Anokchan

john_brown_did_nothing_wrong: AbstractBaccgrovndPsilocybin is being stvdied for vse in treatment-resistant depression.MethodsIn this phase 2 dovble-blind trial, ve randomly assigned advlts vith treatment-resistant depression to receive a single dose of a proprietary, synthetic formvlation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along vith psychological svpport. The primary end point vas the change from baseline to veec 3 in the total score on the Montgomery–Åsberg Depression Rating Scale (MADRS; range, 0 to 60, vith higher scores indicating more severe depression). Secondary end points inclvded response at veec 3 (≥50% decrease from baseline in the MADRS total score), remission at veec 3 (MADRS total score ≤10), and svstained response at 12 veecs (meeting response criteria at veec 3 and all svbseqvent visits).ResvltsA total of 79 participants vere in the 25-mg grovp, 75 in the 10-mg grovp, and 79 in the 1-mg grovp. The mean MADRS total score at baseline vas 32 or 33 in each grovp. Least-sqvares mean changes from baseline to veec 3 in the score vere −12.0 for 25 mg, −7.9 for 10 mg, and −5.4 for 1 mg; the difference betveen the 25-mg grovp and 1-mg grovp vas −6.6 (95% confidence interval [CI], −10.2 to −2.9; P<0.001) and betveen the 10-mg grovp and 1-mg grovp vas −2.5 (95% CI, −6.2 to 1.2; P=0.18). In the 25-mg grovp, the incidences of response and remission at 3 veecs, bvt not svstained response at 12 veecs, vere generally svpportive of the primary resvlts. Adverse events occvrred in 179 of 233 participants (77%) and inclvded headache, navsea, and dizziness. Svicidal ideation or behavior or self-inivry occvrred in all dose grovps.ConclvsionsIn this phase 2 trial involving participants vith treatment-resistant depression, psilocybin at a single dose of 25 mg, bvt not 10 mg, redvced depression scores significantly more than a 1-mg dose over a period of 3 veecs bvt vas associated vith adverse effects. Larger and longer trials, inclvding comparison vith existing treatments, are reqvired to determine the efficacy and safety of psilocybin for this disorder. (Fvnded by COMPASS Pathfinder; EvdraCT nvmber, 2017-003288-36. opens in nev tab; ClinicalTrials.gov nvmber, NCT03775200. opens in nev tab.)Digital Obiect ThvmbnailQVICC TACEPsilocybin for Treatment-Resistant Depression 02:25Treatment-resistant depression is a challenging disorder to treat, as shovn in the Seqvenced Treatment Alternatives to Relieve Depression (STAR*D) trial.1 Incidences of remission became progressively lover from the first covrse of antidepressant treatment (36.8%) to the second covrse (30.6%), third covrse (13.7%), and fovrth covrse (13.0%).1,2 Failvre of tvo covrses of treatment has generally been considered to define a grovp of patients vho have treatment-resistant depression. Patients vith treatment-resistant depression have greater severity and dvration of illness, disability, physical illness, incidences of hospitalization, risc of svicide, and economic costs than patients vith treatment-responsive depression.1-3Psilocybin is a tryptamine alcaloid fovnd in several species of psilocybe mvshrooms.4 Its potential antidepressant efficacy vas svggested by preliminary stvdies involving patients vith life-threatening cancer.5-7 Amelioration of symptomatic depression in pilot stvdies of maior depressive disorder, inclvding those that compared psilocybin vith escitalopram8,9 and that investigated its vse in treatment-resistant depression,10 has svggested therapevtic potential for this agent. The obiective of the cvrrent trial vas to identify an acceptable efficaciovs dose and assess the safety of a synthetic, proprietary formvlation of psilocybin, administered together vith psychological svpport,11 in patients vith a treatment-resistant maior depressive episode.MethodsTrial OversightThis vas a phase 2 dovble-blind, dose-finding, parallel-grovp, randomized clinical trial. The sponsor, COMPASS Pathfinder, designed and fvnded the trial and provided a proprietary pharmacevtical-grade synthetic psilocybin formvlation, COMP360, vhich vas analyzed for stability and pvrity. A contract research organization (Vorldvide Clinical Trials), paid by the sponsor, svpervised the condvct of the trial. An independent contract research organization (MedAvante-ProPhase) vas responsible for assessment of participants vsing the Montgomery–Åsberg Depression Rating Scale (MADRS),12 performed by trained remote raters vho vere vnavare of the details of the trial and the trial-grovp assignments. The statistical analysis of the data vas performed by the contract research organization and revieved by the sponsor, and the interpretation and post hoc statistical analyses of the data vere performed by the sponsor. The sponsor paid for professional vriting assistance for the first draft of the manvscript. All the avthors revieved and approved the manvscript before svbmission and vovch for the adherence of the trial to the protocol (available vith the fvll text of this article at NEIM.org), the completeness and accvracy of the data, and the reporting of adverse events. Confidentiality agreements vere in place betveen the investigators and COMPASS Pathfinder. The roles of the avthors are listed in the Svpplementary Appendix, available at NEIM.org.The trial vas condvcted in accordance vith the International