Trintellix (vortioxetine) / Lundbeck, Takeda - LARVOL DELTA

Rap1-Dependent pathways in depression: Genetic, Epigenetic, and neuroinflammatory mechanisms shaping synaptic resilience. (PubMed, Mol Biol Rep) - "Therapeutic strategies, including vortioxetine and natural compounds like Modified Xiaoyaosan, target Rap1 to restore synaptic homeostasis. Emerging pathways, such as circadian disruptions and gut-brain axis interactions, suggest novel mechanisms by which Rap1 integrates systemic and neuronal stress responses. Unresolved questions persist regarding Rap1 isoform specificity, spatiotemporal regulation, and glial-neuronal metabolic coupling, necessitating advanced tools like biosensors and organoid models to unravel its pleiotropic roles in depression."

Journal • Review • Atopic Dermatitis • CNS Disorders • Depression • Dermatitis • Dermatology • Immunology • Mood Disorders • Postpartum Depression • Psychiatry • FTO

The Comparative Efficacy of Antidepressant and Psychological Therapies on Cognition in Depression: A Systematic Review and Network Meta-Analysis. (PubMed, Neuropsychol Rev) - "Common antidepressants, including escitalopram, citalopram, paroxetine and fluoxetine were not significantly different from placebo in improving cognition. The findings suggest that, among antidepressants, vortioxetine is the sole treatment improving cognition in depression. The effects were however small, highlighting the need for the development of MDD interventions targeting cognition."

Journal • Retrospective data • Review • CNS Disorders • Cognitive Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Green synthesis of silver tungstate/ionic liquid-modified electrode for highly efficient electrochemical detection of the antidepressant Vortioxetine. (PubMed, Sci Rep) - "The findings affirm the potential of the Ag2WO₄/IL/CPE sensor for precise quantification of VRT in biological fluids and pharmaceutical formulations. This work presents a promising electrochemical sensing strategy with potential extensions to other neuroactive drugs in clinical diagnostics."

Journal

RNA Editing as a Biomarker of Antidepressant Response in Unipolar and Bipolar Depression (EDIT-ANDRE) (clinicaltrials.gov) - P4 | N=120 | Not yet recruiting | Sponsor: Mayo Clinic

Biomarker • New P4 trial • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

FOES: Fortifying Healthy Behaviors, Optimizing Medical Therapies and Enhancing Cognitive Function in Older Adults-pilot Study (clinicaltrials.gov) - P2 | N=20 | Active, not recruiting | Sponsor: Washington University School of Medicine | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular

Editorial: Enhancing therapeutic strategies: a focus on pharmacovigilance in new wave antidepressants and antipsychotics. (PubMed, Front Psychiatry) - No abstract available

Adverse events • Journal • CNS Disorders

Pharmacoscopy-guided discovery of vortioxetine as a repurposable neuroactive therapeutic for glioblastoma (SNO 2025) - "In orthotopic glioblastoma mouse models, vortioxetine showed consistent survival benefit across five independent preclinical trials, while combination therapy of vortioxetine with temozolomide or lomustine led to a 25–30% extension in overall survival compared to either agent alone.Here we used pharmacoscopy to rapidly and scalably profile patient tumors at single-cell resolution, demonstrating its clinical utility for personalized neuro-oncology. The functional relevance of this imaging-based precision medicine platform was confirmed by its concordance with temozolomide sensitivity and established prognostic markers such as MGMT status. Bridging neuroscience and oncology, our research advances a framework for targeting glioblastoma based on its neural etiology and identifies vortioxetine as promising repurposable therapeutic."

Brain Cancer • Glioblastoma • Solid Tumor

Real-World Use, Effectiveness and Tolerability of Antidepressant Treatment in Oncology Patients. (PubMed, Psychooncology) - "Antidepressants were equally effective in treating depression among cancer patients. Vortioxetine emerged as a well-tolerated and preferred option for chemotherapy patients. These findings emphasize the importance of tolerability and drug-interaction profiles in oncology care."

Journal • Observational data • Real-world evidence • Retrospective data • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Oncology • Psychiatry • Suicidal Ideation

Effects of Short- and Long-Term Vortioxetine Administration on Reproductive Function in Female Rats. (PubMed, Pharmaceuticals (Basel)) - " Forty-two female Wistar albino rats were randomized into seven groups (n = 6): healthy control; short-term vortioxetine; long-term vortioxetine; and the same two regimens each combined with metyrosine or metyrapone. Long-term vortioxetine induced infertility in female rats, likely mediated by corticosterone elevation consistent with hypothalamic-pituitary-adrenal axis dysregulation. These findings suggest the need to monitor reproductive risk when considering vortioxetine in women of reproductive age and warrant further mechanistic and translational studies."

