Psychiatry Month in Review: April 2025

Recent developments in psychiatry highlight both setbacks and emerging opportunities in treatment. Cobenfy (xanomeline-trospium) fell short in a phase 3 trial as an adjunctive schizophrenia therapy, though safety and subgroup findings point to future potential. Survey data revealed a disconnect between patient and provider preferences for long-acting antipsychotics, and another stressed the need for improved adherence strategies.

This Month in Review also features advances in trial design with EEG biomarkers for Major Depressive Disorder (MDD), new evidence supporting mindfulness-based therapy for opioid use disorder, and a troubling rise in binge drinking among young adult women.

New Phase 3 Trial on Cobenfy as an Adjunctive Therapy

Cobenfy Falls Short in Phase 3 ARISE Trial as Adjunctive Schizophrenia Therapy

In the phase 3 ARISE trial, xanomeline and trospium chloride (Cobenfy) failed to show a significant benefit over placebo as an adjunctive schizophrenia treatment (P = .11), despite numerical improvements in symptoms. Approved in September 2024 as the first antipsychotic targeting cholinergic receptors, Cobenfy showed promise in select subgroups and maintained a favorable safety profile.

A post-hoc analysis revealed greater efficacy when Cobenfy was paired with non-risperidone antipsychotics (P = .03) vs risperidone (P = .66). Investigators emphasized the need for further investigation to better understand its role as an adjunctive therapy and explore its potential in treatment-resistant populations.

Surveys on Schizophrenia Treatment

TEV ‘749 Survey Shows Many Nurses Prefer Intramuscular Injections, with Andrew Cutler, MD

In a recent survey tied to the SOLARIS trial, most patients favored the once-monthly subcutaneous antipsychotic TEV-‘749, yet 50% of nurses and 45.5% of physicians still preferred intramuscular injections—likely due to greater familiarity. Despite this, TEV-‘749 showed high satisfaction rates among patients (90%), nurses (87%), and physicians (73%),

In an interview with investigator Andrew Cutler, MD, a clinical associate psychiatry professor at SUNY Upstate Medical University, emphasized the importance of long-acting injectables (LAIs) like TEV-‘749 for patients struggling with adherence, noting their potential to prevent relapses and brain damage.

Alberto Augsten, PharmD, Interprets National Provider Survey on Schizophrenia, BD

In an interview with HCPLive, psychopharmacologist Alberto Augsten, PharmD, shared key insights from a national provider survey on schizophrenia and bipolar I disorder. Augsten emphasized the importance of improving medication adherence, particularly through long-acting injectables, to reduce relapse risk.

He noted cognitive burden as a major factor affecting quality of life and highlighted how newer treatments aim to simplify regimens and minimize adverse effects. Despite promising options, many providers hesitate to adopt innovations, often awaiting more efficacy and safety data. Augsten encourages clinicians to consider quality-of-life metrics and patient-centered care when making treatment decisions.

New Discoveries in MDD, OUD, Binge Drinking

EEG Biomarker Helps Identify Placebo Responders in MDD Trials

At SOBP 2025, Alto Neuroscience announced data supporting an EEG biomarker that predicts placebo response in MDD trials. Validated across multiple datasets, the biomarker showed no link to demographic or clinical factors. By identifying likely placebo responders, the tool may reduce trial variability and improve detection of true therapeutic effects.

In the EMBARC trial, the biomarker predicted placebo response, while in ALTO-100 trials, it predicted antidepressant response. Findings suggest this approach could enhance psychiatric drug development by refining patient selection and boosting effect sizes in clinical trials.

Mindfulness Therapy Reverses Pleasure Deficits in OUD

A study found that opioid use disorder (OUD) impairs the brain’s ability to experience natural, healthy pleasure—a deficit that can be reversed through mindfulness-based interventions. The randomized clinical trial tested Mindfulness-Oriented Recovery Enhancement (MORE) in patients with chronic pain, revealing it improved positive emotion regulation and significantly reduced opioid craving, use, and anhedonia. MORE participants showed increased brain responses to positive emotions compared to those in supportive therapy.

Binge Drinking Rates Increasing Among Young Female Adults, Study Finds

New research highlights shifting sex-based patterns in alcohol use, revealing that young adult females now binge drink more than their male peers—a reversal of past trends. Using NSDUH data from 2017–2019 and 2021–2023, investigators found that while males still lead in overall binge and heavy drinking, young women aged 18–25 reported higher binge drinking rates in the most recent data. This shift coincides with rising alcohol-related liver disease and mortality among females.