Vilazodone Research Articles

Vilazodone exposure during pregnancy: Effects on embryo-fetal development, pregnancy outcomes and fetal neurotoxicity by BDNF/Bax-Bcl2/5-HT mediated mechanisms

The high prevalence of major depressive disorder (MDD) among women of childbearing age necessitates careful consideration of antidepressant use during pregnancy. Although newer antidepressants, such as Vilazodone (VLZ), are preferred for their enhanced therapeutic profiles; however, their safety during pregnancy and long-term effects on offspring brains remain inadequately addressed. Therefore, this study aimed to investigate the reproductive and developmental neurotoxicity of VLZ given at equivalent therapeutic doses during gestation in a rat model. Pregnant Wistar dams were orally administered either with 1mg/day or 2mg/day of VLZ from gestation day (GD) 6 to 21. The dams were sacrificed at GD 21, and the placentas and fetuses were collected. Fetal brains were then subjected to neurohistopathological, neurochemical, and biochemical analysis. Prenatal exposure to VLZ at 2mg/day resulted in significant maternal, reproductive, and embryo-fetal toxicity, characterized by reduced food intake, diminished weight gain in pregnant dams, and smaller litter sizes, along with decreased fetal and placental weights. These effects were associated with developmental neurotoxicity, which manifested as decreased fetal brain size and weight, a substantial reduction in neocortical layer thickness, brain-derived neurotrophic factor (BDNF) expression, serotonin, dopamine, and norepinephrine neurotransmitter levels (5-HT, DA, and NE), and increased apoptotic activity (Bax and Bcl-2 ratio) and acetylcholinesterase levels in the developing brain. 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.

Vilazodone Alleviates Neurogenesis-Induced Anxiety in the Chronic Unpredictable Mild Stress Female Rat Model: Role of Wnt/β-Catenin Signaling

Defective β-catenin signaling is accompanied with compensatory neurogenesis process that may pave to anxiety. β-Catenin has a distinct role in alleviating anxiety in adolescence; however, it undergoes degradation by the degradation complex Axin and APC. Vilazodone (VZ) is a fast, effective antidepressant with SSRI activity and 5-HT1A partial agonism that amends somatic and/or psychic symptoms of anxiety. Yet, there is no data about anxiolytic effect of VZ on anxiety-related neurogenesis provoked by stress-reduced β-catenin signaling. Furthermore, females have specific susceptibility toward psychopathology. The aim of the present study is to uncover the molecular mechanism of VZ relative to Wnt/β-catenin signaling in female rats. Stress-induced anxiety was conducted by subjecting the rats to different stressful stimuli for 21 days. On the 15th day, stressed rats were treated with VZ(10 mg/kg, p.o.) alone or concomitant with the Wnt inhibitor: XAV939 (0.1 mg/kg, i.p.). Anxious rats showed low β-catenin level turned over by Axin-1 with unanticipated reduction of APC pursued with elevated protein levels of neurogenesis-stimulating proteins: c-Myc and pThr183-Erk likewise gene expressions of miR-17-5p and miR-18. Two weeks of VZ treatment showed anxiolytic effect figured by alleviation of hippocampal histological examination. VZ protected β-catenin signal via reduction in Axin-1 and elevation of APC conjugated with modulation of β-catenin downstream targets. The cytoplasmic β-catenin turnover by Axin-1 was restored by XAV939. Herein, VZ showed anti-anxiety effect, which may be in part through regaining the balance of the reduced β-catenin and its subsequent exaggerated response of p-Erk, c-Myc, Dicer-1, miR-17-5p, and miR-18.Graphical

Activating SRC/MAPK signaling via 5-HT1A receptor contributes to the effect of vilazodone on improving thrombocytopenia.

