The Psychiatric Pipeline in Review: Quarter 4, 2025

The final quarter of 2025 had several prominent developments in the psychiatric treatment pipeline. Here, learn more about what percentage of that news was positive vs negative, what disease states were most prominently featured, and what treatments you should keep an eye on.

Check out all the specifics of our coverage from the from the fourth quarter below.

BMS-986446 Granted Fast Track Designation for the Treatment of Alzheimer Disease

Bristol Myers Squibb announced that the US Food and Drug Administration (FDA) has granted Fast Track Designation to BMS-986446, a potential best-in-class anti-microtubule binding region-tau (anti-MTBR-tau) antibody in phase 2 development for the treatment of early Alzheimer disease. BMS-986446 is a humanized monoclonal antibody that targets multiple domains of the microtubule binding region of tau. In preclinical models, investigators noted that BMS-986446 demonstrated significant reductions in tau uptake and spread, protection against behavioral deficits, and was localized with tau pathology in AD brain tissue. BMS-986446 was also shown to be safe and well tolerated across 3 dose cohorts in a phase 1 study of healthy participants.

ALTO-101 Receives FDA Fast Track Designation for Treatment of Cognitive Impairment Related to Schizophrenia

Alto Neuroscience announced FDA fast track designation for ALTO-101, a transdermally administered treatment for cognitive impairment associated with schizophrenia. There are currently no FDA-approved treatments for cognitive impairment in schizophrenia. The FDA based the fast track designation on data from a phase 1 trial of the drug which found greater exposure and fewer adverse events with novel transdermal administration of ALTO-101 vs an oral PDE4 inhibitor.

Lithium-Loaded Gold Nanoparticle Nasal Spray to Treat Neuropsychiatric Diseases

Investigators discovered a new nanotechnological device for the treatment and prevention of neuropsychiatric and neurodegenerative diseases: lithium-loaded gold nanoparticles in the form of a nasal spray that delivers treatment directly to the brain. This could be a revolutionary approach to neuropsychiatric diseases such as bipolar disorder, neurodegenerative diseases such as Alzheimer disease, and brain infections such as those caused by Herpes Simplex Virus type 1. In the study, investigators demonstrated the effectiveness of this nanotechnology in inhibiting the activity of the glycogen synthase kinase-3 beta (GSK-3β) enzyme in the hippocampus and restoring memory already compromised in an experimental model of Alzheimer disease.

New ECNP Poster Data on Adjunctive Lumateperone for Major Depressive Disorder

According to data presented at the 38th European College of Neuropsychopharmacology (ECNP) Annual Congress, lumateperone, a novel antipsychotic, significantly improves symptoms of anhedonia and sexual dysfunction in patients with MDD and inadequate antidepressant therapy response. Results show that treatment with antidepressants plus lumateperone led to significant improvements in symptoms of anhedonia, sexual dysfunction, and a broad range of other depressive symptoms.

Early Dose Management and Up-Titration of Esketamine: ECNP Poster Data

In the double-blind induction phase of the randomized, active-controlled, phase 3 TRANSFORM-2 study (NCT02418585), investigators explored early dose management and up-titration from 56 to 84 mg of esketamine for treatment-resistant depression. According to the results, both esketamine nasal spray doses resulted in clinically relevant improvement in symptoms severity with no adverse effects, but some patients may benefit from early up-titration during esketamine induction.

Phase 3 Data Support CT-155 as a Novel Digital Therapeutic for Negative Symptoms in Schizophrenia at ECNP

Phase 3 data from the CONVOKE study (NCT05838625) of CT-155 demonstrated a statistically significant reduction in negative symptoms in patients with schizophrenia. Treatment via CT-155 resulted in a 6.8-point improvement on the CAINS-MAP vs 4.2 for the control arm, showing statistical significance via Cohen’s D effect size of -0.36 (P=0.0003). CT-155 also demonstrated a good safety profile with no serious adverse effects, and its design was informed by input from over 150 people living with schizophrenia.

FDA Accepts NDA for CTx-1301 for Treatment of ADHD

The FDA accepted for review the New Drug Application (NDA) for dexmethylphenidate (CTx-1301), Cingulate’s lead candidate for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adults. CTx-1301 is a once-daily, multi-core tablet that utilizes Cingulate’s proprietary Precision Timed Release platform to deliver 3 precisely timed releases of active medication across the day, a design that aims to provide rapid onset of effect and entire active-day duration. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of May 31, 2026.

