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1.
Pharmacol Biochem Behav ; 217: 173393, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35513119

RESUMEN

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.


Asunto(s)
Discinesia Inducida por Medicamentos , Enfermedad de Parkinson , Amantadina/farmacología , Amantadina/uso terapéutico , Animales , Antiparkinsonianos/efectos adversos , Modelos Animales de Enfermedad , Discinesia Inducida por Medicamentos/tratamiento farmacológico , Discinesia Inducida por Medicamentos/etiología , Antagonistas de Aminoácidos Excitadores/uso terapéutico , Humanos , Levodopa/efectos adversos , Oxidopamina , Enfermedad de Parkinson/tratamiento farmacológico , Ratas , Ratas Sprague-Dawley , Serotonina/metabolismo , Clorhidrato de Vilazodona/uso terapéutico
2.
Psychopharmacology (Berl) ; 239(7): 2119-2132, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35275226

RESUMEN

Parkinson's disease is a neurodegenerative disease often characterized by motor deficits and most commonly treated with dopamine replacement therapy. Despite its benefits, chronic use of L-DOPA results in abnormal involuntary movements known as L-DOPA-induced dyskinesia. Growing evidence shows that with burgeoning dopamine cell loss, neuroplasticity in the serotonin system leads to the development of L-DOPA-induced dyskinesia through the unregulated uptake, conversion, and release of L-DOPA-derived dopamine into the striatum. Previous studies have shown that coincident 5-HT1A agonism and serotonin transporter inhibition may have anti-dyskinetic potential. Despite this, few studies have explicitly focused on targeting both 5-HT1A and the serotonin transporter. The present study compares the 5-HT compounds Vilazodone, YL-0919, and Vortioxetine which purportedly work as simultaneous 5-HT1A receptor agonists and SERT blockers. To do so, adult female Sprague Dawley rats were rendered hemiparkinsonian and treated daily for two weeks with L-DOPA to produce stable dyskinesia. The abnormal involuntary movements and forehand adjusting step tests were utilized as measurements for L-DOPA-induced dyskinesia and motor performance in a within-subjects design. Lesion efficacy was determined by analysis of striatal monoamines via high-performance liquid chromatography. Compounds selective for 5-HT1A/SERT target sites including Vilazodone and Vortioxetine significantly reduced L-DOPA-induced dyskinesia without compromising L-DOPA pro-motor efficacy. In contrast, YL-0919 failed to reduce L-DOPA-induced dyskinesia, with no effects on L-DOPA-related improvements. Collectively, this work supports pharmacological targeting of 5-HT1A/SERT to reduce L-DOPA-induced dyskinesia. Additionally, this further provides evidence for Vilazodone and Vortioxetine, FDA-approved compounds, as potential adjunct therapeutics for L-DOPA-induced dyskinesia management in Parkinson's patients.


Asunto(s)
Discinesia Inducida por Medicamentos , Enfermedades Neurodegenerativas , Animales , Antiparkinsonianos/farmacología , Cuerpo Estriado , Modelos Animales de Enfermedad , Dopamina/farmacología , Discinesia Inducida por Medicamentos/tratamiento farmacológico , Femenino , Humanos , Levodopa/farmacología , Oxidopamina , Piperidinas , Piridonas , Ratas , Ratas Sprague-Dawley , Serotonina/farmacología , Proteínas de Transporte de Serotonina en la Membrana Plasmática , Clorhidrato de Vilazodona/farmacología , Clorhidrato de Vilazodona/uso terapéutico , Vortioxetina/uso terapéutico
3.
Cochrane Database Syst Rev ; 5: CD013674, 2021 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-34029378

