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Carol R. Reed - One of the best experts on this subject based on the ideXlab platform.
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The Effect of Vilazodone on Sexual Function During the Treatment of Major Depressive Disorder
The journal of sexual medicine, 2012Co-Authors: Anita H. Clayton, John Edwards, Susan Gallipoli, Sidney H. Kennedy, Carol R. ReedAbstract:Introduction. Sexual dysfunction is common in major depressive disorder (MDD), and many serotonergic antide- pressants adversely affect sexual function. Vilazodone, a novel serotonin (5-HT) reuptake inhibitor and 5-HT1A partial agonist approved for MDD, exerts its effects at the 5-HT transporter and at both presynaptic and postsynaptic 5-HT1A receptors. This mechanism may limit sexual dysfunction. Aim. To summarize effects of Vilazodone (40 mg/day, with food) on sexual function in adults with MDD. Methods. Data sources were three Phase III studies: two 8-week, placebo-controlled studies (NCT00285376 and NCT00683592) and a 52-week open-label study (NCT00644358). Sexual function was assessed by analyzing changes from baseline to end of treatment (EOT) using validated measures. Main Outcome Measure. Arizona Sexual Experience Scale or Changes in Sexual Functioning Questionnaire. Results. Population included 869 patients (Vilazodone, 436; placebo, 433) from placebo-controlled studies and 599 patients from the open-label study. Sexual dysfunction prevalence was high (50%, men; 68%, women) before treatment and declined during treatment in Vilazodone and placebo groups, indicating improvement on average. At EOT, stable/improved sexual function was observed in 91% of patients in placebo-controlled studies; treatment group differences in sexual dysfunction at EOT were not statistically significant for either sex. Differences vs. placebo in changes from baseline of sexual function scores were small and were generally not statistically significant; effect sizes (Cohen's D) were generally of low magnitude. In the placebo-controlled studies, 8.0% of Vilazodone-treated patients and 0.9% of placebo-treated patients reported 1 sexual-function-related treatment-emergent adverse event (P < 0.001). Conclusion. Half of men and two thirds of women with MDD had sexual dysfunction at baseline; sexual function improved on average in both Vilazodone and placebo groups. Results suggest that Vilazodone may have a small adverse impact on sexual function in adults with MDD relative to the high prevalence of sexual dysfunction at baseline. Clayton AH, Kennedy SH, Edwards JB, Gallipoli S, and Reed CR. The effect of Vilazodone on sexual function during the treatment of major depressive disorder. J Sex Med 2013;10:2465-2476.
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the safety and tolerability profile of Vilazodone a novel antidepressant for the treatment of major depressive disorder
Psychopharmacology Bulletin, 2011Co-Authors: Michael Liebowitz, Maria Athanasiou, Susan Gallipoli, Harry A Croft, Daniel K Kajdasz, Heidi Whalen, Carol R. ReedAbstract:OBJECTIVE Vilazodone is a selective serotonin reuptake inhibitor and 5-HT1A receptor partial agonist approved for the treatment of major depressive disorder (MDD). This report summarizes the safety and tolerability of Vilazodone 40 mg/day during short- and long-term treatment of adult MDD. METHODS Pooled data from two 8-week, double-blind studies of Vilazodone (n = 436) vs placebo (n = 433) and data from one 52-week, open-label study (n = 616, Vilazodone only) were analyzed. Patients aged 18-70 with DSM-IV-TR-defined MDD received Vilazodone or placebo (8-week studies only) once daily, with food, titrated to 40 mg/day over 2 weeks. Safety and tolerability assessments included adverse events (AEs), laboratory tests, vital signs, electrocardiograms, and weight. RESULTS The most common AEs in all studies were diarrhea, nausea, and headache. Vilazodone-associated AEs in the two 8-week studies, defined as an incidence rate of ≥5% in the Vilazodone group and at least twice that for placebo, were diarrhea (28.0% vs 9.2%), nausea (23.4% vs 5.1%), and insomnia (6.0% vs 2.1%), with the majority reported as mild to moderate and <5% of those patients requiring concomitant (directed) treatment for these conditions. Discontinuation rates due to AEs were 7.1% (Vilazodone) and 3.2% (placebo) in the 8-week studies and 20.7% in the 52-week study. Vilazodone had no clinically significant effects on vital signs, laboratory tests, or electrocardiograms. CONCLUSION Vilazodone 40 mg/day was well tolerated during short- and long-term MDD treatment in these trials. Safety profiles associated with 8- and 52-week exposure were consistent.
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The Safety and Tolerability Profile of Vilazodone, A Novel Antidepressant for the Treatment of Major Depressive Disorder.
