Viibryd (vilazodone) / AbbVie - LARVOL DELTA

IDENTIFYING MEANINGFUL PATIENT SAVINGS ON GENERICS: DIRECT-TO-CONSUMER PRICES VS COMMERCIAL INSURANCE (ISPOR 2026) - "DTC pharmacies such as MCCPDC meaningfully lower out-of-pocket costs for higher-cost generic prescriptions which could otherwise be difficult to afford. Commercially insured patients should consider DTC pharmacies when their copayment or coinsurance for a generic medication exceeds $15, and particularly when it exceeds $100."

Clinical • Reimbursement • US reimbursement • CNS Disorders • Depression • Endocrine Disorders • Erectile Dysfunction • Multiple Sclerosis

Comparative efficacy of antidepressants for acute adolescent major depressive disorder: a source-verified systematic review and network meta-analysis. (PubMed, Front Psychiatry) - "The antidepressant-only primary SMD network contained 4 parent trials and 11 randomized arms, including desipramine, amitriptyline, fluoxetine, levomilnacipran 40 mg, levomilnacipran 80 mg, vilazodone 15 mg, vilazodone 30 mg, and pill placebo. The only statistically significant estimate was derived from a small historical desipramine trial with important data-quality limitations. Adolescent-specific arm-level evidence was too sparse and methodologically limited to support a stable comparative efficacy hierarchy among antidepressants."

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

Sex differences in cannabis use disorder study outcomes: An aggregated secondary analysis of medication trials. (PubMed, Drug Alcohol Depend) - "Males exhibited more positive responses to candidate CUD medications, especially those targeting nicotinic and serotonergic mechanisms. These findings highlight the importance of investigating sex-specific biological mechanisms and developing more effective treatments for women."

Journal • Substance Abuse

Vilazodone inhibits NLRP3 inflammasome assembly by targeting the NACHT domain and alleviates inflammatory disease. (PubMed, Int Immunopharmacol) - "Importantly, vilazodone exerted anti-inflammatory effects in vivo, reducing cytokine production in mouse models of MSU-induced peritonitis and LPS-induced systemic inflammation. Collectively, these findings identify vilazodone as a direct inhibitor of NLRP3 inflammasome assembly and highlight its potential for repurposing in inflammasome-driven diseases."

Journal • Inflammation • Targeted Protein Degradation • IL1B • NLRP3

Design, synthesis, and anti-SARS-CoV-2 activity of vilazodone derivatives as METTL3 inhibitors. (PubMed, Eur J Med Chem) - "Among these derivatives, compound D4 exhibited the most potent anti-SARS-CoV-2 activity, surpassing that of the positive control remdesivir. However, its moderate binding to METTL3 and weak inhibitory activity suggest that its antiviral activity may be mediated through targets other than METTL3. Although this finding poses a challenge to the METTL3-targeting strategy, it also opens up new research directions for further dissecting the mechanism of action of this compound and exploring its potential targets."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • METTL3

Department of Defense PTSD Adaptive Platform Trial - Master Protocol (clinicaltrials.gov) - P2 | N=800 | Suspended | Sponsor: Global Coalition for Adaptive Research | Recruiting ➔ Suspended

Trial suspension • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

Unraveling Protracted Neuropsychiatric Symptoms in a Patient With Altered Post-Bariatric Pharmacokinetics: A Diagnostic Puzzle. (PubMed, Case Rep Psychiatry) - "We present the case of a 61-year-old male with a history of gastric sleeve surgery and major depressive disorder (MDD) who developed acute serotonin syndrome (SS) following the concomitant use of fluoxetine, buspirone, and linezolid...Management remains challenging due to medication sensitivity, including recent parasomnias during a cautious trial of vilazodone...It emphasizes how an acute organic insult-whether serotonin toxicity, prolonged SSRI discontinuation, or a combination of both-can serve as a physiological trigger for complex FND and PNES, requiring multidisciplinary management. The limitations inherent in single-case observations are discussed."