RESUMEN

BACKGROUND: Major depressive disorders have a significant impact on children and adolescents, including on educational and vocational outcomes, interpersonal relationships, and physical and mental health and well-being. There is an association between major depressive disorder and suicidal ideation, suicide attempts, and suicide. Antidepressant medication is used in moderate to severe depression; there is now a range of newer generations of these medications. OBJECTIVES: To investigate, via network meta-analysis (NMA), the comparative effectiveness and safety of different newer generation antidepressants in children and adolescents with a diagnosed major depressive disorder (MDD) in terms of depression, functioning, suicide-related outcomes and other adverse outcomes. The impact of age, treatment duration, baseline severity, and pharmaceutical industry funding was investigated on clinician-rated depression (CDRS-R) and suicide-related outcomes. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Specialised Register, the Cochrane Library (Central Register of Controlled Trials (CENTRAL) and Cochrane Database of Systematic Reviews (CDSR)), together with Ovid Embase, MEDLINE and PsycINFO till March 2020. SELECTION CRITERIA: Randomised trials of six to 18 year olds of either sex and any ethnicity with clinically diagnosed major depressive disorder were included. Trials that compared the effectiveness of newer generation antidepressants with each other or with a placebo were included. Newer generation antidepressants included: selective serotonin reuptake inhibitors; selective norepinephrine reuptake inhibitors (SNRIs); norepinephrine reuptake inhibitors; norepinephrine dopamine reuptake inhibitors; norepinephrine dopamine disinhibitors (NDDIs); and tetracyclic antidepressants (TeCAs). DATA COLLECTION AND ANALYSIS: Two reviewers independently screened titles/abstracts and full texts, extracted data, and assessed risk of bias. We analysed dichotomous data as Odds Ratios (ORs), and continuous data as Mean Difference (MD) for the following outcomes: depression symptom severity (clinician rated), response or remission of depression symptoms, depression symptom severity (self-rated), functioning, suicide related outcomes and overall adverse outcomes. Random-effects network meta-analyses were conducted in a frequentist framework using multivariate meta-analysis. Certainty of evidence was assessed using Confidence in Network Meta-analysis (CINeMA). We used "informative statements" to standardise the interpretation and description of the results. MAIN RESULTS: Twenty-six studies were included. There were no data for the two primary outcomes (depressive disorder established via clinical diagnostic interview and suicide), therefore, the results comprise only secondary outcomes. Most antidepressants may be associated with a "small and unimportant" reduction in depression symptoms on the CDRS-R scale (range 17 to 113) compared with placebo (high certainty evidence: paroxetine: MD -1.43, 95% CI -3.90, 1.04; vilazodone: MD -0.84, 95% CI -3.03, 1.35; desvenlafaxine MD -0.07, 95% CI -3.51, 3.36; moderate certainty evidence: sertraline: MD -3.51, 95% CI -6.99, -0.04; fluoxetine: MD -2.84, 95% CI -4.12, -1.56; escitalopram: MD -2.62, 95% CI -5.29, 0.04; low certainty evidence: duloxetine: MD -2.70, 95% CI -5.03, -0.37; vortioxetine: MD 0.60, 95% CI -2.52, 3.72; very low certainty evidence for comparisons between other antidepressants and placebo). There were "small and unimportant" differences between most antidepressants in reduction of depression symptoms (high- or moderate-certainty evidence). Results were similar across other outcomes of benefit. In most studies risk of self-harm or suicide was an exclusion criterion for the study. Proportions of suicide-related outcomes were low for most included studies and 95% confidence intervals were wide for all comparisons. The evidence is very uncertain about the effects of mirtazapine (OR 0.50, 95% CI 0.03, 8.04), duloxetine (OR 1.15, 95% CI 0.72, 1.82), vilazodone (OR 1.01, 95% CI 0.68, 1.48), desvenlafaxine (OR 0.94, 95% CI 0.59, 1.52), citalopram (OR 1.72, 95% CI 0.76, 3.87) or vortioxetine (OR 1.58, 95% CI 0.29, 8.60) on suicide-related outcomes compared with placebo. There is low certainty evidence that escitalopram may "at least slightly" reduce odds of suicide-related outcomes compared with placebo (OR 0.89, 95% CI 0.43, 1.84). There is low certainty evidence that fluoxetine (OR 1.27, 95% CI 0.87, 1.86), paroxetine (OR 1.81, 95% CI 0.85, 3.86), sertraline (OR 3.03, 95% CI 0.60, 15.22), and venlafaxine (OR 13.84, 95% CI 1.79, 106.90) may "at least slightly" increase odds of suicide-related outcomes compared with placebo. There is moderate certainty evidence that venlafaxine probably results in an "at least slightly" increased odds of suicide-related outcomes compared with desvenlafaxine (OR 0.07, 95% CI 0.01, 0.56) and escitalopram (OR 0.06, 95% CI 0.01, 0.56). There was very low certainty evidence regarding other comparisons between antidepressants. AUTHORS' CONCLUSIONS: Overall, methodological shortcomings of the randomised trials make it difficult to interpret the findings with regard to the efficacy and safety of newer antidepressant medications. Findings suggest that most newer antidepressants may reduce depression symptoms in a small and unimportant way compared with placebo. Furthermore, there are likely to be small and unimportant differences in the reduction of depression symptoms between the majority of antidepressants. However, our findings reflect the average effects of the antidepressants, and given depression is a heterogeneous condition, some individuals may experience a greater response. Guideline developers and others making recommendations might therefore consider whether a recommendation for the use of newer generation antidepressants is warranted for some individuals in some circumstances. Our findings suggest sertraline, escitalopram, duloxetine, as well as fluoxetine (which is currently the only treatment recommended for first-line prescribing) could be considered as a first option. Children and adolescents considered at risk of suicide were frequently excluded from trials, so that we cannot be confident about the effects of these medications for these individuals. If an antidepressant is being considered for an individual, this should be done in consultation with the child/adolescent and their family/caregivers and it remains critical to ensure close monitoring of treatment effects and suicide-related outcomes (combined suicidal ideation and suicide attempt) in those treated with newer generation antidepressants, given findings that some of these medications may be associated with greater odds of these events. Consideration of psychotherapy, particularly cognitive behavioural therapy, as per guideline recommendations, remains important.