Thrombocytopenia caused by long-term radiotherapy and chemotherapy exists in cancer treatment. Previous research demonstrates that 5-Hydroxtrayptamine (5-HT) and its receptors induce the formation of megakaryocytes (MKs) and platelets. However, the relationships between 5-HT1A receptor (5-HTR1A) and MKs is unclear so far. We screened and investigated the mechanism of vilazodone as a 5-HTR1A partial agonist in promoting MK differentiation and evaluated its therapeutic effect in thrombocytopenia. We employed a drug screening model based on machine learning (ML) to screen the megakaryocytopoiesis activity of Vilazodone (VLZ). The effects of VLZ on megakaryocytopoiesis were verified in HEL and Meg-01 cells. Tg (itga2b: eGFP) zebrafish was performed to analyze the alterations in thrombopoiesis. Moreover, we established a thrombocytopenia mice model to investigate how VLZ administration accelerates platelet recovery and function. We carried out network pharmacology, Western blot, and immunofluorescence to demonstrate the potential targets and pathway of VLZ. VLZ has been predicted to have a potential biological action. Meanwhile, VLZ administration promotes MK differentiation and thrombopoiesis in cells and zebrafish models. Progressive experiments showed that VLZ has a potential therapeutic effect on radiation-induced thrombocytopenia in vivo. The network pharmacology and associated mechanism study indicated that SRC and MAPK signaling are both involved in the processes of megakaryopoiesis facilitated by VLZ. Furthermore, the expression of 5-HTR1A during megakaryocyte differentiation is closely related to the activation of SRC and MAPK. Our findings demonstrated that the expression of 5-HTR1A on MK, VLZ could bind to the 5-HTR1A receptor and further regulate the SRC/MAPK signaling pathway to facilitate megakaryocyte differentiation and platelet production, which provides new insights into the alternative therapeutic options for thrombocytopenia.

Activating SRC/MAPK signaling via 5-HT1A receptor contributes to the effect of vilazodone on improving thrombocytopenia

Thrombocytopenia caused by long-term radiotherapy and chemotherapy exists in cancer treatment. Previous research demonstrates that 5-Hydroxtrayptamine (5-HT) and its receptors induce the formation of megakaryocytes (MKs) and platelets. However, the relationships between 5-HT1A receptor (5-HTR1A) and MKs is unclear so far. We screened and investigated the mechanism of vilazodone as a 5-HTR1A partial agonist in promoting MK differentiation and evaluated its therapeutic effect in thrombocytopenia. We employed a drug screening model based on machine learning (ML) to screen the megakaryocytopoiesis activity of Vilazodone (VLZ). The effects of VLZ on megakaryocytopoiesis were verified in HEL and Meg-01 cells. Tg (itga2b: eGFP) zebrafish was performed to analyze the alterations in thrombopoiesis. Moreover, we established a thrombocytopenia mice model to investigate how VLZ administration accelerates platelet recovery and function. We carried out network pharmacology, Western blot, and immunofluorescence to demonstrate the potential targets and pathway of VLZ. VLZ has been predicted to have a potential biological action. Meanwhile, VLZ administration promotes MK differentiation and thrombopoiesis in cells and zebrafish models. Progressive experiments showed that VLZ has a potential therapeutic effect on radiation-induced thrombocytopenia in vivo. The network pharmacology and associated mechanism study indicated that SRC and MAPK signaling are both involved in the processes of megakaryopoiesis facilitated by VLZ. Furthermore, the expression of 5-HTR1A during megakaryocyte differentiation is closely related to the activation of SRC and MAPK. Our findings demonstrated that the expression of 5-HTR1A on MK, VLZ could bind to the 5-HTR1A receptor and further regulate the SRC/MAPK signaling pathway to facilitate megakaryocyte differentiation and platelet production, which provides new insights into the alternative therapeutic options for thrombocytopenia.

Novel spectrofluorometric approach for assessing vilazodone by blocking photoinduced electron transfer: analytical performance, and greenness-blueness evaluation.

In this paper, vilazodone (VLD), a serotonin modulator prescribed for major depressive disorder, was investigated using a rapid, highly sensitive, and eco-friendly spectrofluorometric approach. The native fluorescence of VLD, originating from its indole moiety, exhibited an emission peak at 486 nm upon excitation at 241 nm. However, the presence of a piperazinyl nitrogen atom in the VLD structure, acting as an electron donor, significantly diminished the fluorescence intensity through photoinduced electron transfer (PET) to the indole ring. However, by protonating this nitrogen atom using 0.02 M Teorell-Stenhagen buffer (pH 3.5), inhibition of the PET process effectively blocked electron transfer, restoring the fluorescent properties of the drug. Further, an enhancement in the fluorescence was achieved by employing methanol as the solvent, resulting in a 1.5-fold increase. The combined use of PET blockage and methanol enabled the detection of VLD at levels as low as 0.78 ng mL-1. Calibration analysis demonstrated linearity within the range 5-400 ng mL-1, exhibiting a correlation coefficient of 0.9998 and a limit of quantification of 2.37 ng mL-1. The method obeyed the requirements of International Council on Harmonization (ICH). The proposed approach was applied for the accurate measurement of VLD in pharmaceutical tablets, content uniformity testing based on USP requirements, and determining VLD concentration in spiked human plasma. Moreover, the environmental impact, in addition to practical effectiveness, of the proposed approach was evaluated using different metrics.

