TY - JOUR
T1 - Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression
AU - Goodwin, Guy M.
AU - Aaronson, Scott T.
AU - Alvarez, Oscar
AU - Arden, Peter C.
AU - Baker, Annie
AU - Bennett, James C.
AU - Bird, Catherine
AU - Blom, Renske E.
AU - Brennan, Christine
AU - Brusch, Donna
AU - Burke, Lisa
AU - Campbell-Coker, Kete
AU - Carhart-Harris, Robin
AU - Cattell, Joseph
AU - Daniel, Aster
AU - DeBattista, Charles
AU - Dunlop, Boadie W.
AU - Eisen, Katherine
AU - Feifel, David
AU - Forbes, MacKenzie
AU - Haumann, Hannah M.
AU - Hellerstein, David J.
AU - Hoppe, Astrid I.
AU - Husain, Muhammad I.
AU - Jelen, Luke A.
AU - Kamphuis, Jeanine
AU - Kawasaki, Julie
AU - Kelly, John R.
AU - Key, Richard E.
AU - Kishon, Ronit
AU - Knatz Peck, Stephanie
AU - Knight, Gemma
AU - Koolen, Martijn H.B.
AU - Lean, Melanie
AU - Licht, Rasmus W.
AU - Maples-Keller, Jessica L.
AU - Mars, Jan
AU - Marwood, Lindsey
AU - McElhiney, Martin C.
AU - Miller, Tammy L.
AU - Mirow, Arvin
AU - Mistry, Sunil
AU - Mletzko-Crowe, Tanja
AU - Modlin, Liam N.
AU - Nielsen, René E.
AU - Nielson, Elizabeth M.
AU - Offerhaus, Sjoerd R.
AU - O’Keane, Veronica
AU - Páleníček, Tomáš
AU - Printz, David
AU - Rademaker, Marleen C.
AU - van Reemst, Aumer
AU - Reinholdt, Frederick
AU - Repantis, Dimitris
AU - Rucker, James
AU - Rudow, Samuel
AU - Ruffell, Simon
AU - Rush, A. John
AU - Schoevers, Robert A.
AU - Seynaeve, Mathieu
AU - Shao, Samantha
AU - Soares, Jair C.
AU - Somers, Metten
AU - Stansfield, Susan C.
AU - Sterling, Diane
AU - Strockis, Aaron
AU - Tsai, Joyce
AU - Visser, Lucy
AU - Wahba, Mourad
AU - Williams, Samuel
AU - Young, Allan H.
AU - Ywema, Paula
AU - Zisook, Sidney
AU - Malievskaia, Ekaterina
N1 - Funding Information:
Supported by COMPASS Pathfinder .
Publisher Copyright:
Copyright © 2022 Massachusetts Medical Society.
PY - 2022/11/3
Y1 - 2022/11/3
N2 - BACKGROUND Psilocybin is being studied for use in treatment-resistant depression. METHODS In this phase 2 double-blind trial, we randomly assigned adults with treatmentresistant 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.
AB - BACKGROUND Psilocybin is being studied for use in treatment-resistant depression. METHODS In this phase 2 double-blind trial, we randomly assigned adults with treatmentresistant 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.
UR - http://www.scopus.com/inward/record.url?scp=85141170646&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa2206443
DO - 10.1056/NEJMoa2206443
M3 - Article
SN - 0028-4793
VL - 387
SP - 1637
EP - 1648
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 18
ER -