Psychopharmacology bulletin, 2011Co-Authors: Michael Liebowitz, Maria Athanasiou, Susan Gallipoli, Harry A Croft, Daniel K Kajdasz, Heidi Whalen, Carol R. ReedAbstract:OBJECTIVE Vilazodone is a selective serotonin reuptake inhibitor and 5-HT1A receptor partial agonist approved for the treatment of major depressive disorder (MDD). This report summarizes the safety and tolerability of Vilazodone 40 mg/day during short- and long-term treatment of adult MDD. METHODS Pooled data from two 8-week, double-blind studies of Vilazodone (n = 436) vs placebo (n = 433) and data from one 52-week, open-label study (n = 616, Vilazodone only) were analyzed. Patients aged 18-70 with DSM-IV-TR-defined MDD received Vilazodone or placebo (8-week studies only) once daily, with food, titrated to 40 mg/day over 2 weeks. Safety and tolerability assessments included adverse events (AEs), laboratory tests, vital signs, electrocardiograms, and weight. RESULTS The most common AEs in all studies were diarrhea, nausea, and headache. Vilazodone-associated AEs in the two 8-week studies, defined as an incidence rate of ≥5% in the Vilazodone group and at least twice that for placebo, were diarrhea (28.0% vs 9.2%), nausea (23.4% vs 5.1%), and insomnia (6.0% vs 2.1%), with the majority reported as mild to moderate and
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a randomized double blind placebo controlled 8 week study of Vilazodone a serotonergic agent for the treatment of major depressive disorder
The Journal of Clinical Psychiatry, 2011Co-Authors: Arif Khan, Maria Athanasiou, Susan Gallipoli, Daniel K Kajdasz, Heidi Whalen, Andrew J Cutler, Donald S Robinson, Carol R. ReedAbstract:Objective To evaluate the efficacy, and further establish the safety profile, of oral once-daily Vilazodone, a potent and selective serotonin 1A receptor partial agonist and reuptake inhibitor, in the treatment of major depressive disorder (MDD). Method This phase 3, randomized, double-blind, placebo-controlled, 8-week study (conducted March 2008-February 2009) enrolled 481 adults with DSM-IV-TR-defined MDD. Patients received Vilazodone (titrated to 40 mg/d) or placebo. The primary efficacy endpoint was change in Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline to end of treatment. Secondary efficacy measures included MADRS and 17-item Hamilton Depression Rating Scale (HDRS-17) response and change in HDRS-17, HDRS-21, Hamilton Anxiety Rating Scale (HARS), Clinical Global Impressions-Severity of Illness (CGI-S), and Clinical Global Impressions-Improvement (CGI-I) scores. The Changes in Sexual Functioning Questionnaire (CSFQ) was administered at baseline and week 8. Results Vilazodone-treated patients had significantly greater improvement (P = .009) according to the MADRS than placebo patients (intent-to-treat; least-squares mean changes: -13.3, -10.8). MADRS response rates were significantly higher with Vilazodone than placebo (44% vs 30%, P = .002). Remission rates for Vilazodone were not significantly different based on the MADRS (Vilazodone, 27.3% vs placebo, 20.3%; P = .066) or HDRS-17 (Vilazodone, 24.2% vs placebo, 17.7%; P = .088). Vilazodone-treated patients had significantly greater improvements from baseline in HDRS-17 (P = .026), HDRS-21 (P = .029), HARS (P = .037), CGI-S (P = .004), and CGI-I (P = .004) scores than placebo patients. Rates of discontinuation due to adverse events were 5.1% (Vilazodone) and 1.7% (placebo). The most common adverse events (Vilazodone vs placebo) were diarrhea (31% vs 11%), nausea (26% vs 6%), and headache (13% vs 10%). Treatment-related effects on sexual function as measured by the CSFQ were small and similar to placebo. Effects on weight were no different from placebo. Conclusions Vilazodone 40 mg/d was well tolerated and effective in adult patients with MDD. Trial registration clinicaltrials.gov Identifier: NCT00683592.
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Evidence for efficacy and tolerability of Vilazodone in the treatment of major depressive disorder: a randomized, double-blind, placebo-controlled trial.
The Journal of clinical psychiatry, 2009Co-Authors: Karl Rickels, Maria Athanasiou, Heidi Whalen, Donald S Robinson, Michael Gibertini, Carol R. ReedAbstract:OBJECTIVE The efficacy and tolerability of Vilazodone, a combined selective serotonin reuptake inhibitor and partial 5-hydroxytryptamine-1A (5-HT(1A)) receptor agonist, were evaluated in adult patients with major depressive disorder (MDD). METHOD This was a randomized, double-blind, placebo-controlled trial conducted from February 2006 to May 2007. Patients aged 18 through 65 years with MDD (DSM-IV criteria) and a baseline 17-item Hamilton Rating Scale for Depression (HAM-D-17) score of >or= 22 were randomly assigned to Vilazodone or placebo for 8 weeks. Vilazodone was titrated from 10 mg to 40 mg once a day over 2 weeks. Efficacy was assessed by mean change from baseline to week 8 on the Montgomery-Asberg Depression Rating Scale (MADRS), HAM-D-17, and Hamilton Rating Scale for Anxiety. Response rates were determined at week 8 for the MADRS, HAM-D-17, and Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales. Data were analyzed using a modified last-observation-carried-forward method in the intention-to-treat (ITT) sample. The Arizona Sexual Experience Scale (ASEX) was also measured at baseline and week 8. RESULTS Of 410 randomly assigned patients, 198 receiving Vilazodone and 199 receiving placebo were included in the ITT population. The mean changes in MADRS and HAM-D-17 total scores from baseline to week 8 were significantly (p = .001 and p = .022, respectively) greater with Vilazodone than with placebo. Significant (p < .05) improvements in MADRS and HAM-D-17 scores were noted at week 1, the earliest time point measured. Response rates were significantly higher with Vilazodone than with placebo on the MADRS (p = .007), HAM-D-17 (p = .011), and CGI-I (p = .001). Treatment-emergent adverse events with Vilazodone included diarrhea, nausea, and somnolence; most adverse events were of mild or moderate intensity. There were no clinically significant differences for either gender in ASEX scores at end of treatment. CONCLUSIONS Vilazodone is effective for the treatment of MDD in adults, with symptom relief starting at 1 week, and is well tolerated at a dose of 40 mg/day. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00285376.
