CNS neuroscience & therapeutics
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Randomized Controlled Trial Multicenter Study
A multicenter, placebo-controlled, double-blind, randomized study of efficacy and safety of ocinaplon (DOV 273,547) in generalized anxiety disorder.
Preclinical studies demonstrated that ocinaplon, a positive allosteric modulator of GABA(A) receptors, possesses anxiolytic-like actions at doses devoid of the side effects typically associated with benzodiazepines. The aim of this study was to evaluate the effects of ocinaplon in a multicenter, double-blind proof-of-concept trial of male and female outpatients who met DSM-IV criteria for GAD with no coexisting depression, and had a baseline score of > or =20 on the Hamilton Scale for Anxiety (HAM-A). Patients with <20% reduction in HAM-A to placebo in a single-blind 7-day run-in period were randomly assigned to treatment with ocinaplon 90 mg t.i.d. (n = 31) or placebo for 28 days (n = 29). ⋯ The overall safety profile revealed no patterns of TEAEs, including those effects typically associated with other anxiolytic and/or benzodiazepine compounds, such as sedation. Ocinaplon appears to be a well-tolerated and effective treatment for GAD. It produces a rapid onset of anxiolytic action absent the side effects (e.g., dizziness, sedation) typically reported following anxiolytic doses of benzodiazepines.
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The association between migraine and psychiatric disorders has been reported in both clinical and epidemiological studies. The prevalence of psychiatric disorders has been found to be increased among individuals with migraine. Studies assessing migraine in psychiatric patients are limited and the majority of these studies have focused solely on examining patients with major depression. ⋯ This study suggests that there is an increased prevalence of migraine headaches among anxiety disorder patients as compared to the general population. Migraine comorbidity may have important clinical implications, such that the treatment of one condition could potentially ameliorate the development or progression of the other. Further research is required to better understand the nature and implications of the association between migraine and psychiatric disorders.
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Comparative Study
Gender and anxiety in Nepal: the role of social support, stressful life events, and structural violence.
Throughout the world, anxiety disorders are 1.5-2 times more prevalent among women than men but the reasons for this gender disparity remain elusive. Despite frequent attribution to cultural roles of men and women, data regarding gendered risk factors in non-Western settings are scant. ⋯ Women are at a greater risk of anxiety in Nepal. Social support moderates the risk of anxiety among men but not among women. Ethnography and mixed-methods research are needed to identify other forms of support that may be protective for women and such factors should be promoted in gender-focused mental health interventions.
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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. ⋯ 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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Searching brain and peripheral biomarkers is a requisite to cure Huntington's disease (HD). To search for markers indicating the rate of brain neurodegenerative changes in the various disease stages, we quantified changes in brain atrophy in subjects with HD. We analyzed the cross-sectional and longitudinal rate of brain atrophy, quantitatively measured by fully-automated multiparametric magnetic resonance imaging, as fractional gray matter (GM, determining brain cortex volume), white matter (WM, measuring the volume of axonal fibers), and corresponding cerebral spinal fluid (CSF, a measure of global brain atrophy), in 94 gene-positive subjects with presymptomatic to advanced HD, and age-matched healthy controls. ⋯ Finally, the CSF volume increase began many years before age at onset. Its volume measured in presymptomatic subjects contributed to improve the CAG-based model of age at onset prediction. The progressive CSF increase depended on CAG mutation size and continued linearly until the last stages of HD, perhaps representing the best marker of progression rate and severity in HD (R(2)= 0.25, P < 0.0001).