I have nearly life-long chronic major depression that can’t be cured with socialization, sex, money, sleep, diet, exercise or various forms of therapy. I’ll take a random stab that it is mostly genetic and partly by having had a tyrannical, histrionic, screaming father whom caused frequent stress: this then setup poor vagal tone and “walking-on-egg-shells” hyper-vigilance which then neuroplasticized towards reinforcing pain-depression complex of the military-industrial kind.

I now have depression again after mirtazapine tachyphylaxis. It’s a widely-hitting NaSSA and powerful antihistamine (which also means hypnotic). It’s also the most effective antidepressant (I was on a heavy dose, 60 mg) but it causes weight gain (+25% body mass) and G.I. slow-down. That’s great when it works, but now I’m letting the old black dog have another ride as buproprion XL 300 mg isn’t doing anything useful so far. Maybe, still really foggy, confused and increased pain perception.

Not being depressed is awesome: like the clouds parted, quieted inward observation, less reading, less writing, less sleeping-in, pain set aside, more energy, enjoyment and orderly thinking; almost manic but, presumably, not bet-kid’s-education-fund-on-18 far.

Looking at next alternatives:

* Bupropion XL 450mg

* AXS-05 (60 mg DM with bupropion)

* Venlafaxine ER

* Venlafaxine ER + Lamotrigine

* Venlafaxine ER + Mirtazapine

PS: Paxil gave me serotonin syndrome and Zoloft did jack shit.