Evaluation of vilazodone for the treatment of depressive and anxiety disorders

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.     

Atención recibida al final de la vida en los servicios de urgencias desde la perspectiva de los cuidadores: estudio cualitativo

Objective

To discover the experiences of end-of-life patients attended by the emergency services, through the discourse of the family caregivers who accompanied the family member in this care transit.

Mourning Bit by Bit

In this piece I describe the process of mourning my mother since her death in 2001, via my short animated documentary ‘Oneironauts – the Dream Travellers’ (2011) and my more recent experiences as the mother of a young baby. I consider my experience in the context of Freud's ‘Mourning and Melancholia’.     

Local demineralization as a model for bone strength reductions in lytic transcortical metastatic lesions.

The structural consequences of bone density changes associated with lytic metastatic lesions were investigated using an experimental model of regular, lytic metastatic lesions in bone. Circular holes were drilled in the mid-diaphyseal cortex of paired adult canine femora. The region around the defect was demineralized in one bone of each pair with 0.8 N HCl. Specimens were tested to failure in four-point bending. Defect size was determined from conventional planar radiographs as the maximum apparent defect diameter divided by the periosteal diameter. Demineralization resulted in irregular defect geometries, which increased the maximum defect dimension 33% to 57% with respect to the original drill hole diameter. Demineralization resulted in additional strength reductions beyond those expected from the original drill hole alone. Despite the irregular demineralization patterns observed, strength reductions were in close agreement with those predicted from data for regular, nondemineralized holes (r2 = 0.93). The results demonstrate that irregular diaphyseal defect borders may not require more complex fracture risk predictors than can be determined from analytic and experimental studies of regular defect geometries. Our results also demonstrate that errors of over 100% can occur when measuring diaphyseal defect size from radiographs that are not optimally aligned with respect to the defect.     

Gated myocardial perfusion single photon emission computed tomography in the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial, Veterans Administration Cooperative study no. 424

Background  Stress gated myocardial perfusion single photon emission computed tomography (gSPECT) is increasingly used before and after intercurrent therapeutic intervention and is the basis for ongoing evaluation in the Department of Veterans Affairs clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial. Methods and Results  The COURAGE trial is a North American multicenter randomized clinical trial that enrolled 2287 patients to aggressive medical therapy vs percutaneous coronary intervention plus aggressive medical therapy. Three COURAGE nuclear substudies have been designed. The goals of substudy 0 are to examine the diagnostic accuracy of the extent and severity of inducible ischemia at baseline in COURAGE patients compared with patient symptoms and quantitative coronary angiography and to explore the relationship between inducible ischemia and the benefit from revascularization when added to medical therapy. Substudy 1 will correlate the extent and severity of provocative ischemia with the frequency, quality, and instability of recurrent symptoms in postcatheterization patients. Substudy 2 (n _ 300) will examine the usefulness of sequential gSPECT monitoring 6 to 18 months after therapeutic intervention. Together, these nuclear substudies will evaluate the role of gSPECT to determine the effectiveness of aggressive risk-factor modifications, lifestyle interventions, and anti-ischemic medical therapies with or without revascularization in reducing patients’ ischemic burdens. Conclusions  The unfolding of evidence on the application of gSPECT in trials such as COURAGE defines a new era for nuclear cardiology. We hope the evidence that emerges from the COURAGE trial will further establish the role of nuclear imaging in the evidence-based management of patients with stable coronary disease. The COURAGE trial was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development in collaboration with the Canadian Institutes of Health Research. Unrestricted research grants were obtained from Merck & Co; Pfizer Pharmaceuticals; Bristol-Myers Squibb Medical Imaging; Astellas Pharma; Kos Pharmaceuticals; Data Scope; Astra Zeneca Pharmaceuticals; Astra-Zeneca-Canada; Schering-Plough Coorporation, Ltd; Sanofi-Aventis, Inc; First Horizon; and GE Healthcare. All industrial funding for this trial was directed through the Department of Veterans Affairs. Additional funding for this substudy was provided by grants to the Department of Veterans Affairs and Canadian Institutes of Health Research from Astellas Pharma and Bristol-Myers-Squibb Medical Imaging.     

Early results of immediate repair of obstetric third-degree tears: 65% are completely asymptomatic despite persistent sphincter defects in 61%

OBJECTIVE: The outcome of immediate repair of obstetric third-degree tears is poorly documented. Immediate repair may give better functional results than delayed repair because scarring is reduced. This aim of this prospective study was to examine the early outcome of immediate repair of third-degree tears. METHOD: A total of 121 women who had immediate repair of obstetric third-degree tears underwent interview, anal ultrasonography and anorectal physiology. RESULTS: At review, 79 (65%) were completely asymptomatic (score = 0), 23 (19%), had minor flatus incontinence or mild urgency causing no compromise to their quality of life (score 1-4), and 19 (16%) had clinically embarrassing faecal incontinence (score 5-24). Thirty-nine (32%) had an intact internal anal sphincter (IAS) and external anal sphincter (EAS) (i.e. a successful repair), eight (7%) had a defect in the IAS alone but the EAS was intact (i.e. a successful repair but a residual IAS defect), 43 (35%) had a residual defect in the EAS alone (IAS intact) and 31 (26%) had a persistent defect in the IAS and EAS. Residual defects in either or both of the sphincters were associated with a significantly higher incidence of abnormal resting and squeeze anal pressures. Anal manometry had no correlation with symptoms. The highest proportion of severe incontinence was in those with an IAS defect alone (37%) and when there was a residual IAS and EAS defect (24%). Only 2 of 39 (5%) with an intact IAS and EAS had severe incontinence and only 8 of 43 (18%) with a residual EAS defect alone had severe faecal incontinence. CONCLUSION: These results indicate a good outcome following immediate repair of third-degree obstetric tears and emphasize the role of the IAS in providing continence.