gap between the cells. The "presynaptic" cell sends the information, releasing serotonin (or other neurotransmitters) into that gap. The serotonin is then recognized by receptors on the surface of the receiving - "postsynaptic" - cell, which upon this stimulation, relays the signal. Probably around 10% of the serotonin is lost in this process and the other 90% is released from the receptors and taken by monoamine transporters back into the presynaptic cell - which is called "reuptake". You can imagine basically the same thing happening with regards to norepinephrine from an NRI.

SRIs reduce this reuptake of serotonin. This causes the serotonin to stay in the gap longer than it normally would, so it can repeatedly stimulate the receptors of the recipient cell. The current theory is that SRIs can help with certain types of depression because presumably a lower homeostatic level of serotonin is primarily responsible for some types of depression. (This is unclear and somewhat disputed, however).

So I would assume when you stop taking an SRI, the drug will slowly be eliminated from your system, causing less and less inhibition of reuptake, until reuptake is back to normal. It's not like there is really a build-up of huge amounts of serotonin sitting in your brain that is suddenly taken up all at once. Does that make sense?

BUT you also have to consider that SRIs/SNRIs cause changes in the brain, including downregulating (lowering the sensitivity and/or number) of certain receptors. This may be partly responsible for the fact that these drugs tend to not "work" for the first several weeks of taking them, and why people get withdrawal symptoms upon stopping abruptly.

Another potential factor that I'm wondering about is if it's possible that your brain starts making less serotonin in response to the constant presence of an SRI? If so, that would play a role in your levels of serotonin returning to "normal".

 

[manman]

I would def. get off the effexor first, wait a month or two, than tackle the diaz.
No point in going off both at the same time, unless you must, imo.

 

[Swimmingdancer]

I'm not sure I wouldn't consider doing it the other way around, tapering off the diazepam first and then the venlafaxine...? Generally venlafaxine is easier to quit and some doctors even use it to help with benzo withdrawal (although I'm not sure how effective that is). Maybe someone who has used benzos during SNRI withdrawal and vice versa can tell you if it helped or not? I guess it also depends if you want to tackle the easier one first or the harder one first and which you were hoping to quit soonest. I agree that it's probably a bad idea to try to get off them both at the same time.

 

[optimuswind]

Another potential factor that I'm wondering about is if it's possible that your brain starts making less serotonin in response to the constant presence of an SRI? If so, that would play a role in your levels of serotonin returning to "normal".

I wasn't expecting such a great reply, so thanks for that.

This is also something I was wondering about aswell, because if that's the case then that may mean a lower-than-normal/average levels for a while also after stopping, before then going back up as the brain starts making more of it's own again?

The main reason I wanted to know about the complexities of the neurotransmitters is that I plan to take up smoking marijuana again after a long break, but I have read that people who are taking it with Effexor can experience really bad side effects which sound like serotonin syndrome, so I wanted to figure out how long it would be before I could safely smoke after stopping. Also while this does seem to be a common thing, there are also other people (forum posts etc) that say they have been taking Effexor for years and at greater amounts than those that have had bad side effects and not had anything happen to them while smoking, so like with most things everybody is different, but I just don't want to take the risk.

On top of that, it's for the best in general to get off this drug (aswell as the benzos) as neither seem to help much at all for what I am prescribed them for (anxiety / social phobia). Well, the diazepam did at first, but you quickly develop a tolerance to the anxiolytic effects and at this point I would need to take around 80-100mg to feel any anxiolytic effect, yet it seems you gain no tolerance to the anterograde amnesia side-effect of the drug (have also tried alprazolam and clonazepam, same deal except the alprazolam was more potent yet lasted about half an hour, the clonazepam was probably the best (when self medicating) but here in the UK it's not licensced for prescription for my diagnosis so the doctor won't give me it. The Diazepam was pretty ineffective to begin with anyway with regards to the anxiolytic effect it gave.

Anyway I digress, but I think I understand your explaination of the way that we currently think SSRI/SNRI's work, and if I do understand correctly and the medical thinking behind them is right, it shouldn't be long after cessation of administration before the levels are reduced, perhaps even before you finish feeling the physical effects of withdrawal?

 

[Swimmingdancer]

Anyway I digress, but I think I understand your explaination of the way that we currently think SSRI/SNRI's work, and if I do understand correctly and the medical thinking behind them is right, it shouldn't be long after cessation of administration before the levels are reduced, perhaps even before you finish feeling the physical effects of withdrawal?

Yes, that's what I think. The falling level of reuptake inhibition combined with the changes that have happened in your receptors etc are probably responsible for withdrawals, and then it takes a while for everything to return to normal. Withdrawal is probably more complicated than that too. When I quit an SNRI abruptly I had strange withdrawal symptoms, I'm not really sure what causes them, the withdrawal syndrome is not well understood. Personally I didn't really find it that bad mentally though, it was certainly easy compared to other drugs I've quit and they didn't last all that long for me. Gradually tapering off of it should greatly reduce or eliminate withdrawal symptoms.

I don't know about the cannabis thing. I find smoking weed very unpleasant during any drug withdrawal, I'm sure it varies greatly from person to person. I believe the half-life of one of venlafaxine's active metabolites is 6-14 hours. So that would mean that 5 half-lifes (around 97% elimination) could be up to 70 hrs. So it has a relatively short half-life compared to some other antidepressants. People tend to find the acute withdrawal symptoms to emerge within the first 3 days after stopping and then start to improve (according to one study on venlafaxine WDs). So I would also assume that after the drug is eliminated it should be safe to smoke some weed (as far as an interaction with the venlafaxine itself is concerned). I would start with a very small amount to see how it affects you though.

