Forecast Ledgerinterventional psychiatry and psychedelic medicineQuoted, dated predictions scored against public outcomes under one written method. Every score links to the words, the rule and the evidence.

Pending · due 21 Jul 2027

Rules 1.1.0 · as of 14 Sep 2026

Owen Scott Muir · Said 21 Jul 2025 · owen-1809

Quote

“This is one that (probably) didn’t clear the bar. The advisory committee vote isn’t binding, but the overwhelming majority were clear in their decision—the data isn’t there yet.”
· The FDA AdCom Rejects Brexpiprazole/Sertraline for PTSD this Week · substack post

The FDA advisory committee (CDER) voted 10-1 against Otsuka/Lundbeck's brexpiprazole/sertraline (Rexulti plus Zoloft) supplemental application for PTSD; only one of two Phase III trials separated from placebo and the FDA usually requires two replicated trials. The author judges the application probably did not clear the bar and notes the vote is not binding, implying he expects the FDA to decline the application.

Intake

EventA proposition written from a template on the asset, with a resolution criterion and a named public source, before the outcome is looked up. The same event resolves every person's items on it. Method ›
FDA approval of brexpiprazole plus sertraline for PTSD
AreaOne of five topic classes: regulatory decisions, clinical trial outcomes, company and market outcomes, payer and policy, practice adoption. Every event has one area. Method ›
Regulatory decisions
DeadlineThe date by which the event must happen for the item to be true. It comes only from the person's words through the anchor table. Method ›
None stated · undated panelItems with no deadline in the person's words, scored on a uniform 24-month window from the statement date. Part of the headline panel since rules 1.1.0; also shown on its own. Method ›, 24-month window to 21 Jul 2027
Probability
0.30 LexiconThe fixed five-bin table that turns a phrase into a probability. The strongest phrase in the claim sentence decides; coders never read tone. Method › · binOne of five lexicon steps: A 'will' 0.90, B 'probably' 0.70, C 'may' 0.50, D 'unlikely' 0.30, E 'never' 0.10. A stated number goes to the nearest bin for calibration only. Method › B · “(probably)” · denialA statement that the event will not happen. Its probability on the event side is 1 minus the bin value. Method ›
Base rateThe probability a published external study gives an event of that class and stage, fixed at intake. Halved when the item window is shorter than the class median time to decision. Never learned from the ledger's own items. Method ›
negative_adcomm_to_approval · 0.33
Tags
denial, retrospective
Coder BCohen's kappa: agreement between two coders beyond chance, from -1 to 1. Reported for admit, event, deadline, bin and asserts from the second-coder match test. Method ›
admittedA statement that passed intake: sincere, the person's own claim, forward-looking, inside the five areas, and not excluded by a reason code. Only admitted statements become items. Method › · event E-0039 · deadline none · bin B
Registry entry

The FDA approves brexpiprazole (Rexulti) in combination with sertraline for the treatment of post-traumatic stress disorder.

TRUE on the date of the FDA approval letter or Drugs@FDA supplement entry (the sponsor's approval announcement is the secondary source) that adds a PTSD indication for brexpiprazole used in combination with sertraline. A complete response letter, a positive advisory committee vote or a filing acceptance is not an approval; a complete response letter does not resolve the event FALSE, the event stays open to the end of the window. A label that names PTSD with any sertraline co-administration wording counts. FALSE when no such indication appears in Drugs@FDA by the deadline.

Resolution source: Drugs@FDA; sponsor press release as a secondary source

Readings: 'Didn't clear the bar' read as: the FDA does not approve the application. The next sentence ('the advisory committee vote isn't binding, but ...') shows the sentence is about the FDA decision, not only the committee vote.; Rexulti, brexpiprazole and 'brexpiprazole/sertraline' name the same asset; the indication is PTSD as filed in the supplemental application.

How to read
The event, criterion and deadline were written at intake, before the outcome1 if the registry event happened on or before the item's deadline, 0 if it did not. Written by a resolver who never sees p. Method › was looked up. Coder B coded the statement independently.

Coder A

Resolution

State
PendingAn item whose deadline has not passed. Counted, never scored. Method ›
Effective deadlineAn item enters the score only when its deadline has passed and the outcome is true or false. A claim already known true still waits for its deadline. Method ›
21 Jul 2027
Outcome1 if the registry event happened on or before the item's deadline, 0 if it did not. Written by a resolver who never sees p. Method ›
not occurred · checked through 13 Sep 2026
Resolver note
Drugs@FDA for NDA 205422 shows the latest actions as SUPPL-14 (2025-05-09, efficacy-labeling change with clinical data) and SUPPL-17 (2026-04-30, labeling-package insert); no PTSD efficacy supplement is approved. The current label (revised 4/2026, DailyMed updated 2026-05-06) lists three indications: adjunctive treatment of MDD, schizophrenia (age 13+), and agitation associated with dementia due to Alzheimer's disease; PTSD appears only in the safety-population description. The sNDA for brexpiprazole with sertraline in PTSD received a complete response letter (Otsuka release 2025-09-20) after the 2025-07-18 advisory committee voted 1-10 against efficacy; the FDA said additional adequate and well-controlled trials would be needed. Otsuka's 2026 newsroom shows no PTSD resubmission or approval. Per the criterion the CRL does not close the event; it is not occurred as of 2026-09-13.
Evidence
BrierThe squared gap between a probability and the outcome, (p - o)^2. 0 is perfect, 0.25 is the constant coin flip, 1 is confidently wrong. Lower is better. Method ›
Not scored
How to read
State at window close; the outcome comes from the registry, the score from the rule.

