Unmet Needs, Future Research in Schizophrenia and Muscarinic Agonists

Author(s):

Sam Clark, MD, PhD,Andrew Cutler, MD

Key Takeaways

The approval of xanomeline and tropsium chloride capsules represents a transformative shift in schizophrenia treatment, marking the "third wave" of drug development.
New treatments target acetylcholine and dopamine, aiming to address cognitive impairments and negative symptoms inadequately treated by previous medications.
Experts anticipate diverse patient responses, akin to the "atypical wars" of the 1990s, with potential for improved schizophrenia management.
Clinicians express enthusiasm for this paradigm shift, indicating a promising future for schizophrenia treatment.

In part 5 of 5, experts discuss ongoing unmet needs and future research priorities in schizophrenia management.

EP: 1.Embracing New Therapies in Schizophrenia Management: Introductions

EP: 2.Mechanism of Action of Xanomeline and Trospium Chloride Capsules in Schizophrenia

EP: 3.Applying EMERGENT Trial Results to Real-World Clinical Practice for Schizophrenia

EP: 4.Balancing the Benefits and Risks of Xanomeline and Trospium Chloride Capsules

Now Viewing

EP: 5.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:

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.