Lee A Dawson - One of the best experts on this subject based on the ideXlab platform.
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The discovery and development of Vilazodone for the treatment of depression: a novel antidepressant or simply another SSRI?
Expert opinion on drug discovery, 2013Co-Authors: Lee A DawsonAbstract:Introduction: Vilazodone is the newest serotonergic antidepressant to be approved by the FDA for the treatment of major depressive disorder (MDD). Vilazodone is a combined serotonin specific reuptake inhibitor (SSRI) and 5-HT1A receptor partial agonist. It was originally designed based on the premise that negative feedback circuitry mediated through somatodendritic 5-HT1 autoreceptors, limits the acute SSRI-induced enhancements in serotonergic neurotransmission. Therefore, the combination of SSRI with 5-HT1A receptor agonism should temporally enhance the neuroplastic adaptation and subsequently hasten therapeutic efficacy compared to current treatments. Areas covered: This review provides the history and preclinical development of Vilazodone, highlighting the available data on its putative mechanism of action, potential clinical profile and possible areas for differentiation. These preclinical hypotheses will be contextualised with an overview of the key findings from the current clinic data on Vilazodone...
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Vilazodone a 5 ht1a receptor agonist serotonin transporter inhibitor for the treatment of affective disorders
CNS Neuroscience & Therapeutics, 2009Co-Authors: Lee A Dawson, Jeannette M WatsonAbstract:Vilazodone (EMD 68843; 5-{4-[4-(5-cyano-3-indolyl)-butyl]-1-piperazinyl}-benzofuran-2-carboxamide hydrochloride) is a combined serotonin specific reuptake inhibitor (SSRI) and 5-HT1A receptor partial agonist currently under clinical evaluation for the treatment of major depression. This molecule was designed based on the premise that negative feedback circuitry, mediated via 5-HT1 receptors, limits the acute SSRI-induced enhancements in serotonergic neurotransmission. If the hypothesis is correct, combination of SSRI with 5-HT1A partial agonism should temporally enhance the neuroplastic adaptation and subsequently hasten therapeutic efficacy compared to current treatments. Preclinical in vitro evaluation has confirmed Vilazodone's primary pharmacological profile both in clonal and native systems, that is, serotonin reuptake blockade and 5-HT1A partial agonism. However, in vivo and in contrast to combination of 8-OH-DPAT and paroxetine, Vilazodone selectively enhanced serotonergic output in the prefrontal cortex of rats. Behavioral evaluations, in the ultrasonic vocalization model of anxiety in rats, demonstrated anxiolytic efficacy. In the forced swim test (a putative model of depression), Vilazodone also showed efficacy but at a single dose only. In man, Vilazodone abolished REM sleep and demonstrated clinical antidepressant efficacy equivalent to an SSRI. Ongoing clinical evaluations will hopefully reveal whether the founding hypothesis was valid and if Vilazodone will produce a more rapid onset of antidepressant efficacy.
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Vilazodone: A 5-HT1A Receptor Agonist/Serotonin Transporter Inhibitor for the Treatment of Affective Disorders
CNS neuroscience & therapeutics, 2009Co-Authors: Lee A Dawson, Jeannette M WatsonAbstract:Vilazodone (EMD 68843; 5-{4-[4-(5-cyano-3-indolyl)-butyl]-1-piperazinyl}-benzofuran-2-carboxamide hydrochloride) is a combined serotonin specific reuptake inhibitor (SSRI) and 5-HT1A receptor partial agonist currently under clinical evaluation for the treatment of major depression. This molecule was designed based on the premise that negative feedback circuitry, mediated via 5-HT1 receptors, limits the acute SSRI-induced enhancements in serotonergic neurotransmission. If the hypothesis is correct, combination of SSRI with 5-HT1A partial agonism should temporally enhance the neuroplastic adaptation and subsequently hasten therapeutic efficacy compared to current treatments. Preclinical in vitro evaluation has confirmed Vilazodone's primary pharmacological profile both in clonal and native systems, that is, serotonin reuptake blockade and 5-HT1A partial agonism. However, in vivo and in contrast to combination of 8-OH-DPAT and paroxetine, Vilazodone selectively enhanced serotonergic output in the prefrontal cortex of rats. Behavioral evaluations, in the ultrasonic vocalization model of anxiety in rats, demonstrated anxiolytic efficacy. In the forced swim test (a putative model of depression), Vilazodone also showed efficacy but at a single dose only. In man, Vilazodone abolished REM sleep and demonstrated clinical antidepressant efficacy equivalent to an SSRI. Ongoing clinical evaluations will hopefully reveal whether the founding hypothesis was valid and if Vilazodone will produce a more rapid onset of antidepressant efficacy.
