In this bonus episode, host Ben Everett, PhD, reconnects with Ilan Melnick, MD, chief medical officer of Passageway, a South Florida forensic community control program, who also maintains a private concierge practice. Dr. Melnick chaired a JCP consensus panel of early adopters of xanomeline-trospium chloride (XT), and nearly two years after approval, he shares what clinicians have learned putting this first-in-class muscarinic agent into everyday practice.
Unlike dopamine D2 blockers, XT activates M1 and M4 muscarinic receptors to lower presynaptic dopamine, while trospium limits peripheral cholinergic effects. The conversation covers EMERGENT trial findings on positive, negative, and general psychopathology symptoms; early use in first-episode psychosis; titration to maintenance doses; prophylactic ondansetron and empty-stomach dosing; distinguishing cholinergic from anticholinergic adverse events; class-specific cross-titration; and antipsychotic dose sparing. Dr. Melnick also reviews two new Psych Congress posters: a real-world prescriber survey and a post hoc analysis of EMERGENT-5 examining GI side effects and treatment retention.
🎯 KEY EPISODE HIGHLIGHTS:
💊 ONDANSETRON BEFORE NAUSEA STARTS [31:00]
“One of the things we know about ondansetron is that it's a better preventer than it is a fixer.”
Prophylactic ondansetron at initiation is a simple step that can prevent early GI-related discontinuation.
⚖️ CHOLINERGIC OR ANTICHOLINERGIC? [36:00]
“If they're cholinergic in nature, go up to the one twenty-five. But if they're anticholinergic in nature then we have to see what other medicines are causing that extra anticholinergic effect.”
Identifying the type of adverse event determines whether to titrate up or review concomitant medications such as OTC sleep aids.
📈 STALLING AT 100 MG AND DROPOUT [49:41]
“So those that stay there and don't move up to the 125 milligram dose ended up usually dropping out due to higher GI issues.”
A post hoc EMERGENT-5 analysis suggests that titrating to the higher dose may support retention rather than threaten it.
CHAPTERS:
00:00 – Introduction: Revisiting the XT Consensus Panel
02:04 – Forensic Community Care and a Concierge Practice
05:26 – From Postsynaptic Blockade to Presynaptic Modulation
08:34 – M1/M4 Agonism and the Role of Trospium Chloride
13:03 – EMERGENT Trial Results and Early Cognitive Benefits
18:17 – Inside the Panel: Early Adopters and Experiential Evidence
22:35 – Early Use in First-Episode Psychosis and Dose Titration
28:28 – Patient Selection and Prophylactic Ondansetron
31:47 – Empty-Stomach Dosing and Cholinergic vs Anticholinergic Effects
37:15 – Cross-Titrating From Dones, Pines, and Partial Agonists
40:33 – Antipsychotic Dose Sparing, the ARISE Trial, and LAIs
44:17 – Psych Congress Poster: Real-World Prescriber Survey
49:07 – EMERGENT-5 Retention Data and the Future of Muscarinics
LINKS:
Full transcript and show notes:
https://www.psychiatrist.com/jcp/ep25-lessons-early-adopters-xt-schizophrenia-ilan-melnick/
Journal of Clinical Psychiatry
https://www.psychiatrist.com/jcp/
Publisher of peer-reviewed research discussed in this episode.
Real-World Implementation of Xanomeline-Trospium in Schizophrenia: A Consensus Panel Report
https://www.psychiatrist.com/jcp/real-world-implementation-xanomeline-trospium-schizophrenia-consensus-report/
The JCP consensus panel report chaired by Dr. Melnick and discussed throughout this episode.
Dr. Ilan Melnick - LinkedIn
https://www.linkedin.com/in/ilan-melnick-516b4468/
#Schizophrenia #XanomelineTrospium #MuscarinicAgonist #FirstEpisodePsychosis #Psychopharmacology