Journal • PK/PD data • CNS Disorders • Depression • Epilepsy • Genetic Disorders • Hematological Disorders • Major Depressive Disorder • Metabolic Disorders • Migraine • Pain • Psychiatry • Sleep Disorder • SLC6A4

Department of Defense PTSD Adaptive Platform Trial - Master Protocol (clinicaltrials.gov) - P2 | N=800 | Recruiting | Sponsor: Global Coalition for Adaptive Research | Trial completion date: Sep 2026 ➔ Jul 2029 | Trial primary completion date: Mar 2026 ➔ Jul 2028

Trial completion date • Trial primary completion date • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

Department of Defense PTSD Adaptive Platform Trial - Intervention B - Vilazodone (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: Global Coalition for Adaptive Research | Trial completion date: Sep 2026 ➔ May 2028 | Trial primary completion date: Mar 2026 ➔ May 2028

Trial completion date • Trial primary completion date • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

Association of Antidepressant Class With Suicide Risk in Adults (APA 2026) - "Exposures: Initiation of SSRI monotherapy (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, or vilazodone) versus TCA monotherapy (trimipramine, clomipramine, desipramine, doxepin, imipramine, amitriptyline, amoxapine, or nortriptyline). Among matched patients (mean age 47.8 years; 67% female), SSRI initiation was associated with higher 30-day suicide-related risk compared with TCAs (HR, 1.59; 95% CI, 1.39–1.80), with elevation persisting to 1 year (HR, 1.27; 95% CI, 1.20–1.35) and attenuating thereafter. Young adults had the greatest early risk (18–24 years: 30-day HR, 3.72; 95% CI, 2.03–6.81). Findings were consistent across sex and racial groups and robust to sensitivity analyses."

Clinical • Alzheimer's Disease • CNS Disorders • Dementia • Depression • Major Depressive Disorder • Mood Disorders

UNEXPECTED MECHANISMS OF REPURPOSED DRUGS IN THE PATHOGENIC PATHWAYS OF NEURODEGENERATIVE DISEASES. DISCOVERING NEW NEUROPROTECTIVE THERAPIES IN CELLULAR MODELS. (PubMed, Neuropharmacology) - "Several compounds demonstrated significant efficacy, with chlorpromazine showing broad-spectrum activity (neuroprotection, Caᵥ1.2 and P2X7 antagonism, anti-inflammatory effects), trimipramine emerging as a potent antioxidant, and vilazodone displaying synergistic neuroprotection in combination with procyclidine. These findings reveal multi-target pharmacological profiles in well-tolerated drugs not currently used for neurodegenerative indications. By highlighting both individual and combinatorial strategies, this work provides a foundation for translational studies aimed at repurposing approved agents for complex neurological disorders, with particular relevance to Parkinson's disease."

Journal • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Huntington's Disease • Inflammation • Movement Disorders • Multiple Sclerosis • Parkinson's Disease

Sexually dimorphic and time-dependent influence of active avoidance learning by vilazodone in C57BL/6J mice. (PubMed, Acta Pharm) - "Interestingly, these group differences and correlations diminished on day 3, implying that the facilitation was restricted to early training phases. Collectively, VZD facilitates the acquisition of active avoidance behaviour in mice with distinct sexual dimorphism and temporal dynamics."

