Tools for Practice Outils pour la pratique

#365 Shrooms for Glooms: Evidence for psilocybin for depression

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

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. 

CFPCLearn Logo

Reading Tools for Practice Article can earn you MainPro+ Credits

La lecture d'articles d'outils de pratique peut vous permettre de gagner des crédits MainPro+

Join Now S’inscrire maintenant

Already a CFPCLearn Member? Log in

Déjà abonné à CMFCApprendre? Ouvrir une session

  • 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

  • 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

Latest Tools for Practice
Derniers outils pour la pratique

#365 Shrooms for Glooms: Evidence for psilocybin for depression

What are the benefits and harms of psilocybin for treatment-resistant/recurrent depression?
Read Lire 0.25 credits available Crédits disponibles

#364 Facing the Evidence in Acne, Part II: Oral Antibiotics

How effective are oral antibiotics in treating acne of at least mild-moderate severity?
Read Lire 0.25 credits available Crédits disponibles

#363 Making a difference in indifference? Medications for apathy in dementia

In patients with dementia, how safe and effective are stimulants, antidepressants, and antipsychotics for treating apathy?
Read Lire 0.25 credits available Crédits disponibles

This content is certified for MainPro+ Credits, log in to access

Ce contenu est certifié pour les crédits MainPro+, Ouvrir une session

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

1. Kisely S, Connor M, Somogyi AA, et al. Aust N Z J Psychiatry. 2023; 57(3):362-378.

2. Ko K, Kopra EI, Cleare AJ, et al. J Affect Disord. 2023; 322:194-204.

3. Romeo B, Karila L, Martelli C, et al. J Psychopharmacol. 2020; 34(10):1079-85.

4. Galvão-Coelho NL, Marx W, Gonzalez M, et al. Psychopharmacology (Berl). 2021; 238(2):341-354.

5. Leger RF, Unterwald EM. J Psychopharmacol. 2022; 36(1):20-30.

6. van Amsterdam J, van den Brink W. Expert Opin Drug Saf. 2022; 21(6):833-840.

7. IsHak WW, Garcia P, Pearl R, et al. Innov Clin Neurosci. 2023 Spring; 20(4-6):39-48.

8. Hodge AT, Sukpraprut-Braaten S, Narlesky M, et al. J Psychoactive Drugs. 2023 Jan-Mar; 55(1):40-50.

9. Rossi GN, Hallak JEC, Bouso Saiz JC, et al. Expert Opin Drug Saf. 2022; 21(6):761-776.

10. Goel DB, Zilate S. Cureus. 2022; 14(10):e30214.

11. Li NX, Hu YR, Chen WN, et al. J Affect Disord. 2022; 296:26-34.

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.