Ketamine is quite different than psychedelics, so the two can't be compared. It's also important to note that the recent study of psilocybin in treatment-resistant depression was extremely preliminary and not of good quality. The sample size was very small (n=12), there was no placebo control group (huge red flag in any depression study), and nearly half of the patients indicated previous psilocybin use.

Placebo control groups are absolutely critical in depression studies because the placebo response rate for depression is incredibly high. Moreover, placebo response rates are actually rising in recent years for unknown reasons. It's not uncommon for the placebo control group in a depression study to have response rates upwards of 60%, at least in the short-term timeframes of clinical studies. When you read sensational news articles about how SSRIs are barely better than placebo, remember that placebo is pretty damn good (again, in the short-term) at producing a response in depression studies. The story changes in clinical practice over the long-term, of course, but the point is that separating placebo response from actual treatment effects is critical for assessing anti-depressant efficacy, and psychedelic (not ketamine) studies lately have omitted placebo control groups completely, which is unfortunate.

It gets more complicated, though. In the case of psychedelics, the placebo effect may actually play a central role in the anti-depressant effects. Psychedelics are known to induce suggestibility and create a false sense of enlightenment. If that suggestibility and sense of enlightenment is deliberately framed in the context of depression treatment and actively guided by clinicians, as in the studies, then perhaps it's possible that the psychedelics are at least partially acting as an instrument for amplifying the placebo effect. To the depressed patient, it doesn't matter if the result is placebo effect or not, as long as the end result is the same. At that point, the real question is whether or not the end result is the same.

> However, it also gives people the false impression that all they need to do is chew on some shrooms and listen to the Grateful Dead for a couple of hours and suddenly they will be free of all addiction and depression forever.

I completely agree that public and media perception of these experimental depression treatments is completely off base. There is a lot of interesting potential in here, but many people are walking away with an idea that they can self-medicate their problems away by themselves in their basements. There are many people in forums and subreddits chasing ill-conceived plans to treat themselves with psychedelics or NMDA antagonists in ways that don't match the study protocols at all, and it's all very concerning.

> Every time a study like this comes out there is a predictable pattern in patients' depression scores: immediately after psychedelic treatment, depression signs plunge, wade around the low end for a while, then steadily creep back up.

Unfortunately, the same pattern is observed in placebo control groups for depression studies. That's why it's so critical to have a placebo control group such in depression studies.

> With the exception of people whose brains simply do not work as they should (I have a friend who is chronically depressed because his body can't produce enough serotonin even with antidepressants), depression is often as influenced by external factors as internal ones.

Your comments on external factors are spot-on. Training the brain to have healthy responses and coping mechanisms, as in CBT, is critical to depression treatment.

However, the comments about your friend's brain not producing enough serotonin is more pseudo-science than real science. I don't doubt that doctors have told your friend that, but it's a metaphor at best. SSRIs don't cause the brain to produce more serotonin, they modify the dynamics of serotonin transmission. The anti-depressant effects come from downstream changes that result from that alteration in serotonin dynamics, which are complex and multi-faceted.

But depression isn't simply a function of serotonin levels or balances like the over-simplified explanations would suggest. It's entirely possible to increase extra-synaptic serotonin functions well beyond normal, healthy ranges with medications without making the patient "feel" good. Depression is massively complex, and we modulate serotonin because it's one of the easiest and safest paths to manipulate brain function, not necessarily because patients don't have "enough" of it.

> mental health will always be vastly more complex and harder to cure than any physical ailment.

You're absolutely right that effective mental health treatment requires more than just a pill. But having effective medications to augment healthy mental habits, coping mechanisms, and CBT-type treatments makes it a whole lot easier.