Development a green analytical methodology for the sensitive determination of antidepressant drugs using fabric phase sorptive extraction as a simple sample pretreatment procedure

A new enrichment and determination method including HPLC-DAD analysis after fabric phase sorptive extraction (FPSE) has been developed to monitor trace amounts of antidepressant drugs including Amitriptyline (AMP), Fluoxetine (FLU), Vilazodone (VLZ), and Duloxetine (DUL). The target antidepressant drug molecules were retained onto the medium-polar sol–gel polytetrahydrofuran (PTHF) coated fabric phase sorptive extraction membrane in the presence of pH 9.0 medium, and back-extracted by desorbing to a smaller volume of acetonitrile (ACN) before chromatographic determinations. Chemical characterization of the used fabric phase sorptive extraction membrane and experimental variables of FPSE were studied step by step and optimized. HPLC analysis of antidepressant drugs were carried out by isocratic elution of 20 % methanol, 50 % trifluoroacetic acid (0.1 %, v:v) (TFA), 30 % acetonitrile (ACN). In the developed method. After enrichment of antidepressant molecules, 20 % Methanol, 50 % trifluoroacetic Acid (0.1 % TFA), and 30 % ACN by using C18 column. The detection limits for target antidepressant drugs under optimized conditions were found lower than 0.38 ng mL−1. The relative standard deviation (% RSD) values were calculated below 4.80 %. The developed method has been successfully applied to synthetic urine, real urine and pharmaceutical tablet samples and quantitative results have been obtained in recovery experiments.

Use of newly synthetized magnetic Fe3O4 nanoparticles modified with hexadecyl trimethyl ammonium bromide for the sensitive analysis of antidepressant drugs, duloxetine and vilazodone in wastewater and urine samples.

A new enrichment and determination method involving HPLC-DAD analysis following magnetic solid-phase extraction (MSPE) was developed to detect trace amounts of two antidepressant drugs, namely, duloxetine (DUL) and vilazodone (VIL). In this study, a solid-phase sorbent was newly synthesized for use in the MSPE and its characterization was carried out by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy and X-ray diffraction (XRD) techniques. In this proposed method, DUL and VIL molecules were enriched using newly synthesized magnetic-based nanoparticles in the presence of pH 10.0 buffer and desorbed with acetonitrile to a smaller volume prior to chromatographic determinations. After experimental variables were optimized, the VIL and DUL molecules were analyzed at wavelengths of 228 nm for DUL and 238 nm for VIL with isocratic elution of methanol, trifluoroacetic acid (TFA) (0.1%), and acetonitrile (10 : 60 : 30). The detection limits obtained under optimized conditions were 1.48 ng mL-1 and 1.43 ng mL-1, respectively. The %RSD values were found to be lower than 3.50% with model solutions containing 100 ng mL-1 (N:5). Finally, the developed method was successfully applied to wastewater samples and simulated urine samples, and quantitative results were obtained in the recovery experiments.

Characterizing the relationship between L-DOPA-induced-dyskinesia and psychosis-like behaviors in a bilateral rat model of Parkinson's disease

Parkinson's disease associated psychosis (PDAP) is a prevalent non-motor symptom (NMS) that significantly erodes patients' and caregivers' quality of life yet remains vastly understudied. One potential source of PDAP in late-stage Parkinson's disease (PD) is the common dopamine (DA) replacement therapy for motor symptoms, Levodopa (L-DOPA). Given the high incidence of L-DOPA-induced dyskinesia (LID) in later phases of PD, this study sought to characterize the relationship between PDAP and LID in a bilateral medial forebrain bundle 6-hydroxydopamine hydrobromide (6-OHDA) lesion rat model. To assess PDAP in this model, prepulse inhibition (PPI), a well-validated assay of sensorimotor gating, was employed. First, we tested whether a bilateral lesion alone or after chronic L-DOPA treatment was sufficient to induce PPI dysfunction. Rats were also monitored for LID development, using the abnormal involuntary movements (AIMs) test, to examine PPI and LID associations. In experiment 2, Vilazodone (VZD), a serotonin transporter (SERT) blocker and 1A receptor (5-HT1A) partial agonist was administered to test its potential efficacy in reducing LID and PPI dysfunction. Once testing was complete, tissue was collected for high performance liquid chromatography (HPLC) to examine the monoamine levels in motor and non-motor circuits. Results indicate that bilateral DA lesions produced motor deficits and that chronic L-DOPA induced moderate AIMs; importantly, rats that developed more severe AIMs were more likely to display sensorimotor gating dysfunction. In addition, VZD treatment dose-dependently reduced L-DOPA-induced AIMs without impairing L-DOPA efficacy, although VZD's effects on PPI were limited. Altogether, this project established the bilateral 6-OHDA lesion model accurately portrayed LID and PDAP-like behaviors, uncovered their potential relationship, and finally, demonstrated the utility of VZD for reducing LID.

