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.

Comparative evaluation of efficacy and tolerability of vilazodone, escitalopram, and amitriptyline in patients of major depressive disorder: A randomized, parallel, open-label clinical study.

OBJECTIVES: To evaluate and compare efficacy and tolerability of Vilazodone with Escitalopram and Amitriptyline in patients of major depressive disorder(MDD). METHODS: This was a randomized, prospective, parallel-group, open label clinical study in which newly diagnosed patients of MDD were randomized to receive Tab Vilazodone 20 mg daily or Tab Escitalopram 20mg daily or Tab Amitriptyline 75mg daily for 12 weeks. Antidepressant activity was assessed by change in score from baseline to week 12 on HAMD-17 and MADRS scales while change in score on HAM-A scale was used to assess antianxiety effect. Change in scores on the three scales was also compared between the three treatment groups. Severity and causality of adverse events were assessed by the modified Hartwig & Siegel scale and Naranjo scale respectively. Data was analyzed in accordance with per protocol analysis. RESULTS: Reduction in HAMD-17 and MADRS scores was significantly more in vilazodone group compared to the other two drugs indicating that vilazodone is more efficacious antidepressant. Number of remitters were also significantly more in the vilazodone group (n=11) compared to escitalopram (n=4) (p<0.05) and amitriptyline (n=0) (p<0.001) at 12 weeks. Similar results were also obtained with HAM-A score. Number of patients showing MADRS sustained response at 12 weeks was statistically significantly more in vilazodone (n=12) and escitalopram (n=12) groups compared to amitriptyline (n=01) (p<0.001). Reported adverse events were constipation and sedation(amitriptyline group); nausea and headache(escitalopram and vilazodone groups). These adverse events were of mild severity. Most adverse events belonged to probable category. CONCLUSION: Vilazodone is more efficacious and well tolerated antidepressant compared to escitalopram and amitriptyline.

Relapse prevention in adults with major depressive disorder treated with vilazodone: a randomized, double-blind, placebo-controlled trial.

This randomized withdrawal study assessed relapse prevention with vilazodone in adults with major depressive disorder. After 20 weeks of open-label treatment with vilazodone 40 mg/day, responders were randomized (1 : 1 : 1) to 28 weeks of double-blind, fixed-dose treatment with vilazodone 20 mg/day, vilazodone 40 mg/day, or placebo. The primary efficacy endpoint was time to first relapse, defined as Montgomery-Åsberg Depression Rating Scale total score of at least 18 and meeting major depressive episode criteria, Montgomery-Åsberg Depression Rating Scale total score of at least 18 at two consecutive visits, or discontinuation for an insufficient therapeutic response. Of 1204 patients who received open-label treatment, 564 completed treatment and were randomized (placebo=192, vilazodone 20 mg/day=185, vilazodone 40 mg/day=187). No significant difference was detected in time to relapse during the double-blind period (P>0.05). The crude percentage of patients that relapsed was similar between treatment groups (placebo=12.6%; vilazodone 20 mg/day=11.4%; vilazodone 40 mg/day=13.4%). The most common treatment-emergent adverse events were diarrhea (29.6%), nausea (24.0%), and headache (14.0%) during open-label treatment and headache (8.9%), nasopharyngitis (8.4%), and diarrhea (7.5%) during double-blind treatment in the combined vilazodone groups (20 and 40 mg/day). In conclusion, time to relapse with vilazodone was not statistically different from placebo. Vilazodone was generally well tolerated in adults with major depressive disorder.

Efficacy and safety of levomilnacipran, vilazodone and vortioxetine compared with other second-generation antidepressants for major depressive disorder in adults: A systematic review and network meta-analysis.

