Norepinephrines role in panic and anxiety disorders

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Can anyone explain to me why the use of Norepinephrine blocking medications can have a positive effect on anxiety disorders. Ie. SNRI’s and TCA’s I can’t understand how these types of medication can lower anxiety levels, in particular imipramine and clomiprimine, along with venlafaxine and other SNRI’s ???

Can someone kindly advise if switching from vorteoxatine to one of the above could be beneficial please. I really need to understand the rationale. So if it comes to it I can make an informed decision all thoughts would be greatly welcomed Thank You

[panic_down_under]

Can anyone explain to me why the use of Norepinephrine blocking medications can have a positive effect on anxiety disorders. Ie. SNRI's and TCA's I can't understand how these types of medication can lower anxiety levels, in particular imipramine and clomiprimine, along with venlafaxine and other SNRI's ???

Antidepressants don't directly lower anxiety levels (or depression), but work by stimulating the growth of neurons in the hippocampal regions of the brain. The new cells and the connections they forge create the therapeutic response, not the meds per se. How the ADs do this is complicated and still poorly understood, but lowering the synthesis and expression of serotonin and/or noradrenaline aka norepinephrine (NA) - and probably also dopamine in the case of MAOI class ADs, although, afaik, there in no research demonstrating this - seems to be a vital part of the process. Noradrenaline reuptake inhibitors (NRIs) like desipramine, nortriptyline, lofepramine and reboxetine can be just as effective as SSRIs. Hitting both serotonin and noradrenaline pathways seems to be more potent than targeting just one of the neurotransmitters and also lowers the risk of the med pooping-out.

Clomipramine (Anafranil) is the second most potent serotonin reuptake inhibitor (SRI) after paroxetine (Paxil) whereas imipramine (Tofranil) inhibits serotonin less, but it a more potent NRI. Amitriptyline is an even weaker SRI, but the most potent NRI of the serotonergic TCAs.

BTW - venlafaxine is not a true SNRI. Its designation is mostly about marketing, not chemistry. It only begins to inhibit NA reuptake at doses around 200mg and then still only modestly. Fluoxetine (Prozac), paroxetine (Paxil) and sertraline (Zoloft) are much more potent NRIs, albeit still only weak ones. Vortioxetine also inhibits NA to some extent being second only to paroxetine among the SSRIs.

Can someone kindly advise if switching from vorteoxatine to one of the above could be beneficial please. I really need to understand the rationale.

It is impossible to say whether you'd do better on a SNRI like duloxetine (Cymbalta), or one of the TCAs. Unfortunately, the only way to know is to try them.

[SideFX]

Antidepressants don't directly lower anxiety levels (or depression), but work by stimulating the growth of neurons in the hippocampal regions of the brain. The new cells and the connections they forge create the therapeutic response, not the meds per se. How the ADs do this is complicated and still poorly understood, but lowering the synthesis and expression of serotonin and/or noradrenaline aka norepinephrine (NA) - and probably also dopamine in the case of MAOI class ADs, although, afaik, there in no research demonstrating this - seems to be a vital part of the process. Noradrenaline reuptake inhibitors (NRIs) like desipramine, nortriptyline, lofepramine and reboxetine can be just as effective as SSRIs. Hitting both serotonin and noradrenaline pathways seems to be more potent than targeting just one of the neurotransmitters and also lowers the risk of the med pooping-out.

Clomipramine (Anafranil) is the second most potent serotonin reuptake inhibitor (SRI) after paroxetine (Paxil) whereas imipramine (Tofranil) inhibits serotonin less, but it a more potent NRI. Amitriptyline is an even weaker SRI, but the most potent NRI of the serotonergic TCAs.

BTW - venlafaxine is not a true SNRI. Its designation is mostly about marketing, not chemistry. It only begins to inhibit NA reuptake at doses around 200mg and then still only modestly. Fluoxetine (Prozac), paroxetine (Paxil) and sertraline (Zoloft) are much more potent NRIs, albeit still only weak ones. Vortioxetine also inhibits NA to some extent being second only to paroxetine among the SSRIs.



It is impossible to say whether you'd do better on a SNRI like duloxetine (Cymbalta), or one of the TCAs. Unfortunately, the only way to know is to try them.

That’s a surprise cause peroxatine was my savour in 2001 it was a wonderful med, until I stopped and started it too many times and then it caused seizures and all sorts, when I reinstated for the 3rd time. I always thought clomiprimine was the stronger serotonin inhibitor of the 2. I have looked at the ki values of both and they seem very similar. Also my mum was on imipramine for decades and it suited her great.

Guess if things don’t work out with upping the pregabalin I will have to go through withdrawals from vortioxatine and try a TCA. The thought itself is so so scary I can’t tell you how afraid I am right now PDU

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always thought clomiprimine was the stronger serotonin inhibitor of the 2. I have looked at the ki values of both and they seem very similar.

Ki values can vary from lab to lab. Some have paroxetine as the more potent SRI, others clomipramine, but the difference is so small as to make no practicable difference.

Also my mum was on imipramine for decades and it suited her great.

That would be my choice. I was on it for about 5 years at very high doses with minimal side-effects.

Guess if things don't work out with upping the pregabalin I will have to go through withdrawals from vortioxatine and try a TCA.

Switching from vortioxetine to imipramine can be done via a cross-taper which should minimise any withdrawal and/or side-effects. The switch to clomipramine does require a short washout period. See the NHS guideline: Vortioxetine to other antidepressants: switching in adults.

The thought itself is so so scary I can't tell you how afraid I am right now

Why?