Journal • Preclinical • Mood Disorders • Psychiatry

Onvansertib and vilazodone inhibit SARS-CoV-2 replication via suppression of METTL3 RNA-m6A enzymatic activity. (PubMed, Antiviral Res) - "Mechanistically, each compound potentially enhanced the innate antiviral response of the host and repressed the expression of viral entry-associated host factors during infection; this observation is consistent with the established proviral role of METTL3. In summary, these findings not only substantiate METTL3 as a viable antiviral target but also lay the foundation for further research on the therapeutic potential of onvansertib and vilazodone against COVID-19."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • METTL3

Antidepressant Use and Risk of Reoperation After Distal Radius Open Reduction and Internal Fixation: A Propensity Score-Matched Cohort Study. (PubMed, J Hand Surg Glob Online) - "Two mutually exclusive exposure comparisons were analyzed: SSRI users versus nonusers and non-SSRI serotonergic users (serotonin-norepinephrine reuptake inhibitors), tricyclic antidepressants, serotonergic monoamine oxidase inhibitors, vortioxetine, or vilazodone versus nonusers, defined by ≥2 prescriptions in the 180 days preindex. Preoperative antidepressant exposure to SSRIs or non-SSRI serotonergic agents was associated with a small but clinically relevant increase in unplanned reoperation after distal radius ORIF. Prognostic III."

Journal • Musculoskeletal Diseases • Orthopedics

Unraveling the Cycle: A Scoping Review Exploring the Impact of Antidepressants on the Female Reproductive Cycle. (PubMed, Cureus) - "Both human and preclinical studies were considered, covering a range of antidepressant classes: SSRIs, SNRIs, atypical antidepressants, tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), and newer agents such as vortioxetine and vilazodone.  Out of 34 eligible studies, 16 were included in the final synthesis. SSRIs, especially fluoxetine, sertraline, paroxetine, escitalopram, and citalopram, were most frequently studied...Bupropion, venlafaxine, and other SNRIs showed cycle-phase-dependent pharmacokinetics and variable hormonal interactions...Across studies, reproductive effects varied by antidepressant class, duration of use, and underlying mood pathology. Observed trends support a drug- and class-dependent impact on estrogen, progesterone, prolactin, and reproductive function, with additional implications for systemic health."

Journal • Review • CNS Disorders • Depression • Mood Disorders • Psychiatry • Sexual Disorders • Women's Health

Investigating Refill Patterns of Vilazodone and Vortioxetine in the Tuscaloosa VA Health System (ASHP 2025) - No abstract available

Post-lanosterol inhibition profile based classification of commonly used prescription medications. (PubMed, Transl Psychiatry) - "Using LC-MS/MS we measured 13 post-lanosterol intermediates in control, DHCR7 +/- and DHCR7-/- human dermal fibroblasts exposed to cariprazine, nebivolol, rotigotine, buspirone, lurasidone, fluoxetine, hydroxyzine, amiodarone, spiroxamine, vilazodone and ziprasidone. In addition, DHCR7 +/- fibroblasts responded with greater sterol profile disruptions to all medications, while DHCR7 fibroblasts from patients with Smith-Lemli-Opitz syndrome showed generally a more plateaued response. Knowing the inhibition profile-based classification of medications that have a sterol inhibiting side effect might ultimately translate into safety recommendations during pregnancy and could be critical for new drug development."

Journal • DHCR7

Comparative gastrointestinal effects of antidepressants for the acute treatment of adults with major depressive disorder: a network and dose‒response meta-analysis. (PubMed, Transl Psychiatry) - "Commonly used antidepressants have different gastrointestinal effects. Duloxetine, levomilnacipran, and vilazodone carry a higher risk of inducing nausea and vomiting, whereas trazodone, amitriptyline, agomelatine, and mirtazapine tend to be better tolerated. Amitriptyline, clomipramine, and reboxetine are more prone to induce constipation. Diarrhoea is more commonly associated with vilazodone, fluvoxamine, and sertraline. Amitriptyline, reboxetine, and duloxetine are more likely to cause anorexia. Amitriptyline, reboxetine, and trazodone are related to causing dry mouth. Compared with the placebo, amitriptyline, fluoxetine, and paroxetine were associated with a greater incidence of dyspepsia."

