Ketamine is, by far, the most likely thing to work, and it seems microdoses work. Second place come psychedelics, tho their antidepressant effect is probably via completely separate mechanism, probably a side effect of their moodenhancement. Again, microdoses work both against depression and general mood improvement. There's that whole thing with people prone to psychosis-related disorders possibly developing schizophrenia, but this doesn't seem to happen with microdoses. Mescaline is probably the safest psychedelic. Still, as far as I know, this latent schizophrenia thing isn't a problem with ketamine.
Just be aware that no method is 100%. For example, people with hypertension, hyperglycemia or hyperlipidemia show diminished response at the first doses of ketamine, but sustained treatment worked just as well:
sci-hub.se/10.1097/JCP.0000000000001149Also it seems that AMPA receptor impairment blocks the antidepresant effect. A study said that opioid receptor impairment also did it, but apparently that was debunked.
There's plenty of anecdotal evidence of ketamine analogues having the antidepressant effect, but, for now, only K itself is scientifically confirmed. Keep in mind some of its analogues might induce activity of the 5-HT2A receptor, which is the suspected mechanism of the schizophrenia problem. MXE, for example, most likely has the antidepressant effect but acts on this receptor.