Vilazodone-phospholipid mixed micelles for enhancing oral bioavailability and reducing pharmacokinetic variability between fed and fasted states

Despite the effectiveness and high tolerability of vilazodone (VLZ) as an antidepressant, its use is still limited due to its poor solubility and food dependent absorption. This study aims to load VLZ-phospholipid complex into self-assembled micelles forming VLZ-PL mixed micelles (VLZ-PL-MM), that can enhance VLZ solubility, improve its bioavailability and reduce the pharmacokinetic variability between the fed and fasting conditions. The effect of surfactant type and concentration was assessed using four different non-ionic surfactants (Brij 58, Tween 80, Labrasol and Pluronic F127) in four different weight ratios between the drug-complex and surfactant (1:0.5, 1:1, 1:2 and 1:3 w/w). Two VLZ-PL-MM formulae prepared using Brij 58 and Labrasol in 1:3 w/w ratio were selected as optimised ones since they have the highest encapsulation efficiency (100.83 and 93.87%, respectively), a particle size below 250 nm (206.73 and 221.33 nm, respectively) and negative zeta potential values (−29.63, −17.20 mV, respectively). Lyophilisation of these formulations using 3% sucrose was successful with no statistical changes in particle size and zeta potential upon rehydration. Both formulations elicited faster and higher in-vitro drug release profiles compared to the pure drug and the marketed tablet. In addition, both selected formulae improved ex-vivo permeation across rabbit intestinal membrane compared to the pure drug and the marketed tablet, with marked superiority of the one prepared using Brij 58. The results of the in-vivo study in male albino rabbits revealed similar AUC0-24 values after the oral administration of the best achieved VLZ-PL-MM system under fed and fasted conditions (769.89 and 741.55 ng.h mL−1, respectively). On the other hand, the marketed product showed significantly lower values of the AUC0-24 relative to the VLZ-PL-MM system and there was a marked enhancement of absorption of drug from the marketed product in presence of food (244.24 and 174.96 ng.h mL−1 under fed and fasted conditions, respectively). In addition, VLZ concentrations in the brain after 24 h obtained from the selected VLZ-PL-MM were significantly higher than those obtained from marketed tablet under fed and fasted conditions. Thus, the phospholipid mixed micelles formulation enhances the oral bioavailability of the poorly soluble drug and reduces the pharmacokinetic variability between fasting and fed conditions.

The multimodal serotonin compound Vilazodone alone, but not combined with the glutamate antagonist Amantadine, reduces l-DOPA-induced dyskinesia in hemiparkinsonian rats

Parkinson's disease (PD) is a progressive, neurodegenerative movement disorder caused by loss of nigrostriatal dopamine (DA) neurons. DA replacement therapy using L-3,4-dihydroxyphenylalanine (l-DOPA) improves motor function but often results in l-DOPA-induced dyskinesia (LID) typified by abnormal involuntary movements (AIMs). In states of DA depletion, striatal serotonin (5-HT) hyperinnervation and glutamate overactivity are implicated in LID. To target these co-mechanisms, this study investigated the potential anti-dyskinetic effects of FDA-approved Vilazodone (VZD), a 5-HT transport blocker and partial 5-HT1A agonist, and Amantadine (AMAT), a purported NMDA glutamate antagonist, in 6-hydroxydopamine-lesioned hemiparkinsonian Sprague-Dawley rats. Dose-response curves for each drug against l-DOPA-induced AIMs were determined to identify effective threshold doses. A second cohort of rats was tested using the threshold doses of VZD (1, 2.5 mg/kg, s.c.) and/or AMAT (40 mg/kg, s.c.) to examine their combined, acute effects on LID. In a third cohort, VZD and/or AMAT were administered daily with l-DOPA for 14 days to determine prophylactic effects on LID development. In a final cohort, rats with established LID received VZD and/or AMAT injections for 2 weeks to examine their interventional properties. Throughout experiments, AIMs were rated for dyskinesia severity and forepaw adjusting steps (FAS) were monitored l-DOPA motor efficacy. Results revealed that acute and chronic VZD + l-DOPA treatment significantly decreased AIMs and maintained FAS compared to l-DOPA alone. AMAT + l-DOPA co-administration did not exert any significant effects on AIMs or FAS, while the co-administration of VZD and AMAT with l-DOPA demonstrated intermediate effects. These results suggest that co-administration of low-dose VZD and AMAT with l-DOPA does not synergistically reduce LID in hemiparkinsonian rats. Importantly, low doses of VZD (2.5, 5 mg/kg) did reduce the development and expression of LID while maintaining l-DOPA efficacy, supporting its potential therapeutic utility for PD patients.

