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Re: Tolerance is just so low!!

Posted by SLS on November 21, 2022, at 7:10:32

In reply to Re: Tolerance is just so low!! linkadge, posted by jay2112 on November 20, 2022, at 19:21:45

> > I am having so much difficulty tolerating ANY venlafaxine. Even 1/4 of 37.5mg is giving me chest tightness. My tolerance of bupropion is much higher.
> >
> > Trying to restart the venlafaxine is proving difficult.
> >
> > Linkadge
> Try just taking the 37.5 and you should feel a bit better within a week or two. Do you have access to any benzo's, clonidine, or propranolol? Those will crumple the norepinephrine uptake. Propranolo, in particular, has made me actually tolerate and do not bad on Effexor. It won't work until you boost the Effexor so it can down-regulate the norepinephrine on it's own.

These are excellent ideas - except, perhaps. for the clonidine. I have seen clonidine be robustly depressogenic. Of course, this might not be true when added to Effexor when psychiatric side effects emerge.

> It's like taking a horrible tasting cough medicine, and then you get used of it.

...and maybe even like it.

What are your beliefs regarding Effexor and NE receptor downregulation?

In the early 1980s, it was considered putative that NE reuptake inhibitors downregulated NE *beta* receptors. At the time, this was believed to be the mechanism of action of tricyclic antidepressants. If this beta downregulation property of NE reuptake inhibitors is still advocated by neuroscientists, a beta-blocker like propranolol might make the most sense to ease into establishing higher dosages of Effexor. I like pindolol as an alternative. Aside from being a NE beta-blocker, it also blocks serotonin 5-HT1a axo-dentritic receptors. Pindolol has been found to accelerate an antidepressant response, and perhaps potentiate it.

I get the impression that 150 mg/day is the lowest effective dosage of Effexor. Infequently, 75 mg/day. For me, Effexor does not produce its maximum antidepressant effect until I get to 300 mg/day, although the improvement was only partial. I found this dosage to be easily tolerable once established, despite having side effects after the very first dose of 25 mg. The side effects were of an uncomfortable stimulation. I had a sort of "warmth" and tingling in my head during my de novo treatment with Effexor. None of my subsequent trials of Effexor produced this effect. Also, I never experienced these side effects with Pristiq. Of course, this could have been an artifact of being treated with Effexor previously.

Speaking of side effects - and perhaps the receptivity to treatment - drug reactions are often changed by pre-treatment with another compound. Effexor was always helpful until I switched to it immediately after a trial of vortioxetine (Trintellix). It is a well-known and often-used experimental strategy to elucidate the mechanisms behind neuronal functions in normal versus manipulated biological states. This most often involves assaying receptor states to reveal how they control regional and global brain functions.

- Scott

Some see things as they are and ask why.
I dream of things that never were and ask why not.

The only thing necessary for the triumph of evil is that good men do nothing.




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