Potential for psilocybin antidepressant treatment highlighted by study

University of Oxford researchers reviewed seven trials involving 436 participants (52% female; 90% white Anglo-Saxon) to conclude that psilocybin use was linked to improved depression scores compared to other treatments.

The peer-reviewed study found the change in patients' depression scores was significantly greater after treatment with psilocybin than with a comparator treatment, with an overall Hedge's g of 1.64, indicating a large effect size favouring psilocybin.

They also found benefits of psilocybin were more pronounced among people with depression related to an underlying disease, older people and those who had previously used psychedelics.

An estimated 300 million people worldwide are affected by depression, and it is a known and leading cause of disability.

For those who are prescribed antidepressant drugs, treatment effects do not appear until about 4-7 weeks after they are taken, and the likelihood of relapse is high, with 40-60% of people with depression experiencing a further depressive episode.

A combination of studies was also examined, some involving psychotherapy treatment and some without that support.

But the evidence is not certain enough, due to the high levels of variation (heterogeneity) in the studies, to confirm psilocybin's strong antidepressant effect. And, before psilocybin treatment can be established in clinical settings, issues such as cost, lack of regulatory guidelines and legal safeguards must first be resolved.

In an associated editorial authored by researchers unconnected to the study, experts said the analysis identified psilocybin was more effective than alternative treatments for depression such as placebo, niacin (vitamin B) or psychedelics microdosing.

"Psilocybin's mechanism of action differs from that of classic selective serotonin reuptake inhibitors (SSRIs) and might improve the treatment response rate, decrease time to improvement of symptoms, and prevent relapse post-remission," the paper read.

"Moreover, more recent assessments of harm have consistently reported that psilocybin generally has low addictive potential and toxicity and that it can be administered safely under clinical supervision."

The experts said pragmatic clinical trials and real-world data were needed to provide more evidence about the effectiveness of psilocybin in treating depression under 'real-world' conditions.

"As per all analyses using aggregate data, we cannot differentiate between those individuals most likely to benefit from psilocybin and those who might instead experience adverse events," they said.

"Overall, future studies should explore psilocybin's exact mechanism of treatment effectiveness and outline how its physiological effects, mystical experiences, dosage, treatment setting, psychological support, and relationship with the therapist all interact to produce a synergistic antidepressant effect.

"Although this may be difficult to achieve using an explanatory randomised trial design, pragmatic clinical trial designs may be better suited to psilocybin research, as their primary objective is to achieve high external validity and generalisability."

Debate was still ongoing, the experts noted, about whether psychedelics on their own could express antidepressant activity or whether they worked only to assist specific forms of psychotherapy.  And, a lack of participant diversity affected the "generalisability of findings".

The experts said the factors that maximised the treatment potential of psilocybin for symptoms of depression need to be clarified.

This included a need to investigate the impact of moderating factors such as the type of depression, past use of psychedelics, dosage, and publication bias.

"[These promising findings] support a prudent approach in both scholarly and public settings, because more and better evidence is needed before any clinical recommendation can be made about the therapeutic use of psilocybin," the researchers said.

"More large-scale randomised trials with long follow-up are needed to fully understand psilocybin's treatment potential, and future studies should aim to recruit a more diverse population.

"Another factor that would make clinical trials more representative of routine practice would be to recruit patients who are currently using or have used commonly prescribed serotonergic antidepressants."

The researchers concluded that while the findings were encouraging, further evidence was needed before any clinical recommendations about its large-scale use could be made.

'Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis' was published in BMJ on Thursday.

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