Psychiatry Month in Review: January 2025

January 2025 brought significant updates in psychiatry, including the US Food and Drug Administration’s (FDA) approval of esketamine (SPRAVATO) for treatment-resistant depression and a label update for viloxazine extended-release capsules (Qelbree) to include lactation data. Promising phase 2 results were reported for LB-102 in schizophrenia, while setbacks occurred for iclepertin and navacaprant. Other notable findings included research on SP-624 for depression and new insights into retinal alterations linked to schizophrenia and multiple sclerosis.

FDA Updates in Psychiatry

FDA Approves Esketamine as First Monotherapy for Treatment-Resistant Depression

The FDA approved esketamine nasal spray as the first monotherapy for treatment-resistant depression (TRD) in adults. This decision, based on a phase 4 study, demonstrated esketamine’s rapid efficacy in improving depressive symptoms, with significant MADRS score reductions at 4 weeks. The approval provides an alternative for patients unresponsive to ≥ 2 oral antidepressants, potentially improving symptoms within 24 hours.

FDA Approves Label Update for Viloxazine Capsules to Include New Lactation Data

The FDA approved an updated label for Supernus Pharmaceuticals’ viloxazine extended-release capsules, a current ADHD treatment, to include lactation data confirming its low transfer into breastmilk. A study found minimal viloxazine secretion into breast milk but did not assess its effects on infants. The update also details viloxazine’s pharmacodynamics, highlighting its serotonin 5-HT2C receptor activity and norepinephrine transporter inhibition.

Recent Phase 3 or 2 Data in Psychiatry

LB-102 Shows Promise in Reducing Acute Schizophrenia Symptoms: New Phase 2 Data

Phase 2 trial data show LB-102, a potential first-in-class benzamide antipsychotic, significantly reduces acute schizophrenia symptoms. The NOVA trial met its primary endpoint, with LB-102 demonstrating a meaningful reduction in PANSS total scores at 4 weeks. The drug was well-tolerated, with minimal side effects and a safety profile comparable to amisulpride. LB Pharmaceuticals plans to consult regulators and initiate phase 3 trials by 2026.

Iclepertin Fails to Improve Cognition in Schizophrenia Phase 3 Study

Phase 3 trial results show iclepertin failed to improve cognition or functioning in schizophrenia, missing primary and secondary endpoints. Boehringer Ingelheim will discontinue its long-term extension trial but remains committed to mental health research, with over 20 therapies in development. The CONNEX program, the largest study of cognitive impairment in schizophrenia, found iclepertin well-tolerated but ineffective.

Phase 3 KOASTAL-1 Trial Fails to Show Navacaprant Significantly Improves MDD

The phase 3 KOASTAL-1 trial found navacaprant did not significantly improve depression symptoms in major depressive disorder (MDD), failing its primary endpoint. However, female participants showed greater improvements in MADRS and SHAPS scores than males. Despite the setback, navacaprant was well tolerated with no serious adverse events. Neumora Therapeutics continues its navacaprant development program, with ongoing phase 3 trials and an open-label extension study, while analyzing trends in the KOASTAL-1 data.

Other Exciting Findings in the Field of Psychiatry

Genetic Variants in OUD Risk Algorithm Do Not Meet Standards in Identifying Risk

A recent study found that genetic variants in the FDA-approved opioid use disorder (OUD) risk algorithm lack clinical utility. Investigators found that age and sex predicted OUD risk more accurately than the 15 genetic variants. The study also highlighted concerns about the algorithm’s validity, as most variants lacked validation in genome-wide studies.

Exploratory Study Shows Promise of SP-624 for Improving Depression, Cognition

An exploratory study found that SP-624, a SIRT6 activator, may improve depression symptoms and cognition, particularly in females with MDD. Investigators observed increased beta power and decreased delta power, suggesting enhanced synaptic plasticity and neural connectivity. The study supports SP-624’s potential as a novel treatment for MDD and cognitive disorders. Further trials are underway, including a Phase 2b/3 study to evaluate its clinical efficacy.

Retinal Alterations Reveal Insights into Schizophrenia, Sclerosis Risk

A recent study linked schizophrenia risk to amacrine cells and multiple sclerosis risk to retinal immune cells, suggesting retinal alterations reflect neurodevelopmental and immune-related changes. Genetic analysis identified key schizophrenia-associated genes, including CACNA1I and DRD2. Findings highlight the retina’s potential for studying brain disorders and advancing diagnostic imaging.

Long-Acting Injectables Effectively Manage Bipolar Mania in Adolescents

A study found long-acting injectable (LAI) antipsychotics significantly reduced bipolar mania and schizoaffective symptoms in adolescents, lowering Young Mania Rating Scale scores over a year. Most participants resumed school or work, with no suicide attempts reported. Investigators advocate for FDA trials to explore LAI use in this high-risk population.

Glutamatergic Medications Show Promise in Improving OCD Symptoms

A meta-analysis shows glutamatergic medications, including N-acetylcysteine and memantine, significantly improve symptoms in obsessive-compulsive and related disorders (OCRDs), with moderate certainty for OCD symptom reduction. The treatments yielded large effect sizes and minimal adverse events, suggesting potential as adjunctive therapies for these conditions.

Protein ADM Mediates Loneliness’ Association With CVD, Stroke, Mortality

A study identified specific proteins, including ADM, as key mediators linking loneliness to increased risks of cardiovascular disease, stroke, dementia, and mortality. ADM was the primary protein associated with these risks, particularly cardiovascular conditions, emphasizing loneliness' significant impact on health outcomes and mortality.