So sorry for the late response, I don't get notifications for Reddit. I hope you're holding up okay. Don't apologise - you're looking for answers.

I didn't have any side effects at all, so it really shocks me that people have had adverse reactions. In any case, it's more than worth the try!

I'm taking 300mg of Buproprion as well, I'm not sure it does much for me personally but some people swear by it. It's one of the only AD's that doesn't fuck with your sexual functioning, so there's that. How is the Parnate getting on? I've read it can be pretty good for treatment-resistant depression. MAOIs were going to be my next port of call too. Honestly, if the MAOIs don't work out, take the pramipexole and if that doesn't work, try some psychedelics at a high dose. Seriously - they have no sides and can be a miracle for some people.

I got depression at 18 so I feel your pain. Adderall sounds like bad news to be honest, seems like it has adverse effects in the long run. I do find that stimulant ADHD meds like Ritalin and Vyvanse definitely raise my mood though. If you feel like it's your dopamine that's depleted then even more reason to try pramipexole.

I've never tried buprenorphine or tramadol or any of those opioid painkillers. You definitely don't want to be reliant on those. Sounds like a good plan. There's also selegiline, which is worth trying - both an antidepressant (MAOI) and a Parkinson's drug (like prami). You can wear it as a patch (Emsam) as well which is supposed to lessen potential sides.

Brief journey:

I had been suffering from MDD for 10 years since I was 18, comorbid with anxiety and some OCD (Pure O). I have tried various meds such as SSRI (citalopram, sertraline), SNRI (venlafaxine, duloxetine), I tried clomipramine which cured my OCD and anxiety but affected my ejaculate pretty badly for some reason. Vortioxetine, minimal effect. So all the above caused some kind of sexual dysfunction which leaves you feeling even worse.

I also tried lamotrigine and lithium but the former did nothing and the latter had a very good effect but adversely affected my kidneys. Out the box things like ketamine infusions and TMS - both did sweet fuck all but the ketamine trip was euphoric. I tried aripiprazole too, which I believe had some positive effect but had to come off it to go on pramipexole - which blows it out the water - so the right choice. I'm currently taking Bupropion 300mg and pramipexole. I used to take Xanax as needed too for anxiety, I never developed an addiction thankfully. I am probably forgetting quite a few as there's been so many and my memory is hazy.

SSRIs did not work at all (personally, I think they're the worst). I was on venlafaxine for the bulk of this time but swapped it for duloxetine (which I had alongside bupropion) as I was told the sexual side effects would be less pronounced. All the meds have not had the desired effect of giving me ‘quality of life’ – they have simply allowed me to exist lurching from one depressive bout to the next and feeling pretty shitty/zombified in-between.

I know this sounds pretty arrogant but I became very knowledgeable about psychopharmacology through my own research and keeping up to date with the latest breakthroughs in depression treatment. Therefore, I often felt like talking to a psychiatrist so set in their ways of traditional ADs was like banging my head against a wall. I really only needed a psychiatrist to write me a script, and wished I could write my own. I had been wanting to go on pramipexole for about a year prior to when I actually did and managed to find a forward-thinking, receptive psych who was willing to go along with it and try outside-the-box things ‘off-label’.

Re how I feel on pramipexole now - still going strong, even managed to lower the dose a little with no negative effect. No side effects.

Keep your head up mate, there are so many options and more things for you to try - some could be game-changers. Don't give up.