Don't Know What To Do

[KK77]

That might be the intent, but I'm not sure this is what actually happens. I suspect any increase in response is driven by other factors.

One way of testing whether a noradrenaline reuptake inhibitor has a real clinical effect in humans is the tyramine pressor response. When tyramine is ingested (or in research injected), it raises adrenaline levels which in turn increases blood pressure (this is the basis of the potential dietary issues with MAOIs). NAT/NET inhibitors block the adrenaline response and the subsequent BP spike. Of the two studies I'm aware of which specifically tested the venlafaxine pressor response, one found no impact at 300mg (Blier P, 2007 - PDF) and the other by the same research team did at 225mg and 300mg (Debonnel G, 2007 PDF). So make of that what you will, but given the binding affinity data I know which I'd put my money on.

---------- Post added at 18:50 ---------- Previous post was at 18:35 ----------



No, I said while it was classified as a SNRI it only really acted as a SSRI. I also said that yes, it was "an extremely weak noradrenaline/norepinephrine reuptake inhibitor." If you want to use that to claim it as a SNRI then you would also have to call the SSRIs with even greater NAT/NET inhibition SNRIs too. They seem to be more worthy of the title.



Only about half the venlafaxine is metabolized to desvenlafaxine and that which is is also only a weak NAT/NET inhibitor with Ki value of 558.4. The lack of a paroxetine metabolite is neither here nor there, it is a much more potent NAT/NET inhibitor right out of the box.

You are not a doctor, not medically trained, nor are you a pharmacist. It is not up to you to classify drugs either. Venlafaxine and other meds are categorised and classed by professional bodies based on many criteria.

I doubt whether you have even tried most of these meds, as you say you've been taking Tricyclics for "many years". People can give their experience of having taken a certain med but armchair pharmacology is a dangerous biz - esp when you are giving erroneous information.

[panic_down_under]

I'm not sure why this is, I've never needed to know, but I'm wary of the class in this case and it's obviously more important to look at what it actually does.

Exactly. Debating about the minutia is irrelevant to those taking it like Shelly whose issue seems to have been lost in this.

But I need to correct one item in the interests of full disclosure. There is a third tyramine pressor study which also found an effect (Harvey AT, 2000). However, the two Canadian studies previously cited still have me thinking that if there is an effect it can't be that strong if the same guys come up with two different results. The only difference between them seems to be one was supported by the drug company behind venlafaxine. OTOH, similar studies into other NAT inhibitors appear to be unequivocal.

I've quoted neuropharmacologist Ken Gillman several times in relation to serotonin syndrome, a subject on which he is an acknowledged expert. He seems to have no doubt: Venlafaxine: an enduring SNRI myth

[MyNameIsTerry]

I started CBT again today and he said he wants me on medication as I'm not currently anymore which my doctor was fine with. I've been on citalopram which I stopped for side effects, sexual and it just made me numb emotionally.
She put me on mirtazapine which I gained a stone in weight in very little time so I said I didn't want to continue with them.
Since I've gone through a break up and starting a new full time job and coped pretty well I think.
The CBT guy today said he thinks my main issue isn't social anxiety it's depression and trauma and I need to be on medication.

I didn't want to go back on any medication for the fact I don't want the side effects and also I want a family and I don't want to have to come off them if I get pregnant and don't want to be taking medication if pregnant anyway.

The CBT guy stated this medication as the SSRI gave the side effects numb and sexual issues which I don't want. He said this one wouldn't cause it, is this true?

He also said maybe sertraline though I know that's an SSRI.

I don't know what to do. I'd prefer to try the CBT without but he scared me saying I wouldn't get better without medication as well. He was very forceful about it. Thank you for reading.

Just to get back to this as I'm conscious of interupting to ask Ian a few questions (thanks Ian).

Wellbutrin is expensive and licenced for smoking cessation so it's hard to access and a GP may not be willing so you may need someone specalised for that one.