BACKGROUND: Second-generation antidepressants dominate the medical management of major depressive disorder (MDD). Levomilnacipran, vilazodone and vortioxetine are the latest therapeutic options approved for the treatment of MDD. This systematic review aims to compare the benefits and harms of vilazodone, levomilnacipran, and vortioxetine with one another and other second-generation antidepressants. METHODS: We searched electronic databases up to September 2017 and reviewed reference lists and pharmaceutical dossiers to detect published and unpublished studies. Two reviewers independently screened abstracts and full text articles, and rated the risk of bias of included studies. Randomized controlled trials (RCTs) and controlled observational studies including adult outpatients with MDD were eligible for inclusion. We conducted network meta-analyses on response to treatment using frequentist multivariate meta-analyses models. Placebo- and active-controlled trials were eligible for network meta-analyses. RESULTS: Twenty-four studies met our inclusion criteria. Direct comparisons were limited to vilazodone versus citalopram, and vortioxetine versus duloxetine, paroxetine, or venlafaxine XR (extended release). Results of head-to-head trials and network meta-analyses, overall, indicated similar efficacy among levomilnacipran, vilazodone, or vortioxetine and other second-generation antidepressants. Although rates of overall adverse events and discontinuation due to adverse events were similar, RCTs reported several differences in specific adverse events. For most outcomes the strength of evidence was low. LIMITATIONS: Limitations are the focus of literature searches on studies published in English, possible reporting biases, and general methodological limitations of network meta-analyses. CONCLUSIONS: Overall, the available evidence does not indicate greater benefits or fewer harms of levomilnacipran, vilazodone, and vortioxetine compared with other second-generation antidepressants.

Efficacy and tolerability of different doses of three new antidepressants for treating major depressive disorder: A PRISMA-compliant meta-analysis.

In last decade, the US FDA has approved three new antidepressants: vortioxetine, levomilnacipran, and vilazodone. Many studies have researched the effects of these antidepressants on major depressive disorder (MDD), but they have not determined the optimum dosage. This meta-analysis investigated the efficacies of these three drugs at different dosages in the treatment of MDD. The PubMed, Embase, Cochrane Library, psycINFO, and ClinicalTrials.gov databases were searched to identify relevant literature. The primary outcomes were efficacy [quantified as the change from baseline in total score on the Montgomery-Asberg Depression Rating Scale (MADRS)] and tolerability (discontinuations due to adverse events). The effect size was quantified as the weighted mean difference for continuous data and the risk ratio (RR) for dichotomous data. Overall 22 studies were included. The changes in the MADRS total score were significantly higher for vortioxetine at 5, 10, 20, and 10-20 mg/day than for placebo. The tolerability was significantly worse for 20 mg/day vortioxetine than for placebo (RR = 1.84, 95% confidence interval = 1.13 to 3.02). In addition, increasing the dosage improved the efficacy of vortioxetine but worsened the tolerability. Levomilnacipran and vilazodone at any dosage produced a significantly higher mean change from baseline in the MADRS total score and a worse tolerability than for placebo. In conclusion, considering both efficacy and tolerability, 10 mg/day vortioxetine might be optimal for the treatment of MDD. The long-term efficacy and safety of vortioxetine needed to be investigated, and more studies of levomilnacipran and vilazodone are needed to define their optimal dosages.

A Double-Blind, Placebo-Controlled Randomized Trial of Vilazodone in the Treatment of Posttraumatic Stress Disorder and Comorbid Depression.

OBJECTIVE: To determine the efficacy, safety, and tolerability of vilazodone in the treatment of posttraumatic stress disorder (PTSD) with comorbid mild-to-moderate depression. METHODS: A 12-week randomized, double-blind, placebo-controlled trial was conducted in adult outpatients who met DSM-IV criteria for PTSD with comorbid depression between February 2013 and September 2015. Participants were randomly assigned to receive vilazodone 40 mg/d or placebo, and outcome measures were obtained at scheduled visits. Primary outcome measures included change in PTSD symptoms from baseline to end of study as indexed by the Clinician-Administered PTSD Scale (CAPS) and PTSD Symptom Scale-Self-Report (PSS-SR). Secondary outcome measures of anxiety, depression, and impairment were obtained, as well as biomarker assessment at baseline and end of study. RESULTS: A total of 59 patients were randomly assigned to receive vilazodone (n = 29) or placebo (n = 30). Of those who were randomized, there were 25 completers in the vilazodone group and 22 completers in the placebo group. No significant differences were observed between the groups on any of the primary or secondary outcome measures. Vilazodone was generally well tolerated with few differences in the rate of adverse events between groups. CONCLUSIONS: Treatment with vilazodone 40 mg/d did not improve symptoms of PTSD and comorbid depression. Further investigation of the biological mechanisms underlying PTSD may lead to identification of improved therapeutic targets. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01715519.

