Neurological changes made by SSRI

[npanth]

I wrote an article about the neurological changes that SSRI make. I was thinking about the differences and similarities to other drugs, and what structural mechanism in the brain causes withdrawal symptoms. I'm not an expert in neurophysiology, but I studied it as an undergrad and since I started tapering.

http://npanth.wordpress.com/2012/06/12/how-ssri-work-in-withdrawal/

[Pandora]

Great article. I wish I'd read it before I did my way-too-fast taper.

 

Thanks.

[strawberry17]

Thanks for sharing.

[peggy]

nice, clear well written article

[Altostrata]

Interesting. Another explanation involves downregulation or desensitization of serotonin receptors, which means that even the new neural networks are poorly equipped with receptors to absorb serotonin. See http://survivingantidepressants.org/index.php?/topic/392-one-theory-of-antidepressant-withdrawal-syndrome/

 

This makes withdrawal syndrome not a condition of too much serotonin in the brain, but a condition where the receptors cannot sense a normal production (or even excessive production, as when serotonergic supplements are taken) of serotonin and pass dysregulation down the chain of hormonal homeostasis.

[strawberry17]

I only skimmed it this morning, just read it properly, it is really well written. I've always found it hard to get my head round the neurological info, it is interesting about serotonin in the gut, I had terrible problems with my gut in cold turkey withdrawal which explains a lot.

[abkflorida]

This really helped me understand withdrawal. Thanks.

[npanth]

Interesting. Another explanation involves downregulation or desensitization of serotonin receptors, which means that even the new neural networks are poorly equipped with receptors to absorb serotonin. See http://survivingantidepressants.org/index.php?/topic/392-one-theory-of-antidepressant-withdrawal-syndrome/

 

This makes withdrawal syndrome not a condition of too much serotonin in the brain, but a condition where the receptors cannot sense a normal production (or even excessive production, as when serotonergic supplements are taken) of serotonin and pass dysregulation down the chain of hormonal homeostasis.

 

I was combining what I know about the structure and function of neurons with the new theory of neuroplasticity. It's always seemed intuitively right that neural networks extend themselves and make new connections in response to thoughts or chemical changes. I think you are right that the specific mechanism could be deregulation of the new receptors.

As new Axon terminals extend into an area of the brain that has been affected by an SSRI, they either produce desensitized Serotonin receptors, or the normal receptors are blocked by the drug. My guess is that the new receptors are blocked by the drug because that would provide a physiological explanation for drug tolerance (it takes more drug to block more receptors) and withdrawal symptoms (the sudden over abundance of Serotonin absorption capacity) once the drug is removed. Desensitization would also provide a compelling explanation for tolerance and withdrawal. I'll have to ponder and read a bit more about it. Thanks.

[Altostrata]

Yes, researchers who have looked into this attribute it to desensitization.

 

The much-heralded neurogenesis supposedly stimulated by antidepressants, if it exists, may be of such downregulated networks.

[jr1985]

Is it possible the neurogenesis seen with AD's is actually due to death of old neurons? In other words, could the SSRI be killing brain cells, so the brain has to make more to recover?

[Altostrata]

If I recall correctly, a repair reaction is one of the theories to explain this.

 

Another is that antidepressants interfere with the normal healthy pruning of neural networks that takes place during REM sleep -- they disrupt sleep architecture.

[npanth]

If I recall correctly, a repair reaction is one of the theories to explain this.

 

Another is that antidepressants interfere with the normal healthy pruning of neural networks that takes place during REM sleep -- they disrupt sleep architecture.

 

I've read this, too. I read an interesting article a while ago that focused on SSRI's affect on the Pineal Gland and described how SSRI disrupt sleep and dream patterns. The brain responds by intruding the dream state into waking life. In other words, SSRI literally makes us walk around in a dream.

[Petunia]

 

 I read an interesting article a while ago that focused on SSRI's affect on the Pineal Gland and described how SSRI disrupt sleep and dream patterns. The brain responds by intruding the dream state into waking life. In other words, SSRI literally makes us walk around in a dream.

