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#365 Shrooms for Glooms: Evidence for psilocybin for depression


CLINICAL QUESTION
QUESTION CLINIQUE
 What are the benefits and harms of psilocybin for treatment-resistant/recurrent depression?

BOTTOM LINE
RÉSULTAT FINAL
 Psilocybin, given in treatment facilities with >10 hours psychological support, improves short-term (≤6 weeks) depression scores, helping 20-30% more patients attain response over control. Effects biased by unblinding, short-term trials and mostly inactive comparators.  Psychological distress during treatment is common (75-90%) and requires monitoring/supports. 


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EVIDENCE
DONNÉES PROBANTES
  • Statistically significant unless indicated.
  • 12 Systematic reviews of randomized controlled trials (RCTs) had serious limitations:
    • Meta-analyzed different conditions/treatments,1-3 included people without depression,4,5 descriptive reviews only,6-10 missed key studies,11 or dose-response effects.12
  • Higher-quality RCTs with comparators:13-16 Most patients had long-term/treatment-resistant/recurrent depression14-16 and current antidepressants stopped.13-16 Response generally ≥50% depression score reduction.
  • RCT versus placebo:13
    • 52 patients. Psilocybin ~16mg/70kg versus placebo, one dose. At two weeks:
      • Montgomery-Asberg Depression Rating Scale (MADRS, 0-60, higher=worse) baseline=24: Psilocybin reduced 13 versus 3.5.
        • Minimal important difference17=3-6.
      • Response: Psilocybin 58% versus 15%, number needed to treat (NNT)=3.
  • RCTs versus very-low-dose or inactive comparator:14,15
    • 233 patients. Psilocybin 25mg, 10mg or 1mg, one dose.14 At three weeks:
      • MADRS baseline=32: 25mg reduced 12 versus 1mg reduced 5.
      • Response: 37% (25mg) versus 18% (1mg), NNT=6.
      • No statistical difference at 12 weeks, or 10mg versus 1mg anytime.
    • 104 patients. Psilocybin 25mg versus niacin 100mg, one dose.15 At six weeks:
      • MADRS baseline=35: Psilocybin reduced 19 versus 7.
      • Response: 42% psilocybin versus 11%, NNT=4.
  • RCT versus escitalopram16
    • 59 patients. Psilocybin 25mg every 3 weeks x2 doses versus escitalopram daily. At six weeks:
      • Remission: Psilocybin 57% versus escitalopram 28%, NNT=4.
      • Other depression outcomes not different.
  • Adverse Events:13-16 Headache and nausea 4-42% more common than control on day 1.
    • Distress common during treatment:18 Examples “I felt like crying” (92%), sadness (79%), or emotional/physical suffering (77%).
    • 10-15mmHg systolic blood pressure rise x3-hours.13
  • Limitations: Blinding 93-97% ineffective.19
CONTEXT
CONTEXTE
  • Resource intense: Two counsellors for preparation (2-8 hours), during treatment (6-11 hours), and follow-up (2-4 hours).13-16,18
  • Presently, guidelines recommend psilocybin in research20,21 or special access-settings only.20
    • Longer-term effectiveness (>6 weeks) and serious harms unclear.
  • Psilocybin micro-dosing RCTs: patients didn’t have depression/anxiety.22,23

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Author(s)
Auteur(s)
  • G. Michael Allan MD CCFP
  • Jessica Kirkwood MD CCFP (AM)
  • Jennifer Young MD CCFP-EM

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12. Perez N, Langlest F, Mallet L, et al. Eur Neuropsychopharmacol. 2023; 76: 61-76.

13. von Rotz R, Schindowski EM, Jungwirth J, et al. eClinicalMedicine. 2023; 56:101809.

14. Goodwin GM, Aaronson ST, Alvarez O, et al. N Engl J Med. 2022; 387:1637-48.

15. Raison CL, Sanacora G, Woolley J, et al. JAMA. 2023; 330(9):843-53.

16. Carhart-Harris R, Giribaldi B, Watts R, et al. N Engl J Med. 2021; 384(15):1402-11.

17. Hengartner MP, Plöderl M. BMJ Evid Based Med. 2022; 27(2):69-73.

18. Davis AK, Barrett FS, May DG, et al. JAMA Psychiatry. 2021; 78(5):481-489.

19. Hovmand OR, Poulsen ED, Arnfred S, et al. J Psychopharmacol. 2023 Jul; 37(7):649-59.

20. Rosenblat JD, Husain MI, Lee Y, et al. Can J Psychiatry. 2023;68(1):5-21

21. McQuaid JR, Buelt A, Capaldi V, et al. Ann Intern Med. 2022; 175(10):1440-1451

22. Marschall J, Fejer G, Lempe P, et al. J Psychopharmacol. 2022; 36(1):97-113.

23. Cavanna F, Muller S, de la Fuente LA, et al. Transl Psychiatry. 2022; 12(1):307.

Authors do not have any conflicts of interest to declare.