Mirtazepine sounds fun (to decipher). I mean, just looking at targets, it's a tricky path (I think alpha2 antagonists would have an "upper" effect?)
And I've always wondered about the subjective experience of antagonizing 5-HT2A, given the psychedelics are all agonists there.
No mention (wikipedia table) of 5-HT1 at all. And strongest binding for H1 (I have to click refs to see if that's agonist or antagonist or otherwise).
But you @emkee say it blocks MDMA action? So you'd think it still binds SERT.
ANYWAY: you have to be careful though, when you say "make the symptoms worse". I can see with what I think of as a deep gray depression, there is no energy or pleasure, no humor or pity, you would not want something that dampened you further.
But for me, my issue is typically too much emotion. Rapid swings between them. Such that my day can wind up dependent on how tiny things affected me. So during a long-crisis like I'm having now, dampening those is helpful, or I might be wailing and gnashing my teeth all day long. Or at least, that's the logic.
I've been starting to think of my situation ass less "dysthymia" (original diagnosis) or plain depression, and more like an anxiety disorder. That fits a lot better with the drugs I abuse. And so far cheap, regular old gabapentin has been the best "antidepressant" of any drug I've played with (I'm including the illegal ones here).
So I agree, wait for a huge shift in how shrinks look at SSRIs and the whole serotonin hypothesis. These drugs were chosen for their safety profile and tolerance; the old tricyclics and MAOIs worked a whole lot better. The "age of Prozac" might end pretty soon.
(I will personally rub Obama's feet if the Secret Service wouldn't shoot me. I only have what little healthcare I do because of his ACA. I get to see an actual MD for free, who prescribes actual meds for diabetes, which is kind of important. (Meds are free, but only like $4/month anyway.) But, that's because there're MDs willing to "accept" government insurance in my area. I was told in the hospital after a kind of crisis episode, that there was a single psychiatrist in my county of over a million people who would accept the government insurance (it doesn't pay as well), who might be able to tell me a better med for my situation.
You can sell the insurance, but there's no law that says a doctor has to take it. Doctors also don't want to live far from golf courses, and want nice views from their McMansions, so they avoid flat rural areas too. So really, being broke in, say West Texas small town, all the Obamacare out there and you might still be screwed--cause you know, doctors are all about helping people, right? As long as they're paid handsomely.)