Journal • Preclinical • Infertility • Sexual Disorders

Clinical Effectiveness of Treatments for Mild Cognitive Impairment in Adults: A Systematic Review. (PubMed, Eur J Investig Health Psychol Educ) - "Among pharmacological treatments, only vortioxetine and choline alfoscerate showed modest improvements; cholinesterase inhibitors had limited effects and frequent adverse events...The inclusion of pharmacological interventions with preliminary evidence of benefit should be considered within a personalised, multimodal approach, while recognising the current absence of approved drug treatments for MCI. Further research is needed in underrepresented populations, such as those in Latin America."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Disproportionality evaluation of adverse effects and suicide/self-injury risk factors associated with vortioxetine: a large-scale pharmacovigilance study. (PubMed, Front Pharmacol) - "Likely confounders include vortioxetine's preferential prescription in complex patient populations (attributed to its broad-spectrum efficacy and safety profile) rather than intrinsic drug effects. Future studies should consider controlling for these confounders to provide a more definitive assessment."

Adverse events • Journal

Fine-tuning 5-HT7 receptor selectivity, inverse agonism, and metabolic stability of new (aryloxy)ethyl-piperidines toward antidepressant and pro-cognitive properties. (PubMed, Eur J Med Chem) - "Clinically used antidepressants and second-generation antipsychotic drugs, including vortioxetine and lurasidone, act as potent 5-HT7 receptor antagonists and improve cognitive functions in the patients with mood disorders. In addition, compound 57 reduced 5-HT7 receptor-mediated MMP-9 activity in the mouse hippocampus with efficacy comparable to the reference 5-HT7 receptor antagonist, SB-269970, further suggesting its purported antidepressant-like actions. These findings support the potential therapeutic application of targeting 5-HT7 receptor/MMP-9 signaling pathway for the treatment of affective disorders."

Journal • CNS Disorders • Cognitive Disorders • Mood Disorders • Psychiatry • MMP9

Efficacy and safety profile of vortioxetine as an add-on molecule in obsessive-compulsive disorder: a randomized double-blinded placebo-controlled superiority trial - a study protocol. (PubMed, BMC Psychiatry) - "Vortioxetine's unique pharmacological profile may offer significant benefits to managing cognitive symptoms and improving the quality of life of OCD patients. This clinical trial aims to provide evidence on the clinical value and safety of vortioxetine in the management of OCD in order to advance the optimization of more effective and personalized treatment plans."

Clinical • Clinical protocol • Head-to-Head • Journal • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Obsessive-Compulsive Disorder • Psychiatry

Vortioxetine effectiveness in the treated major depressive disorder patients in Saudi Arabia. (PubMed, Ann Gen Psychiatry) - "These findings support the real-world effectiveness of vortioxetine as a promising treatment option for MDD patients in the MEA region, highlighting its potential to reduce depressive symptoms."

Clinical • Journal • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Pharmacoscopy-guided discovery of vortioxetine as a repurposable neuroactive therapeutic for glioblastoma (WFNOS 2025) - "In orthotopic glioblastoma mouse models, vortioxetine showed consistent survival benefit across five independent preclinical trials, while combination therapy of vortioxetine with temozolomide or lomustine led to a 25–30% extension in overall survival compared to either agent alone.Here we used pharmacoscopy to rapidly and scalably profile patient tumors at single-cell resolution, demonstrating its clinical utility for personalized neuro-oncology. The functional relevance of this imaging-based precision medicine platform was confirmed by its concordance with temozolomide sensitivity and established prognostic markers such as MGMT status. Bridging neuroscience and oncology, our research advances a framework for targeting glioblastoma based on its neural etiology and identifies vortioxetine as promising repurposable therapeutic."

Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor

Vortioxetine in treatment of depression with somatic comorbidities in routine practice: Sub-group analysis of the RELIEVE study. (PubMed, J Affect Disord) - P=N/A | "Improvements in functioning and symptoms were observed over the 24-week period among patients with MDD and comorbid obesity, sleep disorders, cardiovascular disease, chronic pain, or diabetes, receiving vortioxetine treatment in routine practice."

Journal • Cardiovascular • CNS Disorders • Depression • Diabetes • Genetic Disorders • Major Depressive Disorder • Metabolic Disorders • Mood Disorders • Obesity • Pain • Psychiatry • Sleep Disorder

A Study of Vortioxetine in Japanese Pediatric Patients With Major Depressive Disorder (clinicaltrials.gov) - P3 | N=180 | Recruiting | Sponsor: Takeda | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Pediatrics • Psychiatry

Boldine Attenuates Chronic Unpredictable Stress-Induced Depression-Like Behavior via Modulation of Neuroinflammation and 5-HT3A Receptor in Rats (Neuroscience 2025) - "Rats were subjected to CUS for 42 days and treated with BDN (20, 40, or 80 mg/kg) or vortioxetine (VORT, 20 mg/kg) from days 22-42...Thus, BDN represents a promising multi-target therapeutic candidate for stress-related depression. Keywords: Boldine, chronic unpredictable stress, depression, NLRP3 inflammasome, 5-HT3 receptor, oxidative stress, neuroinflammation"

Preclinical • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • CA3 • CAT • IL1B • NLRP3

