Psych Congress 2025: Key Takeaways

Muscarinic Modulators in Psychotic Disorders

Some of the most notable discussions at the conference focused on developing muscarinic modulators as new targets for treating psychotic disorders. Emerging pharmacologic agents for treating schizophrenia are gaining traction with muscarinic modulators continuing to grow in the field. While dopamine dysregulation remains a fundamental tenet in the neurobiology of schizophrenia, M1/M4 receptor agonists, such as xanomeline-trospium (KarXT), can target this dysregulation without directly affecting the dopamine 2 (D2) receptor. KarXT demonstrated efficacy and tolerability, as shown in the EMERGENT clinical trials, and has no direct D2 receptor binding affinity, which makes it the first FDA-approved schizophrenia treatment that is not classified as an antipsychotic.

NBI-568, which is a selective, first-in-class M4 agonist from Neurocrine Biosciences, was safe and tolerated at all doses in early clinical trials. Other agents that are in development include LB-102 (methylated amisulpride), which is a dopaminergic and 5HT7 antagonist, and evenamide, which is a voltage-gated sodium channel inhibitor.

Long-Acting Injectables in Schizophrenia

Also, using long-acting injectables (LAIs) was discussed, especially for treating schizophrenia. Paliperidone palmitate, which is available in multiple LAI formulations, demonstrated low relapse rates in real-world populations with efficacy that is consistent with the findings from the original clinical trial. TV-44749, which is an LAI formulation of olanzapine, demonstrated a safety profile that is consistent with other olanzapine formulations through 48 weeks in the phase 3 SOLARIS clinical trial. All doses demonstrated long-term, continuous symptom improvement and maintained clinical effectiveness. Crucially, improved stability of the plasma concentration of the active agent that was permitted by LAIs resulted in fewer schizophrenia relapse events.

Targeting the Glutamatergic System in Major Depressive Disorder

Mood disorders, including major depressive disorder (MDD), were another key topic at the conference. Conventional monoamine antidepressants that are used to treat MDD have several limitations, including delayed onset of therapeutic effects, frequent residual symptoms, and adverse effects. New therapeutics that are in development for treating MDD have started to shift away from the monoaminergic model and toward glutamate as a target neurotransmitter system. The breadth of glutamatergic receptor subtypes provides a broad range of therapeutic targets: Ionotropic glutamate receptors, such as NMDA and AMPA, are being explored as key targets for clinical trials for depression. NMDA receptor allosteric antagonists, such as esketamine and dextromethorphan-bupropion, have demonstrated efficacy in treatment-resistant depression. Particularly, esketamine has been approved for treating MDD with acute suicidal ideation and is indicated as a monotherapy or an adjunctive treatment with an oral antidepressant for treating treatment-resistant depression. Additionally, osavampator, which is an AMPA receptor modulator from Neurocrine Biosciences, is in phase 3 development after demonstrating positive phase 2 safety and efficacy data in adults with MDD. Also, Supernus recently completed an early-stage clinical trial for a novel, first-in-class modulator of mTORC1 for treating depression.

Blood-Based Biomarkers and New Therapies in Alzheimer's Disease

Alzheimer's disease remains a uniquely complex challenge to identify and treat, but recent advancements offer new possibilities for early detection and disease-modifying treatment development. Blood-based biomarkers are rapidly gaining traction in the field of Alzheimer's disease; they are less invasive, less expensive, and more accessible than other testing methods, such as CSF tests and PET imaging. The first Alzheimer's disease blood biomarker plasma test (Lumipulse G) was cleared by the FDA in May 2025, which paves the way for providing a higher volume of Alzheimer's disease testing in the future. With improved sensitivity and lower detection thresholds, biomarker tests are becoming increasingly widespread as a means of predicting future occurrences of Alzheimer's disease.

On the treatment side, anti-tau and anti-amyloid immunotherapies represent an emerging therapeutic modality for treating Alzheimer's disease with several agents at various stages of clinical development. Disease-modifying therapies that are in phase 3 development for treating Alzheimer's disease include valiltramiprosate, buntanetap, hydromethylthionine mesylate, and semaglutide.

Prescription Digital Therapeutics Close Key Treatment Gaps

The increasing prevalence of prescription digital therapeutics (PDTs) for treating various mental health conditions was another key topic at the conference. PDTs are making a large impact in the field of schizophrenia by addressing cognitive dysfunction and negative symptoms. Software-based interventions and FDA-approved digital therapeutics are making their way into clinical care and enhancing functional outcomes. These include CT-155, which is a smartphone app that is in phase 3 development for treating schizophrenia.

Broadly, PDTs can address residual symptoms that are left behind by traditional medications and therapy. They represent a key opportunity for personalizing and enhancing individual treatment plans. As of July 2025, FDA-cleared or FDA-authorized PDTs span several therapeutic areas, including substance use disorder, PTSD, generalized anxiety disorder, MDD, ADHD, and insomnia.

Psych Congress 2025 provided a platform for participating in groundbreaking discussions and exchanging innovative ideas in the field of psychiatry. Advancements in developing novel therapeutics for treating mental health conditions are paving the way for providing more effective and personalized treatments. We look forward to seeing how these developments will shape the future of mental health.