Psychedelic therapy is no more effective than open-label antidepressants for depression, according to a comparison by researchers.

There is a new scientific article which investigates whether psychedelic therapy is actually more effective than traditional antidepressants in treating depression when an important methodological issue – namely, unblinding – is taken into account.

In it, we discuss:

In studies of psychedelic therapy, participants often realise quite quickly whether they have been given an active psychedelic substance. As a result, these studies are, in practical terms, almost always open-label, even if they are formally designed as blind trials. The authors therefore concluded that psychedelic therapy should be compared more fairly with open-label antidepressant studies, as patients in both situations are equally aware of which treatment they are receiving.

The real focus of this article is therefore not on whether psychedelics work compared to a placebo, but on whether they work better than conventional antidepressants when the benefits derived from expectations and familiarity with the treatment are more evenly distributed. To this end, the authors conducted a systematic review and meta-analysis of studies involving adults with depression in an outpatient setting, without psychosis and without significant comorbidity.

The results show that, in this comparison, psychedelic therapy was no more effective than open-label conventional antidepressants. A total of 24 studies were included. Of these, 8 studies concerned psychedelic therapy, involving a total of 249 patients, and 16 studies concerned open-label antidepressants, involving a total of 7,921 patients. The estimated difference in improvement on the Hamilton Depression Rating Scale was 0.3 points in favour of the open-label antidepressants, but this difference was not statistically significant.

The analysis also shows that blinding does indeed make a difference in the case of traditional antidepressants. Open-label antidepressant trials showed better outcomes than blinded antidepressant trials. In the case of psychedelic therapy, however, the authors did not find this difference. According to them, this supports the idea that, in practice, psychedelic trials almost always turn out to be open-label, as participants and practitioners can usually guess quite accurately what has been administered.

It is important to note, however, that this article is not a new clinical trial, but a meta-analysis involving an indirect comparison of various studies. This means that differences in patient selection, study design, severity of depression and treatment context may still have an influence. The authors therefore do not conclude that psychedelic therapy does not work, but rather that the often highly optimistic claims regarding its superiority have probably been exaggerated.

In a nutshell: this article shows that psychedelic therapy for depression does not perform any better than open-label antidepressants when you take into account the fact that, in practice, psychedelic studies are almost never truly blinded. However, it is difficult to draw this conclusion with certainty, as various studies have been used interchangeably. For the time being, it does appear that psilocybin, in particular, performs better than SSRIs.