Low-dose SSRI to reduce neuronal apoptosis in the stress pathways and amygdala

[hinterland]

I had an appointment with a consultant immunologist recently. One of the treatments suggested was a very low dose SSRI, even though he stated I'm not depressed or anxious.

His rational is that extremely low dose SSRI, or tricyclic, agents can have value in preserving stressed neurons in the amygdala, which, he says, are dysfunctional in patients with ME/CFS. So, he is suggesting I take 1/4 of a 10mg tablet (ie, just 2.5mg) of Citalopram as a neuroprotective agent on a long term basis. Apparently, at this low dosage it can be stopped and started as I like, without the complication of withdrawal issues.

Has anyone else tried this protocol?

Do you think I'd notice any therapeutic effects at all at this very low dose, or it would simply be a treatment to preserve my neurons until such time as a cure is developed?

He told me briefly that the work relates to the jak-3 pathway and ability of SSRI and tricyclics to reduce neuronal apoptosis in the stress pathways and amygdala, and added that it may explain some of the early studies where patients who continued antidepressant therapy, even though they weren't depressed, had a greater chance of improvement.

I wasn't aware there were positive outcome studies for antidepressent treatment in CFS - I wonder what criteria were used, were they studying 'chronic fatigue'? I thought the general consensus was that antidepressants weren't useful in treating ME/CFS, with the exception of low dose tricyclics for symptom relief. However, I'm also aware of a systematic review in which SSRi's showed immune modulating, potentially anti-inflammatory, effects.

Neuroprotective agents are substances that are capable of preserving brain function and structure. I think overall the medical literature reports loss of grey matter in CFS, and this, one assumes, is a bad thing. One thing that slightly puzzles me though, is that practicing meditation on a regular basis is said to reduce the size of the amygdala, along with reducing stress response, (while increasing grey matter density in the hippocampus and some other areas). So, what is it? Do you want a big amygdala, or a small one? I don't know, but that might be missing the point here.

 

[notmyself]

a big amygdala suggest a hyper active stress response..is commonly seen in people with anxiety and ptsd..you don't want that.

 

[Valentijn]

His rational is that extremely low dose SSRI, or tricyclic, agents can have value in preserving stressed neurons in the amygdala, which, he says, are dysfunctional in patients with ME/CFS.

I'm not aware of any support for that statement. But a lot of doctors who believe ME is psychosomatic depression are happy to claim there's a non-psychiatric reason that they want us to take it. I wouldn't believe any of them unless there's extremely good evidence to back up their claims.

I wasn't aware there were positive outcome studies for antidepressent treatment in CFS - I wonder what criteria were used, were they studying 'chronic fatigue'?

There aren't, as far as I know. Even the mainstream psychosocial proponents gave up on anti-depressants decades ago, though they don't oppose the use of them.

One thing that slightly puzzles me though, is that practicing meditation on a regular basis is said to reduce the size of the amygdala, along with reducing stress response, (while increasing grey matter density in the hippocampus and some other areas).

Probably poor quality research. It sounds like it involves brain scans, which are notoriously open to interpretation, and usually based on very small sample sizes.

 

[notmyself]

actually there are countless reasearch about meditation..and how affect the brain..most importantly it can lower chronic inflamation, i found studies showing a decrease in interleukin 6 from before and after 8 weeks meditation course..Unlike ME ,the studies on meditation and it's beneftis replicate all the time ..

 

[Jenny]

Another report:

http://forums.phoenixrising.me/inde...-by-ssris-dr-james-dr-smith-dr-le-fanu.53069/

 

[Woolie]

@hinterland, your doctor deserves a medal for his efforts in rebranding antidepressant treatment as "neurological".

I suspect his thinking goes a bit like this: he doesn't know what wrong with you. He wonders if you're a bit depressed. So he thinks it might be worth trying some antidepressants. But he doesn't want to offend your sensibilities by saying this outright, so he's offering an explanation that he thinks is more palatable to you.

Its up to you whether to try them. I would probably give them a go. But be ready to drop them if you don't see any benefits after six weeks or if anything gets worse. And make sure your doctor knows if they don't work.

For the moment, I would let your doctor save face by not confronting him about all this. But always, always be aware that many doctors will think you have a psychological problem, but never say so to you directly. Its important not to take everything they say at face value. If your doctor continues to offer only psychological treatments and is going to a lot of effort to present them as somehow 'medical', it might be time to find a new doctor.

 

[Snow Leopard]

Low-dose SSRI to reduce neuronal apoptosis in the stress pathways and amygdala

This sentence baffles me.

 

[hinterland]

"Low-dose SSRI to reduce neuronal apoptosis in the stress pathways and amygdala." This sentence baffles me.

Here, I think he is just saying that a low dose SSRI (or Tricyclic) can be used as a neuroprotective agent... I don't think that in itself is such a controversial statement, but quite how it relates to ME/CFS, I don't know.

 

[hinterland]

I'm trying to understand more about the Janus Kinase-3 (jak-3) pathway, and how it might be involved in my doctor's hypothesis, set out above, as it is something he specifically mentioned...

I've found this 2016 paper: "Role of Janus-Kinases in Major Depressive Disorder", looking at the potential role of reduced neurogensis in depression, but whose main findings may generalise and be of some relevance here.

Here, we investigated the role of Janus-Kinase 3 (Jak-3) for stress-induced inhibition of neurogenesis and the induction of major depression symptoms in mice.

Jak-3 inhibitors and the antidepressant amitriptyline were applied to counteract stress.

Results: The data show that stress reduces neurogenesis, which is restored by simultaneous application of Jak-3 inhibitors. Inhibition of neurogenesis correlated with an anxious-depressive behaviour that was also normalized upon application of a Jak-3-inhibitor. Confocal microscopy data revealed that stress triggers a phosphorylation and thereby activation of Jak-3 in the hippocampus. Amitriptyline, a commonly used antidepressant that blocks the acid sphingomyelinase, or acid sphingomyelinase-deficiency reduced stress-induced phosphorylation of Jak-3. Conclusion: Our data show that Jak-3 is activated by stress at least partially via the acid sphingomyelinase and is involved in the mediation of stress-induced major depression.

 

[katurian]

This seems like a bad idea to me, especially because the premise is that an SSRI would be neuroprotective when in reality they can and do cause damage to the brain. Also, depending on how sensitive you are to medication, not even a low dose can be stopped and started without sending your body into withdrawals.

 

[hinterland]

Prof Lombardi has recently been awarded a research grant by the Solve ME/CFS Initiative, to investigate JAK activation profiles in ME/CFS. This quote below is from his project summary:

Characterization of Janus kinase (JAK) activation profiles in ME/CFS subgroups

"Most hematopoietic cytokine receptor signaling is mediated by a family of tyrosine kinases referred to as Janus kinases (JAKs) and their downstream transcription factors, referred to as STATs (signal transducers and activators of transcription). Several diseases that are characterized by chronic cytokine-associated inflammation such as rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus are being successfully treated or the subject of clinical trials with drugs that inhibit the activation of JAKs. In that ME/CFS is also characterized by systemic inflammatory cytokine production, it is reasonable to propose that some of the same drugs that are being used or developed to treat the aforementioned inflammatory diseases, may also be efficacious in treating ME/CFS. Therefore, the overarching goal of our study is to identify specific JAK activation profiles of distinct ME/CFS subgroups, thereby addressing the feasibility of using JAK inhibitors to treat ME/CFS. Our study may additionally provide compelling evidence to justify conducting clinical trials to evaluate the efficacy of JAK inhibitors for the treatment of ME/CFS."