Identification of the Antidepressant Vilazodone as an Inhibitor of Inositol Polyphosphate Multikinase by Structure-Based Drug Repositioning.

Inositol polyphosphate multikinase (IPMK) is required for the biosynthesis of inositol phosphates (IPs) through the phosphorylation of multiple IP metabolites such as IP3 and IP4. The biological significance of IPMK’s catalytic actions to regulate cellular signaling events such as growth and metabolism has been studied extensively. However, pharmacological reagents that inhibit IPMK have not yet been identified. We employed a structure-based virtual screening of publicly available U.S. Food and Drug Administration-approved drugs and chemicals that identified the antidepressant, vilazodone, as an IPMK inhibitor. Docking simulations and pharmacophore analyses showed that vilazodone has a higher affinity for the ATP-binding catalytic region of IPMK than ATP and we validated that vilazodone inhibits IPMK’s IP kinase activities in vitro. The incubation of vilazodone with NIH3T3-L1 fibroblasts reduced cellular levels of IP5 and other highly phosphorylated IPs without influencing IP4 levels. We further found decreased Akt phosphorylation in vilazodone-treated HCT116 cancer cells. These data clearly indicate selective cellular actions of vilazodone against IPMK-dependent catalytic steps in IP metabolism and Akt activation. Collectively, our data demonstrate vilazodone as a method to inhibit cellular IPMK, providing a valuable pharmacological agent to study and target the biological and pathological processes governed by IPMK.

Effect of feeding on the pharmacokinetics of vilazodone in dogs

Vilazodone (VLZ) is a drug approved for the treatment of major depressive disorder in humans but no data are available for dogs. The present study aimed to evaluate the pharmacokinetics of a single oral 40 mg dose of VLZ in healthy Labrador dogs (n = 6) in fasted and fed conditions. Dogs were randomly divided in two (n = 3) groups in a cross-over study design (2 × 2). Group I was administered with VLZ at 40 mg/dog after fasting over-night. Group II was fed prior to and after administration of the same dose. A two-week wash-out period was observed. Plasma samples collected underwent LC-MS/MS analysis.VLZ concentrations were quantified in dogs' plasma in two different windows of time: 30 min to 10 h for the fasted group and 4 h to 35 h for the fed group. The values for t1/2λz were statistically different between the groups (fed, 4.6 ± 1.1 h vs fasted, 1.7 ± 0.2 h). Tmax drastically changed between the groups (fed, 10 h vs fasted, 1.5 h), while Cmax did not significantly vary (fed, 39.4 ± 5.6 ng/mL vs fasted, 38.7 ± 4.8 ng/mL). The AUC value was always statistically higher in the fed group. As a result, the average relative oral fasted bioavailability of VLZ was low, 28.8 ± 6.1%. In conclusion, feeding can affect the pharmacokinetics of VLZ in the dog.

Analytical Method Validation of Vilazodone with Spectrofluorimetric Detection in Rabbit Plasma

