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CONFERENCE REPORTER

“It’s new medicine, brand new mechanism, which is very distinct from what we have for the past 70 years,” Jonathan Meyer, MD said of new xanomeline-trospium (X-T) treatment for schizophrenia. Moving away from traditional dopamine blocking mechanisms, new treatments for schizophrenia pivot to target cholinergic pathways with muscarinic agents. Muscarinic agents may be a solution to the issue of excess dopamine in the presynapse, with X-T showing improvement of positive schizophrenia symptoms and no side effects of tardive dyskinesia like traditional prescriptions.

Gus Alva, MD, Jonathan Meyer, MD, and Chelsie Monroe, APN, presented these latest findings in schizophrenia medication in their session “Visualizing the Role of Novel Muscarinic Agents in the Management of Schizophrenia” at the 2025 Southern California Psychiatry Conference.¹

The long-held belief that positive symptoms of schizophrenia result from excess dopamine in the mesolimbic pathway has recently been questioned, with human models suggesting the issue may actually lie in presynaptic dopamine release specifically in the striatum. Clinicians have managed positive symptoms by using D2 antagonists for decades, but with new drug developments that can adjust presynaptic activity—rather than react to change postsynaptic activity—positive symptoms can be better managed.²

In this session, presenters detailed a promising alternative to D2 antagonists: targeting the muscarinic acetylcholine receptors (focused on M1 and M4) as a way to regulate dopamine release presynaptically without blocking dopamine receptors directly. This new investigational therapy combines xanomeline, a selective M1 and M4 agonist, with trospium, a peripheral anticholinergic that avoids unwanted side effects by limiting activity outside the central nervous system.

The unique action of xanomeline-trospium modulates neurotransmitter pathways upstream of dopamine, thereby avoiding the motor and endocrine side effects commonly seen with D2 antagonists. M1 receptor activation reduces dopamine indirectly through GABA and glutamate signaling, while M4 agonism acts from the lower level, modulating acetylcholine production in the ventral tegmental area. This mechanism allows for much stronger safety profiles because there is not a potential for major motor issues like tardive dyskinesia many patients can suffer from with traditional D2 antagonists.

Data showed significant reductions in Positive and Negative Syndrome Scale (PANSS) scores, with patients seeing average declines of 33.6 points by week 52. Most notably, there were no cases of tardive dyskinesia, and the most common side effects were brief and manageable cholinergic issues. Dr. Alva noted that X-T may be particularly beneficial for chronic schizophrenia patients who have not responded well to traditional treatments. While currently approved by the FDA as a monotherapy, discussions and research are ongoing about X-T’s potential use alongside other antipsychotics.

However, this new medication comes with important practical considerations for prescribers. X-T must be taken one hour before or two hours after a meal, as taking it with food reduces trospium absorption by up to 90%. If a patient has issues with nausea due to being unable to take X-T with food, extra trospium can be added to their regimen to reduce these side effects. Starting X-T also involves titration to mitigate cholinergic side effects like urinary or bowel issues caused by trospium. Patients who are already on other antipsychotic medications also may need a closely watched cross titration process, as many traditional medications have anticholinergic properties that can interfere with X-T.

With this new muscarinic focused approach, there is less focus on reacting to downstream, postsynaptic effects of excess dopamine, and instead X-T alters presynaptic dopamine. The FDA approval of xanomeline-trospium introduces a new chapter in schizophrenia treatment, offering long awaited relief from motor symptoms of traditional antipsychotics and lessening positive psychotic symptoms.

References

1. Alva G, Meyer J, Monroe C. Visualizing the Role of Novel Muscarinic Agents in the Management of Schizophrenia. Conference Proceedings of the Southern California Psychiatry Conference. July 2025;11-12. Huntington Beach, CA.

2. Kaul I, Sawchak S, Claxton A. et al. Efficacy of xanomeline and trospium chloride in schizophrenia: pooled results from three 5-week, randomized, double-blind, placebo-controlled, EMERGENT trials. Schizophr. 2024;10:102.

Strong emotional links between children with chronic conditions and their family caregivers suggest that improving parent well-being may directly benefit a child’s overall health and coping mechanisms, according to a study being presented Saturday at ENDO 2025, the Endocrine Society’s annual meeting in San Francisco, Calif. 

The study observed children with growth hormone deficiency and their caregivers to better understand the impact that physical or emotional distress can have. Findings suggest that when parents or caregivers of children with growth hormone deficiency report symptoms of stress, anxiety and depression, so does the child they are caring for. Conversely, when caregivers exuded hope and emotional stability, children with growth hormone deficiency were better able to cope with their condition and showed improved overall health.