Efficacy and tolerability of vilazodone for the acute treatment of generalized anxiety disorder: A meta-analysis.

PURPOSE: A systematic review and meta-analysis of all relevant randomized controlled trials was conducted to evaluate the safety and efficacy of vilazodone in the acute treatment of generalized anxiety disorder (GAD). METHODS: The literature was searched through all relevant databases in order to identify clinical trials on the use of vilazodone in the treatment of GAD. Once the trials were identified, data was extracted and analyzed using Revman5.3 and open meta-analyst. Assessment of continuous outcomes relied upon standardized mean difference, while binary outcomes were evaluated via relative risk, absolute risk reduction and NNT/NNH. RESULTS: A total of 3 well-designed randomized controlled trials with a duration of 10 weeks were conducted, with a total of 844 (intent to treat population) randomized to vilazodone (20-40mg, mean dose=31.42mg) and 618 to placebo. The study drug was significantly superior (p<0.001) to placebo in continuous primary outcome measures (HAMA reduction at week 8, CGI-S reduction at week 8 and CGI-I score at week 8). Binary outcome measures however are not as promising, probably reflecting a small effect size [NNT=10 (6.67, 21.28) for induction of response according to the HAMA scale and NNT=12 (7.58, 34.48) for the CGI-I scale], although statistical significance (p<0.01) was attained for both. The study drug was significantly (p<0.001) more likely than placebo to induce adverse effects and to be discontinued due to adverse effects NNH=14 (10.31, 22.22), most common of which were nausea and diarrhea. DISCUSSION: Vilazodone was superior to placebo in the short term treatment of GAD. However, due to the small effect size and high incidence of adverse events, the utility of vilazodone in the treatment of GAD remains unclear. Likelihood to be helped (HAMA response) or harmed (discontinuation due to adverse events) was inconclusive [1.4 (0.48, 3.33)], demonstrating a need for further trials and direct comparisons of vilazodone to the standard treatments for the disorder. Thus vilazodone cannot be recommended yet as a first line agent. CONCLUSION AND LIMITATIONS: Vilazodone is an effective treatment for generalized anxiety disorder, though further trials are required for a more adequate comparison with established treatments, as well as long term maintenance studies to determine the validity of claims regarding the absence of sexual side effects.

Effects of vilazodone on suicidal ideation and behavior in adults with major depressive disorder or generalized anxiety disorder: post-hoc analysis of randomized, double-blind, placebo-controlled trials.

Treatment-emergent suicidal ideation and behavior are ongoing concerns with antidepressants. Vilazodone, currently approved for the treatment of major depressive disorder (MDD) in adults, has also been evaluated in generalized anxiety disorder (GAD). Post-hoc analyses of vilazodone trials were carried out to examine its effects on suicidal ideation and behavior in adults with MDD or GAD. Data were pooled from vilazodone trials in MDD (four studies) and GAD (three studies). The incidence of suicide-related events was analyzed on the basis of treatment-emergent adverse event reporting and Columbia-Suicide Severity Rating Scale (C-SSRS) monitoring. Treatment-emergent suicidal ideation was analyzed on the basis of a C-SSRS category shift from no suicidal ideation/behavior (C-SSRS=0) at baseline to suicide ideation (C-SSRS=1-5) during treatment. In pooled safety populations (MDD, n=2233; GAD, n=1475), suicide-related treatment-emergent adverse events occurred in less than 1% of vilazodone-treated and placebo-treated patients. Incidences of C-SSRS suicidal ideation were as follows: MDD (vilazodone=19.9%, placebo=24.7%); GAD (vilazodone=7.7%, placebo=9.4%). Shifts from no suicidal ideation/behavior at baseline to suicidal ideation during treatment were as follows: MDD (vilazodone=9.4%, placebo=10.3%); GAD (vilazodone=4.4%, placebo=6.1%). Data from placebo-controlled studies indicate little or no risk of treatment-emergent suicidal ideation or behavior with vilazodone in adults with MDD or GAD. Nevertheless, all patients should be monitored for suicidal thoughts and behaviors during antidepressant treatment.