Asunto(s)
Antidepresivos/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Adolescente , Antidepresivos/efectos adversos , Sesgo , Niño , Citalopram/uso terapéutico , Trastorno Depresivo Mayor/psicología , Succinato de Desvenlafaxina/uso terapéutico , Clorhidrato de Duloxetina/uso terapéutico , Femenino , Fluoxetina/uso terapéutico , Humanos , Masculino , Mirtazapina/uso terapéutico , Metaanálisis en Red , Paroxetina/uso terapéutico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Sertralina/uso terapéutico , Ideación Suicida , Clorhidrato de Venlafaxina/uso terapéutico , Clorhidrato de Vilazodona/uso terapéutico , Vortioxetina/uso terapéutico
4.
Cells ; 9(10)2020 10 09.
Artículo en Inglés | MEDLINE | ID: mdl-33050305

RESUMEN

Levodopa (L-DOPA) treatment in Parkinson's disease is limited by the emergence of L-DOPA-induced dyskinesia. Such dyskinesia is associated with aberrant gene regulation in neurons of the striatum, which is caused by abnormal dopamine release from serotonin terminals. Previous work showed that modulating the striatal serotonin innervation with selective serotonin reuptake inhibitors (SSRIs) or 5-HT1A receptor agonists could attenuate L-DOPA-induced dyskinesia. We investigated the effects of a novel serotonergic agent, vilazodone, which combines SSRI and 5-HT1A partial agonist properties, on L-DOPA-induced behavior and gene regulation in the striatum in an animal model of Parkinson's disease. After unilateral dopamine depletion by 6-hydroxydopamine (6-OHDA), rats received repeated L-DOPA treatment (5 mg/kg) alone or in combination with vilazodone (10 mg/kg) for 3 weeks. Gene regulation was then mapped throughout the striatum using in situ hybridization histochemistry. Vilazodone suppressed the development of L-DOPA-induced dyskinesia and turning behavior but did not interfere with the prokinetic effects of L-DOPA (forelimb stepping). L-DOPA treatment drastically increased the expression of dynorphin (direct pathway), 5-HT1B, and zif268 mRNA in the striatum ipsilateral to the lesion. These effects were inhibited by vilazodone. In contrast, vilazodone had no effect on enkephalin expression (indirect pathway) or on gene expression in the intact striatum. Thus, vilazodone inhibited L-DOPA-induced gene regulation selectively in the direct pathway of the dopamine-depleted striatum, molecular changes that are considered critical for L-DOPA-induced dyskinesia. These findings position vilazodone, an approved antidepressant, as a potential adjunct medication for the treatment of L-DOPA-induced motor side effects.


