Viibryd (vilazodone) / AbbVie - LARVOL DELTA

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

Dissemination of Information on Selective Serotonin Reuptake Inhibitors on TikTok: Analytical Mixed Methods Study of Creator Types, Content Tone, and User Engagement. (PubMed, JMIR Ment Health) - "Approximately one-third (35/99, 35%) mentioned a specific SSRI (ie, fluoxetine, fluvoxamine, vilazodone, sertraline, paroxetine, citalopram, or escitalopram). These findings are consistent with other research suggesting that the TikTok algorithm and users are more likely to favor and engage with videos that evoke a strong emotional response and are perceived as relatable to viewers. This study highlights the need for medical professionals to improve their approach to content creation on TikTok by using a more positive video tone to increase engagement."

Journal

Management of Antidepressant-Induced Sexual Dysfunction: A Literature Review. (PubMed, Cureus) - "Replacing one antidepressant class for another with a more favorable side effect profile (e.g., mirtazapine, nefazodone, and vortioxetine) may be effective for some patients, especially if the initial antidepressive treatment was not sufficient in controlling the symptoms caused by the primary mental illness. Several adjunctive medications and supplements also show promise in the management of AISD, including bupropion and saffron (Crocus sativus)...Evidence for switching to vilazodone to treat AISD is conflicting, as is data surrounding the effect of Ginkgo biloba on AISD...Further studies are necessary to understand AISD's pathophysiology and current interventions. Development and use of other drugs, supplements, and nonpharmacological agents should be explored in this patient population to broaden effective management options for AISD."

Journal • Review • Bulimia • CNS Disorders • Depression • General Anxiety Disorder • Major Depressive Disorder • Mood Disorders • Obsessive-Compulsive Disorder • Psychiatry • Sexual Disorders

Computational Drug Repositioning for Targeting PfEMP1: Potential Therapeutics for Cerebral Malaria in Plasmodium falciparum. (PubMed, Biotechnol Appl Biochem) - "Among the top candidate molecules are Lumacaftor, Vilazodone, Tucatinib, Lenvatinib, and Hydrocortisone Cypionate, which exhibit favorable docking energies (-9.1 to -8.3 kcal/mol) and potential oral bioavailability, as determined by receptor-based screening and absorbed, distributed, metabolized, and eliminated (ADME) analysis. Gibbs's free energy landscape analysis further reinforces the stability of these drug-protein complexes, underscoring their potential as therapeutic agents. These findings highlight the significant role of computational approaches in drug discovery and offer valuable insights into repurposing FDA-approved drugs for cerebral malaria treatment."

Journal • Infectious Disease • Malaria

Vilazodone ameliorates senescence-related Alzheimer's disease like symptoms by targeting Plau to induce autophagy in senescent cells. (PubMed, Int Immunopharmacol) - "The results indicate that focusing on Plau may offer a hopeful approach for treating AD. Additionally, exploring the ability to inhibit Plau and alter the structure of vilazodone could provide valuable knowledge for developing drugs aimed at targeting Plau in AD-related conditions."

Journal • Alzheimer's Disease • CNS Disorders • PLAU • PTGS2

Targeting PARP14: An in silico framework for identifying novel Competitive inhibitors via 3D-QSAR pharmacophore modeling and molecular dynamics. (PubMed, Comput Biol Med) - "These findings suggest that Furosemide and Vilazodone could be effectively repurposed as PARP14 inhibitors, offering a strategic approach to enhance the efficacy of cancer treatment, whereas STOCK1N-42868 represents an exciting avenue for further research. This study emphasizes the possible applications of computational methods for finding new drugs and stresses the importance of pre-clinical research to examine how these inhibitors work in cancer treatment."

Journal • B Cell Lymphoma • Genito-urinary Cancer • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Prostate Cancer • Solid Tumor

Did Serendipity Contribute to the Discovery of New Antidepressant Drugs? Historical Analysis Using Operational Criteria. (PubMed, Alpha Psychiatry) - "Selective serotonin reuptake inhibitors (fluoxetine, fluvoxamine, citalopram, paroxetine, sertraline, and escitalopram), selective dopamine and noradrenaline reuptake inhibitors (bupropion), noradrenaline and serotonin reuptake inhibitors (venlafaxine, milnacipram, duloxetine, and desvenlafaxine), selective noradrenaline reuptake inhibitors (reboxetine), noradrenergic and specific serotonergic antidepressants (mirtazapine), melatonergic agonists (agomelatine), and serotonin modulators and stimulators (vortioxetine, vilazodone, tianeptine) correspond to the type IV pattern. Ketamine, a glutamatergic modulator, corresponds to the type III pattern, characterized by a non-serendipitous origin (initial development as an anesthetic agent) leading to a serendipitous observation (the discovery of antidepressant efficacy in individuals illicitly using). The majority of new antidepressants adhere to a type IV pattern, characterized by a rational and targeted design process where..."