However, Trazadone might be a possibility as that's a recommended med for depression treatment in NHS Trust prescribing guidelines I've often seen. It's a later stage med though so they may want to try SNRI's first.

(just to add on to what Ian is saying with a bit of local knowledge)

I would get your GP's opinion. If we are talking a therapist, not a psychiatrist, his knowledge may be limited or even be biased. If you are progressing well without, it seems flawed to start introducing meds that come with the potential of side effects and switching.

Your GP can give a more general opinion and help you sort this out with your therapist.

[MyNameIsTerry]

Exactly. Debating about the minutia is irrelevant to those taking it like Shelly whose issue seems to have been lost in this.

But I need to correct one item in the interests of full disclosure. There is a third tyramine pressor study which also found an effect (Harvey AT, 2000). However, the two Canadian studies previously cited still have me thinking that if there is an effect it can't be that strong if the same guys come up with two different results. The only difference between them seems to be one was supported by the drug company behind venlafaxine. OTOH, similar studies into other NAT inhibitors appear to be unequivocal.

I've quoted neuropharmacologist Ken Gillman several times in relation to serotonin syndrome, a subject on which he is an acknowledged expert. He seems to have no doubt: Venlafaxine: an enduring SNRI myth

Thanks Ian, that's an interesting read.

Ven hits about 80% SERT at 75mg and then the rest achieves a bit over 5% from what I've seen. Cit hits 80% SERT at 20mg and advancing to 40 then 60 buys you an extra 5% or so. If Ven isn't delivering above 150mg for NE then it's hard to understand the benefit other than being a drug with a breathy ability to titrate with.

Something I've found strange is that WHO show 60mg Duloxetine equivalent to 100mg Ven. Since Duloxetine is adding in the NE at that point it makes me question how they made that judgement and whether it is based more on SERT?

https://www.whocc.no/atc_ddd_index/?...yes&code=N06AX

Not knowing about the many other meds in that comparator list makes it difficult to understand as I would have thought it to be more 75mg and I don't know what those others are working on at those dosages? I need to check out Duloxetine at 30 & 60mg to understand that better.

[panic_down_under]

Ven hits about 80% SERT at 75mg and then the rest achieves a bit over 5% from what I've seen. Cit hits 80% SERT at 20mg and advancing to 40 then 60 buys you an extra 5% or so. If Ven isn't delivering above 150mg for NE then it's hard to understand the benefit other than being a drug with a breathy ability to titrate with.

I'd be wary about taking NET (or SERT) occupancy as a guide to anything except the likely minimum effective dose. Blocking the transporters does not in itself produce a therapeutic response. It doesn't even seem necessary. By all accounts the French antidepressant tianeptine (Stablon) is at least as effective as the SSRIs (and usually faster to kick-in) yet it is a serotonin reuptake enhancer, i.e. it has the opposite effect (when taken with a SSRI the two cancel each other out and there is no therapeutic response). It seems how SERT is affected is less important than that it is, and this probably applies equally to the NET too.

The other issue is the occupancy data is theoretical. What actually happens in a living brain and body may be completely different and varying from person to person. I need to take very high AD doses because I apparently metabolize meds a little differently, and more efficiently than most (my immune system is also hyperactive which may also be a factor) so 75mg venlafaxine would probably barely register with my brain (I did try it soon after it became available and it had the same immediate manic affect as the SSRIs, duloxetine didn't, but it didn't work for me either although it might have at higher doses than my then psychiatrist was willing to risk).

Something I've found strange is that WHO show 60mg Duloxetine equivalent to 100mg Ven. Since Duloxetine is adding in the NE at that point it makes me question how they made that judgement and whether it is based more on SERT?

It may well be. I suspect what NE activity there is is merely the icing on the cake with serotonin inhibition doing almost all the heavy lifting.

Antidepressant equivalence seems to be a very imprecise 'science.' Much less reliable than BZD equivalence, though that isn't 100% exact either.