From psychopharmacology to sleep science to schizophrenia research, a look at what shaped the conversation at 3 major meetings this year.

APA

This year, the American Psychiatric Association (APA) met in San Francisco, California, to feature a wide range of topics from current clinical data to novel tools and medication repurposing trials. Investigators reviewed up-to-date trials in schizophrenia pharmacology, researchers proposed new directions for medications like GLP-1s, and disciplines overlapped in neurology, dermatology, and technology. Presentations highlighted the field’s creativity—with invention in objective testing, assessment tools, and clinical research—pointing to a continued push for the cutting-edge in psychiatry.

Recognizing and Treating Bipolar With Mixed Features: Practical Tips

Jessica Walters

Roger McIntyre, MD, delivered a clinically oriented review of mixed features in bipolar disorder, urging clinicians toward individualized, in-depth patient characterization.¹

Mixed features—defined by DSM-5 as 3 or more opposite-polarity symptoms occurring during a mood episode—affect an estimated 25% to 35% of depressive episodes and are disproportionately represented in bipolar 2 disorder, rapid-cycling presentations, women, and patients with early illness onset or childhood trauma. McIntyre noted that “pure” bipolar depression without subthreshold hypomanic symptoms is uncommon, given that roughly 70% of patients with bipolar depression demonstrate at least some hypomanic features.

To aid clinical recognition in practice, McIntyre shared what he called the “4 A’s”—anxiety, agitation, anger/irritability, and attentional disturbance—with anhedonia suggested as a possible fifth indicator. He cautioned against misattributing these symptoms to attention-deficit hyperactivity disorder, anxious distress, posttraumatic stress disorder-related hyperarousal, akathisia, or borderline personality disorder, each of which can mimic mixed presentations. Patients with mixed features carry substantially greater illness severity, chronicity, comorbidity, and suicide risk, alongside measurable HPA-axis, autonomic, and immune-inflammatory dysregulation. Validated screening and assessment tools discussed included the Rapid Mood Screener, Bipolar Depression Rating Scale, CUDOS-M, and Hypomania Checklist.

Therapeutically, McIntyre emphasized that antidepressant monotherapy—still the most commonly prescribed approach in bipolar disorder—frequently can destabilize patients with mixed features, and that an option like valproate offers limited efficacy with significant teratogenic risk. Among the 5 approved second-generation antipsychotics for bipolar depression, cariprazine has shown efficacy across both polarities with and without mixed features, while lumateperone is unique as it has the only randomized, placebo-controlled trial designed a priori for a mixed-features population. Olanzapine-samidorphan and newer agents such as xanomeline-trospium were also highlighted as evolving options with differing metabolic profiles.

McIntyre’s practical algorithm focus: deprioritize antidepressants when mixed features are suspected, look to second-generation antipsychotics or lithium, and reconsider diagnosis in antidepressant-refractory MDD.

Reference

1. Walters J. Bipolar disorder with mixed features: recognition and treatment, with Roger McIntyre, MD, at APA. Psychiatric Times. May 20, 2026. https://www.psychiatrictimes.com/view/bipolar-disorder-with-mixed-features-recognition-and-treatment-with-roger-mcintyre-md-at-apa

Using GLP-1s for Substance Use Disorders? Trials Continue to Investigate

Jessica Walters

Joji Suzuki, MD, presented an overview of glucagon-like peptide-1 (GLP-1) receptor agonists as emerging pharmacotherapeutic agents in substance use disorders (SUDs), focusing on alcohol use disorder (AUD) and opioid use disorder (OUD).¹

The GLP-1 drug class traces its origins to an unexpected finding in diabetes research: exendin-4, a peptide isolated from Gila monster venom, shares approximately 53% homology with endogenous human GLP-1 but carries a substantially longer half-life of roughly 2.4 hours, enabling once-daily dosing. Exenatide, derived from exendin-4, received US Food and Drug Administration approval in 2005; semaglutide followed in 2017, and tirzepatide (a dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist) received approvals in 2022 and 2023. Retatrutide, a triple agonist targeting GLP-1, GIP, and glucagon receptors, is the most recent addition to the class, with phase 2 data demonstrating approximately 25% weight loss at one year, approximating bariatric surgery outcomes.