FDA Approves Uzedy Once-Monthly Extended Release Injectable Suspension for Bipolar I Disorder

Teva Pharmaceuticals announced that the FDA has approved risperidone (Uzedy) as a once-monthly extended-release injectable suspension as monotherapy or as adjunctive therapy to lithium or valproate for the maintenance treatment of adults with bipolar I disorder (BD-I). Uzedy is the first subcutaneous, long-acting formulation of risperidone that utilizes SteadyTeq technology, a copolymer technology proprietary to Medincell that controls the steady release of risperidone. Utilizing this technology, therapeutic blood concentrations are reached within 6 to 24 hours of just a single dose. For the BD-I indication, Uzedy is now approved with 3 once-monthly dosing options: 50 mg, 75 mg, and 100 mg.

New Post-Hoc Analysis: Ingrezza 40 mg Leads to Clinically Meaningful Improvements in Tardive Dyskinesia Symptoms

Neurocrine Biosciences announced the presentation of a new post-hoc analysis from the phase 3, open-label KINECT 4 study, which demonstrates that patients treated continuously for 48 weeks with the 40 mg dose of once-daily valbenazine (Ingrezza) capsules experienced clinically meaningful improvements in tardive dyskinesia (TD) symptoms. Ingrezza, a VMAT2 inhibitor, allows starting at a therapeutic dose with flexibility to adjust based on individual response and tolerability.

Positive Phase 3 Results: CTx-1301 for the Treatment of Pediatric ADHD

Cingulate Inc announced the release of positive phase 3 results from its pivotal trial of CTx-1301 (dexmethylphenidate HCl) in pediatric attention-deficit/hyperactivity disorder (ADHD), recently presented by Ann Childress, MD, at the American Academy of Child and Adolescent Psychiatry Annual Meeting in Chicago. CTx-1301 met its primary endpoint, demonstrating dose-dependent improvements on the ADHD ratings scale 5, and Clinical Global Impression-Severity scales, and demonstrated the ability to deliver symptom relief with the convenience of once-daily dosing.

sNDA Submitted for AXS-05 for the Treatment of Alzheimer Disease Agitation

Axsome Therapeutics announced they have submitted a supplemental NDA (sNDA) to the US Food and Drug Administration (FDA) for dextromethorphan-bupropion (AXS-05) for the treatment of Alzheimer disease agitation. AXS-05 is Axsome’s novel, oral, investigational N-methyl-D-aspartate (NMDA) receptor antagonist, sigma-1 agonist, and aminoketone CYP2D6 inhibitor being developed for the treatment of Alzheimer disease agitation and smoking cessation. AXS-05 was granted FDA Breakthrough Therapy designation for Alzheimer disease agitation back in 2020, the second Breakthrough Therapy designation granted to Axsome for AXS-05 (the first being for major depressive disorder).

FDA Approves Caplyta for Adjunctive Treatment of Major Depressive Disorder

The FDA has approved Johnson & Johnson’s lumateperone (Caplyta) as an adjunctive therapy for the treatment of adults with major depressive disorder. The 2 phase 3 double-blind, placebo-controlled clinical trials submitted to the FDA, studies 501 and 502, both demonstrated a significantly superior improvement in the Montgomery-Asberg Depression Rating Scale (MADRS) at week 6 compared with placebo at the dose of 42 mg per day. Study 501, which included 485 patients, demonstrated a 4.9-point decrease in the MADRS score for patients on Caplyta vs to an oral antidepressant plus placebo who all continued on their primary prestudy antidepressant. Study 502, which included 480 patients, demonstrated a 4.5-point decrease in the MADRS score for patients on Caplyta vs placebo who all continued on their primary prestudy antidepressant.

BPL-003: Positive Phase 2b Open-Label Extension Study Data

AtaiBeckley today announced positive topline results from the open-label extension study of a phase 2b clinical trial (NCT05870540) of intranasal mebufotenin benzoate (BPL-003) in patients with treatment-resistant depression. Investigators found that a 12 mg dose of BPL-003 administered 8 weeks after a 0.3 mg, 8 mg, or 12 mg dose of BPL-003 was generally well-tolerated and provided additional rapid, clinically meaningful antidepressant effects, which were sustained for up to 8 weeks.

A “Surprise” Miss: NBI-1070770 for Major Depressive Disorder Fails in Phase 2 Study

Neurocrine Biosciences announced that its phase 2 study evaluating the efficacy, safety, and tolerability of NBI-1070770 in adults with major depressive disorder (MDD) did not meet the primary endpoint compared to placebo. Investigators of this signal-seeking study enrolled 73 adult participants with a diagnosis of MDD who did not adequately respond to at least 1 antidepressant in their current course of treatment. NBI-1070770 is an investigational selective, orally active, negative allosteric modulator of the NR2B subunit-containing N-methyl-D-aspartate receptor.

