October 2025 Global Psychiatric Drug Pipeline Update: Key Advances in Novel Therapeutics

This article summarizes the latest advances in the international psychiatric treatment pipeline as of October 2025, involving potential drugs that have been recently approved or have announced significant research progress:

★ BMS-986446 Granted FDA Fast Track Designation, Poised to BecomeBest-in-class

Bristol-Myers Squibb (BMS) announced that its investigational drug BMS-986446 has received Fast Track designation from the FDA. BMS-986446 is an anti-MTBR-tau antibody currently in Phase II clinical trials for the treatment of early Alzheimer's disease (AD), with the potential to become best-in-class. As a humanized monoclonal antibody, BMS-986446 targets multiple domains of the tau protein’s microtubule-binding region, significantly reducing tau uptake and spread, improving behavioral deficits in preclinical models, and colocalizing with tau pathology in AD brain tissue. Results from a Phase I study in healthy subjects showed that BMS-986446 demonstrated good safety and tolerability across three dose groups.

★ ALTO-101 Granted FDA Fast Track Designation for the Treatment of Cognitive Impairment Associated with Schizophrenia

Alto Neuroscience Announces FDA Fast Track Designation for ALTO-101 Transdermal Patch for the Treatment of Cognitive Impairment Associated with Schizophrenia (CIAS). ALTO-101 is a novel small molecule phosphodiesterase 4 (PDE4) inhibitor that increases cyclic adenosine monophosphate (cAMP) levels, enhances neural circuit function, and improves cognitive impairment.The FDA has not yet approved any treatment regimen for CIAS. This designation is based on the Phase I trial data of ALTO-101: compared with oral PDE4 inhibitors, transdermal administration of ALTO-101 results in higher drug exposure and a lower incidence of adverse reactions.

★ Lithium-loaded gold nanoparticles nasal spray: Lithium saltDirectTransported to the brain

Recently, researchers have developed a new type of nanotechnology device - lithium-containing gold nanoparticles in the form of a nasal spray. This innovative technology can deliver lithium salts.DirectDelivered to the brain, it produces therapeutic effects consistent with orally administered lithium salts but requires significantly lower ion concentrations and enables precise targeting of the brain, thereby reducing the potential risk of adverse reactions. This approach is expected to become a revolutionary method for treating neuropsychiatric disorders such as bipolar disorder, neurodegenerative diseases like AD, and brain infections caused by Herpes Simplex Virus Type 1. Studies have confirmed that drug delivery based on this technology can effectively inhibit the activity of glycogen synthase kinase-3β (GSK-3β) in the hippocampus and restore impaired memory function in Alzheimer's disease models.GSK-3β is an enzyme crucial for many cellular functions, with an estimated 100 or more proteins regulated by this kinase.

★ Lumateperone Improves Anhedonia and Sexual Dysfunction in the Adjunctive Treatment of Depression

Latest data presented at the 38th annual meeting of the European College of Neuropsychopharmacology (ECNP) showed that, for patients with depression who had previously shown poor treatment response, combining the novel antipsychotic lumateperone 42 mg/day with antidepressants significantly improved anhedonia, sexual dysfunction, and all MADRS depressive symptoms except suicidal ideation, compared to antidepressant monotherapy. Lumateperone is an innovative mechanism antipsychotic that modulates serotonin, dopamine, and glutamatergic neurotransmission simultaneously. It has been approved by the FDA for the treatment of schizophrenia, as well as for monotherapy or adjunctive therapy with lithium or valproate for bipolar I and II depressive episodes.

★ EsketamineNew Data on Dose Management:Early dose escalation may bring greater benefits

In the double-blind induction phase of the Phase III TRANSFORM-2 study (NCT02418585), researchers explored an early dose management strategy for esketamine nasal spray, increasing from 56 mg to 84 mg: Among 114 patients with moderate to severe treatment-resistant depression, 113 (99.1%) received 56 mg of esketamine combined with oral antidepressants on the first day of dosing; On the 4th day at the second dosing, 45.8% of participants increased the dose to 84 mg; On the 8th day at the third dosing, 63.0% of participants increased the dose to 84 mg, and the proportion remained largely stable thereafter. Analysis showed that both dosesEsketamine Nasal SprayBoth doses significantly reduced MADRS scores, with a similar safety profile, and the 84 mg group showed a greater reduction compared to the 56 mg group, suggesting that some patients may benefit from early dose escalation.