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neurochemical evaluation of the novel 5 ht1a receptor partial agonist serotonin reuptake inhibitor Vilazodone
European Journal of Pharmacology, 2005Co-Authors: Zoe A Hughes, Gerd Bartoszyk, Kathryn R Starr, Christopher J Langmead, Matthew Hill, James J Hagan, Derek N Middlemiss, Lee A DawsonAbstract:Vilazodone has been reported to be an inhibitor of 5-hydoxytryptamine (5-HT) reuptake and a partial agonist at 5-HT1A receptors. Using [ 35 S]GTPgS binding in rat hippocampal tissue, Vilazodone was demonstrated to have an intrinsic activity comparable to the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Vilazodone (1–10 mg/kg p.o.) dose-dependently displaced in vivo [ 3 H]DASB (N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine) binding from rat cortex and hippocampus, indicating that Vilazodone occupies 5-HT transporters in vivo. Using in vivo microdialysis, Vilazodone (10 mg/kg p.o.) was demonstrated to cause a 2-fold increase in extracellular 5-HT but no change in noradrenaline or dopamine levels in frontal cortex of freely moving rats. In contrast, administration of 8OH-DPAT (0.3 mg/kg s.c.), either alone or in combination with a serotonin specific reuptake inhibitor (SSRI; paroxetine, 3 mg/kg p.o.), produced no increase in cortical 5-HT whilst increasing noradrenaline and dopamine 2 and 4 fold, respectively. A 2-fold increase in extracellular 5-HT levels (but no change in noradrenaline or dopamine levels) was observed after combination of the 5-HT1A receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(pyridinyl)cyclohexanecarboxamide) (WAY-100635; 0.3 mg/kg s.c.) and paroxetine (3 mg/kg p.o.). In summary, Vilazodone behaved as a high efficacy partial agonist at the rat hippocampal 5-HT1A receptors in vitro and occupied 5-HT transporters in vivo. In vivo Vilazodone induced a selective increase in extracellular levels of 5-HT in the rat frontal cortex. This profile was similar to that seen with a 5-HT1A receptor antagonist plus an SSRI but in contrast to 8-OH-DPAT either alone or in combination with paroxetine. D 2005 Elsevier B.V. All rights reserved.
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Neurochemical evaluation of the novel 5-HT1A receptor partial agonist/serotonin reuptake inhibitor, Vilazodone.
European journal of pharmacology, 2005Co-Authors: Zoe A Hughes, Gerd Bartoszyk, Kathryn R Starr, Christopher J Langmead, Matthew Hill, James J Hagan, Derek N Middlemiss, Lee A DawsonAbstract:Vilazodone has been reported to be an inhibitor of 5-hydoxytryptamine (5-HT) reuptake and a partial agonist at 5-HT1A receptors. Using [35S]GTPgammaS binding in rat hippocampal tissue, Vilazodone was demonstrated to have an intrinsic activity comparable to the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Vilazodone (1-10 mg/kg p.o.) dose-dependently displaced in vivo [3H]DASB (N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine) binding from rat cortex and hippocampus, indicating that Vilazodone occupies 5-HT transporters in vivo. Using in vivo microdialysis, Vilazodone (10 mg/kg p.o.) was demonstrated to cause a 2-fold increase in extracellular 5-HT but no change in noradrenaline or dopamine levels in frontal cortex of freely moving rats. In contrast, administration of 8-OH-DPAT (0.3 mg/kg s.c.), either alone or in combination with a serotonin specific reuptake inhibitor (SSRI; paroxetine, 3 mg/kg p.o.), produced no increase in cortical 5-HT whilst increasing noradrenaline and dopamine 2 and 4 fold, respectively. A 2-fold increase in extracellular 5-HT levels (but no change in noradrenaline or dopamine levels) was observed after combination of the 5-HT(1A) receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(pyridinyl)cyclohexanecarboxamide) (WAY-100635; 0.3 mg/kg s.c.) and paroxetine (3 mg/kg p.o.). In summary, Vilazodone behaved as a high efficacy partial agonist at the rat hippocampal 5-HT1A receptors in vitro and occupied 5-HT transporters in vivo. In vivo Vilazodone induced a selective increase in extracellular levels of 5-HT in the rat frontal cortex. This profile was similar to that seen with a 5-HT1A receptor antagonist plus an SSRI but in contrast to 8-OH-DPAT either alone or in combination with paroxetine.