Journal • Anesthesia

Comparative efficacy of antidepressant medication for adolescent depression: a network meta-analysis and systematic review. (PubMed, BMC Psychiatry) - "For symptom severity scales, agomelatine (CDRS-R: SUCRA 86.4%) and paroxetine (MADRS: SUCRA 99.9%) demonstrated the greatest efficacy. For functional improvement, escitalopram ranked highest on CGAS (SUCRA 96.1%). Sertraline showed superiority in clinician-rated severity (CGI-S: SUCRA 100%) and improvement (CGI-I: SUCRA 80.2%). Clinical decisions should prioritize escitalopram for functional recovery and sertraline for severe cases requiring rapid symptom reduction."

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

Drugs repurposed against morphine and heroin dependence: molecular docking, DFT, MM-GBSA-based MD simulation studies. (PubMed, In Silico Pharmacol) - "We found vilazodone, indinavir, and lorazepam as potential drugs based on their affinity and mechanism of action. We propose that these three drugs have huge potential to reverse the morphine and heroin dependence in diseased subjects near future. The online version contains supplementary material available at 10.1007/s40203-025-00347-z."

Journal • Addiction (Opioid and Alcohol) • Pain • TLR4

Development and validation of a novel fluorometric approach utilizing flow injection analysis for the measurement of vilazodone: application to dosage form and spiked human plasma. (PubMed, BMC Chem) - "Additionally, the studied drug was also satisfactorily measured in blood using the suggested flow injection methodology. The approach was validated according to ICH specifications."

Journal

Esketamine Combined With SSRI or SNRI for Treatment-Resistant Depression. (PubMed, JAMA Psychiatry) - "Treatment with esketamine combined with an SSRI (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, or vilazodone) or an SNRI (desvenlafaxine, duloxetine, levomilnacipran, milnacipran, or venlafaxine). In this retrospective comparative effectiveness study, among the study sample, incidence of mortality, hospitalizations, depressive relapses, and suicide attempts was low. The esketamine + SNRI group showed lower incidence of mortality, hospitalizations, and depressive relapses, while the esketamine + SSRI group showed a slightly lower incidence of suicidal attempts."

Journal • CNS Disorders • Depression • Mood Disorders • Psychiatry

Discovery of a Novel Multitarget Analgesic Through an In Vivo-Guided Approach. (PubMed, Pharmaceuticals (Basel)) - "Compound 29, derived from a novel scaffold inspired by opiranserin and vilazodone pharmacophores, was identified through analog screening in the formalin test. Compound 29 is a promising multitarget analgesic with potent efficacy and favorable pharmacokinetics. Ongoing optimization efforts aim to mitigate side effects and enhance its therapeutic profile for clinical application."

Journal • Preclinical • Neuralgia • Pain

Structural basis of vilazodone dual binding mode to the serotonin transporter. (PubMed, Res Sq) - "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 novel molecular insight into the distinct pharmacological profile of a clinically used polymodal antidepressant."

Journal • CNS Disorders • Mental Retardation • Psychiatry

Department of Defense PTSD Adaptive Platform Trial - Master Protocol (clinicaltrials.gov) - P2 | N=800 | Recruiting | Sponsor: Global Coalition for Adaptive Research | N=600 ➔ 800

Enrollment change • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

Country-specific psychopharmacological risk of reporting suicidality comparing 38 antidepressants and lithium from the FDA Adverse Event Reporting System, 2017-2023. (PubMed, Front Psychiatry) - "In the multivariate analysis, compared to fluoxetine and patients aged 25 to 64 years, children [adjusted reporting odds ratio (aROR) = 7.38, 95% CI, 6.02-9.05] and young adults (aROR = 3.49, 95% CI, 2.65-4.59) were associated with an increased risk of reporting suicidality, but not for the elderly (aROR = 0.76, 95% CI, 0.53-1.09)...For the overall study population, desvenlafaxine (aROR = 0.61, 95% CI, 0.46-0.81) and vilazodone (aROR = 0.56, 95% CI, 0.32-0.99) were the only two antidepressants associated with a reduced risk of reporting suicidality. This study shows that with recent antidepressant drug safety data, the US FDA's black-box warning for prescribing antidepressants to children and young adults is valid today in the USA. However, relative to the USA, 15 countries had a significantly lower risk of reporting suicidality, while 16 countries had a higher risk of reporting suicidality from 38 antidepressants and lithium."

Adverse events • Journal • CNS Disorders • Depression • Psychiatry

Revisiting Depression Rating Scales: Analysis of a Randomized Trial. (PubMed, Cureus) - "After 16 weeks of therapy, we noticed substantial drops in HDRS and MADRS scores. The HDRS was proved to be more precise than the analogous MADRS. The MADRS was recalibrated to remove differential and proportional biases."

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

Vilazodone exposure during pregnancy: Effects on embryo-fetal development, pregnancy outcomes and fetal neurotoxicity by BDNF/Bax-Bcl2/5-HT mediated mechanisms. (PubMed, Neurotoxicology) - "Our findings indicate that prenatal VLZ exposure interfere with crucial brain development processes involving the BDNF/Bax-Bcl2/5-HT signalling pathways, leading to long-lasting neurodevelopmental impairments. This study is the first to document the adverse effects of VLZ on fetal brain development, highlighting the need for further research to assess the safety of VLZ use during pregnancy."

IO biomarker • Journal • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • BAX • BCL2 • BDNF