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Shelly06

06-06-17, 01:32

panic_down_under

06-06-17, 06:51

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'm not really sure what you're saying here. Do you think you're coping pretty well and feel you don't need medication? If so, why the CBT?

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.

Unfortunately, this isn't as clearcut a decision as you may think. Uncontrolled maternal anxiety and/or depression can affect the baby too, both immediately and in the longer term. Babies born to anxious or depressed mothers tend to have lower birth weights (http://www.ncbi.nlm.nih.gov/pubmed/20970195), be born prematurely (http://news.health.com/2008/10/23/depression-pregnancy-preterm-birth-risk/) and have impaired neuronal development (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447112/). As children and adults they are more prone to asthma (http://www.ncbi.nlm.nih.gov/pubmed/19348924), dyslexia (http://rense.com/general57/stress.htm") and to have learning difficulties (http://www.psychologytoday.com/blog/singletons/201205/wakeup-call-mothers-be-new-pregnancy-stress-findings). They are also much more likely to develop anxiety disorders and/or depression later in life.

Before becoming pregnant you really need to discuss your treatment options thoroughly with your family doctor and gynecologist and also an obstetrician if possible.

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?

Venlafaxine may, or may not cause emotional numbing. This is something which all antidepressants can potentially do. Whether you're affected depends more on individual reactions than the meds themselves. Just because you experienced it with one SSRI doesn't mean they will all affect you that way.

Venlafaxine is as likely to cause sexual dysfunction as most of the others. The only ones which usually don't are Wellbutrin (bupropion), Remeron (mirtazapine) and Desyrel, Oleptro (trazodone). Trazodone may enhance the libido at doses above 200mg/day.

Wellbutrin is a very stimulating antidepressant which many with anxiety disorders find hard to cope with, but small adjuvant doses (<=75mg) may counter SSRI/TCA caused sexual dysfunction, usually without increasing anxiety. The slow-release versions of the med seem to be a little more effective than the immediate-release formulation.

Supplementing a SSRI with 30mg Buspar (buspirone) can significantly reduce sexual dysfunction. Mianserin (Bolvidon, Depnon, Norval, Tolvon) at 15-20mg/day has been reported to ease dysfunction in about 60% of cases when taken daily (the almost chemically identical mirtazapine can also be beneficial but anecdotally isn't quite as good as its mianserin parent). It may take 3-4 weeks to become active. The 5-HT3 antagonist ondansetron (Zofran), a potentially very effective anti anxiety med BTW, supposedly temporarily reduces dysfunction if taken 2-3 hours beforehand, but cost might limit its use.

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

While classified as a SNRI, venlafaxine is really only a SSRI. Sertraline is generally considered the safest antidepressant to be on if pregnant, or breast-feeding.

I'd prefer to try the CBT without but he scared me saying I wouldn't get better without medication as well.

I'd be getting a second opinion.

Shelly06

06-06-17, 16:44

I'm not really sure what you're saying here. Do you think you're coping pretty well and feel you don't need medication? If so, why the CBT?

------- My issues that everyone has said and I've always believed have been social anxiety and gad. I wanted cbt for the social anxiety (though this has improved as I said I started work full time this year and that job has me being in contact with numerous ppl and taking charge as well) and to help get my life sorted out, he's come out with that he thinks it's moderate depression and if that was sorted the rest would just go away.

Unfortunately, this isn't as clearcut a decision as you may think. Uncontrolled maternal anxiety and/or depression can affect the baby too, both immediately and in the longer term. Babies born to anxious or depressed mothers tend to have lower birth weights (http://www.ncbi.nlm.nih.gov/pubmed/20970195), be born prematurely (http://news.health.com/2008/10/23/depression-pregnancy-preterm-birth-risk/) and have impaired neuronal development (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447112/). As children and adults they are more prone to asthma (http://www.ncbi.nlm.nih.gov/pubmed/19348924), dyslexia (http://rense.com/general57/stress.htm") and to have learning difficulties (http://www.psychologytoday.com/blog/singletons/201205/wakeup-call-mothers-be-new-pregnancy-stress-findings). They are also much more likely to develop anxiety disorders and/or depression later in life.

Before becoming pregnant you really need to discuss your treatment options thoroughly with your family doctor and gynecologist and also an obstetrician if possible.

------- I've read about things like that, in this day and age though who isn't anxious etc to some extent or down from time to time. I think me feeling down is just due to my miserable life right now to be honest with you, anyone living the life I do right now would feel down.

Venlafaxine may, or may not cause emotional numbing. This is something which all antidepressants can potentially do. Whether you're affected depends more on individual reactions than the meds themselves. Just because you experienced it with one SSRI doesn't mean they will all affect you that way.

Venlafaxine is as likely to cause sexual dysfunction as most of the others. The only ones which usually don't are Wellbutrin (bupropion), Remeron (mirtazapine) and Desyrel, Oleptro (trazodone). Trazodone may enhance the libido at doses above 200mg/day.