Austedo Phase 4 Data Shows Reduction in Tardive Dyskinesia Severity

Phase 4 data from Teva Pharmaceuticals on deutetrabenazine (Austedo) showed significant reduction in involuntary movement and improvements in quality of life in adults with tardive dyskinesia. Up to 77% of participants taking Austedo reported that after 3 months there were meaningful improvements in impacts of tardive dyskinesia.

Alixorexton for Treatment of Narcolepsy Type 2: New Positive Phase 2 Data

Alkermes announced positive topline results from the Vibrance-2 dose-ranging phase 2 study evaluating alixorexton in patients with narcolepsy type 2 (NT2). Alixorexton, formerly referred to as ALKS 2680, is a novel, investigational, oral, selective orexin 2 receptor agonist in phase 2 development for the treatment of narcolepsy type 1, NT2, and idiopathic hypersomnia. In Vibrance-2, participants with NT2 (n=93) were randomly assigned (1:1:1:1) to receive a once-daily dose of alixorexton (10 mg, 14 mg, or 18 mg) or placebo for 8 weeks. Once-daily alixorexton met the dual primary endpoints, demonstrating statistically significant and clinically meaningful improvements from baseline compared with placebo on the Maintenance of Wakefulness Test and Epworth Sleepiness Scale at week 8.

Iclepertin Found Ineffective in Treating Cognitive Impairment Associated With Schizophrenia

n an analysis of 3 phase 3 trials, iclepertin showed no significant improvement in cognitive impairment for adults with schizophrenia. The drug was well tolerated but did not result in significant changes in cognition in patients with schizophrenia. The analysis included the CONNEX 1, 2, and 3, trials—all randomized, double-blind, placebo-controlled phase 3 studies conducted across 41 countries. Patients were randomized 1:1 to oral iclepertin 10 mg or placebo once daily for 26 weeks. At week 26, there was no significant difference between treatment and placebo groups in individual trials or the pooled population. The adjusted mean difference for drug vs placebo in MCCB overall composite T-score was 0.127 (P=0.63)

Planned FDA Investigational New Drug Application: SPC-15 for the Treatment of PTSD

Silo Pharma today announced that it has chosen to partner with Allucent, a global full-service clinical research organization, to support their planned submission of an investigational new drug application to the FDA for a phase 1 clinical trial of SPC-15 for the treatment of posttraumatic stress disorder (PTSD). SPC-15 is a its intranasal prophylactic and novel serotonin 4 (5-HT4) receptor agonist that utilizes biomarkers for the treatment of PTSD, anxiety, and other stress-induced affective disorders.

Tonmya Available Commercially for Treatment of Fibromyalgia

Tonix Pharmaceuticals announced that Tonmya (cyclobenzaprine HCl) is now available by prescription in the United States. The treatment was approved by the FDA in August of 2025 and is now commercially available. The most recent phase 3 trial for this drug showed significant improvements in symptoms and functioning for patients with fibromyalgia. The trial, RESILIENT, showed significant improvement (P < .001) in daily pain intensity scores at week 14. The study also showed improvement (P < .001) in Patient Global Impression of Change scores, Fibromyalgia Impact Questionnaire (Revised) Symptoms and Function domains, Patient Reported Outcomes Measurement Information System instruments for Sleep Disturbance and Fatigue, and daily diary sleep quality scores.

New Review on VMAT2 Inhibitors and Ingrezza for Treatment of Tardive Dyskinesia

Neurocrine Biosciences has announced publication of a narrative review paper on FDA-approved vesicular monoamine transporter 2 (VMAT2) inhibitors Ingrezza (valbenazine) and deutetrabenazine. The review covers clinical research on these drugs for treatment of tardive dyskinesia and highlights the unique profile of Ingrezza. Ingrezza and deutetrabenazine were noted to have key differences. Both medications target VMAT2 receptors, but Ingrezza was found to work with a single metabolite with high affinity for VMAT2 and had no off-target receptor activity.

Phase 3 Trial of LPCN 1154 for Postpartum Depression Shows Positive Progress

Lipocine announced completion of a scheduled independent review by the Data Safety Monitoring Board of the ongoing phase 3 trial of LPCN 1154 (oral brexanolone) for treatment of postpartum depression. The board recommended the trial continue with no modifications, after 30 patients completed at least the 7 day follow up visit. The current phase 3 trial is a randomized, double-blind study evaluating LPCN 1154 in women 15 to 45 years old diagnosed with severe postpartum depression.

FDA Clears Investigational New Drug Application for TNX-102 SL for Treatment of Major Depressive Disorder

Tonix Pharmaceuticals announced that the FDA has cleared the Investigational New Drug application for development of TNX-102 SL (cyclobenzaprine hydrochloride) for treatment of major depressive disorder in adults. With millions of patients suffering from bipolar disorder every year, this investigation may provide a new treatment option for major depressive disorder.

