Psilocybin bests SSRI for major depression in first long-term comparison

If you actually read the effectiveness and safety research with a critical eye, you would realize “rigorous” is often the wrong adjective, whereas “cherry picked” to the point of “fraudulent” is often more in line with reality.

Case in point: 50,000 people died, with about 5 times as many suffering life-changing serious adverse events, from “rigorous research” on the safety of Vioxx. Yes, it has since been pulled from the market, which FDA apologists often construe as “system working as designed”. No, it isn’t, even in the least, when you go into the details.

Also: Purdue and OxyContin.

Regulatory capture of the FDA is decades old at this point. Ignoring that is not a rational or healthy position.

I don't know, why don't we ask my colon? Oh, wait, we can't. I was prescribed accutane, subsequently got ulcerative colitis so bad that they had to remove the organ entirely. The surgeon said my colon was literally falling apart in his hands as he took it out. Blind deference to authority of doctors lead to this situation. They do not always make great decisions, especially if there is a financial incentive for them to do otherwise.

signs point to no:

https://www.cbsnews.com/news/magic-mushrooms-found-in-recall...

I'm not saying psylocybin can't be used safely, nor have I made any claims about its relative toxicity or harm relative to other scheduled drugs. If you're arguing anything else, I don't think that report says what you think it says. As for my position, I live in SF, it's decriminalized here, I support that. So there's no need for your rude presumption that I find it generally unsafe.

I'm also unfamiliar with the dose of SSRIs that would send you into a coma, but I'm fairly certain it's shockingly large. Happy to be informed otherwise.

edit to reflect parent edit: yes, I'm aware that breakthrough experiences can be helpful. I'm also saying they should not be your first resort.

This comment ignores the possible effectiveness of both psilocybin and SSRIs and focuses on the usefulness of the research itself. I actually believe that both have a role in psychiatry, but this study tells me nothing with regards to therapy.

Working as a clinical psychologist, who also reads a lot of research, this study is just another brick in the wall that I am banging my head against when it comes to doing actual evidence-based therapy. I actually read the entire paper and the pre-registration. The title on Medscape and the article are, to me, completely reading the research wrong, and just another example of the actual research design and findings living in a different universe than the press release and subsequent discussion.

Let me try to communicate why I feel this way by summarizing the research in my way, as opposed to the title: "Psilocybin Bests SSRI for Major Depression in First Long-Term Comparison."

Hers my take: Research finds no significant difference between psilocybin and SSRI in the primary outcome from pre-registration (self-reported depression on an emailed form), even when only administering SSRI for 6 weeks, where the maximum effect of SSRI is expected at 12 weeks. As such, this does not even qualify as standard treatment with SSRI. This is after excluding 90% of the applicants for the study. The effectiveness is primary supported by p-hacking, as seen by reporting additional measures not in the registered, where some of them favor psilocybin. And SSRI actually scores BETTER in the main outcome.

Now, someone might come along and call me cynical, mistaken, or worse. But having been through this with biofeedback, metacognitive therapy, light therapy, mindfulness therapy, and ketamine treatment already, I can clearly see the same pattern: lying by omission, p-hacking, not taking into account the "decline effect," borderline acceptable results. It all culminates in a big nothingburger, and any progress for my field remains stagnant. Based on the quality of this study, I am certain that if we just aggressively started treating depression with psilocybin, I just know that it wouldn't make much difference, because I have been through it before with the exact same numbers and effect sizes, just different treatment modalities.

Here is the best indication I found for SSRI: Resistant phobic anxiety (panic attacks that don't stop even after long exposure), and burnout-related depression (person worked normally their whole life but is suddenly just empty of energy and does not look forward to anything with joy). These are examples that very often make a big difference with SSRI, in conjunction with therapy.

Psilocybin seems to work best for existential depression and anxiety that is driven by pathological self-focus (not egotism, but inability to stop focusing on one's own inner states).

But these personal theories are just that, and the studies that keep getting funding are very seldom useful, at least for me, as I genuinely am trying my best to help my patients.