Asunto(s)
Discinesias/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Clorhidrato de Vilazodona/farmacología , Animales , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Cuerpo Estriado/patología , Modelos Animales de Enfermedad , Dopamina/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Levodopa/metabolismo , Levodopa/uso terapéutico , Masculino , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Enfermedad de Parkinson/genética , Ratas , Ratas Sprague-Dawley , Serotonina/metabolismo , Clorhidrato de Vilazodona/metabolismo , Clorhidrato de Vilazodona/uso terapéutico
5.
Indian J Pharmacol ; 52(2): 79-85, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32565594

RESUMEN

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.


Asunto(s)
Afecto/efectos de los fármacos , Amitriptilina/uso terapéutico , Antidepresivos/uso terapéutico , Citalopram/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Clorhidrato de Vilazodona/uso terapéutico , Adulto , Amitriptilina/efectos adversos , Antidepresivos/efectos adversos , Citalopram/efectos adversos , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/psicología , Femenino , Humanos , India , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento , Clorhidrato de Vilazodona/efectos adversos , Adulto Joven
6.
J Child Adolesc Psychopharmacol ; 30(6): 355-365, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32460523

RESUMEN

Objective: To evaluate the efficacy and long-term safety of vilazodone in children and adolescent outpatients with major depressive disorder (MDD). Methods: Children and adolescents aged 7-17 years of age with MDD were randomized 2:2:1 to 8 weeks of double-blind placebo, vilazodone 15 or 30 mg/day or fluoxetine 20 mg/day, respectively. The primary and secondary efficacy outcomes, respectively, were change from baseline to week 8 in Children's Depression Rating Scale-Revised (CDRS-R) score total score and Clinical Global Impressions-Severity (CGI-S) score analyzed using a mixed model for repeated measurement approach. Patients who completed the 8-week randomized controlled trial (RCT), as well as new (de novo) patients, could participate in a 26-week, vilazodone-only, open-label extension (OLE) study. Results: The RCT enrolled 473 patients (60% female) with an average age of 13 years. Change in CDRS-R and CGI-S scores from baseline to week 8 did not differ between patients who received vilazodone and those randomized to placebo. The least-squares mean change from baseline in CDRS-R scores was similar for vilazodone and placebo (-20.7 vs. -20.3, p = 0.77; least-squares mean difference [LSMD] = -0.40). For fluoxetine, the LSMD versus placebo was -2.3 (p = 0.14). The OLE enrolled 330 patients (60% female) with an average age of 13-14 years. Overall, no new safety concerns were identified compared to what is known in adults. Conclusions: Similar improvements in depressive symptoms were observed in all arms. This study does not support the efficacy of vilazodone 15 or 30 mg/day for pediatric patients with MDD. No new or unexpected safety concerns were detected during the RCT or OLE studies.


Asunto(s)
Trastorno Depresivo Mayor/tratamiento farmacológico , Fluoxetina/uso terapéutico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Clorhidrato de Vilazodona/uso terapéutico , Adolescente , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Masculino , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Resultado del Tratamiento
7.
Indian J Pharmacol ; 52(1): 10-15, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32201441

RESUMEN

BACKGROUND: Depressive disorders are considered to be one of the leading causes of morbidity and mortality accounting for 4.3% of total disability-adjusted life years. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors have greater efficacy and lesser side effects; at the same time, these drugs cause sexual dysfunction and weight gain. Vilazodone was supposed to have better efficacy and less sexual dysfunction and weight gain. AIM OF THE STUDY: The aim is to compare efficacy (in terms of Hamilton Depression Rating Scale [HDRS]), sexual dysfunction (in terms of Arizona Sexual Experience Scale [ASEX]), and weight gain caused due to vilazodone and sertraline. MATERIALS AND METHODS: This is a randomized controlled study; 60 patients diagnosed with depressive episode were divided into two groups of 30 each; using block randomization technique, one group was prescribed vilazodone and another sertraline. The groups were compared on the basis of efficacy, weight gain, and sexual dysfunction using HDRS and ASEX at baseline, 4-week, and 12-week intervals. Statistical analysis was done by applying Chi-square test, Fisher's exact test, t-test, and repeated measures ANOVA using Wilks' lambda test. RESULTS: On comparing both vilazodone and sertraline, it was observed that both molecules have equal efficacy in terms of HDRS, but vilazodone does not cause weight gain and sexual dysfunction in terms of ASEX, and these findings are statistically very highly significant. CONCLUSIONS: Our study shows that vilazodone has similar efficacy but can be a better antidepressant due to lesser weight gain and sexual dysfunction compared to sertraline.