Preclinical evidence shows that GLP-1 receptor agonist exposure reduces self-administration of alcohol, cocaine, fentanyl, heroin, and tobacco, implicating modulation of mesolimbic reinforcement circuits. Population-level analyses have associated semaglutide use with reductions in AUD-related hospitalizations, incident and recurrent AUD diagnoses, and opioid overdose events. A recently published randomized, double-blind, placebo-controlled trial of once-weekly semaglutide in patients with AUD represents a significant advance, Suzuki highlighted.

For OUD specifically, brenipatide—an investigational GLP-1–based agent—is under active study and, if approved, would represent the first new pharmacotherapy for OUD since buprenorphine. Active trials are also evaluating oral semaglutide in combination with naltrexone for AUD, reflecting interest in multimodal strategies.

Suzuki noted clinicians should consider pharmacokinetics as well: GLP-1 receptor agonists delay gastric emptying and alter drug absorption kinetics, with lithium cited as one agent warranting monitoring when coprescribed. Suzuki framed GLP-1 agents as attenuating the core wanting-and-craving circuitry driving compulsive substance use—a mechanistic rationale supporting continued investigation.

Reference

1. Walters J. GLP-1s for treatment of alcohol use disorder: current and future directions. Psychiatric Times. May 16, 2026. https://www.psychiatrictimes.com/view/glp-1s-for-treatment-of-alcohol-use-disorder-current-and-future-directions

Positive Real-World Adherence Data for Olanzapine-Samidorphan

Jessica Walters

Christoph Correll, MD, presented at APA on efficacy and real-world data for olanzapine-samidorphan to treat schizophrenia and bipolar disorder.¹ The μ-opioid receptor-preferring antagonist drug modulates appetite and satiety signaling, attenuating the weight gain associated with olanzapine. While it does not reverse all weight gain related to olanzapine, the combination preserves efficacy of olanzapine while reducing cardiometabolic burden.

To isolate a more specific signal in a recent trial of the drug, researchers analyzed subgroups with both prominent positive and negative symptoms, and separately those with predominant negative symptoms and relatively few positive symptoms. Reductions of approximately 8 to 9 points on the negative symptom subscale of the Positive and Negative Syndrome Scale were observed in both subgroups, suggesting a degree of specificity. Correll emphasized this distinction matters clinically, noting that “having treatments that treat both positive but also have a beneficial effect on negative symptoms is really important.” Latest analysis showed this negative symptom reduction, and a real-world analysis showed reduced emergency visits and hospitalizations over 6 months. Compared to other antipsychotics (and olanzapine monotherapy) the olanzapine-samidorphan combination showed stronger treatment adherence and longer medication continuation in both bipolar and schizophrenia populations.

Reference

1. Walters J, Correll C. Olanzapine-samidorphan for schizophrenia: new real-world adherence data. Psychiatric Times. May 19, 2026. https://www.psychiatrictimes.com/view/olanzapine-samidorphan-for-schizophrenia-new-real-world-adherence-data

Real-World Tardive Dyskinesia Data: 23% of Young Adults With Mood Disorders and TD Are Diagnosed

Leah Kuntz

Teva Pharmaceuticals today shared new data from the ongoing, real-world IMPACT-TD Registry—the largest tardive dyskinesia (TD) study to date—which highlights a significant gap in diagnosing TD in patients with comorbid mood disorders.¹ While the findings demonstrate that a majority of patients across all age groups experience multidimensional impact from TD, young adults (aged 18-29, n=13) had the lowest rate of formal diagnosis (23%) despite having one of the highest rates of personal impact (85%).

