Viibryd (vilazodone) / AbbVie - LARVOL DELTA

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

Vilazodone, a Novel SSRI Antidepressant with 5-HT1A Partial Agonist Properties: Diminished Potentiation of Chronic Oral Methylphenidate-Induced Dynorphin Expression in the Striatum in Adolescent Male Rats. (PubMed, Mol Neurobiol) - "Selective serotonin reuptake inhibitor (SSRI) antidepressants such as fluoxetine are used in combination with the medical psychostimulant methylphenidate (Ritalin) in a variety of treatments in children and adults. This diminished impact on gene regulation was seen throughout the striatum, including the nucleus accumbens, where increased dynorphin expression has previously been associated with various aspects of addiction. Our findings suggest that vilazodone may serve as a better adjunct SSRI with reduced addiction-facilitating properties."

Journal • Preclinical • CNS Disorders • Psychiatry

SSRI Use and Weight Gain in a Child and Adolescent Population (AACAP 2024) - "We received charts from the electronic health record and collected data from a population of 3- to 18-year-olds; these patients were prescribed any type of SSRI medication, including citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and vilazodone. The results we found were statistically significant (p < .001) and indicated that SSRI is associated with weight gain in our population of children and adolescents. Limitations of our study include not differentiating weight changes between different types of SSRI prescribed, not differentiating duration of treatment, not differentiating by specific age groups, and not excluding persons taking other psychotropic medications, persons with certain medical conditions, or substance use, which may affect weight gain.ADOL, MAE, SAC"

Clinical • Pediatrics

TRIM21 induces selective autophagic degradation of c-Myc and sensitizes regorafenib therapy in colorectal cancer. (PubMed, Proc Natl Acad Sci U S A) - "Targeting TRIM21 to disrupt KRAS/MT-driven phosphorylation using the antidepressant vilazodone shows potential for enhancing the efficacy of regorafenib in treating KRAS-mutant CRC in preclinical models. These findings are instrumental for KRAS-mutant CRC treatment aiming at activating TRIM21-mediated selective autophagic degradation of c-Myc."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Sarcoma • Solid Tumor • Targeted Protein Degradation • KRAS • MYC • TRIM21

A Proposed Algorithm for the Pharmacological Treatment of Generalized Anxiety Disorder in the Older Patient. (PubMed, J Geriatr Psychiatry Neurol) - "Selective serotonin reuptake inhibitors (SSRIs) are considered to be first-line medications, with a preference for sertraline or escitalopram...If response is inadequate, the second recommended trial is with a different SSRI or one of the serotonin-norepinephrine update inhibitors (SNRIs), venlafaxine or duloxetine. For a third medication trial, additional alternatives added to the previous options now include pregabalin/gabapentin, lavender oil, and agomelatine. If there is an unsatisfactory response to the third option chosen, quetiapine may be considered. We recommend caution with the following for acute treatment in this population: benzodiazepines and hydroxyzine. Other agents given low priority but having some supportive evidence were vilazodone, vortioxetine, mirtazapine, and cannabidiol. Acknowledging that the median age of onset of GAD is in early adulthood, many patients with GAD will have been started on benzodiazepines (or other medications that require..."

Journal • Review • CNS Disorders • General Anxiety Disorder • Mood Disorders • Psychiatry

Effect of antidepressants on ejaculation dysfunction in patients with depression and anxiety: A systematic review and network meta-analysis. (PubMed, Andrology) - "For patients undergoing SAEs following the administration of antidepressants, trazodone, vortioxetine, vilazodone and agomelatine are alternative antidepressants."

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

A Randomized Controlled Trial Comparing the Effects of Vilazodone, Escitalopram, and Vortioxetine Monotherapy on the Metabolic Parameters in Patients With Major Depressive Disorder. (PubMed, Cureus) - "Irrespective of the diabetic situation, all three drugs substantially lowered HDRS scores. People with diabetes experienced noticeable declines in glycemic indices. Despite this, the patients' other metabolic indicators showed no significant alterations. We urge additional research with a larger sample size to investigate these medications' long-term impact on various metabolic indicators."

Journal • Monotherapy • CNS Disorders • Depression • Major Depressive Disorder • Metabolic Disorders • Mood Disorders • Psychiatry • Type 2 Diabetes Mellitus

MDD, antidepressants and sexual dysfunction (ECNP 2024) - "Selective serotonin reuptake inhibitors (SSRIs) and venlafaxine have prevalence rates of 70-80%; tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and escitalopram demonstrate rates of 40-45%; antidepressants with unique mechanisms of action like bupropion, mirtazapine, vortioxetine, vilazodone, gepirone-ER and agomelatine have rates similar to placebo at <10% in double-blind, open-label, cross-sectional and retrospective studies. Individualizing interventions based on patient preferences are needed for appropriate dosing, effective management of MDD, patient satisfaction, quality of life and treatment adherence. Discussion will consider factors impacting SD and a broad range of interventions."