Matthew D. Krasowski - One of the best experts on this subject based on the ideXlab platform.
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Accidental intoxications in toddlers: lack of cross-reactivity of Vilazodone and its urinary metabolite M17 with drug of abuse screening immunoassays
BMC Clinical Pathology, 2019Co-Authors: Christina D. Martinez-brokaw, Sean Ekins, Joshua B. Radke, Joshua G. Pierce, Alexandra Ehlers, Kelly E. Wood, Jon Maakestad, Jacqueline A. Rymer, Kenichi Tamama, Matthew D. KrasowskiAbstract:Background Vilazodone is an FDA approved medication used to treat major depressive disorder. The authors describe two cases of accidental Vilazodone exposure in toddlers who presented with symptoms similar to amphetamine exposure and also with unexplained positive amphetamine urine immunoassay drug screens. Given a lack of published data on cross-reactivity of Vilazodone and its metabolites with drug of abuse screening tests, the authors investigated drug of abuse immunoassay cross-reactivity of Vilazodone and metabolites using computational and empirical approaches. Methods To ascertain the likelihood that Vilazodone would cross-react with drug of abuse screening immunoassays, the authors assessed the two-dimensional (2D) similarity of the Vilazodone parent molecule and known metabolites to an array of antigenic targets for urine immunoassay drug screens. To facilitate studies of the commercially unavailable M17 metabolite, it was prepared synthetically through a novel scheme. Urine and serum were spiked with Vilazodone and M17 into urine (200–100,000 ng/mL) and serum (20–2000 ng/mL) samples and tested for cross-reactivity. Results Computational analysis using 2D similarity showed that Vilazodone and metabolites have generally low similarity to antigenic targets of common drug of abuse screening immunoassays, predicting weak or no cross-reactivity. The M17 metabolite had 2D similarity to amphetamines and tricyclic antidepressants in a range similar to some other compounds exhibiting weak cross-reactivity on these immunoassays. Cross-reactivity testing was therefore performed on two different urine amphetamines immunoassays and a serum tricyclic antidepressant immunoassay. However, actual testing of cross reactivity for Vilazodone and the M17 metabolite did not detect cross-reactivity for any urine amphetamines screen at concentrations up to 100,000 ng/mL and for a serum tricyclic antidepressants assays at concentrations up to 2000 ng/mL. Conclusion While the Vilazodone metabolite M17 has weak 2D structural similarity to amphetamines and tricyclic antidepressants, the current study did not demonstrate any experimental cross-reactivity with two different urine amphetamines immunoassays and a serum tricyclic antidepressant immunoassay. Vilazodone ingestions in young children present a diagnostic challenge in their similarity to amphetamine ingestions and the lack of routine laboratory tests for Vilazodone. Further work is needed to understand the metabolic profile for Vilazodone in children versus adults.
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Accidental intoxications in toddlers: lack of cross-reactivity of Vilazodone and its urinary metabolite M17 with drug of abuse screening immunoassays.
BMC clinical pathology, 2019Co-Authors: Christina D. Martinez-brokaw, Sean Ekins, Joshua B. Radke, Joshua G. Pierce, Alexandra Ehlers, Kelly E. Wood, Jon Maakestad, Jacqueline A. Rymer, Kenichi Tamama, Matthew D. KrasowskiAbstract:Vilazodone is an FDA approved medication used to treat major depressive disorder. The authors describe two cases of accidental Vilazodone exposure in toddlers who presented with symptoms similar to amphetamine exposure and also with unexplained positive amphetamine urine immunoassay drug screens. Given a lack of published data on cross-reactivity of Vilazodone and its metabolites with drug of abuse screening tests, the authors investigated drug of abuse immunoassay cross-reactivity of Vilazodone and metabolites using computational and empirical approaches. To ascertain the likelihood that Vilazodone would cross-react with drug of abuse screening immunoassays, the authors assessed the two-dimensional (2D) similarity of the Vilazodone parent molecule and known metabolites to an array of antigenic targets for urine immunoassay drug screens. To facilitate studies of the commercially unavailable M17 metabolite, it was prepared synthetically through a novel scheme. Urine and serum were spiked with Vilazodone and M17 into urine (200–100,000 ng/mL) and serum (20–2000 ng/mL) samples and tested for cross-reactivity. Computational analysis using 2D similarity showed that Vilazodone and metabolites have generally low similarity to antigenic targets of common drug of abuse screening immunoassays, predicting weak or no cross-reactivity. The M17 metabolite had 2D similarity to amphetamines and tricyclic antidepressants in a range similar to some other compounds exhibiting weak cross-reactivity on these immunoassays. Cross-reactivity testing was therefore performed on two different urine amphetamines immunoassays and a serum tricyclic antidepressant immunoassay. However, actual testing of cross reactivity for Vilazodone and the M17 metabolite did not detect cross-reactivity for any urine amphetamines screen at concentrations up to 100,000 ng/mL and for a serum tricyclic antidepressants assays at concentrations up to 2000 ng/mL. While the Vilazodone metabolite M17 has weak 2D structural similarity to amphetamines and tricyclic antidepressants, the current study did not demonstrate any experimental cross-reactivity with two different urine amphetamines immunoassays and a serum tricyclic antidepressant immunoassay. Vilazodone ingestions in young children present a diagnostic challenge in their similarity to amphetamine ingestions and the lack of routine laboratory tests for Vilazodone. Further work is needed to understand the metabolic profile for Vilazodone in children versus adults.
