A double-blind switch study of paroxetine and venlafaxine in obsessive-compulsive disorder

BACKGROUND: The treatment guidelines for obsessive-compulsive disorder (OCD) propose to switch serotonin reuptake inhibitors (SRIs) in case of refractoriness. However, no controlled research has been published yet that prospectively examined the effects of changing SRIs. This article describes the first double-blind switch study of 2 SRIs in patients with OCD. METHOD: 150 patients with primary OCD, according to DSM-IV criteria, were randomly assigned in a 12-week, double-blind trial to receive dosages titrated upward to 300 mg/day of venlafaxine (N = 75) or 60 mg/day of paroxetine (N = 75). Primary efficacy was assessed by the change from baseline on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and nonresponse was defined as less than 25% reduction on the Y-BOCS. After a 4-week tapering phase, 43 nonresponders were switched to 12 additional weeks of the alternate antidepressant, of which 16 patients received venlafaxine and 27 received paroxetine. RESULTS: Eighteen of 43 patients benefited from a switch to the alternate SRI with a mean +/- SD decrease of at least 25% on the Y-BOCS. At the end of 12 weeks, responder rates were 56% for paroxetine (15/27) and 19% for venlafaxine (3/16). An intent-to-treat, last-observation-carried-forward analysis demonstrated a mean decrease on the Y-BOCS of 1.8 +/- 3.5 in the venlafaxine group and 6.5 +/- 7.1 in the paroxetine group. After 2 consecutive SRI trials, 109 of 150 patients (73%) achieved a Y-BOCS decrease of at least 25%. CONCLUSION: The results of the current study show that 42% of the nonresponders benefited from a crossover to the other SRI, and that paroxetine was more efficacious than venlafaxine in the treatment of nonresponders to a previous SRI trial. Switching SRIs in case of refractoriness may be considered a useful strategy for patients with OCD.     

Platelets in patients with acute ischemic stroke are exhausted and refractory to thrombin, due to cleavage of the seven-transmembrane thrombin receptor (PAR-1)

Platelet activation is involved in the pathogenesis of cerebrovascular ischemia, but the major agonist involved has yet to be identified. To investigate the role of thrombin in platelet activation in patients with acute ischemic stroke, and while thrombin is the most likely candidate for activation of the thrombin receptor PAR-1 in vivo, we assessed its cleavage and internalization using the antibodies SPAN12, binding to uncleaved PAR-1, and WEDE15, recognizing cleaved and uncleaved, but not internalized PAR-1. In contrast to healthy age-matched controls, platelets from stroke patients exhibited significant cleavage and internalization of PAR-1 (P<0.001) and failed to respond to thrombin in vitro. Enhanced surface expression of CD62P, CD63, TSP-1 and less mepacrine uptake showed platelet degranulation during stroke. Platelets from patients with acute cerebral ischemia are exhausted and desensitized to thrombin through cleavage of PAR-1, indicating that high concentrations of thrombin occur with acute cerebrovascular ischemic events in vivo.     

Image quality of the temporal bone window examined by transcranial Doppler sonography and correlation with postmortem computed tomography measurements

BACKGROUND AND PURPOSE: The major limitation of native transcranial colour-coded duplex sonography (TCCS) in older stroke patients is the relatively frequent occurrence of an insufficient temporal window. Our goal was to investigate the relationship between the in vivo Doppler ultrasound image quality of the temporal bone, and computed tomography (CT)-determined thickness, density, and homogeneity of cadaver temporal bone. METHODS: Thirty-three moribund neurological patients who eventually died were examined by TCCS using the transtemporal approach. The sonographer categorized the quality of the TCCS image (excellent, intermediate, and poor). During autopsy, a rectangular sample of the temporal squama was removed, which corresponded to the area of the in vivo acoustic window. The thickness of the whole temporal bone, cortical, and cancellous (= diploe) bone as well as the density and homogeneity were determined by high-resolution CT. RESULTS: Thirty-seven temporal bones were obtained. The quality of the acoustic window was classified as excellent in 13, intermediate in 6 and poor in 18 cases. A significant correlation between the complete bone thickness, as well as between the absolute thickness of the diploe and the quality of the acoustic window was found: the thinner the bone/diploe, the better the colour Doppler signal. The thickness of the cortical plates and the homogeneity of the bones were identical in the three image quality categories. CONCLUSION: The transtemporal TCCS image quality depends mainly on the thickness of the cancellous component of the temporal bone.     

The effect of nitrostyrene on cell proliferation and macrophage immune responses

The use of mood enhancing drugs such as amphetamine and ecstasy are now prevalent in society. These compounds are known to produce serious psychological and physiological problems in users, which can, in some circumstances result in death. While there has been much research into the effects of these drugs on the body, little if any research has investigated the effect of the side products and synthetic reaction by-products which are a consequence of there illegal production. In the study the effects of nitrostyrene, a reaction by-product in one of the routes to synthesis of amphetamine sulphate, on cell viability and macrophage function was determined. Treatment with nitrostyrene at doses >0.75 microg/mL had a significant suppressive effect on the proliferation of stomach cancer lines. Treatment of macrophages with doses as high as 10 microg/mL did not effect cell viability. Nitrostyrene treatment of macrophages, stimulated with IFN gamma and LPS, resulted in a dose dependent differential inhibition in IL12, IL6 and nitrite production, even using doses < 0.5 microg/mL. Thus ranking of the three, on the basis of the suppressive effect obtained, is IL12 > nitrite > IL6. Thus ingestion of nitrostyrene contaminated ecstasy is likely to have a adverse effect on the immune responses of the recreational user.     

