Personal experience here. My depression has been an unending struggle since my tweens. I&#x27;ve been on every medication, spent fortunes in therapy. I also abused dissociatives like Ketamine. Ketamine&#x27;s antidepressant effects seemed very real after the initial high and it was qualitatively different from SSRIs. SSRIs seemed <i>more</i> like a drug than Ketamine which felt more like relief (again, for the days following the high - the actual high was, you know, psychedelic and stuff). I think for some people research into this area would be a real boon. Not everyone responds well to traditional treatments. I&#x27;m not sure what&#x27;s different about my brain that makes even high doses of SSRIs ineffective or even unpleasant, but I don&#x27;t think we understand all that well how depression actually works at all, other than SSRIs and similar seem to kind of work.<p>If you think depression is about just increasing serotonin in the brain, let me point out that &quot;serotonin syndrome&quot; is a very real risk of using antidepressants. It&#x27;s essentially an overdose on serotonin. It&#x27;s clear that messing with serotonin in the brain, you can give a sort of neurochemcial nudge that can help you overcome depression, but happiness is not itself the amount of serotonin in your system.<p>Either way, I quit using drugs and alcohol many years ago and regular exercise with exercise, tons of CBT, and lots of vigilance has helped the best. But it would be nice to have a drug on the market that would make keeping depression at bay so effortful and so much hard, consistent work.<p>Anecdote isn&#x27;t worth much in medicine, but there really is something special about Ketamine.