John Kane, MD: Shifts in Antipsychotics for Schizophrenia

While many advances in clinical research have catalyzed psychiatry’s understanding of schizophrenia management, the practical application of those lessons learned have lagged behind.

In an interview with HCPLive during the American Psychiatric Association (APA) 2024 Annual Meeting in New York, NY, this weekend, John Kane, MD, co-director and professor at the Institute of Behavioral Science at Feinstein Institutes for Medical Research, discussed his planned presentation topic regarding the progression of antipsychotic therapies for schizophrenia.

As Kane explained, research and therapeutic development has been promising of late in schizophrenia—including the anticipated US Food and Drug Administration (FDA) decision for Karuna Therapeutics’ xanomeline-trospium (KarXT) for the treatment of adults with schizophrenia.¹ But he also perceives a difficulty in implementing new clinical evidence and drug indications into care strategies in a timely fashion.

A pair of examples that speak to that struggle, Kane said, is the implementation of proven long-acting injectables (LAIs) and clozapine.

“A substantial proportion of patients do not respond adequately to the first or second medication that they receive,” Kane said. “The long-acting injectable medications have been shown to facilitate adherence and reduce the risk of relapse and re-hospitalization, as well as discontinuation of medication. So, unfortunately, they are also underutilized particularly in early-phase patients.”

With the development of later-generation antipsychotics, Kane has observed a notable improvement in safety profiles—only clozapine stands out for particular treatment efficacy, being the lone FDA-approved therapy indicated for treatment-resistant depression. However, that trend may change with the development of up-and-coming antipsychotic medications: muscarinic agonists that differentiate from the common dopamine D2 receptor-targeting drugs that constitute the traditional early classes of schizophrenia drugs.²

“We will wait to see if those drugs are more effective, or more efficacious than the medicines that we currently have available,” Kane said. “But they do seem to work, and they do seem to be working via a different mechanism. So that's very exciting.”

One avenue by which schizophrenia care has improved in practice, Kane noted, is the addition of multidisciplinary care team members earlier into a patient’s diagnosis. Facets of disease management—including psychosocial care, family-based education, supportive employment and education—have become better embedded into the initiation of schizophrenia treatment at institutions like his own.

“And we believe that the combination of these modalities and these professionals is really necessary to bring about the best chance of recovery for someone in the early phase of schizophrenia, and we've seen the growth of programs across the US and around the world that are delivering this type of treatment,” Kane said. “I think we still have a long way to go. But that's been a very positive development, as well.“

^{Kane is a consultant and/or has received honoraria from Alkermes, Allergan, Boehringer-Ingelheim, Cerevel, Dainippon Sumitomo, H. Lundbeck, HealthRhythms, HLS Therapeutics, Indivior, Intracellular Therapies, Janssen Pharmaceutical, Johnson & Johnson, Karuna Therapeutics, LB Pharmaceuticals, Merck, Minerva, Neurocrine, Newron, Novartis, NW PharmaTech, Otsuka, Roche, Saladax, Sunovion, Teva.}

References

1. ^{Armstrong A. After long journey, Karuna's schizophrenia drug gets FDA decision date. Fierce Biotech. Published November 29, 2023. https://www.fiercebiotech.com/biotech/after-long-journey-karunas-schizophrenia-drug-gets-fda-decision-date}
2. ^{Foster DJ, Bryant ZK, Conn PJ. Targeting muscarinic receptors to treat schizophrenia. Behav Brain Res. 2021;405:113201. doi:10.1016/j.bbr.2021.113201}