MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial

被引:188
作者
Mitchell, Jennifer M. [1 ,2 ,3 ]
Ot'alora, G. Marcela [4 ]
van der Kolk, Bessel [5 ]
Shannon, Scott [6 ]
Bogenschutz, Michael [7 ]
Gelfand, Yevgeniy [8 ]
Paleos, Casey [9 ]
Nicholas, Christopher R. [10 ]
Quevedo, Sylvestre [2 ,11 ]
Balliett, Brooke [12 ]
Hamilton, Scott [13 ]
Mithoefer, Michael [14 ]
Kleiman, Sarah [15 ]
Parker-Guilbert, Kelly [16 ]
Tzarfaty, Keren [17 ,18 ]
Harrison, Charlotte [13 ]
de Boer, Alberdina [19 ]
Doblin, Rick [20 ]
Yazar-Klosinski, Berra [13 ]
机构
[1] Univ Calif San Francisco, Dept Neurol, Neuroscape, San Francisco, CA 94118 USA
[2] Univ Calif San Francisco, Dept Psychiat & Behav Sci, San Francisco, CA 94118 USA
[3] San Francisco VA Med Ctr, Dept Vet Affairs, Res Serv, San Francisco, CA 94121 USA
[4] Aguazul Bluewater Inc, Boulder, CO USA
[5] Boston Univ, Sch Med, Boston, MA USA
[6] Wholeness Ctr, Ft Collins, CO USA
[7] NYU, Grossman Sch Med, Dept Psychiat, New York, NY USA
[8] Zen Therapeut Solut, Mt Pleasant, SC USA
[9] Nautilus Sanctuary, New York, NY USA
[10] Univ Wisconsin, Sch Med & Publ Hlth, Dept Family Med & Community Hlth, Madison, WI USA
[11] San Francisco Insight & Integrat Ctr, San Francisco, CA USA
[12] New Sch Res LLC, Los Angeles, CA USA
[13] MAPS Publ Benefit Corp, San Jose, CA USA
[14] Med Univ South Carolina, Charleston, SC USA
[15] Kleiman Consulting & Psychol Serv PC, Ivyland, PA USA
[16] KPG Psychol Serv LLC, Brunswick, ME USA
[17] Univ Haifa, Haifa, Israel
[18] MAPS Israel, Hod Hasharon, Israel
[19] Tulip Med Consulting LLC, Port Townsend, WA USA
[20] Multidisciplinary Assoc Psychedel Studies MAPS, San Jose, CA USA
关键词
POSTTRAUMATIC-STRESS-DISORDER; UNITED-STATES; 3,4-METHYLENEDIOXYMETHAMPHETAMINE; PSYCHOTHERAPY; SAFETY;
D O I
10.1038/s41591-023-02565-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
This multi-site, randomized, double-blind, confirmatory phase 3 study evaluated the efficacy and safety of 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) versus placebo with identical therapy in participants with moderate to severe post-traumatic stress disorder (PTSD). Changes in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity score (primary endpoint) and Sheehan Disability Scale (SDS) functional impairment score (key secondary endpoint) were assessed by blinded independent assessors. Participants were randomized to MDMA-AT (n = 53) or placebo with therapy (n = 51). Overall, 26.9% (28/104) of participants had moderate PTSD, and 73.1% (76/104) of participants had severe PTSD. Participants were ethnoracially diverse: 28 of 104 (26.9%) identified as Hispanic/Latino, and 35 of 104 (33.7%) identified as other than White. Least squares (LS) mean change in CAPS-5 score (95% confidence interval (CI)) was -23.7 (-26.94, -20.44) for MDMA-AT versus -14.8 (-18.28, -11.28) for placebo with therapy (P < 0.001, d = 0.7). LS mean change in SDS score (95% CI) was -3.3 (-4.03, -2.60) for MDMA-AT versus -2.1 (-2.89, -1.33) for placebo with therapy (P = 0.03, d = 0.4). Seven participants had a severe treatment emergent adverse event (TEAE) (MDMA-AT, n = 5 (9.4%); placebo with therapy, n = 2 (3.9%)). There were no deaths or serious TEAEs. These data suggest that MDMA-AT reduced PTSD symptoms and functional impairment in a diverse population with moderate to severe PTSD and was generally well tolerated. ClinicalTrials.gov identifier: NCT04077437.
引用
收藏
页码:2473 / +
页数:18
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