New Drug Application Submitted for Centanafidine for Treatment of ADHD

Otsuka Pharmaceutical has submitted a new drug application to the FDA for centanafadine for treatment of attention deficit hyperactive disorder (ADHD) in children, adolescents, and adults. Centanafadine is the first investigational norepinephrine, dopamine, and serotonin reuptake inhibitor for ADHD therapy. NDA submission for this drug is based on results from 4 phase 3 clinical trials which evaluated the efficacy and safety of centanafadine. In these phase 3 studies, centanafadine showed statistically significant and clinically meaningful improvements in symptoms of ADHD.

Delay on Cobenfy Alzheimer Disease Psychosis Data Following Phase 3 Study “Irregularities,” New Patients Enrolled

Bristol Myers Squibb announced that it will enroll additional patients in the ADEPT-2 study—a phase 3, multicenter, randomized, double-blind, placebo-controlled trial assessing the safety and efficacy of xanomeline/trospium (Cobenfy) in participants with psychosis associated with Alzheimer disease dementia. Following a thorough blinded review of the ADEPT-2 study data, BMS identified irregularities due to clinical trial execution at a limited number of study sites. After reviewing these findings and before a database lock, BMS decided to exclude the patient data from those select sites from the primary analysis. Following this analysis, the DMC recommended the study should continue and enroll additional patients to the original target study population. Based on this recommendation, BMS will continue patient enrollment and advance the program as advised by the DMC, while remaining blinded to study data.

Psychedelic PSX-001 for Generalized Anxiety Disorder: A Conversation With Lou Barbato, MD

Earlier this year, Incannex Healthcare shared positive data from a phase 2 clinical trial of PSX-001 (formerly known as Psi-GAD), a psilocybin-assisted psychotherapy treatment for generalized anxiety disorder (GAD). Investigators found statistically significant and clinically meaningful improvements across every key endpoint assessed in the study, reinforcing PSX-001’s potential as a potential therapy for patients with moderate to severe GAD. Psychiatric Times sat down with Lou Barbato, MD, the chief medical officer of Incannex, to discuss this news and the overall potential of psychedelics in treating mental health disorders.

Favorable Profile Data On MK-2214 for Treatment of Alzheimer Disease

Merck pharmaceutical company shared new data on MK-2214 for treatment of Alzheimer disease at the 2025 Clinical Trials on Alzheimer’s Disease conference, December 1-4 in San Diego, California. Phase 1 trials on the drug showed a favorable profile to slow the progression of Alzheimer disease.

Evenamide for Treatment-Resistant Schizophrenia: Initiation of ENIGMA-TRS 2 Phase 3 Clinical Study

Newron Pharmaceuticals today announced the initiation of its ENIGMA-TRS 2 phase 3 clinical study in the US, following approvals from the US Food and Drug Administration and the Institutional Review Board. The first site to initiate the study will be the Semel Translational Research Center for Neuropsychiatry, University of California, Los Angeles. ENIGMA-TRS 2 is a phase 3, global, 12-week, randomized, double-blind, placebo-controlled trial evaluating the efficacy, safety, and tolerability of evenamide 15 mg twice daily as an add-on therapy to current antipsychotics, including clozapine, compared with placebo, in patients with treatment-resistant schizophrenia.

NDA Submission: Olanzapine Extended-Release Injectable Suspension for Treatment of Schizophrenia

Teva Pharmaceuticals has submitted a New Drug Application to the US Food and Drug Administration for olanzapine extended-release injectable suspension (TEV-'749) for the treatment of adults with schizophrenia. The NDA for olanzapine long-acting injectable is based on results from the phase 3 SOLARIS trial, including week 56 results studying its efficacy, safety, and tolerability in participants aged 18 to 64 with schizophrenia.

FDA Accepts NDA for TRN-257 for Treatment of Narcolepsy and Idiopathic Hypersomnia

Tris Pharma today announced that the US Food and Drug Administration has accepted the New Drug Application for TRN-257—a controlled-release, low-sodium oxybate product—for the treatment of cataplexy or excessive daytime sleepiness in adults with narcolepsy and the treatment of idiopathic hypersomnia in adults. When compared with other oxybate treatment options, TRN-257 is the lowest sodium (80 mg sodium for 9 g dose), once-nightly treatment currently in development for adults with narcolepsy and idiopathic hypersomnia.

Be sure to follow us on LinkedIn, Facebook, or X, or subscribe to our eNewsletters to stay up to date with the latest news.