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’.     

Sustainability of pyrethroid-impregnated bednets for malaria control in Afghan communities.

Between 1992 and 1995 a series of studies was undertaken to assess the long-term suitability of pyrethroid-impregnated bednets (PIBs) for malaria control in Afghan refugee communities in two villages in North-West Frontier Province, Pakistan. During 1992, 86% of bednet owners volunteered to have their bednets re-impregnated, and a further 15% of families purchased nets at two-thirds of cost price. From 1992 onwards, 27% of the villagers returned to Afghanistan, and annual house spraying campaigns were introduced to protect those still resident but sleeping without bednets. Within 3 years, these campaigns, together with PIBs, reduced the annual incidence of malaria by 87%, from 597 to 78 cases per 1000 population. Nevertheless, 65% of resident families continued to re-impregnate their nets annually with permethrin. To assess whether PIBs were still being used and were still protective, in view of these reduced transmission rates, we carried out a case--control study in 1994 on febrile or otherwise symptomatic patients presenting at village health centres. Comparison of the slide-positivity rates of PIB users and those without bednets showed that regular usage reduced the odds of contracting falciparum and vivax malaria to 0.22 (95% confidence interval (CI): 0.09-0.55) and 0.31 (95% CI: 0.19-0.51), respectively. There was no evidence of a sex- or age-bias in bednet use or in protective effect. The results indicate that a community-based PIB programme is an appropriate malaria control measure in areas where management or security problems make traditional house-spraying campaigns impossible. A relevant finding for those involved in the monitoring of bednet distribution projects is that the local coverage of bednets and the local impact on malaria, even when introduced to remote areas, can be estimated very cheaply by health centre microscopists who simply catalogue blood film diagnoses according to patients'' bednet use practices.     

Chlormethiazole, dizocilpine and haloperidol prevent the degeneration of serotonergic nerve terminals induced by administration of MDMA (‘Ecstasy’) to rats

An investigation has been made into the effect of 3,4-methylenedioxymethamphetamine (MDMA or ‘Ecstasy’) administration on the concentration of 5-hydroxytryptamine (5-HT), uptake of [³H]5-HT and [³H]paroxetine binding in rat cerebral cortex tissue. Four days after 2 injections of MDMA (20 mg/kg i.p., 6 hr apart) the concentrations of 5-HT and its metabolite 5-HIAA were reduced by 60%. The binding of [³H]paroxetine to the presynaptic 5-HT transporter was decreased and high affinity uptake of [³H]5-HT was reduced by a similar amount, indicating neurodegeneration of 5-HT terminals. Pretreatment with chlormethiazole (100 mg/kg i.p.), 10 min before each MDMA injection prevented the decrease in both [³H]parotextine binding and uptake of [³H]5-HT. The loss in 5-HT and 5-HIAA content was also attenuated. Pretreatment with dizocilpine (1 mg/kg i.p.) or haloperidol (2 mg/kg i.p.) also prevented the MDMA-induced loss of [³H]paroxetine binding and attenuated the loss of 5-HT and 5-HIAA content. All three compounds also decreased the degree of hyperthermia that follows MDMA administration, although previous studies suggest that the long term neurodegeneration is not associated with the acute hyperthermic response. These data support the findings of others that MDMA injection produces degeneration of 5-HT nerve terminals in the cortex, confirm that chlormethiazole, dizocilpine and haloperidol attenuate MDMA-induced neurotoxic loss of 5-HT and demonstrate for the first time that these compounds prevent the neurodegeneration of 5-HT nerve terminals that follows MDMA administration.     

Partial tolerance in rat renal allograft recipients following multiple blood transfusions and concomitant cyclosporine

Multiple prior administrations of donor-strain blood while under limited cyclosporine cover, consistently induce extensive rat renal allograft survival and transplantation tolerance. Yet it was hypothesized that some chronic rejection mechanisms were nevertheless operative since consistent but nonprogressive minor renal dysfunction was observed long-term. A histopathologic study on these putative tolerant rats was undertaken to test this hypothesis. Twenty long-term LEW recipients of BN renal allografts receiving the blood-CsA regimen were examined histopathologically at day 100 post-transplant. Sixteen control LEW recipients receiving only a BN renal allograft were studied acutely at day 7 posttransplant. The control recipients demonstrated a range of lesions consistent with previous studies on acute renal allograft rejection in the rat. However, tolerant recipients demonstrated mild-to-moderate lesions consistent with chronic mechanisms of rejection including the following: moderate focal interstitial mononuclear inflammatory cellular infiltration, with periglomerular and perivascular accumulation; occasional arteriolar luminal obliteration and glomerular atrophy; focal areas of moderate interstitial fibrosis; mild interstitial hemorrhage; mild-to-moderate tubular atrophy; and focal tubular necrosis. Previously our laboratory has documented that tissue-specific renal basement membrane antigens may be responsible for inciting this pattern of focal chronic interstitial inflammation. However, from the present histopathologic studies, it would appear likely that chronic rejection mechanisms in these recipients, which were defined as tolerant by immunologic criteria, involve both tissue-specific and MHC determinants. Therefore, induction of transplantation tolerance in these indefinite survivors is partial or incomplete.