Sunday, November 06, 2022

Psilocybin Relieves Some (but not all) Treatment-Resistant Depression Cases: Largest trial to date

As far as severe depressions are concerned, treatment progress seems to be excruciatingly slow! Suicidal ideation or behavior or self-injury are among the largest risks for these individuals.

Should we allow individuals suffering from severe, essentially otherwise untreatable or treatment-resistant depression to experiment with psychoactive substances under medical supervision? Why not?

Did they not use placebos for this study? It appears so!

The positive effects were wearing off after 12 weeks. That sounds like a very good result.

I have a hunch that perhaps longer treatment at low dosages maybe more promising in the long term? E.g. the study chose 3 weeks as the "primary end point" for evaluation, which seems to be too short a period.

"For years, some researchers have looked to psychedelic drugs, including psilocybin (the active ingredient in so-called magic mushrooms), as a potential treatment for some psychiatric conditions. The largest trial to date of psilocybin for depression, published today (November 3) in the New England Journal of Medicine, finds that a dose of synthetic psilocybin combined with counseling did alleviate symptoms for some patients. But for some participants who did respond, the effects wore off within 12 weeks of the treatment. ...
The Phase 2 clinical trial, funded in part by the mental health care startup Compass Pathways, which makes the synthetic psilocybin used in the study, included 233 patients for whom at least two depression medications had not worked. The participants were randomly assigned to receive psilocybin at one of three dosing levels: 25 mg, 10 mg, or 1 mg (used as a control). ..."

From the abstract:
"BACKGROUND
Psilocybin is being studied for use in treatment-resistant depression.
METHODS
In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery–Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits).
RESULTS
A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were −12.0 for 25 mg, −7.9 for 10 mg, and −5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was −6.6 (95% confidence interval [CI], −10.2 to −2.9; P<0.001) and between the 10-mg group and 1-mg group was −2.5 (95% CI, −6.2 to 1.2; P=0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups.
CONCLUSIONS
In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder. ..."

Psilocybin Relieves Some Treatment-Resistant Depression Cases: Trial | The Scientist Magazine® The research has caveats, including side effects and a lack of durability in the benefits of a single dose.

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