Background: I've had secondary POIS for 2.5 years. Symptoms are cognitive (memory, agitation), emotional, physiological (fatigue, joint/muscle aches, digestional, pressure headache, full body inflammation, racing heart, jumpiness, headache, temperature modulation issues -- freezing feet etc). Originally symptom onset was 1.5 days post O and peaking at 4 days. More recently boundaries are fuzzier, the symptoms are less pronounced but last for weeks and recur even long after O.
Past Treatment: So I've had some success on a regimen of Propranolol, sudafed (increases norepinephrine levels), hydroxyzine (H1 blocker that crosses blood brain barrier) and Pepcid (H2 blocker), and adderrall. I also had to go gluten free. This course has made life tolerable though I have bad brain fog and still feel generally impaired. I have been convinced that POIS is primarily a mast cell reaction.
New Treatment: My psychiatrist thought it would be worth trying Wellbutrin. Main effect is a dopamine and norepinephrine reuptake inhibitors. Idea was I could sub out adderrall and perhaps the sudafed.
Results: Starting with 150 mg dosage. I am 3 days in. I have O'd twice and so far essentially no symptoms, besides perhaps a slight skin reaction that suggests I still may need the antihistamine. I am still taking Propranolol. Generally, I have somewhat higher alertness levels and less fatigue. I am aware that this could be placebo or a honeymoon period so remaining CAUTIOUSLY optimistic.
I am out of my depth here, but it suggests to me that POIS may for some reflect a norepinephrine deficiency. I gather that after orgasm norepinephrine levels increase but then drop before returning to a baseline. People with norepinephrine deficiency have poor memory, low mood, fatigue etc. Makes you wonder whether POIS sufferers have a norepinephrine dump that takes longer to refill or remains low/empty.
I am also not ready to give up on the mast cell theory either and would not be surprised to find additional links.
In any event, for me this is an exciting development and I will keep you all posted.