Carl Gommoll - One of the best experts on this subject based on the ideXlab platform.
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Relapse prevention in adults with major depressive disorder treated with Vilazodone: a randomized, double-blind, placebo-controlled trial.
International clinical psychopharmacology, 2018Co-Authors: Suresh Durgam, Carl Gommoll, Raffaele Migliore, Changzheng Chen, Cheng-tao Chang, Michelle Aguirre, Michael E. ThaseAbstract: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-Asberg Depression Rating Scale total score of at least 18 and meeting major depressive episode criteria, Montgomery-Asberg 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.
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effects of Vilazodone on sexual functioning in healthy adults results from a randomized double blind placebo controlled and active controlled study
International Clinical Psychopharmacology, 2017Co-Authors: Anita H. Clayton, Suresh Durgam, Carl Gommoll, Changzheng Chen, Maju Mathews, Laishun Chen, Armin SzegediAbstract:The aim of this study is to evaluate the effects of Vilazodone on sexual functioning in healthy, sexually active adults and assess the impact of medication nonadherence in this type of trial. Participants were randomized to Vilazodone (20 or 40 mg/day), paroxetine (20 mg/day), or placebo for 5 weeks of double-blind treatment. The primary endpoint was change from baseline to day 35 in Change in Sexual Functioning Questionnaire (CSFQ) total score in the intent-to-treat (ITT) population. Post-hoc analyses were carried out in modified intent-to-treat (mITT) populations that excluded participants in the active-treatment groups with undetectable plasma drug concentrations at all visits (mITT-I) or at least one visit (mITT-II). In the ITT population (N=199), there were no statistically significant differences between any treatment groups for CSFQ total score change: placebo, -1.0; Vilazodone 20 mg/day, -1.4; Vilazodone 40 mg/day, -1.9; and paroxetine, -3.5. In mITT-I (N=197) and mITT-II (N=159), CSFQ total score change was not significantly different between Vilazodone (either dose) versus placebo; the CSFQ total score decreased significantly (P<0.05) with paroxetine versus both placebo and Vilazodone 20 mg/day, but not versus Vilazodone 40 mg/day. Vilazodone exerted no significant effect on sexual functioning in healthy adults. Medication nonadherence can alter study results and may be an important consideration in trials with volunteer participants.
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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.
International clinical psychopharmacology, 2017Co-Authors: Michael E. Thase, Suresh Durgam, Changzheng Chen, Cheng-tao Chang, John Edwards, Maju Mathews, Carl GommollAbstract:Abstract 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.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.
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Effects of Vilazodone on sexual functioning in healthy adults: results from a randomized, double-blind, placebo-controlled, and active-controlled study.
International clinical psychopharmacology, 2017Co-Authors: Anita H. Clayton, Suresh Durgam, Carl Gommoll, Changzheng Chen, Maju Mathews, Laishun Chen, Armin SzegediAbstract:The aim of this study is to evaluate the effects of Vilazodone on sexual functioning in healthy, sexually active adults and assess the impact of medication nonadherence in this type of trial. Participants were randomized to Vilazodone (20 or 40 mg/day), paroxetine (20 mg/day), or placebo for 5 weeks of double-blind treatment. The primary endpoint was change from baseline to day 35 in Change in Sexual Functioning Questionnaire (CSFQ) total score in the intent-to-treat (ITT) population. Post-hoc analyses were carried out in modified intent-to-treat (mITT) populations that excluded participants in the active-treatment groups with undetectable plasma drug concentrations at all visits (mITT-I) or at least one visit (mITT-II). In the ITT population (N=199), there were no statistically significant differences between any treatment groups for CSFQ total score change: placebo, -1.0; Vilazodone 20 mg/day, -1.4; Vilazodone 40 mg/day, -1.9; and paroxetine, -3.5. In mITT-I (N=197) and mITT-II (N=159), CSFQ total score change was not significantly different between Vilazodone (either dose) versus placebo; the CSFQ total score decreased significantly (P
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Characterizing sexual function in patients with generalized anxiety disorder: a pooled analysis of three Vilazodone studies.