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

CA10 – MDD, antidepressants and sexual dysfunction (ECNP 2024) - "Selective serotonin reuptake inhibitors (SSRIs) and venlafaxine have prevalence rates of 70-80%; tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and escitalopram demonstrate rates of 40-45%; antidepressants with unique mechanisms of action like bupropion, mirtazapine, vortioxetine, vilazodone, gepirone-ER and agomelatine have rates similar to placebo at <10% in double-blind, open-label, cross-sectional and retrospective studies. Individualizing interventions based on patient preferences are needed for appropriate dosing, effective management of MDD, patient satisfaction, quality of life and treatment adherence. Discussion will consider factors impacting SD and a broad range of interventions."

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

A Randomized Controlled Trial Comparing the Quality of Life and Medication Adherence in Patients on Antidepressant Monotherapy. (PubMed, Cureus) - "Limited studies are looking at how vortioxetine, escitalopram, and vilazodone affect these parameters. Clinical improvements were evident in the individuals' drug adherence levels. Larger-scale studies are advised to investigate the effects of these medications on the quality of life, medication adherence, and treatment outcomes."

Adherence • HEOR • Journal • Monotherapy • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Prenatal exposure to vortioxetine and vilazodone: Impact on depressive- and anxiety-like behavioral manifestations in young rat offspring. (PubMed, Behav Brain Res) - "Additionally, neurotransmitter (serotonin, dopamine, and nor-epinephrine) levels in the prefrontal cortex region of the brain were substantially reduced in exposed offspring. No sex specific neurobehavioral and neurochemical implications were observed in the present study. Our findings suggest that prenatal exposure to VOX and VLZ disrupts neurochemical balance in the fetal brain, leading to long-lasting neurobehavioral impairments in offspring of both sexes."

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

Design of vilazodone-donepezil chimeric derivatives as acetylcholinesterase inhibitors by QSAR, molecular docking and molecular dynamics simulations. (PubMed, Phys Chem Chem Phys) - "Subsequently, four new compounds with good comprehensive ability are selected for molecular dynamics simulation, and the simulation results confirm that the newly designed compounds have a certain degree of reliability and stability. This study provides guidance for vilazodone-donepezil chimeric derivatives as a potential AChE inhibitor and has certain theoretical value."

Journal • Alzheimer's Disease • CNS Disorders • Pain

Evaluation of the on-off fluorescence method for facile measurement of vilazodone in pharmaceutical dosage form; Application to content uniformity testing and greenness evaluation. (PubMed, Spectrochim Acta A Mol Biomol Spectrosc) - "Furthermore, it was also successfully used for content uniformity testing. Lastly, using four advanced tools namely the Eco-Scale, the National Environmental Method Index (NEMI), the Green Analytical Procedure Index (GAPI), and the Analytical Greenness metric approach (AGREE), the greenness of the established technique was evaluated."

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

Identification of vilazodone as a novel plasminogen activator inhibitor to overcome Alzheimer's disease through virtual screening, molecular dynamics simulation, and biological evaluation. (PubMed, Arch Pharm (Weinheim)) - "These findings suggest that targeting PLAU could represent a promising therapeutic strategy for AD. Furthermore, investigating the inhibitory potential and structural modifications based on vilazodone may provide valuable insights for future drug development targeting PLAU in AD disorders."

Journal • Alzheimer's Disease • CNS Disorders

A Randomized Controlled Trial Comparing Efficacy and Safety of Antidepressant Monotherapy. (PubMed, Cureus) - "Compared to escitalopram and vilazodone, vortioxetine demonstrated a statistically significant reduction in HDRS and MADRS scores. It also had fewer and milder side effects. We recommend conducting studies involving a broader population to investigate the antidepressant effects of these medications further."

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

Allosteric Inhibition and Pharmacochaperoning of the Serotonin Transporter by the Antidepressant Drugs Trazodone and Nefazodone. (PubMed, Mol Pharmacol) - "Here we show that - similar to the chemically related drug vilazodone - trazodone and nefazodone are allosteric ligands, which inhibit uptake by and transport-associated currents through SERT in a mixed-competitive and non-competitive manner, respectively. Trazodone and nefazodone rescued a folding-deficient variant of the serotonin transporter. This finding demonstrates that folding defects of mutated solute carrier-6 family members can also be corrected by allosteric ligands."

Journal • SLC6A4

Exploring adverse events of Vilazodone: evidence from the FAERS database. (PubMed, BMC Psychiatry) - "Although Vilazodone presents a positive prospect in the management of MDD, the discovery of AEs linked to its use, particularly the newly identified potential risks such as sleep and sexual dysfunctions, necessitates heightened vigilance among clinicians."

Adverse events • Journal • CNS Disorders • Depression • Gastroenterology • Gastrointestinal Disorder • Insomnia • Major Depressive Disorder • Mental Retardation • Psychiatry • Sexual Disorders • Sleep Disorder