Exploring New Frontiers in Depression Treatment at the APA Annual Meeting: A Call for Precision Psychiatry

In an interview with Psychiatric Times during the 2025 American Psychiatric Association Annual Meeting in Los Angeles, Dana Hilt, MD, emphasized the need to expand beyond traditional antidepressant strategies to better serve patients with major depressive disorder (MDD).

“If you look at patients with major depressive disorder, how many different antidepressants do they cycle through? At least 2 or 3,” said Hilt. Although the agents are effective for many, Hilt pointed to the significant number of patients who do have fully successful treatment, either due to residual symptoms or adverse events associated with the commonly used agents. “What fraction of patients that with major depressive disorder have been tried on one or two of the common antidepressants yet aren’t taking any because of side effects?” According to some estimates, as many as 30% of patients fall in that realm, he told Psychiatric Times.

Most current treatments still target monoaminergic pathways—serotonin and dopamine—despite the fact that a substantial subset of patients either fail to respond or cannot tolerate the medications. “This is a major chronic disease, and so far it's largely been treated with this one family of mechanisms,” he said. “Most chronic diseases, in my experience, require multiple medications, and importantly, with multiple different pathogenetic mechanisms to really treat the full population of patients.”

Hilt drew a comparison between the state of neuropsychiatry today and oncology 2 to 3 decades ago. “If you have a tumor and you went in to see an oncologist and the oncologist says, ‘Well, you have breast cancer or you have lung cancer,’ and said nothing more, as a patient, I would get up and walk out. I want to know: How do you characterize the tumor? Which type of intervention is going to be most effective for my tumor at this stage of disease? And oncologists, of course, now understand that and do that. They tailor the medication to the patient's specific biology, genetics, stage,” he said.

“We are finally at the stage of… precision medicine,” Hilt added, citing advances in molecular biology and genetics. “Genetics has been a huge advance… many of these conditions are linked to particular genetic polymorphisms, mutations, changes in gene expression.”

Hilt believes that psychiatry is stands at a turning point. “I think this era of precision medicine, genetics, molecular cellular biology, is really informing us better on how to try to develop therapies for patients.” The goal, he said, is to move from phenomenological observation to biologically informed interventions that can transform the treatment landscape for complex, chronic neuropsychiatric diseases.

Hilt, who is chief medical officer at Actinogen Medical, is presenting research data at the APA Annual Meeting exploring an agent addressing a new mechanism of action.¹ Xanamem (emestedastat), Actinogen’s lead investigational drug, is a selective inhibitor of 11β-HSD1 (hydroxysteroid dehydrogenase type 1), an enzyme that facilitates cortisol synthesis in the brain. Research data shows promise as a new modality of treatment.²

To learn more about the data presented at the meeting, see the first part of this discussion with Dr Hilt.

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References

1.Hilt D, Berk M. Xanamem a selective 11β HSD1 inhibitor has positive effects on depression in a phase 2 trial of moderate major depressive disorder. Presented at the 2025 American Psychiatric Association Annual Meeting; May 17-21, 2025; Los Angeles, California.

2. Actinogen. Cognitive Impairment in Major Depressive Disorder. Accessed May 16, 2025. https://actinogen.com.au/major-depressive-disorder/