 

 

What can happen, when the serotonergic system isn't cycling anymore, in a natural circadian rhythm, is that daily consciousness will shift closer and closer to the "dream state". The verge between reality and dreaming will gradually become blurred. The lack of rhythm is the cause. Under the influence of an SSRI-AntiDepressant, serotonin levels won't fluctuate anymore, but remain continuously high. Many SSRI-AntiDepressant users reported that they had problems to distinguish reality from dreaming when they woke up from a dream and that it took quiet some time to realize that they had been dreaming instead of experiencing something real.

 

http://www.network54.com/Forum/182310/message/1057587694/SSRIs+and+the+PINEAL+GLAND+in+the+brain

 

(original full article with references and links here:  http://www.antidepressantsfacts.com/pinealstory.htm )

 

This was happening to me a lot when I stopped taking lexapro. It was worse during the first 6 months or so. I would have intense dreams which seemed to continue for hours after I woke up. It wasn't like I was still dreaming exactly, but it was like I couldn't seem to let go of the dream, believing that it was more real than my waking reality. The worst time was after one particular dream it took me 9 hours of being awake to finally feel like I was back into normal reality again.

 

I was still having problems transitioning between the dream/sleep state and waking consciousness 3 years later.

[oskcajga]

I wrote an article about the neurological changes that SSRI make. I was thinking about the differences and similarities to other drugs, and what structural mechanism in the brain causes withdrawal symptoms. I'm not an expert in neurophysiology, but I studied it as an undergrad and since I started tapering. http://npanth.wordpress.com/2012/06/12/how-ssri-work-in-withdrawal/

 

So from what you're describing, the brain doesn't down regulate serotonin receptors in response to the flood of serotonin in the synapse, instead, it synthesizes entire new neuronal networks that are meant to absorb this excess serotonin.  Wouldn't it seem energetically less expensive for the cells to just change protein synthesis pathways and downregulate serotinin receptors in pre existing neuronal networks rather than synthesize an entire new network of cells?

 

I'm also not sure that I understand how these changes can produce the wide range of symptoms that individuals experience when withdrawing or having an adverse reaction to these medications.  Why would someone have tingling, burning, and numbness of limbs and extremities if there was just a simple chemical imbalance of serotonin?  It seems to me like there's more nefarious actions taking place in some people that produce a toxic neuropathy of sorts.  This idea of neuropathy has been echoed by experts in the field, including David Healy.

 

Many of the symptoms, such as flattened mood, anhedonia, mood swings, sleep disturbances, anxiety, depreonslization, etc would be very much consistent with your theory and I find it consistent with what you're describing - but other symtpoms, such as the numbness of the face, the involutnary twiches, the burning in the hands and feet, and genetilia seem like something entirely different.

 

Moreover - how could this explain the hypersensitivity?  From what I can garner, the hypersensitivity is a result of some sort of neuronal inflammation or damage - something akin to the swelling and twisting of neurons that has been described in the literature.  How else could someone who had no problems drinking or eating a variety of substances suddenly experience sensitivity to these substances?  I have a hard time believing that a too little seritonin in the synapses is causing a sudden intolerance of fast food, alcohol, drugs, supplements, etc - that doesn't really make too much sense.  It would seem to me, in my opinion, that this hypersensitivity goes along the lines with the neuropathy that has been posited by Dr. Healy.

 

So I'd argue that IN ADDITION to some of the changes that you are describing, there are also other changes occurring simultaneously in some people.  Especially in those who have had adverse reactions to the medications themselves, or an adverse reaction during tapering (etc).

[Altostrata]

I don't believe npanth's description is correct. You would have to correspond with npanth on his blog to find out his sources.

 

That SSRIs cause downregulation or depopulation of serotonin receptors is well-documented.

 

The nervous system tries to compensate for dysregulation of the serotonergic receptors with changes in other neuronal networks -- this is the alternative homeostasis postulated by Giovanni Fava and Paul Andrews -- but it's not to absorb serotonin.

[oskcajga]

I don't believe npanth's description is correct. You would have to correspond with npanth on his blog to find out his sources.

 

That SSRIs cause downregulation or depopulation of serotonin receptors is well-documented.

 

The nervous system tries to compensate for dysregulation of the serotonergic receptors with changes in other neuronal networks -- this is the alternative homeostasis postulated by Giovanni Fava and Paul Andrews -- but it's not to absorb serotonin.

 

Thank you for clarifying.

[servadei]

Can I still heal if I quit CT?