Adverse effects and treatment satisfaction among online users of four antidepressants.

Adverse effects (AEs) are an important factor in antidepressant treatment decision-making, though common AE profiles from clinical trial research highlight physical AEs to the neglect of emotional and behavioral AEs. First-hand accounts of antidepressant users on the Internet can supplement AE profiles with information gained from real-world treatment experiences. We examined online user reviews of two older (escitalopram; duloxetine) and two newer (vilazodone; vortioxetine) antidepressants for differences in their AE profiles and determined which categories of AEs were associated with users' satisfaction. A codebook of 60 physical, emotional, and behavioral AEs was used for line-by-line coding of effects reported among 3243 user reviews from three popular health websites. Emotional and behavioral effects were commonly reported (41%), followed by sleep (31.9%) and gastrointestinal (25.0%) effects. Specific AEs statistically significantly varied across drugs, creating potentially meaningful differences in AE profiles. Users of newer drugs more often reported emotional instability, while users of older drugs reported more emotional blunting. Emotional and behavioral AEs demonstrated moderate to substantial relationships with users' satisfaction, whereas gastrointestinal, metabolic, or sexual AEs were minimally related. More specific and systematic assessment of a broader range of AEs is needed in both research and practice.

Double-blind switch study of vilazodone in the treatment of major depressive disorder.

Approximately 40% of patients treated for depression do not respond to a trial of an antidepressant. The aim of the proposed study was to evaluate the efficacy and safety of switching to vilazodone in patients with major depressive disorder who are unresponsive or only partially responsive to a trial of citalopram. Seventy-nine adults with major depressive disorder were enrolled in an open-label study of citalopram (20 mg/day) for 6 weeks. Those still symptomatic after 6-weeks of citalopram were randomly assigned to either a higher dose of citalopram (40 mg/day) or to vilazodone in a double-blind trial for 6 weeks. Of those who received citalopram 20 mg/day for 6 weeks, 20.3% were 'responders' (defined as ≥50% reduction on the Montgomery-Åsberg Depression Rating Scale). Of the 42 who did not respond, 23 were assigned to citalopram 40 mg/day and 19 were randomized to 40 mg/day of vilazodone. Both groups showed decreases in all outcome measures, but there were no significant differences between groups. Initial nonresponders to a low dose of citalopram seem equally likely to respond to a higher dose of citalopram or to vilazodone. Whether to increase an selective serotonin reuptake inhibitor or switch to a different antidepressant may be best determined on the basis of their adverse event profile.

Efficacy and tolerability of vilazodone for major depressive disorder: evidence from phase III/IV randomized controlled trials.

Vilazodone is a new molecule approved for major depressive disorder (MDD). This report focuses on the efficacy and tolerability of vilazodone for MDD. MEDLINE, EMBASE, and Cochrane Library were searched. A total of 1,930 patients from four trials were included. A significant improvement in the Montgomery-Asberg Depression Rating Scale (MADRS) total score was seen as early as week 2 (P<0.01) in vilazodone-treated patients. The results showed a higher rate of MADRS response with vilazodone compared with placebo (P<0.001). There were also greater improvements in the Hamilton Rating Scale for Anxiety as well as the Clinical Global Impressions (severity of illness and improvement of illness) scores from baseline in vilazodone-treated patients compared to placebo patients (P<0.001). Discontinuation rates due to adverse events were higher with vilazodone than placebo (P=0.0002). The most common adverse events of vilazodone were vomiting, nausea, diarrhea, insomnia, somnolence, dizziness, and dry mouth (P<0.05). Treatment-related effects on sexual function were mild compared to placebo in men (P=0.03). In conclusion, 40 mg/day of vilazodone had a rapid onset of response and showed good improvement in anxiety symptoms as well as good tolerability during short-term treatment (8-10 weeks) for MDD. Further studies should focus on the efficacy and tolerability of vilazodone over a longer duration and should utilize active comparators.

