Unmet Needs, Future Research in Schizophrenia and Muscarinic Agonists

The recent approval of new schizophrenia treatments, such as xanomeline and tropsium chloride capsules (Cobenfy, formerly KarXT), signals a transformative shift in psychopharmacology, ushering in what leading subject matter experts are calling the "third wave" of drug development. Historically, the field has evolved from the introduction of tricyclic antidepressants and typical antipsychotics in the 1950s to the atypical antipsychotics of the 1980s, which focused on improved tolerability and safety.

As Andrew Cutler, MD, notes in the segment, this new generation leverages innovative mechanisms—particularly targeting acetylcholine alongside dopamine—aiming to address the heterogeneous nature of schizophrenia. With a range of muscarinic agonists in development, there is hope for better management of cognitive impairments and negative symptoms that have long been inadequately treated.

“We're entering an era that I'm calling the ‘muscarinic wars’ right now, which is like the old atypical wars that I lived through before Rishi entered the field, probably in the 90s, when we had a number of these atypicals,” Cutler said. “It was terrific because they're all different. Some patients we know do better with one than another, and I think the same will hold true here.”

Rishi Kakar, MD, echoed this same sentiment—noting, in his 15 years conducting studies, he has noticed more enthusiasm among clinicians with the paradigm shift.

“Let's ride the wave and see where we go,” said Kakar, on entering this new era in management.

Series Segments:

• Introductions
• Mechanism of Action of Xanomeline and Trospium Chloride Capsules
• Applying EMERGENT Trial Results to Real-World Clinical Practice for Schizophrenia
• Balancing the Benefits and Risks of Xanomeline and Trospium Chloride Capsules
• Unmet Needs, Future Research in Schizophrenia and Muscarinic Agonists

Subject Matter Experts

• Sam Clark, MD, PhD, (Moderator) is a former practicing psychiatrist and is the founder and chief executive officer of Terran Biosciences.
• Andrew Cutler, MD, is a clinical associate professor in the Department of Psychiatry and Behavioral Sciences at SUNY Upstate Medical University and the chief medical officer of the Neuroscience Education Institute.
• Rishi Kakar, MD, is a psychiatrist based out of southern Florida as well as the medical director and chief scientific officer of Segal Trials. Kakar served as the principal investigator on the pivotal EMERGENT trials.

Relevant disclosures for Cutler include Karuna, Bristol Myers Squibb, and others. Relevant disclosures for Kakar include Karuna, Bristol Myers Squibb, and others. Relevant disclosures for Clark include Terran Biosciences.