Asunto(s)
Antidepresivos/uso terapéutico , Depresión/tratamiento farmacológico , Sertralina/uso terapéutico , Clorhidrato de Vilazodona/uso terapéutico , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Población Blanca
8.
Mol Cells ; 43(3): 222-227, 2020 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-32209735

RESUMEN

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.


Asunto(s)
Antidepresivos/uso terapéutico , Reposicionamiento de Medicamentos/métodos , Fosfotransferasas (Aceptor de Grupo Alcohol)/efectos de los fármacos , Clorhidrato de Vilazodona/uso terapéutico , Antidepresivos/farmacología , Humanos , Clorhidrato de Vilazodona/farmacología
10.
Expert Opin Pharmacother ; 20(3): 251-260, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30475091

RESUMEN

INTRODUCTION: Major Depressive Disorder (MDD) and General Anxiety Disorder (GAD) significantly contribute to the global burden of disease. Vilazodone, a combined serotonin reuptake inhibitor and 5-HT1A partial agonist, is an approved therapy for the treatment of MDD and which has been further investigated for GAD. Areas covered: This article covers the pharmacokinetics and pharmacodynamics of vilazodone and provides an evaluation of the clinical usefulness of vilazodone for the treatment of MDD and anxiety disorders. A literature search was performed using PubMed/MEDLINE, Web of Science and the Cochrane Library. Expert opinion: Studies have shown that vilazodone is significantly superior to placebo. However, vilazodone cannot as yet be recommended as a first-line treatment option for MDD as it is unclear whether the drug's dual mechanism of action provides greater efficacy than prevailing treatment options. Moreover, more phase IV studies are needed to establish its efficacy and long-term safety in larger and more diverse populations. Although vilazodone may have an additional advantage for the treatment of anxiety symptoms in MDD, here also additional studies are required to confirm its efficacy over and above SSRI alternatives and other antidepressant treatments. Therefore, presently, vilazodone should be considered as a second- or third-line treatment option for MDD and GAD.


Asunto(s)
Trastornos de Ansiedad/tratamiento farmacológico , Trastorno Depresivo Mayor/tratamiento farmacológico , Clorhidrato de Vilazodona/uso terapéutico , Animales , Antidepresivos/uso terapéutico , Humanos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico
11.
Mov Disord ; 33(11): 1740-1749, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30485908

RESUMEN

BACKGROUND: The serotonergic system is a well-established modulator of l-dopa-induced dyskinesia. To date, targeting serotonin transporters or serotonin receptor subtype 1A (5-HT1A ) reduces l-dopa-induced dyskinesia in animal models; however, these strategies have failed to translate clinically. Ideally, a compound acting at both known antidyskinetic sites could optimize serotonin-mediated approaches. Vilazodone is a selective serotonin reuptake inhibitor and a partial 5-HT1A agonist approved by the U.S. Food and Drug Administration, situating Vilazodone in a unique position to reduce l-dopa-induced dyskinesia without compromising l-dopa-mediated motor improvements. OBJECTIVES: The goal of the present study was to characterize Vilazodone's effects on l-dopa-induced behaviors, neurochemistry and gene expression in unilateral 6-hydroxydopamine-lesioned hemi-parkinsonian rats. METHODS: In experiments 1 and 2, l-dopa-naïve and l-dopa-primed animals were coadministered Vilazodone and l-dopa daily for 3 weeks to model subchronic use, and behavioral, neurochemical, and messenger RNA (mRNA) expression changes were measured. In experiment 3, dyskinetic behavior was assessed following 5-HT1A or serotonin receptor subtype 1B blockade prior to Vilazodone-l-dopa coadministration. RESULTS: Vilazodone significantly suppressed developing and established l-dopa-induced dyskinesia without compromising the promotor effects of l-dopa therapy. In the dopamine-depleted striatum, Vilazodone-l-dopa cotreatment increased dopamine content, suggesting a normalization of dopamine kinetics in dyskinetic brain, and reduced l-dopa-induced c-Fos and preprodynorphin mRNA overexpression, indicative of attenuated dopamine D1 receptor-mediated direct pathway overactivity. Only 5-HT1A antagonism partially attenuated Vilazodone's antidyskinetic efficacy, suggesting both serotonin transporter-dependent effects and 5-HT1A receptors in Vilazodone's actions. CONCLUSIONS: Our findings show Vilazodone has a serotonin-dependent effect on rodent l-dopa-induced dyskinesia and implicate the potential for repositioning Vilazodone against l-dopa-induced dyskinesia development and expression in Parkinson's disease patients. © 2018 International Parkinson and Movement Disorder Society.