Efficacy and Safety of Vilazodone in Patients With Generalized Anxiety Disorder: A Randomized, Double-Blind, Placebo-Controlled, Flexible-Dose Trial.

OBJECTIVE: To evaluate the efficacy, safety, and tolerability of vilazodone as an acute treatment for generalized anxiety disorder (GAD). Vilazodone is a selective serotonin reuptake inhibitor and 5-HT1A receptor partial agonist approved for the treatment of major depressive disorder in adults. METHODS: This was a randomized, placebo-controlled, parallel-group, multicenter, flexible-dose study conducted from May 2013-March 2014. Adult patients (18-70 years, inclusive) who met DSM-IV-TR criteria for GAD were randomized (1:1) to placebo or vilazodone 20-40 mg/d for 8 weeks of double-blind treatment. Primary and secondary efficacy parameters were change from baseline to week 8 in the Hamilton Anxiety Rating Scale (HARS) total score and in the Sheehan Disability Scale (SDS) total score, respectively, analyzed using a mixed-effects model for repeated measures approach on a modified intent-to-treat population. Safety outcomes were summarized descriptively. RESULTS: Efficacy analyses were based on 400 patients (placebo = 200, vilazodone = 200); 76% completed the study (placebo = 81%, vilazodone = 71%). The least squares mean difference (95% CI) in total score change from baseline to week 8 was statistically significant for vilazodone versus placebo on the HARS (-2.20 [-3.72 to -0.68]; P = .0048) and on the SDS (-1.89 [-3.52 to -0.26]; P = .0236). Treatment-emergent adverse events reported in ≥ 5% of vilazodone patients and at least twice the rate of placebo were nausea, diarrhea, dizziness, fatigue, delayed ejaculation, and erectile dysfunction. CONCLUSION: Statistically significant differences in favor of vilazodone 20-40 mg/d versus placebo were seen on all measures of anxiety and functional impairment in patients with GAD. Vilazodone was generally well tolerated, and no new safety concerns were noted. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01844115.

Vilazodone: a review in major depressive disorder in adults.

Vilazodone (Viibryd(®)) exhibits the combined properties of a selective serotonin reuptake inhibitor (SSRI) and a serotonin 5-HT1A receptor partial agonist, and is approved in the US for the treatment of major depressive disorder (MDD) in adults. In four randomized, double-blind, clinical trials, oral vilazodone 20 or 40 mg once daily for 8 or 10 weeks reduced from baseline (improved) the Montgomery-Åsberg Depression Rating Scale (MADRS) total score significantly more than placebo in adult patients with MDD. In these trials, significantly greater reductions in MADRS total score with vilazodone compared with placebo were seen from either week 1, week 2 (two trials) or week 6. In a noncomparative study, MADRS total scores continued to improve throughout therapy for up to 1 year. Vilazodone was generally well tolerated, with the most common treatment-emergent adverse events being mild or moderate diarrhoea, nausea and headache. Vilazodone had only limited adverse effects on sexual function or bodyweight. Therefore, vilazodone is an effective agent for treating MDD in adults.

Vilazodone in patients with generalized anxiety disorder: a double-blind, randomized, placebo-controlled, flexible-dose study.