Vilazodone (VLZ) is an antidepressant agent approved in 2011 by Food and Drug Administration (FDA) for the treatment of major depressive syndromes. Its chemical structure derives from trazodone which is used as an off-label drug for dogs and cats in order to induce sedation and reduce anxiety, behavioural and pre-and post-operative stress. VLZ could be a potentially useful compound in reducing severe anxiety responses in pet animals. The aim of the present research was to develop and validate a method to quantify VLZ in rabbit plasma. A 500 μL aliquot of rabbit control plasma was added to 50 µL of IS (0.1 ug/mL) and 100 µL of NaOH 0.1M. Then 1 mL of Et2O:EtOAc (70:30 v/v) was added and the sample, shaken and centrifuged. The organic layer was transferred into a clean polypropylene vial. This procedure was repeated twice. The combined supernatants were evaporated under nitrogen at 40°C and reconstituted with 100 µL of mobile phase. 50 µL of this latter solution was injected onto HPLC-FL. The mobile phase consisted of Na2HPO4 (0.02M, pH 5):ACN (67:33 v/v) at a flow rate of 1 mL/min. The analytical column (C18) was maintained at 40°C. Excitation and emission wavelengths were set at 353 and 486 nm, respectively. Times of retention of VLZ and IS were 3.26±0.09 and 4.70±0.08 minutes, respectively. The recovery of VLZ was about 83%. Limits of quantification and detection were 0.005 µg/mL and 0.001 µg/mL, respectively. This method was verified by determining VLZ concentration in rabbit plasma after a 1 mg/kg single IV administration. The analysis of samples allowed the calculation of the main pharmacokinetic parameters. In conclusion, the present research was able to quantify VLZ in rabbit plasma after VLZ administration. This method might have application for pharmacokinetic or toxicological studies.

Formulation and Evaluation of Fast Dissolving Tablet Containing Vilazodone Nanocrystals for Solubility and Dissolution Enhancement Using Soluplus: In vitro-In vivo Study

Orally disintegrating tablets : formulation, preparation techniques and evaluationPriyanka Nagar, Kusum Singh, Iti Chauhan, Madhu Verma, Mohd Yasir,Azad Khan, Rajat Sharma, Nandini Gupta

Vilazodone does not inhibit sexual behavior in male rats in contrast to paroxetine: A role for 5-HT1A receptors?

Vilazodone (VLZ) is a selective serotonin reuptake inhibitor (SSRI) and 5-HT1A receptor partial agonist approved for the treatment of major depressive disorder in adults. In preclinical studies, VLZ had significantly lower sexual side effects than SSRIs and reduced serotonin transporter (SERT) levels in forebrain regions. In the current study, once-daily paroxetine (PAR, 10 mg/kg), VLZ (10 mg/kg), PAR + buspirone (BUS, 3 mg/kg; a 5-HT1A partial agonist), or vehicle (VEH) was administered to male rats for 2 weeks then switched for 7 days (eg, PAR switched to VLZ, PAR + BUS, or VEH). Sexual behavior (eg, ejaculation frequency and latency) was evaluated 1-hr postdose on days 1, 7, 14, and 21. After 2 weeks, treatment with PAR but not VLZ resulted in a significant decrease in sexual behavior. In a 30-min test, the range of ejaculation frequency was 3.08–3.5 with VLZ and 1.00–1.92 with PAR (P < 0.05 vs VEH). After switching from PAR to VEH, PAR + BUS, or VEH, sexual behaviors were normalized to control levels. In contrast, the switch from VLZ to PAR resulted in reduced sexual behaviors. This preclinical study showed that unlike PAR, an SSRI with no 5-HT1A receptor activity, initial treatment with VLZ did not result in sexual side effects at therapeutically relevant doses. Results in male rats switched from PAR to VLZ or PAR + BUS strongly suggest that activation of 5-HT1A receptors may mitigate the sexual side effects associated with conventional SSRIs.

Serotonin Syndrome With Standard-Dose Vilazodone (Viibryd ® ) Monotherapy

There is a deficiency in published literature describing serotonin syndrome with standard vilazodone (Viibryd®) treatment. This is the case of a 28-year-old female with anxiety treated with vilazodone. Prior to the initiation of vilazodone, vital signs were normal and the patient exhibited no signs of excessive serotonin. The patient was prescribed vilazodone with the appropriate 2-week titration per the FDA-approved prescribing information. During the first week, the patient reported excessive perspiration and gastrointestinal symptoms. On day 17 of vilazodone therapy, the patient reported a major neurologic reaction and discontinued vilazodone. The patient was diagnosed with possible serotonin syndrome. Symptoms of elevated serotonin, including hyperhidrosis and nausea, did not resolve until 2 weeks after discontinuation of therapy. In this case, the patient developed early warning signs of excessive serotonin in the periphery and eventually a potential life-threatening neurologic adverse event on vilazodone monotherapy. Practitioners should counsel on early warning signs of excessive serotonin and the potential for serotonin syndrome, even with a single serotonergic agent. J Med Cases. 2014;5(11):567-569 doi: http://dx.doi.org/10.14740/jmc1956w