★ CT-155 May Become a New Digital Therapy Option for Negative Symptoms of Schizophrenia

Results from the Phase III CONVOKE study (NCT05838625) showed that CT-155, a digital therapeutic program co-developed by Boehringer Ingelheim (BI) and Click Therapeutics, significantly improved negative symptoms in patients with schizophrenia. The study included 464 adult patients with schizophrenia who had stable positive symptoms but exhibited negative symptoms, with a follow-up period of 16 weeks. Findings demonstrated that the CT-155 treatment group achieved a 6.8-point improvement on the Clinical Assessment Interview for Negative Symptoms-Motivation and Pleasure scale (CAINS-MAP), compared to 4.2 points in the group receiving standard care alone (Cohen’s d=-0.36, P=0.0003). CT-155 demonstrated a favorable safety profile with no serious adverse events; its design incorporated feedback from over 150 patients with schizophrenia.

★ FDA Accepts CTx-1301 New Drug Application for Review, Can BeThree timed drug releases in one day

FDA Accepts Cingulate’s New Drug Application (NDA) for CTx-1301 (Active Ingredient: Dexmethylphenidate) to Treat Attention Deficit Hyperactivity Disorder (ADHD) in Children and Adults. CTx-1301 is an extended-release multilayer tablet taken once daily, utilizing Cingulate’s proprietary Precision Timed Release™ (PTR™) technology to deliver the active ingredient at three precise times throughout the day, providing both rapid onset and all-day efficacy while controlling a gradual decline in blood concentration. In Phase III studies, CTx-1301 demonstrated rapid onset with sustained effects into the afternoon and evening, along with a low incidence of treatment-related adverse events (9%）Lower than the placebo group (30%).

★ Risperidone Subcutaneous Injection Long-Acting Formulation Approved for Bipolar I Disorder Maintenance Treatment

Teva Pharmaceutical Industries announced that the FDA has approved risperidone extended-release injectable suspension (Uzedy) for the maintenance treatment of adult patients with Bipolar I Disorder (BD-I), which can be used as monotherapy or in combination with lithium or valproate. Uzedy is the first subcutaneous long-acting risperidone formulation using SteadyTeq technology (Medincell's patented copolymer sustained-release technology), enabling precise control of steady-state drug release, with blood concentrations reaching therapeutic levels within 6-24 hours after a single dose. For the BD-I indication, Uzedy is now approved in three once-monthly dosing regimens: 50 mg, 75 mg, and 100 mg.

★ Valbenazine 40 mg Significantly Improves Tardive Dyskinesia After 48 Weeks of TreatmentObstructive Symptoms

Neurocrine Biosciences Announced Post-Hoc Analysis Results of the Phase III Open-Label KINECT 4 Study: Valbenazine40 mg/dayContinuousTreatment48 WeeksSignificantly improves symptoms of tardive dyskinesia (TD), with a reduction in AIMS total score exceeding the minimal clinically important difference threshold, indicating clinically meaningful symptom improvement; overall safety and tolerability are good, with no new safety issues identified. The most common adverse reactions are somnolence and fatigue. As one of the vesicular monoamine transporter 2 (VMAT-2) inhibitors, Ingrezza can be initiated directly at the therapeutic dose and allows for individualized adjustment based on the patient’s treatment response and tolerability.

Source: Kuntz L. October in Review: Updates on the Psychiatric Treatment Pipeline. Psychiatric Times. October 31, 2025. Available from: https://www.psychiatrictimes.com/view/october-in-review-updates-on-the-psychiatric-treatment-pipeline.

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