SNRI vs SSRI w/d theory

[alexjuice]

Alto researched and articulated a theory of prolonged antidepressant withdrawal resultant from discontinuation of SSRIs. I think my problems originate mainly from the beastly Effexor(venlafaxine) and wonder how that drug's features (targeting primarly 5-HT & NE directly, rather than 5-HT solely) differentiate its w/d symptoms from those suffered by individuals who d/c SSRI medications.

 

I'm in a spot. My GI system is not working right and I'd like to plausibly attribute my symptoms to d/c of effexor before my next round of doctor appt.

 

I am not fleunt in neurophysiological function, so any assistance would be appreciated. If my thoughts are hopelessly underinformed, realize I am an amateur in a tough spot.

 

....

 

I've studied the medical literature on antidepressant withdrawal syndrome. What I've learned about the alerting system and glutamatergic system in antidepressant withdrawal syndrome may be informative.

 

Antidepressants cause downregulation of serotonin receptors.

 

Reasonable then to assume SNRI causes an effect, likely similar, on norepinephrine receptors as well?

 

....

Even among people suffering the most severe antidepressant withdrawal syndrome, repopulation of serotonin receptors probably occurs long before symptoms disappear. However, while the serotonin system is repairing itself, an imbalance occurs in the autonomic nervous system. The locus coeruleus "fight or flight" center becomes disinhibited and the glutamatergic system becomes more active than normal. This is called disinhibition of the alerting system, and it generates symptoms that are awful: panic, anxiety, sleeplessness, and dreadful imagery among them.

 

Essentially, at the most simple level, we are talking about too few receptors relative to serotonin causing overactivation of glutmate system?

 

Ok, what reasonable assumptions can be made about an environment facing a similar receptor condition for NE as well as 5-HT? How might this affect glutamate? How might this state affect the enteric nervous system?

 

From colorado State:

Enteric neurons secrete an intimidating array of neurotransmitters. One major neurotransmitter produced by enteric neurons is acetylcholine. In general, neurons that secrete acetylcholine are excitatory, stimulating smooth muscle contraction, increases in intestinal secretions, release of enteric hormones and dilation of blood vessels. Norepinephrine is also used extensively for neurotransmission in the gastrointestinal tract, but it derives from extrinsic sympathetic neurons; the effect of norepinephrine is almost always inhibitory and opposite that of acetylcholine.

 

http://www.vivo.colostate.edu/hbooks/pathphys/digestion/basics/gi_nervous.html

 

Would it be safe to speculate that inability to digest food, motility dysfunction, could result from a.) inhibition of GI system due to abnormal norepinephrine influence from disruptions caused by removal of venlafaxine? Or b.) decreased ACh, an effect of some process happening upstream, but also due to 'imbalance' caused by removal of venlafaxine.

 

....

The third phase is when glutamatergic hyperactivity and autonomic instability take over. Often the autonomic instability causes wide hypersensitivity to drugs, supplements, and even foods.

 

Out of control, unrelated to environmental or psychological triggers, the alerting system sends intense, spontaneous signals to the adrenals, which produce the stress hormones cortisol and adrenaline.

 

My gastrointestinal problems started when I manipulated diazepam. Seems that benzos would provide ying to the yang of glutamatergic hyperactivity, no?

 

Theoretically then, if overactive glutamate is affecting NE or, better yet, if overactive NE is adding to glutamatergic overactivity, could a GABA-boost counter all this excitement?

 

Perhaps NE activates greater glutmate activity -> disrupting 5-HT in the gut? Thus, venlafaxine w/d causes more GI symptoms? Admittedly I am straw-grasping. But there is a conspicuous option that emerges from all of these assumptions.

 

Increase Valium.

 

Increasing GABA activity should balance the glutamate, no?

 

Obviously, more valium isn't ideal. But temporarily might it not quiet things down?

 

I hesitate to even mention the dreaded diazepam as I would not recommend anyone initiate, but as I am already stuck with it, why not uptick?

 

---

 

In any event, if my thinking is all error, I'd be interested in any views on why venlafaxine frequently wreaks havoc with GI tract. And, of course, any possible theories for this. Theories are equal to solutions as first order is convincing doc of viability of the venlafaxine hypothesis.

 

Thanks for your help guys... hope everyone is doing well today.

 

Alex.i

[Altostrata]

I wouldn't even presume to unravel how SNRIs affect the gut. One would have to be a neurogastroenterologist.

 

Downregulation of any kind of receptor is only part of the withdrawal story. In the vacuum created by lack of feedback from the serotonin receptors, other systems jump in and add their own disregulation.

 

Point being, after x time has passed, the downregulation issue becomes moot. All kinds of other things are going on. You can't figure out a recipe based on neurotransmitters -- the very few that have been identified -- to counteract adverse effects from any of these drugs, or any combination of them.

 

Psychiatry is trying to follow that kind of logic, and look at where polypharmacy gets us.

[lupe]

Well said Alto! I went to a 45 min presentation today... a researcher who has been doing work in one of the signaling pathways in the intestines that leads from stem cells (we still have stem cells in the small intestine because the cell turnover is sooooo fast there)to progenitor cells to the mature cells of the intestine. And just that single pathway is something a person could spend a lifetime studying because there are so many genes involved!

[Altostrata]

That sounds fascinating, lupe. Is that your field?

[alexjuice]

Thanks for the replies.

 

Obviously I am not capable of a thorough theory of any usefulness. I posted more of an ulterior motive. I hoped perhaps others would suggest that I updose my benzos, despite the general unsoundness of such a move, as I was looking for encouragement to try, in my desperation, more desperate measures. This post was intended to encourage that suggestion.

 

Instead, I was reminded of that which I know so well; because I advocate it myself. General attempts to explain the action of neuro-modulating drugs, especially by an amateur like moi, are not typically useful because I, like pharmacologists and neuro-scientists, don't yet really know. If everybody really understood the why, what, how, and thenwhat actions of these drugs, we largely wouldn't be in the situation we are in.

 

Alex.i

[Barbarannamated]

Thanks for the replies.

 

Obviously I am not capable of a thorough theory of any usefulness. I posted more of an ulterior motive. I hoped perhaps others would suggest that I updose my benzos, despite the general unsoundness of such a move, as I was looking for encouragement to try, in my desperation, more desperate measures. This post was intended to encourage that suggestion.

 

Alex,

You are hilarious, my friend! And so honest. ;-)

 

I just read a review about adrenals and cortisol that mentioned a GI connection. I thought of you. It wasnt a scientific article, so didnt post it, but thought I'd mention.

Barb