Registry

Receding horizon

Muir promised FDA approval of brexpiprazole plus sertraline for PTSD 2 times; it has not happened.

promised datehappened
2026202720262027TODAY2025-07-20: by 2027-07-20 · p 0.302025-07-21: by 2027-07-21 · p 0.30X SAID ON · Y PROMISED BY · DASHED: PROMISED = SAID · DOT AREA = P

Cluster E-0039

Timeline

1 claim against 35 events in the field.

saiddueevent
31 Jul 2025 · FDA / Janssen: FDA approves Spravato REMS modification S-024.4 Sep 2025 · FDA: FDA publicly releases the Lykos MDMA complete response letter, citing unreported4 Sep 2025 · FDA / Lykos Therapeutics: FDA publicly releases the August 2024 Lykos CRL, detailing concerns on safety re18 Sep 2025 · BrainsWay (Deep TMS): FDA clears BrainsWay's accelerated Deep TMS protocol for MDD, shortening treatme22 Sep 2025 · Otsuka / Lundbeck (Rexulti, PTSD): FDA issues a CRL for brexpiprazole plus sertraline in PTSD, citing insufficient 9 Oct 2025 · FDA / Janssen: FDA approves Spravato REMS modification S-025 with vendor-related changes to the6 Nov 2025 · Johnson & Johnson (Caplyta, adjunctive MDD): FDA approves Caplyta (lumateperone) as adjunctive treatment for MDD based on two13 Nov 2025 · BrainsWay (Deep TMS): FDA clears BrainsWay Deep TMS as an adjunct for MDD in adolescents aged 15 to 215 Dec 2025 · New Mexico Department of Health: At the Medical Psilocybin Advisory Board's first meeting, DOH says patient acces18 Dec 2025 · President Trump: Executive order directs the Attorney General to complete marijuana rescheduling 31 Dec 2025 · DEA and HHS: Fourth temporary extension of telemedicine flexibilities for controlled medicati1 Jan 2026 · Czech Republic: Czech medical psilocybin framework takes effect: psychiatrists may administer ps5 Jan 2026 · GH Research (GH001): FDA lifts the clinical hold on GH001, clearing a global phase 3 program in TRD t12 Jan 2026 · Neurolief (Proliv Rx): FDA grants PMA approval to Neurolief's Proliv Rx, the first at-home brain neurom23 Jan 2026 · FDA / Janssen: FDA approves Spravato REMS modification S-027, reverting the October 2025 vendor3 Mar 2026 · AtaiBeckley (BPL-003): AtaiBeckley reports a successful End-of-Phase 2 meeting with FDA for BPL-003 in ATAIBECKLEY (BPL-003): ATAIBECKLEY REPORTS A SUCCESSFUL END-OF-PHASE 2 MEETING WITH FDA FOR BPL-003 IN 13 Apr 2026 · FDA / Janssen: FDA approves Spravato REMS modification S-028 adding Spanish translations of REM18 Apr 2026 · President Trump: EO 14401 orders FDA priority vouchers for breakthrough psychedelics, an ibogaine23 Apr 2026 · DOJ / DEA (Acting AG Blanche): Final order moves FDA-approved marijuana products and state-licensed medical mar24 Apr 2026 · FDA: FDA awards Commissioner's National Priority Vouchers to Compass (COMP360 psilocy24 Apr 2026 · FDA / Compass Pathways: FDA grants Compass a rolling NDA submission and review for COMP360 psilocybin in24 Apr 2026 · FDA / Compass Pathways, Usona Institute, Transcend Therapeutics: FDA awards Commissioner's National Priority Vouchers to Compass (COMP360), Usona24 Apr 2026 · FDA Commissioner Marty Makary: Makary says he expects an FDA approval decision on at least one priority psyched30 Apr 2026 · Axsome Therapeutics (Auvelity / AXS-05): FDA approves Auvelity for agitation associated with Alzheimer's disease, the fir23 Jun 2026 · Louisiana Legislature: SB 43 becomes Act 956 without the governor's signature after unanimous votes, cr24 Jun 2026 · FDA / Janssen: FDA approves Spravato REMS modification S-029 with updated REMS website workflow26 Jun 2026 · Oregon Health Authority: OHA proposes fee increases for the psilocybin services program ahead of the Sept29 Jun 2026 · DEA: Expedited administrative hearing opens on broader rescheduling of marijuana, inc13 Jul 2026 · FDA (psychedelic drugs guidance): FDA finalizes 'Psychedelic Drugs: Considerations for Clinical Investigations', s14 Jul 2026 · FDA: FDA finalizes the guidance 'Psychedelic Drugs: Considerations for Clinical Inves14 Jul 2026 · FDA: FDA announces a September 14, 2026 public hearing on future therapeutic use of p10 Aug 2026 · Resilient Pharmaceuticals (ex-Lykos, midomafetamine): Resilient resubmits the MDMA-assisted therapy NDA for PTSD without a new phase 310 Aug 2026 · Resilient Pharmaceuticals (formerly Lykos): Company resubmits its NDA for MDMA-assisted therapy for PTSD (proposed brand Rys25 Aug 2026 · DEA: DEA sends its final telemedicine special registration rule to OIRA for review; t8 Sep 2026 · Definium Therapeutics (DT120): FDA grants Breakthrough Therapy Designation to DT120 (lysergide) ODT in MDD follFDA APPROVAL OF B…FDA approval of brexpiprazole plus sertraline for PTSD · stated 21 Jul 2025FDA approval of brexpiprazole plus sertraline for PTSD · restated 21 Jul 2025 · p 30%30%TODAY20262027

Regulatory decisions

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