 

[optimuswind]

I wasn't planning on getting any [cannabis] for about 3 weeks anyway, so if I start tapering off now and stopping completely before smoking any, then just starting with a small amount, I think that should be fine. Just wanted to make sure the levels wouldn't stay high for so long and I'd end up killing myself with serotonin syndrome or something. Had a scary experience in the past with bk-mdma abuse and thought I had that so now it's caution first.

Thanks again.

 

[MrSpeedyG]

Bit off topic but just in regards to adding in another theory as to why SSRIs take a while to build up/take effect, is that they are highly protein bound in the blood (therefore inactive) so free levels take time to build up. Could be the factor or one of the many factors. IIRC another mechanism through which SSRIs alleviate depression is through neurogenesis I would assume of the serotonin network... I think it was a study but didnt have the link.

 

[optimuswind]

I was wondering if the effects of SSRIs/SNRIs go down so rapidly, like within a week or so, or even days, why does it take 6~ weeks for them to build up and take an effect?

Also I might want to stay on the Effexor but after seeing Erowid list it with cannabis as "Life-Threatening" combination, it kind of scares me, but I can't find any information as to why, chemically, this would happen. Most of the searches come up with people saying they take them both together and nothing happens, others say it allows them to get high(er) with less weed, but the majority say no difference, and nothing about the science as to why it *would* cause a bad/fatal contraindication. Can anyone shed some light on this?

 

[shreddedlettuce]

I can't shed any light on your question, but I just want you to be aware that you need to taper off venlafaxine very carefully if you are going to stop taking it.
Don't just stop taking it, the "brain zaps" are a huge factor with this drug if it isn't tapered down comfortably.

 

[Swimmingdancer]

I was wondering if the effects of SSRIs/SNRIs go down so rapidly, like within a week or so, or even days, why does it take 6~ weeks for Hthem to build up and take an effect?

It's likely due to 2 main factors (which I and the other poster already alluded to). One is that these drugs take a while to build up in the system. This is partly due to their long half-life and the fact that many ADs are quite protein-bound - it can take days or even weeks depending of the specific drug to reach a "steady state" in blood levels. What protein-bound means is they bind to proteins in the blood, so the bound drug is kept in the blood stream while the unbound portion of the drug may be used. So, if a drug is, say, 90% bound to a binding protein and 10% is free, that means that only 10% of the drug is active in the brain causing pharmacological effects or being metabolized (not sure how protein-bound venlafaxine is though and relatively-speaking it doesn't take all that long to reach steady state). The other, and likely primary, reason is that, at I said, these drugs cause complex changes in the brain which happen gradually, which is likely why they can take weeks to start producing noticeable effects. Let me know if you'd like more info on this.

Also I might want to stay on the Effexor but after seeing Erowid list it with cannabis as "Life-Threatening" combination, it kind of scares me, but I can't find any information as to why, chemically, this would happen. Most of the searches come up with people saying they take them both together and nothing happens, others say it allows them to get high(er) with less weed, but the majority say no difference, and nothing about the science as to why it *would* cause a bad/fatal contraindication. Can anyone shed some light on this?

Erowid explains why they list it under potentially life-threatening, it's because one person had a severe adverse reaction from combining them - and they note that some people are fine with combination. I believe the man's Dr said it was likely serotonin syndrome. The idea is that cannabis may increase serotonin and have a mild SRI effect as well, so using it while on an SRI might potentially cause serotonin syndrome. Obviously that doesn't happen with everyone, especially not to the degree that that man experienced, but it's a consideration and I've heard other people say they had bad reactions. I would hazard a guess that it depends on the venlafaxine dose, the amount of weed smoked, the strain of the weed, and if they are using any other drugs (as well as luck and individual brain chemistry). However it 's possible that serotonin syndrome was a misdiagnosis (SS is very hard to diagnose properly). See this thread discussing it: Pot & Effexor caused seratonin syndrome!

 

[Master_Khan]

Very educational, great explanation of the re uptake process; good luck to the OP.

 

[Foreigner]

I was on an SSRI for 3 years and even after tapering the dose I ended up having horrible withdrawals and brain zaps once I reached the point of stopping the drug entirely. I think eventually your brain becomes so dependent on the pharmaceutical to regulate its serotonin functions that it freaks out a bit once that system is taken away. The first week and a half I could barely walk without the room spinning, and it took one week more to start to feel like a normal human being again. I'm told my experience isn't typical - most people who taper do not suffer this intensely, but I did. I went from 10mg to zero and the withdrawals started. For most people, by the time they're down to 10mg their withdrawals are minor. Maybe in sensitive people, the sudden absence is still physically shocking, and the neurotransmitter levels are still not adapted to being produced independently of the drug.

The fact that they call it "SSRI discontinuation syndrome" just goes to show they are trying to cover up the fact that it's straight up withdrawls. The symptoms are the same. I had heavy sweating and worse night sweats, plus minor tremors here and there.

So to answer your question: from the last dose of the SSRI to the time you feel like a normal human being again is 2 weeks give or take. My nickname for this process was the "great thawing". Swimmingdancer said that weed made the withdrawals worse but in my case weed was a godsend.