Journal • Retrospective data • Review • Anorexia • CNS Disorders • Constipation • Depression • Dyspepsia • Gastroenterology • Gastrointestinal Disorder • Major Depressive Disorder • Mood Disorders • Psychiatry • Xerostomia

Structural basis of vilazodone dual binding mode to the serotonin transporter. (PubMed, Nat Commun) - "We substantiate this binding mode by exploring the conformational impact of vilazodone binding to SERT using site-specific insertion of the fluorescent non-canonical amino acid Anap. Our results offer molecular insight into the distinct pharmacological profile of a clinically used polymodal antidepressant."

Journal • CNS Disorders • Mental Retardation • Psychiatry

Vilazodone and its structural analogs. New clues for atypical dopamine transporter inhibitors? (Neuroscience 2025) - "VLZ has very high affinity (Ki=0.101 nM) for the serotonin transporter (SERT), and the 5HT1A receptor (Ki=0.20 nM), but also for the dopamine (DA) transporter (DAT; Ki=11.1 nM), which plays a role in the addictive liability of psychostimulants, like cocaine or methamphetamine. We are currently testing these compounds to assess their effects on DA levels in the rat NAC shell. In conclusion, the mechanism of action of these compounds may provide information that facilitates discovery of pharmacotherapies for the treatment of PSUD and potentially comorbid neuropsychiatric disorders."

CNS Disorders • Depression • Mental Retardation • Psychiatry

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

FDA Drug Repurposing Uncovers Modulators of Dopamine D2 Receptor Localization via Disruption of the NCS-1 Interaction. (PubMed, J Med Chem) - "Azilsartan medoxomil, atorvastatin, and vilazodone disrupt this interaction, reducing D2R surface expression. Structural studies revealed that these compounds target NCS-1, overlap the D2R binding site, and perturb the dynamics of the regulatory helix H10. These findings reveal an unexploited intracellular mechanism to modulate D2R function via PPI modulation, offering a novel strategy to fine-tune dopaminergic tone beyond receptor blockade or direct agonism."

Journal • DRD2 • NCS1

Unveiling conformation-selective regulation of the norepinephrine transporter. (PubMed, Cell) - "Through cryo-electron microscopy analysis of NET complexes with levomilnacipran, vanoxerine, and vilazodone, we identify a previously undefined allosteric site within NET's inner vestibule that enables conformation-selective regulation. Moreover, our structural identification of inhibitor occupancy at this conformation-selective site defines a mechanistic framework for targeted therapeutic intervention. These findings advance our understanding of NET allosteric modulation, providing a structure-guided framework for developing next-generation antidepressants targeting the inward-open conformation of NET for the treatment of neuropsychiatric disorders."

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mental Retardation • Psychiatry

Long-term neuronal and neurocognitive consequences in offspring after prenatal exposure to a novel antidepressant, vilazodone: Role of BDNF/Bax-Bcl-2/AChE mediated pathways. (PubMed, Psychopharmacology (Berl)) - "Prenatal exposure to 2 mg/kg VLZ disrupts neurodevelopment, resulting in persistent cognitive deficits and hippocampal alterations. These findings highlight the need for caution when prescribing VLZ during pregnancy, particularly during crucial phases of fetal brain development."

Journal • Alzheimer's Disease • Cognitive Disorders • Pain • BAX • BCL2 • BDNF

Side effect profile and comparative tolerability of newer generation antidepressants in the acute treatment of major depressive disorder in children and adolescents: protocol for a systematic review and network meta-analysis. (PubMed, BMJ Open) - "The following antidepressants will be considered: agomelatine, alaproclate, bupropion, citalopram, desvenlafaxine, duloxetine, edivoxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, mirtazapine, paroxetine, reboxetine, sertraline, venlafaxine, vilazodone and vortioxetine. The findings will be published in a peer-reviewed journal and may be presented at international conferences. CRD420251011399."

Adverse events • Journal • Retrospective data • CNS Disorders • Depression • Major Depressive Disorder • Mental Retardation • Mood Disorders • Psychiatry • Suicidal Ideation