The IMPACT-TD Registry is a 3-year, prospective, noninterventional, phase 4 study examining how TD progresses over time and the impact it has on patients’ lives. The study, which includes a broad representation of people affected by TD (age, sex, race/ethnicity, underlying conditions, movement severity and treatment status), evaluates 611 participants aged 18 years or older who, at enrollment, had either a score of 2 or higher on at least 1 item of the Abnormal Involuntary Movement Scale (AIMS) and probable TD, or were receiving vesicular monoamine transporter 2 (VMAT2) inhibitor therapy for TD. The current analysis of the IMPACT-TD Registry evaluated 211 adults with TD
who were not receiving VMAT2 inhibitor therapy at enrollment and had concomitant mood disorders, such as bipolar disorder (60%) or major depressive disorder (54%).

Investigators found that most participants, reported a moderate to severe global impact from TD, regardless of age. The burden was particularly high for those aged 18 to 29 (85%) and 50 to 59 (87%, n=57). This shows that TD significantly affects daily life throughout adulthood. Additionally, the psychological impact of TD was most pronounced in adults under age 60. Approximately 77% of those aged 18 to 29 experienced moderate to severe psychological effects despite lower AIMS scores (6.4) on average compared with older adults aged 60 to 69 (8.4, n=56) and older than 69 (9.9, n=28).

Despite the high impact, formal TD diagnosis rates were lowest among adults younger than 40 years old. The rate was 23% for participants aged 18 to 29 and 35% for participants aged 30 to 39 (n=20), as compared with 57% in adults aged 40 to 49 (n=37) and a 47% average in the 50+ age subgroups. Investigators noted a significant delay in diagnosis, with patients waiting an average of more than 3.5 years to be formally diagnosed after their involuntary movements were first recognized.

Reference

1. Kuntz L. New data from IMPACT-TD registry: only 23% of young adults with mood disorders and tardive dyskinesia symptoms are formally diagnosed. Psychiatric Times. May 18, 2026. https://www.psychiatrictimes.com/view/new-data-from-impact-td-registry-only-23-of-young-adults-with-mood-disorders-and-tardive-dyskinesia-symptoms-are-formally-diagnosed

Using Computational Phenotyping to Identify Psychosis Risk in the Schizophrenia Prodrome

Jessica Walters

Cheryl Corcoran, MD, recipient of the Alexander Gralnick Award from the American Psychiatric Association, presented on her research in analyzing schizophrenia risk with computational phenotyping.¹ Approximately 80% of individuals who develop schizophrenia experience a prodromal period characterized by attenuated or subthreshold psychotic symptoms, and among those identified as at risk for psychosis, 10% to 25% ultimately progress to a full psychotic disorder; Corcoran’s research aims to identify patients at highest risk for developing psychosis by analyzing the prodromal window via a variety of biological measurements and machine learning.

Her program combines qualitative open-ended interviews, along with neuroimaging and fluid biomarker studies, to pinpoint biological correlates of psychosis risk. From her work, Corcoran found that language features like semantic incoherence and reduced linguistic complexity were related to higher risk of psychosis conversion. Using large language models, this research takes into account the patient’s suicidal ideation, emotional focus in speech, report of stigma, and affective states. Developing technology allows for analysis of speech acoustics and video facial expression coding, which helps quantify symptoms like blunted affect and assess verbal vs nonverbal expression. Corcoran emphasized the need for an objective clinical measure in this psychosis risk period and shared her optimism for computational phenotyping of language and behavior becoming a platform for patient monitoring and trial outcome measures.

Reference

1. Walters J, Corcoran C. Risk stratification in the schizophrenia prodrome: psychotic symptoms, cannabis use, and stress. Psychiatric Times. May 16, 2026. https://www.psychiatrictimes.com/view/risk-stratification-in-the-schizophrenia-prodrome-psychotic-symptoms-cannabis-use-and-stress