Reacción a "A study suggests that psychedelics are no more effective than antidepressants and confirms that the studies are not double-blind"

Is the study of good quality? Are the conclusions supported by solid data?

“Yes, it is a systematic review and meta-analysis which, according to the hierarchy of scientific evidence, sits at the very top. Meta-analyses are statistical analyses that combine all the studies conducted on a given topic.”

How does this work fit with the existing evidence?

“It fits perfectly, as it evaluates the current evidence for treating depression with psychedelic substances. What’s novel is that it tempers the existing overenthusiasm about the benefits of psychedelic therapies compared to standard treatments.”

Have the authors taken confounding factors into account? Are there important limitations to consider?

“They have considered all possible confounding factors arising from the idiosyncrasies of clinical trials, such as the shorter duration of psychedelic studies, the lack of demographic diversity among participants, the variety of scales used across studies, and the issue of blinding (i.e., how easy it is to detect placebo in clinical trials).

In my opinion, there is one limitation they do not address: namely, that the limitations of these studies stem from epistemological issues rather than purely methodological ones. The methods are sound, but they reflect a bias in trying to fit the efficacy of psychedelics into a clinical trial model. Clinical trials are designed to evaluate drugs where there is a one-to-one relationship between treatment and disease—the prototypical case being infectious and viral diseases. This is why it is called the bacteriological model.

Trying to fit psychological treatments, such as psychedelic-assisted therapies—where the psychological experience is fundamental—into a bacteriological model introduces a foundational bias. Another bias relates to the rigidity of protocols. Psychedelic-assisted therapy involves administering the psychedelic when it is appropriate within the course of a psychological treatment. The clinical trial model, however, centers on the drug rather than the process, as it arguably should not.

There is also a final, unavoidable bias: placebo-controlled clinical trials aim to eliminate the effect of expectation. But expectation is precisely one of the strongest predictors of therapeutic success. Patients need to expect improvement in order to improve. If expectation is removed, one of the most powerful elements of psychological treatment is also removed.

So, although the study is methodologically impeccable, there is a foundational epistemological bias that makes it difficult to extrapolate the results to real clinical practice.”

What are the real-world implications?

“In real-world settings, clinicians work with patients’ expectations, the therapeutic alliance, and a process-focused approach rather than one centered solely on the drug. Unfortunately, depression studies—unlike those on post-traumatic stress disorder with MDMA—tend to focus heavily on eliminating expectation rather than on the therapeutic process.

Finally, the reasons why depression has been chosen as the primary focus for psychedelic treatments are not based on clear evidence. Psychedelics appear to work better for reactive conditions, such as existential distress in people with serious illness, grief, and other disorders related to life circumstances, rather than for more characterological issues.”