Asunto(s)
Antiparkinsonianos/efectos adversos , Discinesia Inducida por Medicamentos/tratamiento farmacológico , Discinesia Inducida por Medicamentos/etiología , Levodopa/efectos adversos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Clorhidrato de Vilazodona/uso terapéutico , Animales , Modelos Animales de Enfermedad , Dinorfinas/genética , Dinorfinas/metabolismo , Encefalinas/genética , Encefalinas/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Oxidopamina/toxicidad , Trastornos Parkinsonianos/inducido químicamente , Trastornos Parkinsonianos/tratamiento farmacológico , Piperazinas/farmacología , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , Proteínas Proto-Oncogénicas c-fos/genética , Proteínas Proto-Oncogénicas c-fos/metabolismo , Piridinas/farmacología , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores de Serotonina/genética , Receptores de Serotonina/metabolismo , Serotonina/metabolismo , Antagonistas de la Serotonina/farmacología , Factores de Tiempo
12.
Int Clin Psychopharmacol ; 33(6): 304-311, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30044247

RESUMEN

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.


Asunto(s)
Trastorno Depresivo Mayor/tratamiento farmacológico , Prevención Secundaria/métodos , Clorhidrato de Vilazodona/uso terapéutico , Adulto , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Factores de Tiempo , Resultado del Tratamiento , Clorhidrato de Vilazodona/efectos adversos
13.
BMJ Evid Based Med ; 23(5): 177-182, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29950314

RESUMEN

The validity of clinical trial results is influenced by researchers' decisions regarding the management of missing data. Inadequate management of missing data has been identified as a significant source of bias that can result in an overestimation of drug efficacy. Transparency related to the management of missing data is essential to assess the strength of evidence reported in publications. In a subset of 17 randomised clinical trials for two new antidepressant medications, we present a case study in which we examined investigators' decisions regarding how to handle missing data and if their chosen method took into account, possible violations of analytic requirements that could affect results. The majority of trials (76%) concluded that there was a benefit of antidepressant treatment and in 94% the methodology for handling missing data was identifiable. Of these, 50% imputed data using the last observation carried forward and half used a mixed-effects model repeated measure approach. Most reports did not provide a rationale for the method used, and no trials described analyses regarding differences between completers and dropouts. Sensitivity analysis was inconsistently reported and correction for multiple comparisons was not uniformly applied. Lack of transparency for analytic choices related to handling of missing data testing was common in this subset of RCTs. Because management of missing data can directly influence the quality of study results, it is critical that journal editors develop and enforce standards for methodological transparency.


Asunto(s)
Antidepresivos/uso terapéutico , Interpretación Estadística de Datos , Sesgo , Trastorno Depresivo Mayor/tratamiento farmacológico , Humanos , Análisis de Intención de Tratar/estadística & datos numéricos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto/normas , Resultado del Tratamiento , Clorhidrato de Vilazodona/uso terapéutico , Vortioxetina/uso terapéutico
14.
Int Clin Psychopharmacol ; 33(4): 217-223, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29608461

