Developing a Small Molecule With Lithium's Benefits, But Not its Baggage: A Conversation With Jonathan M. Meyer, MD, DLFAPA

TALKING WITH TITANS OF PSYCHOPHARMACOLOGY

At the 2025 American Psychiatric Association (APA) Annual Meeting, Psychiatric Times' Editor in Chief, John J. Miller, MD, sat down with leaders in psychopharmacology to discuss the topics they find most important.

Jonathan M. Meyer, MD, DFAPA, presented on lithium, one of the strongest tools in psychiatry, expanding on our understanding of its mechanisms. How can we develop antidepressant drugs to enhance benefits and minimize adverse events?

The known molecular targets of lithium are surprisingly few and include the signaling kinase glycogen synthase kinase-3 beta (GSK-3β).¹

"We now know what the downstream process is, which is being regulated by GSK-3β inhibition. With that insight, people are now trying to find specific and potent GSK-3β inhibitors, which we think will give all of lithium's activities, as best we understand it," said Meyer.

Lithium, because it is an ion, gets into places it does not belong, shared Meyer, who has written an entire book on the subject of lithium.² "If I can develop a small molecule GSK-3β inhibitor, which is not an ion, we are not going to get those problems," said Meyer.

As to current stage of research, this molecule is being studied in animal models currently and is expected to begin human trials next year.

"If we can have something which gives us what lithium does largely, without some of its baggage, wouldn't that be a huge advance for the world of bipolar disorder treatment?" said Meyer. "We need more options."

Dr Meyer is a voluntary clinical professor of psychiatry at the University of California, San Diego.

Dr Miller is Medical Director, Brain Health, Exeter, New Hampshire; Editor in Chief,Psychiatric Times; Voluntary Consulting Psychiatrist at Seacoast Mental Health Center, Exeter/Portsmouth, NH; Consulting Psychiatrist, Insight Meditation Society, Barre, Massachusetts.

References

1. Snitow ME, Bhansali RS, Klein PS. Lithium and therapeutic targeting of GSK-3. Cells. 2021;10(2):255.

2. Meyer JM, Stahl SM. The Lithium Handbook. Cambridge University Press; 2024.