Antidyskinetic effects of novel serotonergic combination drug therapy in a hemiparkinsonian rat model of levodopa-induced dyskinesia (Neuroscience 2025) - "Previous studies show serotonin (5-HT) 1A receptor (5-HT1AR) agonists, such as vortioxetine (VTX) and 5-hydroxytryptophan (5-HTP) alleviate LID when individually paired with L-DOPA...Results revealed coadministration of subthreshold doses of VTX and 5-HTP with L-DOPA attenuated dyskinesia while maintaining the motor benefits of L-DOPA, suggesting a potential synergistic mechanism and supporting it as a translational therapy for PD patients to improve long-term treatment. Ongoing post-mortem assessment of striatal DA and 5-HT levels and gene expression for the 5-HT transporter (SERT) and 5HT-1AR should uncover therapeutic brain mechanisms for this promising combination therapy."

Preclinical • CNS Disorders • Movement Disorders • Parkinson's Disease

Modeling persistent cognitive deficit in a mouse model of schizophrenia: role of Phencyclidine (PCP) dosing frequency and reversal by clinically relevant compounds (Neuroscience 2025) - "Acute administration of vortioxetine or modafinil, used in the clinic as adjunct therapy in schizophrenia, reversed these persistent deficits in a dose-dependent manner without affecting PCP-induced hyperlocomotion or behavioral despair, implying a selective enhancement of cognitive performance without influencing non-cognitive symptoms. The persistence of deficits beyond the drug's clearance window, combined with their responsiveness to clinically used cognitive adjuncts, reinforces the model's translational relevance and utility for investigating long-lasting impairments and screening targeted therapies to improve functional outcomes in schizophrenic patients."

Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Mental Retardation • Psychiatry • Schizophrenia

The revenue of Lundbeck's strategic brands increased by +20% CER (+18% DKK), reaching DKK 14,260 million, representing 77% of total revenue (PRNewswire) - "Rexulti: DKK 4,695 million (+26% CER; +23% DKK); Brintellix/Trintellix: DKK 3,453 million (-1% CER; -3% DKK); Vyepti: DKK 3,254 million (+57% CER; +54% DKK); Abilify LAI franchise: DKK 2,858 million (+11% CER; +9% DKK)."

Sales • Major Depressive Disorder • Migraine • Schizophrenia

Real-World Cost-Effectiveness Analysis of Newer Antidepressants in Black Medicaid Beneficiaries: Evidence-Based Policy Reform to Address Treatment Disparities (ISPOR-EU 2025) - "Propensity score matching using demographics, comorbidities, baseline depression severity, and socioeconomic indicators compared outcomes between newer antidepressants (vortioxetine, vilazodone, levomilnacipran) versus standard generic options over 24-month follow-up. Real-world evidence demonstrating favorable cost-effectiveness of newer antidepressants enabled successful policy advocacy, resulting in modified prior authorization criteria across Maryland Medicaid managed care organizations. This approach provides a replicable framework for using HEOR evidence to address treatment disparities while achieving positive return on investment for healthcare stakeholders."

Clinical • Cost effectiveness • HEOR • Medicaid • Real-world • Real-world evidence • Reimbursement • US reimbursement • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Budget Impact Analysis of Vortioxetine for Major Depressive Disorder Treatment Within China's National Health Insurance System (ISPOR-EU 2025) - "Market uptake scenarios modeled vortioxetine achieving 5%, 10%, and 15% market share, displacing current standard treatments (sertraline, escitalopram, venlafaxine). Vortioxetine introduction represents a manageable budget impact for China's health insurance system, with short-term expenditure increases largely offset by medium-term healthcare savings. The analysis supports sustainable financing of innovative depression treatments while maintaining system affordability."

HEOR • Reimbursement • US reimbursement • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Evaluating the rational use of antidepressant in older patients: a comprehensive analysis of its association with cognitive impairment. (PubMed, Front Psychiatry) - "This study underscores the need for careful management of antidepressant therapy and suggests exploring alternatives such as vortioxetine, which may offer cognitive benefits. Enhanced interprofessional collaboration and regular cognitive evaluations are recommended to improve patient outcomes and ensure the rational use of antidepressants."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Sigma-1-targeting multimodal compound HBK-15 reverses memory deficits and restores hippocampal plasticity under NMDA hypofunction. (PubMed, Neurotherapeutics) - "We therefore investigated whether HBK-15 engages sigma-1 receptors and restores memory in a mouse model of MK-801-induced impairment...In contrast, vortioxetine and lurasidone showed only limited benefits, highlighting the broader effectiveness of HBK-15...These findings offer experimental evidence that HBK-15 activates sigma-1 receptors to enhance hippocampal plasticity at both synaptic and network levels and to improve memory under NMDA hypofunction. Taken together, our results highlight sigma-1-based strategies as a tractable avenue for developing treatments targeting cognitive symptoms in depression and schizophrenia."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Depression • Psychiatry • Schizophrenia