Neuropsychiatric disease and treatment, 2016Co-Authors: Anita H. Clayton, Suresh Durgam, Changzheng Chen, Xiongwen Tang, Adam Ruth, Carl GommollAbstract:Background Vilazodone has been shown to reduce core symptoms of generalized anxiety disorder (GAD) in three randomized, double-blind, placebo-controlled trials. Since sexual dysfunction (SD) is not well characterized in GAD, a post hoc analysis of these trials was conducted to evaluate the effects of Vilazodone on sexual functioning in GAD patients. Materials and methods Data were pooled from one fixed-dose trial of Vilazodone 20 and 40 mg/day (NCT01629966) and two flexible-dose studies of Vilazodone 20-40 mg/day (NCT01766401, NCT01844115) in adults with GAD. Sexual functioning was assessed using the Changes in Sexual Functioning Questionnaire (CSFQ). Outcomes included mean change from baseline to end of treatment (EOT) in CSFQ total score and percentage of patients shifting from SD at baseline (CSFQ total score ≤47 for males, ≤41 for females) to normal functioning at EOT. Treatment-emergent adverse events related to sexual functioning were also analyzed. Results A total of 1,373 patients were included in the analyses. SD at baseline was more common in females (placebo, 46.4%; Vilazodone, 49%) than in males (placebo, 35.1%; Vilazodone, 40.9%). CSFQ total score improvement was found in both females (placebo, +1.2; Vilazodone, +1.6) and males (placebo, +2.1; Vilazodone, +1.0), with no statistically significant differences between treatment groups. The percentage of patients who shifted from SD at baseline to normal sexual functioning at EOT was higher in males (placebo, 40.6%; Vilazodone, 35.7%) than in females (placebo, 24.9%; Vilazodone, 34.9%); no statistical testing was performed. Except for erectile dysfunction and delayed ejaculation in Vilazodone-treated males (2.4% and 2.1%, respectively), no treatment-emergent adverse events related to sexual functioning occurred in ≥2% of patients in either treatment group. Conclusion Approximately 35%-50% of patients in the Vilazodone GAD studies had SD at baseline. Vilazodone and placebo had similar effects on CSFQ outcomes in both females and males, indicating a limited adverse impact on sexual functioning with Vilazodone.
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effects of Vilazodone on sexual functioning in healthy adults results from a randomized double blind placebo controlled and active controlled study
International Clinical Psychopharmacology, 2017Co-Authors: Anita H. Clayton, Suresh Durgam, Carl Gommoll, Changzheng Chen, Maju Mathews, Laishun Chen, Armin SzegediAbstract:The aim of this study is to evaluate the effects of Vilazodone on sexual functioning in healthy, sexually active adults and assess the impact of medication nonadherence in this type of trial. Participants were randomized to Vilazodone (20 or 40 mg/day), paroxetine (20 mg/day), or placebo for 5 weeks of double-blind treatment. The primary endpoint was change from baseline to day 35 in Change in Sexual Functioning Questionnaire (CSFQ) total score in the intent-to-treat (ITT) population. Post-hoc analyses were carried out in modified intent-to-treat (mITT) populations that excluded participants in the active-treatment groups with undetectable plasma drug concentrations at all visits (mITT-I) or at least one visit (mITT-II). In the ITT population (N=199), there were no statistically significant differences between any treatment groups for CSFQ total score change: placebo, -1.0; Vilazodone 20 mg/day, -1.4; Vilazodone 40 mg/day, -1.9; and paroxetine, -3.5. In mITT-I (N=197) and mITT-II (N=159), CSFQ total score change was not significantly different between Vilazodone (either dose) versus placebo; the CSFQ total score decreased significantly (P<0.05) with paroxetine versus both placebo and Vilazodone 20 mg/day, but not versus Vilazodone 40 mg/day. Vilazodone exerted no significant effect on sexual functioning in healthy adults. Medication nonadherence can alter study results and may be an important consideration in trials with volunteer participants.
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Effects of Vilazodone on sexual functioning in healthy adults: results from a randomized, double-blind, placebo-controlled, and active-controlled study.
International clinical psychopharmacology, 2017Co-Authors: Anita H. Clayton, Suresh Durgam, Carl Gommoll, Changzheng Chen, Maju Mathews, Laishun Chen, Armin SzegediAbstract:The aim of this study is to evaluate the effects of Vilazodone on sexual functioning in healthy, sexually active adults and assess the impact of medication nonadherence in this type of trial. Participants were randomized to Vilazodone (20 or 40 mg/day), paroxetine (20 mg/day), or placebo for 5 weeks of double-blind treatment. The primary endpoint was change from baseline to day 35 in Change in Sexual Functioning Questionnaire (CSFQ) total score in the intent-to-treat (ITT) population. Post-hoc analyses were carried out in modified intent-to-treat (mITT) populations that excluded participants in the active-treatment groups with undetectable plasma drug concentrations at all visits (mITT-I) or at least one visit (mITT-II). In the ITT population (N=199), there were no statistically significant differences between any treatment groups for CSFQ total score change: placebo, -1.0; Vilazodone 20 mg/day, -1.4; Vilazodone 40 mg/day, -1.9; and paroxetine, -3.5. In mITT-I (N=197) and mITT-II (N=159), CSFQ total score change was not significantly different between Vilazodone (either dose) versus placebo; the CSFQ total score decreased significantly (P
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Characterizing sexual function in patients with generalized anxiety disorder: a pooled analysis of three Vilazodone studies.
