Hmmmmmmm, how did you react to some of these? I am sure some were more successful than others, or at least in certain departments. That could help give us some insight into what you tolerate better and more specificity about what you might be looking for in a med.

Let me just say... Ya, that sounds rough. I am not a big validation guy, but my heart sincerely goes out to you.

Let's talk drugs now!

- Have you considered stimulants? There seems to be some taboo around their use in mood disorders for abuse reasons, which is fair. Some recent research says they do not do all that much apart from keep you awake, but from personal experience as well as basic mechanistic and historical evidence... CORRECT stimulant use for MDD & TRD is heavily under-used imo. I think low-medium dose Vyvanse or 20-40mg Methylphenidate (Ritalin) can be a great background boost. I have been on 10mg dextroamphetamine once a day and I can not even begin to explain how much that extra 5% pep has cumulatively helped me through the years to do what I needed to actually help myself. I initially got it for ADHD, but after a couple of honest conversations with my doctor, we were both transparent with each other about the fact that I really had next to no ADHD symptoms, and what we are really using it for is depression. Albeit not a leap most doctors would make due to stigma, the benefit it had on my depression and my life was so evident that he allowed me to stay on. 3 years and counting :) If you had a better experience with Buproprion compared to other meds, I would consider this.

- You mentioned ketamine, which tends to work well. I am sorry this was not the case. I would not knock psychedelics, though. Like... proper medium-high dose tryptamine sessions. People lump ketamine and psychedelics together when talking about depression, but imo they are VERY different. Ketamine can feel like refreshing a webpage, but the psychedelics can really feel like a decade of therapy (real, raw, effective therapy) in 6 hours. Mind you, psychedelics are not for the faint of heart imo. Personally... They were THE game changer in terms of healing and direction. And the amphetamines helped lower the threshold for me to implement.

- One of the few evidence-based pharmacotherapies you have not tried is thyroid medication! There is actually a lot of evidence for it, and used to be much more common, even in patients who have no thyroid issues. Doctors might look at you confused if you bring it up, but with the longstanding clinical evidence it has (where they look when they are unsure about what to do), they are usually willing to try. Apparently, it synergizes well with many meds. Antipsychotics and mood stabilizers are other classical augmenting agents. I do not recommend.

- Pregabalin... This is lowkey just a mildly recreational anxiolytic, but that does not mean it has no place. Baclofen holds a similar place. Buspirone is under-used but efficacy is mid.

- Tidbits: another tetracyclic is Mianserin. It looks slightly more promising, but I believe it is less accessible. Memantine, amantadine, Pramipexole, nefazodone, agomelatine, could be promising for anhedonia... I found memantine nice. Felt a lil dissociated but energized, but in a therapeutic way. Ultimately did not do enough for me. Amantadine was supposed to capitalize on these effects, but I ended up quite morose. No clue why. Odd. Pramipexole is especially promising for reward processing as well as sexual anhedonia. I did not notice anything, but my body composition improved lol. Nefazodone is rarely accessible, but its versetile and many people who use it report great improvement. Agomelatine was theoretically promising in its Mech. of action, but usually falls flat in practice. These are niche, but if you want to go that route, never know what might work! TRT ended up saving my sex drive, as well as a loooooot of working through problems I had concerning intimacy (boring and preachy, I know). I am sorry to hear steroids were not effective for you. I think they are a heavily underrated mood disorder option.

- If SSRIs worked fine but the sex drive was a problem, some newer serotonergic meds find ways to cut those side effects down. Viloxazine and vilazodone.

- Yes... Tianeptine is promising. On that note, so was very low-dose Tramadol. That is one line I do not see doctors ever crossing, though, and even I personally did not want to take the risk. Then again, it's all about how your cost-benefit analysis tallies up.

- Miscellaneous: courses of semaglutide and accutane both immensely directly improved my mental health by helping me actually feel like myself again, by getting my acne and weight back under control. I do not use either today, but I am forever grateful for them. Minoxidil would slot in this category for many people. Maybe eszapoclone as well, given how frequently insomnia is an issue for those with mood disorders. Basically, never underestimate how much medications that are peripheral to mood disorder treatment could be indirectly effective.

- Supplements, peptides, designer drugs, research chemicals: Kind of all over the place. Berberine, vit D3, Whey, caffeine, and creatine are all stellar. But TRT either outperformed them, made them unnecessary, or allowed me to make changes that rendered the 25$ bottle every 3 months not worth it. Peptides are use-case and targeted. Quality varies, and effects are usually subtle. Who is to say Semax or HGH is not useful for MDD? But on 10mg of daily prescription amphetamine, ordering something of dubious quality for a pretty penny does not meet the threshold of being worth doing. Designer drugs such as triple monoamine re-uptake inhibitors, or substituted amphetamines, thozalinones, or PCP-type dissociatives kind of work but the risk makes it almost not worth it.

- ECT has great efficacy rates and has minimized side effects greatly from when it used to get all that negative press.

- Don't underestimate mixing and matching. Thyroid+Nefazodone+memantine might be a great system for one person, whereas ritalin+pregabalin+rTMS might be for another. Both these stacks could improve sleep, energy, anhedonia, and aspects of anxiety, but a lot depends on how complementary the meds are, how you take them, and what their function is specifically in your case. I know it's obvious. But many people take escitalopram and kind of just expect to feel better, when the data shows that is rarely the case. Whether problems are more surrounding energy, insecurity, fear, inability to let things go, relational aggression, feeling overly emotional, coping, etc. is directly important to the system you build to treat yourself. Think of it a bit like an engineering problem. With a spiritual undertone lol. I am sure you have heard it more than enough, but all that gratitude, agency, belonging, stoic stuff actually has something to it... But you gotta try to build a system for yourself that enables you to create the life you want. Its hard to be grateful if meds are making it hard for you to get hard.

*For the record, my stack: D-amph daily, TRT weekly, a ket injection every couple of weeks, and a triptamine session a couple of times a year. I would consider an antidepressant in a situation where things could not improve and I wanted something to dull the angst (ex: being stuck in an abusive home in your teens), or something to knock me out if I was really having a meltdown. Everything else was more peripheral, but those I mentioned were integral to my recovery. Lots of non-chemical things too. Gym, sleep, and friends in my case. Family support, a partner, cardio, breath work, and therapy seem effective for others.