------- this is the side effect I didn't want to go through again either I don't want the sexual issues on top. I've had mirtazapine due to the weight gain issues wouldn't again. Is wellbutrin and the other avaliable over here. And I'm presuming if at anytime did I get pregnant they wouldn't be OK to take.

Wellbutrin is a very stimulating antidepressant which many with anxiety disorders find hard to cope with, but small adjuvant doses (<=75mg) may counter SSRI/TCA caused sexual dysfunction, usually without increasing anxiety. The slow-release versions of the med seem to be a little more effective than the immediate-release formulation.

Supplementing a SSRI with 30mg Buspar (buspirone) can significantly reduce sexual dysfunction. Mianserin (Bolvidon, Depnon, Norval, Tolvon) at 15-20mg/day has been reported to ease dysfunction in about 60% of cases when taken daily (the almost chemically identical mirtazapine can also be beneficial but anecdotally isn't quite as good as its mianserin parent). It may take 3-4 weeks to become active. The 5-HT3 antagonist ondansetron (Zofran), a potentially very effective anti anxiety med BTW, supposedly temporarily reduces dysfunction if taken 2-3 hours beforehand, but cost might limit its use.

------ So there's nothing apart from those three that doesn't cause the sexual issues or to take an SSRI and have to take something else as well to counter the sexual issues effects of it.

While classified as a SNRI, venlafaxine is really only a SSRI. Sertraline is generally considered the safest antidepressant to be on if pregnant, or breast-feeding.

----- Sertraline was the other he mentioned wanting me to be on maybe, I just don't want the sexual issues it frustrates me even more.

I just don't have time to wait years in my eyes with wanting a family I'm 35 now which is making me wary about going back on medication as well, though when I have been on medication before I didn't noticed a difference apart from the side effects.

I'm back to see him a couple of weeks. Just never had one before trying to hound me into medication. I do have to see my doctor soon about an unrelated issue but I'll ask her what she thinks as well.

I'd be getting a second opinion.

Thank you for your response my replies are within the above

panic_down_under

06-06-17, 23:03

------- this is the side effect I didn't want to go through again either I don't want the sexual issues on top. I've had mirtazapine due to the weight gain issues wouldn't again. Is wellbutrin and the other avaliable over here. And I'm presuming if at anytime did I get pregnant they wouldn't be OK to take.

Wellbutrin, buspirone and trazodone are all available, but as I understand it NHS GPs are restricted in what they can prescribe so you may need to see either a private GP, or psychiatrist. Getting a psychiatrist's opinion would be a good idea anyway.

------- I've read about things like that, in this day and age though who isn't anxious etc to some extent or down from time to time. I think me feeling down is just due to my miserable life right now to be honest with you, anyone living the life I do right now would feel down.

That may be the case, but after a while anxiety disorders and depression take on a life of their own independent of their triggers so getting your life sorted won't necessarily resolve the psych issues.

------ So there's nothing apart from those three that doesn't cause the sexual issues or to take an SSRI and have to take something else as well to counter the sexual issues effects of it.

There is no way of knowing how a particular med will affect libido except by trying it, but those 3 are the only ones which rarely have an adverse impact.

though when I have been on medication before I didn't noticed a difference apart from the side effects.

What were you on before and at what dose?

KK77

14-06-17, 00:20

While classified as a SNRI, venlafaxine is really only a SSRI.

This is not true. Venlafaxine is classed as an SSRI up to 150mg. Above this it is an SNRI and at 300mg even has some weak doperminergic effects. You are giving false information.

panic_down_under

14-06-17, 01:14

This is not true. Venlafaxine is classed as an SSRI up to 150mg. Above this it is an SNRI and at 300mg even has some weak doperminergic effects. You are giving false information.

Venlafaxine is only an extremely weak noradrenaline/norepinephrine reuptake inhibitor (NAT/NET) with binding affinity of around 2,700 *Ki (https://en.wikipedia.org/wiki/Pharmacology_of_antidepressants). The SSRIs fluoxetine (660 Ki), fluvoxamine (1,892 Ki), sertraline (667 Ki), vilazodone (56 Ki (https://www.drugs.com/pro/viibryd.html)), vortioxetine (113 Ki) and especially paroxetine (56.7 Ki) are much, much more potent noradrenaline/norepinephrine transporter inhibitors than venlafaxine. The other commonly prescribed SNRI, duloxetine, has a NAT/NET of 5.9 Ki. A Ki of 2,700 is clinically insignificant.

* Ki (inhibitory constant) values (https://www.ebmconsult.com/articles/inhibitory-constant-ki-drug-interactions) are based on the amount of the chemical needed to block 50% of the target receptors or transporters so the lower the value the greater the binding potential.

