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.