Vilazodone is a selective serotonin reuptake inhibitor and a 5-HT1A receptor partial agonist that is approved for treatment of major depressive disorder in adults in the USA and Mexico. The efficacy, safety, and tolerability of vilazodone for generalized anxiety disorder (GAD) were investigated in a clinical trial (NCT01766401 ClinicalTrials.gov). Participants (18-70 years, inclusive) who met Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision, criteria for GAD were randomized (1:1) to placebo or flexible-dose vilazodone (20-40 mg/day) for 8 weeks of double-blind treatment. Primary and secondary efficacy parameters were changes from baseline to week 8 in Hamilton Rating Scale for Anxiety and Sheehan Disability Scale total scores, respectively. Analysis was based on a mixed-effects model for repeated measures approach on the intent-to-treat population. The intent-to-treat population comprised 395 patients (placebo=197, vilazodone=198); 77% completed the study. The least squares mean difference in change from baseline to week 8 in the Hamilton Rating Scale for Anxiety total score was statistically significant for vilazodone versus placebo [-1.50 (-2.96, -0.04), P=0.0438]. The mean change from baseline to week 8 in the Sheehan Disability Scale total score for vilazodone versus placebo was not statistically significant. Adverse events were reported in 60% of placebo-treated and 83% of vilazodone-treated patients. This was a positive clinical trial of 20-40 mg/day vilazodone versus placebo in the treatment of GAD.

Sexual dysfunction during treatment of major depressive disorder with vilazodone, citalopram, or placebo: results from a phase IV clinical trial.

Sexual dysfunction commonly occurs with major depressive disorder (MDD). Vilazodone, a selective serotonin reuptake inhibitor and 5-HT1A receptor partial agonist antidepressant approved for the treatment of MDD in adults, was evaluated to determine its effects on sexual function. The primary study was a double-blind, randomized, controlled trial comparing vilazodone 20 and 40 mg/day with placebo; citalopram 40 mg/day was an active control (NCT01473381; http://www.clinicaltrials.gov). Post-hoc analyses evaluated change from baseline to week 10 on the Changes in Sexual Functioning Questionnaire (CSFQ); no inferential statistics were performed. CSFQ scores increased for women [1.2 (citalopram) to 3.0 (vilazodone 40 mg)] and men [1.2 (vilazodone 40 mg) to 3.5 (placebo)] in all treatment groups. Greater changes in CSFQ scores were seen in responders [women: 2.33 (citalopram) to 5.06 (vilazodone 40 mg); men: 2.26 (vilazodone 40 mg) to 4.35 (placebo)] versus nonresponders. CSFQ change from baseline was small for patients with normal baseline sexual function; in patients with baseline sexual dysfunction, CSFQ scores improved across groups [women: 2.35 (citalopram) to 4.52 (vilazodone 40 mg); men 2.83 (vilazodone 40 mg) to 6.43 (placebo)]. Across treatment groups, baseline sexual function improved in women and men, MDD responders, and patients with baseline sexual dysfunction.

Breakthrough seizures after starting vilazodone for depression.

Vilazodone is a new selective serotonin reuptake inhibitor (SSRI) and serotonin 5-HT1a partial agonist that is approved by the United States Food and Drug Administration to treat major depression. SSRI-induced seizures are rare and are more likely to be associated with larger doses and severe symptoms such as those present in serotonin syndrome. Several case reports have implicated SSRIs, buspirone, or the combination of these agents as the cause of seizures, but these reports were confounded with either coingestions or doses that exceeded FDA recommendations. We describe a 22-year-old woman with a history of seizure disorder who had been seizure free for the previous 8 years and experienced two breakthrough seizures shortly after starting vilazodone. Her dose of vilazodone had recently been titrated to 40 mg/day when she experienced the first seizure. She was instructed to taper vilazodone over the next several days, then discontinue the drug, and then follow up with her neurologist. Based on the patient's history, physical examination, and recent dose increase, it was plausible that vilazodone was the cause of the seizures. Use of the Naranjo adverse drug reaction probability scale indicated a possible relationship (score of 4) between her development of seizures and vilazodone therapy. The pharmacodynamics of this particular class of SSRI has both proconvulsive and anticonvulsive mechanisms. This is of particular concern in patients with a history of seizure disorder who are starting antidepressive therapy. In persons with epilepsy who are taking vilazodone and experience breakthrough seizures, practitioners should consider this drug as a potential cause of these seizures. Thus, until future research and experience with vilazodone can provide a definitive answer, clinicians should be cautious when prescribing this medication to treat depression in patients with a history of seizure disorder.