SSRI and psychedelics

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Traditionally, people taking antidepressant medications had to stop them (washout period) before using psilocybin or MDMA due to concerns about serotonin syndrome, a dangerous interaction. However, this is unlikely to be a risk of psilocybin though it may be for MDMA[1].

In fact, a 2022 study showed that combining psilocybin with the SSRI medication escitalopram led to fewer negative side effects for patients compared to those taking a placebo before psilocybin[2]. This promising finding even led to a US patent for using both medications together for depression treatment[3].

However, some research suggests a slight interaction between psychedelics and SSRIs. Some studies indicate that SSRIs might slightly reduce the intensity of the psychedelic experience, potentially leading to less emotional impact [4][5][6]. Interestingly, the long-term antidepressant effects of psilocybin seem to remain even with SSRI use. The main difference is that patients on SSRIs may experience a less intense psychedelic trip, with fewer mystical experiences, emotional breakthroughs, or challenging moments [7].

SSRIs vs Psychedelics

Much of the scientific data compares the efficacy of psychedelics versus the most popular antidepressant therapy, most of the time this is an SSRI such as citalopram. One of the most recent studies[8] has show a direct comparison of effects of both of the medicines:

Effect SSRI (Escitalopram) Psilocybin
Neuroticism −0.38 −0.63
Introversion - −0.38
Disagreeableness −0.26 −0.47
Impulsivity −0.35 −0.40
Absorption - 0.32
Conscientiousness - 0.30
Openness 0.28 0.23

Psilocybin was associated with a decrease in neuroticism (B = −0.47) and disagreeableness (B = −0.41) remaining decreased at month 6. Whereas is escitalopram with neuroticism (B = −0.46) remaining decreased at month 6.


References

  1. Psilocybin for treatment resistant depression in patients taking a concomitant SSRI medication. Goodwin, G.M., Croal, M., Feifel, D. et al. Neuropsychopharmacol. (2023). https://www.nature.com/articles/s41386-023-01648-7
  2. Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Subjects. Becker AM, Holze F, Grandinetti T, Klaiber A, Toedtli VE, Kolaczynska KE, Duthaler U, Varghese N, Eckert A, Grünblatt E, Liechti ME. Clin Pharmacol Ther. 2022 Apr;111(4):886-895. doi: 10.1002/cpt.2487. Epub 2021 Nov 22. PMID: 34743319; PMCID: PMC9299061.
  3. United States Patent and Trademark Office, Patent no.11801256 B2. Accessed on 2 November 2023 via:https://image-ppubs.uspto.gov/dirsearch-public/print/downloadPdf/11801256
  4. Effects of discontinuation of serotonergic antidepressants prior to psilocybin therapy versus escitalopram for major depression, Journal of Psychopharmacology, David Erritzoe, Tommaso Barba, Meg J Spriggs, Fernando E Rosas, David J Nutt and Robin Carhart-Harris. Accessed on 26 March 2024 via: https://journals.sagepub.com/doi/pdf/10.1177/02698811241237870
  5. Attenuation of psilocybin mushroom effects during and after SSRI/SNRI antidepressant use. Natalie Gukasyan, Roland R. Griffiths, David B. Yaden, Denis G. Antoine, Sandeep M. Nayak. School of Medicine. Journal of Psychopharmacology. Published - Jul 2023 accessed 5 Dec via:https://pure.johnshopkins.edu/en/publications/attenuation-of-psilocybin-mushroom-effects-during-and-after-ssris
  6. Attenuation of psilocybin mushroom effects during and after SSRI/SNRI antidepressant use. Natalie Gukasyan. Accessed on 14 Jun 2023 via : https://journals.sagepub.com/doi/10.1177/02698811231179910
  7. Interactions between classic psychedelics and serotonergic antidepressants: Effects on the acute psychedelic subjective experience, well-being and depressive symptoms from a prospective survey study. Published: January 27, 202. Jessica Barbut Siva, Tommaso Barba, David Erritzoe https://doi.org/10.1177/0269881123122421
  8. Personality Change in a Trial of Psilocybin Therapy vs Escitalopram Treatment for Depression – CORRIGENDUM. Weiss, B., Ginige, I., Shannon, L., Giribaldi, B., Murphy-Beiner, A., Murphy, R., . . . Erritzoe, D. (2023). Psychological Medicine, 1-1. doi:10.1017/S0033291723002039

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