RESUMEN

The efficacy of antidepressants to treat major depressive disorder (MDD) varies by patient characteristics. This post-hoc analysis evaluated the effects of vilazodone across patient subgroups in adults with MDD. Data were pooled from four trials of vilazodone (NCT00285376, NCT00683592, NCT01473394, and NCT01473381). Mean change from baseline to week 8 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score, MADRS response (≥50% total score improvement), and MADRS remission (total score≤10) were analyzed in the pooled intent-to-treat population (vilazodone=1254, placebo=964) and in subgroups of patients categorized by sex, age, MDD duration, recurrent episodes, baseline MADRS total score, and current episode duration. MADRS total score improvement was significantly greater with vilazodone versus placebo in the intent-to-treat population and in all patient subgroups (P<0.001). MADRS response and remission rates significantly separated from placebo (P<0.05) regardless of age, sex, MDD duration, recurrent MDD, and baseline symptom severity [except remission in patients with very severe baseline symptoms (MADRS score≥35)] and in patients with a shorter current episode duration (≤12 months). Despite the limitations associated with analyzing uncommon outcomes (e.g. MADRS remission) in small subgroups, vilazodone was an effective treatment in multiple patient populations, including those where reduced efficacy has previously been reported: males, older individuals, patients with a longer duration of MDD, and patients with recurrent depression.


Asunto(s)
Antidepresivos/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Clorhidrato de Vilazodona/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/psicología , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuestionario de Salud del Paciente , Escalas de Valoración Psiquiátrica , Resultado del Tratamiento , Adulto Joven
15.
Paediatr Drugs ; 20(4): 353-363, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29633166

RESUMEN

BACKGROUND: Major depressive disorder (MDD) is a serious illness in children and adolescents. Vilazodone is a selective serotonin reuptake inhibitor approved for MDD in adults. This study evaluated the efficacy, safety, and tolerability of vilazodone in adolescent patients, ages 12-17 years, with MDD (NCT01878292). METHODS: This double-blind, randomized, placebo-controlled, parallel-group, fixed-dose study was conducted at 56 study centers in the United States and was 10 weeks in duration (a 1-week screening period, an 8-week double-blind treatment period, and a 1-week double-blind down-taper period). Outpatients with an MDD diagnosis based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria were included in the study. Clinical inclusion criteria required a Children's Depression Rating Scale-Revised (CDRS-R) total score of ≥ 40 and Clinical Global Impressions-Severity (CGI-S) score of ≥ 4. Patients were randomized 1:1:1 to 8 weeks of double-blind treatment with placebo (n = 174), vilazodone 15 mg/day (n = 175), or vilazodone 30 mg/day (n = 180). The primary and secondary efficacy parameters were change from baseline to week 8 in CDRS-R total score and CGI-S score, respectively. Safety parameters included adverse events (AEs); clinical laboratory, vital sign, and electrocardiogram parameters; and the Columbia-Suicide Severity Rating Scale. RESULTS: Approximately 86% of patients completed double-blind treatment. There was no statistically significant difference between vilazodone 15 mg/day or 30 mg/day and placebo in change from baseline in CDRS-R score. Change in CGI-S score was not significant after adjustment for multiple comparisons. The most common treatment-emergent AEs were nausea, upper abdominal pain, vomiting, diarrhea, nasopharyngitis, headache, and dizziness. Reports of suicidal ideation (placebo, 33.3%; vilazodone 15 mg/day, 36.0%; vilazodone 30 mg/day, 31.1%) and suicidal behavior (placebo, 1.8%; vilazodone 15 mg/day, 1.1%; vilazodone 30 mg/day, 1.1%) were similar between treatment groups. There were no deaths in the study. CONCLUSIONS: The efficacy of vilazodone for the treatment of MDD in adolescent patients could not be confirmed in this study. Vilazodone was generally safe and well tolerated, with treatment-emergent AEs similar to those in adult patients. CLINICAL TRIAL REGISTRATION: NCT01878292.


Asunto(s)
Antidepresivos/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Clorhidrato de Vilazodona/uso terapéutico , Adolescente , Niño , Método Doble Ciego , Femenino , Humanos , Masculino , Resultado del Tratamiento
16.
J Affect Disord ; 228: 1-12, 2018 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-29197738

RESUMEN

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.


