Systematic review of psychedelic trials for treatment-resistant depression

The question

Do psychedelic drugs reduce the severity of depression in people whose depression has not responded to standard treatments?

What they did

The authors searched the published literature for clinical trials in people diagnosed with treatment-resistant depression, meaning depression that has not improved with usual treatments. To be included, a study had to measure depression severity with a rating scale and either report an effect size or give enough data to calculate one. Single-blind, double-blind and open-label trials, including single-arm studies with no comparison group, were all eligible. Fifteen articles met the criteria and were summarized.

What they found

Of the 15 included articles, 10 were randomized double-blind controlled trials and 5 were open-label clinical trials. The authors summarized and analyzed all of them to give an overview of the current literature on both classic and atypical psychedelics in treatment-resistant depression. They concluded that these substances appear to work as an alternative or add-on option alongside standard treatments, with signs of benefit across different drug classes.

The fine print

The abstract gives no total number of participants, no specific drugs, no effect sizes and no follow-up lengths, so the size and durability of any benefit cannot be judged from it. A third of the included studies were open-label with no placebo group, which tends to inflate apparent benefit. There is no pooled statistical analysis and no reported assessment of study quality, bias or side effects in the abstract. This summary is based on the abstract alone.

What it means

The published trial evidence for psychedelics in hard-to-treat depression is growing and mostly positive, but this review reports its conclusions in general terms without the numbers needed to weigh how large or lasting the benefit is.

Evidence grade: Moderate. A systematic review that gathers 10 double-blind randomized trials and 5 open-label trials, but it reports no pooled numbers and includes uncontrolled studies.

This summary is based on the study’s published abstract.