MyNameIsTerry

14-06-17, 01:32

Venlafaxine is only an extremely weak noradrenaline/norepinephrine reuptake inhibitor (NAT/NET) with binding potential of around 2,700 *Ki (https://en.wikipedia.org/wiki/Pharmacology_of_antidepressants). The SSRIs fluoxetine (660 Ki), fluvoxamine (1,892 Ki), sertraline (667 Ki), viloxazine (155 Ki) vortioxetine (113 Ki) and especially paroxetine (56.7 Ki) are much, much more potent noradrenaline/norepinephrine transporter inhibitors than venlafaxine. The other commonly prescribed SNRI, duloxetine, has a NAT/NET of 5.9 Ki. A Ki of 2,700 is clinically insignificant.

* Ki values are based on the amount of the chemical needed to block 50% of the target receptors or transporters so the lower the value the greater the binding potential.

Hi Ian,

Is this why they boost Ven far over the 150mg threshold to get it do what can be achieved with Sertraline or Paroxetine (and obviously Duloxetine) at much lower levels?

I realise Ven doesn't really work enough as a sequential drug until it has filled the first "jug" in the order and without me checking the graphs for this, I'm assuming the Serotonin is pretty much maxed out at 150mg. I know many SSRI's are at 80% at the minimum therapeutic dose so the increases are just getting closer to the 85% many max out at (is that right, I can't remember the graphs showning this).

Sorry for interjecting but I've been meaning to ask this because I've seen you mention it before and it seems appropriate to ask here with you explaining this.

Thanks in advance.

KK77

14-06-17, 01:50

Hang on a min. You said Venlafaxine was an SSRI. Now you say it is an "extremely weak SNRI"?

At low doses (<150 mg/day), it acts only on serotonergic transmission. At moderate doses (>150 mg/day), it acts on serotonergic and noradrenergic systems, whereas at high doses (>300 mg/day), it also affects dopaminergic neurotransmission.[15]

You also have no understanding of pharmacokinetics because Venlafaxine has a powerful active metabolite (Desvenlafaxine) which is an AD in its own right. You mention Paroxetine which has NO active metabolite. It is a double-whammy with Venlafaxine, which the empirical values you copied in do not reflect.

Venlafaxine is extensively metabolized in the liver via the CYP2D6 isoenzyme to desvenlafaxine (O-desmethylvenlafaxine), which is just as potent a SNRI as the parent compound, meaning that the differences in metabolism between extensive and poor metabolisers are not clinically important in terms of efficacy...

This is very important in terms of NE efficacy I believe. Also Paroxetine is far too powerful in terms of 5-HT re-uptake for its NE affinity to manifest clinically. It is in fact the most powerful SSRI.

Venlafaxine also indirectly affects opioid receptors (mu-, kappa1- kappa3- and delta-opioid receptor subtypes) as well as the alpha2-adrenergic receptor, and is shown to increase pain threshold in mice. Chemically it is related to Tramadol - an atypical opiate.

So it is in fact far from "only an SSRI".

panic_down_under

14-06-17, 09:50

Is this why they boost Ven far over the 150mg threshold to get it do what can be achieved with Sertraline or Paroxetine (and obviously Duloxetine) at much lower levels?

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 (https://www.ncbi.nlm.nih.gov/pubmed/6492942). 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 (https://academic.oup.com/ijnp/article-pdf/10/1/41/1749444/10-1-41.pdf)) and the other by the same research team did at 225mg and 300mg (Debonnel G, 2007 PDF (https://academic.oup.com/ijnp/article-pdf/10/1/51/1749455/10-1-51.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 ----------

Hang on a min. You said Venlafaxine was an SSRI. Now you say it is an "extremely weak SNRI"?

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.

You also have no understanding of pharmacokinetics because Venlafaxine has a powerful active metabolite (Desvenlafaxine) which is an AD in its own right. You mention Paroxetine which has NO active metabolite. It is a double-whammy with Venlafaxine, which the empirical values you copied in do not reflect.

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.

MyNameIsTerry

14-06-17, 10:21

Ven is also sometimes classed as a SNDRI despite having a weak effect on Dopamine at high levels.

This raises the same question as this one over it's class as a SNRI.

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.

KK77

14-06-17, 13:03

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 (https://www.ncbi.nlm.nih.gov/pubmed/6492942). 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 (https://academic.oup.com/ijnp/article-pdf/10/1/41/1749444/10-1-41.pdf)) and the other by the same research team did at 225mg and 300mg (Debonnel G, 2007 PDF (https://academic.oup.com/ijnp/article-pdf/10/1/51/1749455/10-1-51.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

14-06-17, 13:49

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 (https://www.ncbi.nlm.nih.gov/pubmed/10807491), 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 (http://www.psychotropical.com/venlafaxine-an-enduring-snri-myth)

MyNameIsTerry

15-06-17, 01:50

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

15-06-17, 06:28

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 (https://www.ncbi.nlm.nih.gov/pubmed/10807491), 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 (http://www.psychotropical.com/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. :shrug:

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/?showdescription=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

16-06-17, 02:44

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 (http://dx.doi.org/10.1055/s-0031-1300156) 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.