Asunto(s)
Antidepresivos de Segunda Generación/uso terapéutico , Ciclopropanos/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Piperazinas/uso terapéutico , Sulfuros/uso terapéutico , Clorhidrato de Vilazodona/uso terapéutico , Adulto , Antidepresivos de Segunda Generación/efectos adversos , Ciclopropanos/efectos adversos , Humanos , Milnaciprán , Metaanálisis en Red , Piperazinas/efectos adversos , Sulfuros/efectos adversos , Clorhidrato de Vilazodona/efectos adversos , Vortioxetina
17.
Artículo en Inglés | MEDLINE | ID: mdl-28858440

RESUMEN

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.


Asunto(s)
Trastorno Depresivo/complicaciones , Trastorno Depresivo/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Trastornos por Estrés Postraumático/complicaciones , Trastornos por Estrés Postraumático/tratamiento farmacológico , Clorhidrato de Vilazodona/uso terapéutico , Adulto , Antidepresivos/efectos adversos , Antidepresivos/uso terapéutico , Comorbilidad , Método Doble Ciego , Femenino , Humanos , Masculino , Escalas de Valoración Psiquiátrica , Autoinforme , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Resultado del Tratamiento , Clorhidrato de Vilazodona/efectos adversos
18.
Int Clin Psychopharmacol ; 32(5): 281-288, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28538024

RESUMEN

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.


Asunto(s)
Trastornos de Ansiedad/psicología , Trastorno Depresivo Mayor/psicología , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Ideación Suicida , Intento de Suicidio , Clorhidrato de Vilazodona/efectos adversos , Adulto , Trastornos de Ansiedad/tratamiento farmacológico , Trastorno Depresivo Mayor/tratamiento farmacológico , Método Doble Ciego , Femenino , Humanos , Masculino , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Clorhidrato de Vilazodona/uso terapéutico , Adulto Joven
19.
Asian J Psychiatr ; 26: 115-122, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28483071

RESUMEN

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.


Asunto(s)
Ansiolíticos/uso terapéutico , Trastornos de Ansiedad/tratamiento farmacológico , Clorhidrato de Vilazodona/uso terapéutico , Ansiolíticos/efectos adversos , Humanos , Resultado del Tratamiento , Clorhidrato de Vilazodona/efectos adversos
20.
Pharmacopsychiatry ; 50(6): 256-263, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28444658

RESUMEN

Vilazodone is a novel antidepressant agent that combines selective serotonin (5-HT) reuptake inhibitor (SSRI) activity and 5-HT(1A) receptor partial agonist activity. A pilot study was conducted to compare vilazodone (novel compound) and paroxetine (gold standard) on antidepressant effects, tolerability, and inflammation and immune modulation. A 12-week, double-blind, randomized clinical trial was conducted with 56 nondemented older adults diagnosed with major depressive disorder (MDD). Between-group differences in mood, tolerability, and safety, as well as genomic markers of inflammation and immune modulation, were examined. Both treatment groups demonstrated similar improvement in depressed mood. Leukocyte gene expression profiles demonstrated reduction of specific proinflammatory gene transcripts and bioinformatic indications of reduced nuclear factor kappa B (NF-κB), activator protein (AP)-1, and cAMP response element binding (CREB) activity in the vilazodone group compared to the paroxetine group. Transcript origin analyses implicated monocytes and dendritic cells as the primary cellular origins of transcript reductions in the vilazodone-treated group. Vilazodone's antidepressant effects may be associated with reduction of proinflammatory gene expression and immune modulation. Further research is required.


Asunto(s)
Antidepresivos/uso terapéutico , Citocinas/metabolismo , Trastorno Depresivo Mayor/tratamiento farmacológico , Paroxetina/uso terapéutico , Factor de Transcripción AP-1/metabolismo , Clorhidrato de Vilazodona/uso terapéutico , Anciano , Anciano de 80 o más Años , Antidepresivos/farmacología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Citocinas/genética , Método Doble Ciego , Femenino , Estudios de Seguimiento , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Evaluación de Resultado en la Atención de Salud , Paroxetina/farmacología , Cooperación del Paciente , Proyectos Piloto , Escalas de Valoración Psiquiátrica , Factor de Transcripción AP-1/genética , Clorhidrato de Vilazodona/farmacología
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