Neuropsychiatric disease and treatment, 2016Co-Authors: Anita H. Clayton, Suresh Durgam, Changzheng Chen, Xiongwen Tang, Adam Ruth, Carl GommollAbstract:Background Vilazodone has been shown to reduce core symptoms of generalized anxiety disorder (GAD) in three randomized, double-blind, placebo-controlled trials. Since sexual dysfunction (SD) is not well characterized in GAD, a post hoc analysis of these trials was conducted to evaluate the effects of Vilazodone on sexual functioning in GAD patients. Materials and methods Data were pooled from one fixed-dose trial of Vilazodone 20 and 40 mg/day (NCT01629966) and two flexible-dose studies of Vilazodone 20-40 mg/day (NCT01766401, NCT01844115) in adults with GAD. Sexual functioning was assessed using the Changes in Sexual Functioning Questionnaire (CSFQ). Outcomes included mean change from baseline to end of treatment (EOT) in CSFQ total score and percentage of patients shifting from SD at baseline (CSFQ total score ≤47 for males, ≤41 for females) to normal functioning at EOT. Treatment-emergent adverse events related to sexual functioning were also analyzed. Results A total of 1,373 patients were included in the analyses. SD at baseline was more common in females (placebo, 46.4%; Vilazodone, 49%) than in males (placebo, 35.1%; Vilazodone, 40.9%). CSFQ total score improvement was found in both females (placebo, +1.2; Vilazodone, +1.6) and males (placebo, +2.1; Vilazodone, +1.0), with no statistically significant differences between treatment groups. The percentage of patients who shifted from SD at baseline to normal sexual functioning at EOT was higher in males (placebo, 40.6%; Vilazodone, 35.7%) than in females (placebo, 24.9%; Vilazodone, 34.9%); no statistical testing was performed. Except for erectile dysfunction and delayed ejaculation in Vilazodone-treated males (2.4% and 2.1%, respectively), no treatment-emergent adverse events related to sexual functioning occurred in ≥2% of patients in either treatment group. Conclusion Approximately 35%-50% of patients in the Vilazodone GAD studies had SD at baseline. Vilazodone and placebo had similar effects on CSFQ outcomes in both females and males, indicating a limited adverse impact on sexual functioning with Vilazodone.
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Sexual dysfunction during treatment of major depressive disorder with Vilazodone, citalopram, or placebo: results from a phase IV clinical trial
International clinical psychopharmacology, 2015Co-Authors: Anita H. Clayton, Carl Gommoll, Rene Nunez, Dalei Chen, Maju MathewsAbstract: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.
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The Effect of Vilazodone on Sexual Function During the Treatment of Major Depressive Disorder
The journal of sexual medicine, 2012Co-Authors: Anita H. Clayton, John Edwards, Susan Gallipoli, Sidney H. Kennedy, Carol R. ReedAbstract:Introduction. Sexual dysfunction is common in major depressive disorder (MDD), and many serotonergic antide- pressants adversely affect sexual function. Vilazodone, a novel serotonin (5-HT) reuptake inhibitor and 5-HT1A partial agonist approved for MDD, exerts its effects at the 5-HT transporter and at both presynaptic and postsynaptic 5-HT1A receptors. This mechanism may limit sexual dysfunction. Aim. To summarize effects of Vilazodone (40 mg/day, with food) on sexual function in adults with MDD. Methods. Data sources were three Phase III studies: two 8-week, placebo-controlled studies (NCT00285376 and NCT00683592) and a 52-week open-label study (NCT00644358). Sexual function was assessed by analyzing changes from baseline to end of treatment (EOT) using validated measures. Main Outcome Measure. Arizona Sexual Experience Scale or Changes in Sexual Functioning Questionnaire. Results. Population included 869 patients (Vilazodone, 436; placebo, 433) from placebo-controlled studies and 599 patients from the open-label study. Sexual dysfunction prevalence was high (50%, men; 68%, women) before treatment and declined during treatment in Vilazodone and placebo groups, indicating improvement on average. At EOT, stable/improved sexual function was observed in 91% of patients in placebo-controlled studies; treatment group differences in sexual dysfunction at EOT were not statistically significant for either sex. Differences vs. placebo in changes from baseline of sexual function scores were small and were generally not statistically significant; effect sizes (Cohen's D) were generally of low magnitude. In the placebo-controlled studies, 8.0% of Vilazodone-treated patients and 0.9% of placebo-treated patients reported 1 sexual-function-related treatment-emergent adverse event (P < 0.001). Conclusion. Half of men and two thirds of women with MDD had sexual dysfunction at baseline; sexual function improved on average in both Vilazodone and placebo groups. Results suggest that Vilazodone may have a small adverse impact on sexual function in adults with MDD relative to the high prevalence of sexual dysfunction at baseline. Clayton AH, Kennedy SH, Edwards JB, Gallipoli S, and Reed CR. The effect of Vilazodone on sexual function during the treatment of major depressive disorder. J Sex Med 2013;10:2465-2476.