“We’ve long recognized the stress caregivers face, but our study shows just how intertwined parent and child health really are,” said Luis Fernandez Luque, Ph.D., chief scientific officer and co-founder of Adhera Health in Santa Cruz, Calif., which developed the digital companion platform used by the caregivers in the study. “Supporting the caregiver isn’t just helpful—it is essential to improving outcomes for children with growth hormone deficiency or other chronic pediatric conditions.”

The study followed 50 caregivers of children with growth hormone deficiency over a three-month period during participation in Adhera Health’s digital health program focused on caregiver wellbeing. Caregivers completed a series of validated assessments measuring their own emotional and mental health and reported on the child’s physical and emotional status.

Findings indicated that a children’s emotional and physical health are strongly correlated with caregiver well-being. Greater child distress, such as negative feelings about treatment or difficulty coping with growth hormone deficiency, was associated with higher caregiver stress, anxiety and depressive symptoms. In addition, caregiver hopefulness about the future was linked to better emotional outcomes in the child.

“This research confirms the well-being of children with chronic conditions is inseparable from the emotional health of their caregivers,” said Ricardo C. Berrios, CEO and co-founder of Adhera Health, who was a co-author of the study. “Adhera’s AI-powered platform was designed from the ground up to support this dynamic, combining behavioral science and responsible AI to empower families—not just patients. These findings strengthen our conviction that improving outcomes for children requires an ecosystem approach, one that puts caregivers at the center of pediatric chronic care.”

The study was supported by Merck KGaA in Darmstadt, Germany.

About Endocrine Society
Endocrinologists are at the core of solving the most pressing health problems of our time, from diabetes and obesity to infertility, bone health, and hormone-related cancers. The Endocrine Society is the world’s oldest and largest organization of scientists devoted to hormone research and physicians who care for people with hormone-related conditions.

The Society has more than 18,000 members, including scientists, physicians, educators, nurses, and students in 122 countries. To learn more about the Society and the field of endocrinology, visit our site at www.endocrine.org. Follow us on X (formerly Twitter) at @TheEndoSociety and @EndoMedia.

Oxytocin, often called “the love hormone,” may play a protective role in mood disturbances triggered by sleep loss and hormonal shifts during key reproductive transitions like postpartum and menopause, according to a study being presented Saturday at ENDO 2025, the Endocrine Society’s annual meeting in San Francisco, Calif. 

Researchers at Brigham and Women’s Hospital and Harvard Medical School studied the combined impact of sleep interruption and estrogen suppression on mood and oxytocin levels in healthy premenopausal women. Their findings suggest that oxytocin may help reduce the negative mood effects brought on by fragmented sleep, which is an often-overlooked consequence of reproductive transitions.

“We found that oxytocin levels rise in response to stress-related sleep disruption, and that women with higher oxytocin levels before disrupted sleep experienced less mood disturbance the next day,” said Irene Gonsalvez, M.D., associate psychiatrist at Brigham and Women’s Hospital and instructor at Harvard Medical School in Boston, Mass. “These results point toward oxytocin as a potential biological buffer during periods of hormonal and emotional vulnerability.”

Women frequently experience disrupted sleep during the postpartum and menopausal periods that are associated with sharp hormonal fluctuations. Yet these disturbances are often minimized or seen as routine inconveniences. The study provides new biological evidence that such sleep interruptions are linked to meaningful changes in emotional health, and that oxytocin may serve as an important protective factor.

In the study, 38 healthy premenopausal women completed two 5-night inpatient protocols: one during a natural hormonal state and another after estradiol suppression. After two nights of uninterrupted sleep, researchers fragmented participants’ sleep for three nights to simulate patterns commonly experienced during postpartum and menopause. Mood disturbance and oxytocin levels were assessed throughout.

Findings indicated that sleep interruption significantly increased both mood disturbance and oxytocin levels, and that higher oxytocin levels before sleep disruption were linked to reduced mood disturbance the following day. Higher incidences of mood disturbance associated with sleep disruptions were also linked to increased oxytocin levels the next day.

“Millions of women struggle with mood symptoms during reproductive transitions, yet treatments often focus narrowly on antidepressants or hormone therapy,” Gonsalvez said. “Understanding oxytocin’s potential as a natural mood modulator could help us better support women’s mental health during these times.” 

This research was supported by the Brigham and Women’s Hospital Connors Center WHISPR Award, the Dupont-Warren HMS Research Fellowship, and the National Institute on Aging.

About Endocrine Society
Endocrinologists are at the core of solving the most pressing health problems of our time, from diabetes and obesity to infertility, bone health, and hormone-related cancers. The Endocrine Society is the world’s oldest and largest organization of scientists devoted to hormone research and physicians who care for people with hormone-related conditions.

The Society has more than 18,000 members, including scientists, physicians, educators, nurses, and students in 122 countries. To learn more about the Society and the field of endocrinology, visit our site at www.endocrine.org. Follow us on X (formerly Twitter) at @TheEndoSociety and @EndoMedia.