A double blind comparison of venlafaxine and paroxetine in obsessive-compulsive disorder

SUMMARY: While the usefulness of clomipramine and selective serotonin reuptake inhibitors (SSRIs) in obsessive-compulsive disorder (OCD) has been established, the efficacy of serotonin-norepinephrine reuptake inhibitors remains to be determined. This report describes the first randomized double-blind comparison study of an SNRI in patients with obsessive-compulsive disorder. The current study compares the efficacy and tolerability of venlafaxine with paroxetine. One hundred and fifty patients with primary OCD according to DSM-IV criteria were randomly assigned in a 12-week double-blind trial to receive dosages titrated upward to 300 mg/d of venlafaxine (n = 75) or 60 mg/d of paroxetine (n = 75). Primary efficacy was assessed by the change from baseline on the Yale-Brown obsessive-compulsive scale (Y-BOCS). Other assessments throughout the trial included the Hamilton depression rating scale, and the Hamilton anxiety rating scale. An intent-to-treat, last-observation-carried-forward analysis demonstrated a mean decrease on the Y-BOCS of 7.2 +/- 7.5 in the venlafaxine group and of 7.8 +/- 5.4 in the paroxetine group. In both treatment groups, a responder rate (decrease > 35% on the Y-BOCS) of approximately 40% was found. There were no significant differences between venlafaxine and paroxetine with regard to response or responder rates. The incidence of adverse events for venlafaxine and paroxetine was comparable. The most common side effects for venlafaxine were somnolence, insomnia, a dry mouth, and sweating; and for paroxetine somnolence, sweating, nausea, and headache. These results show that venlafaxine was equally effective to paroxetine in treating patients with OCD. Venlafaxine may be a useful therapy for obsessive-compulsive patients, but is not superior to SSRIs.     

Influence of regular voluntary exercise on spontaneous and social stress-affected sleep in mice

To investigate the impact of regular physical exercise on sleep, we assessed sleep-wake behaviour in male C57BL/6N mice with and without long-term access (i.e. 4 weeks) to a running wheel. We studied sleep-wake behaviour during undisturbed conditions as well as after social stress. The exercising mice ran approximately 4 km/day, which affected their physical constitution, their spontaneous sleep-wake pattern and their endocrine and sleep responses to stress. When compared with the control mice, exercising animals had more muscle substance, less body fat and heavier adrenal glands. At baseline, exercising mice showed fewer, but longer-lasting, sleep episodes (indicating improved sleep consolidation) and less rapid-eye-movement sleep. In both control and exercising mice, mild social stress (elicited by a 15-min social conflict) evoked elevated plasma levels of adrenocorticotrophic hormone and corticosterone, an increase in non-rapid-eye-movement sleep, an enhancement of low-frequency activity in the electroencephalogram within non-rapid-eye-movement sleep (indicating increased sleep intensity) and a decrease in wakefulness. However, as compared with the control animals, exercising mice responded to social stress with higher corticosterone levels, but not adrenocorticotrophic hormone levels, suggesting an increased sensitivity of their adrenal glands to adrenocorticotrophic hormone. Moreover, in control mice, social stress increased rapid-eye-movement sleep in parallel to non-rapid-eye-movement sleep, whereas this stressor selectively decreased rapid-eye-movement sleep in exercising animals. Corticosterone is known to decrease rapid-eye-movement sleep. Therefore, changes in the regulation of the hypothalamic-pituitary-adrenocortical axis as a result of the long-term exercise may contribute to the observed differences in spontaneous and social stress-affected sleep. In conclusion, regular exercise appears to increase sleep quality and reverses the effects of mild social stress on rapid-eye-movement sleep.     

Absence of circulating microemboli in patients with atrial fibrillation undergoing electric cardioversion

Electrical cardioversion (CV) of atrial fibrillation (AF) is associated with an increased risk of stroke, and its appropriate prevention is still a matter of debate. It is known that, besides dislodgement of pre-existing intra-atrial thrombi, the "stunned" atrium after CV is an important cause of thrombus formation and subsequent embolism. We investigated whether CV of AF is associated with occurrence of circulating microemboli (ME) representing a sensitive marker of the actual thromboembolic activity. Twenty-nine patients (22 men) aged 54 +/- 13 years suffering from valvular (n = 5) or nonvalvular (n = 24) AF were studied. All but 1 patient (with recent-onset AF) had been put on oral anticoagulation (INR >2.0) for at least 3 weeks before and 4 weeks after successful CV. In all patients, exclusion of internal carotid artery stenosis and atrial thrombus was performed prior to CV. Five unilateral 1-hour transcranial Doppler ME monitorings over the middle cerebral artery were performed (1) before CV, and (2) immediately, (3) 4-6 h, (4) 24 h, and (5) 2-4 weeks after CV. Total absence of circulating ME was found before CV as well as during a cumulative monitoring time of 115 h after successful CV. Electrical CV of AF after at least 3 weeks of effective anticoagulation is not associated with occurrence of cerebral circulating ME. This finding requires further investigation including high-risk patients with AF undergoing CV based on different treatment protocols.     

Preoperative B-mode ultrasound plaque appearance compared with carotid endarterectomy specimen histology

In carotid artery stenosis both the degree of the lesion and its plaque morphology are thought to be associated with the carrier's thromboembolic risk. In this study we evaluated the diagnostic preciseness of non-invasively B-mode ultrasound in predicting the histopathological plaque structure. We examined 44 patients with > 50% ICA stenosis by B-mode within 6 weeks prior to carotid endarterectomy. At the affected bifurcations, up to 10 different regions of interest (ROI) per artery were investigated. Plaque appearance was classified according to 6 subtypes considering different ultrasonic plaque features. Postoperatively, plaque specimens were examined histopathologically for their relative content of calcification, fibrous tissue and different soft tissue. B-mode ultrasound was compared with histopathological features in ROI. A total of 265 regions of interest were evaluated. In mainly echolucent types of plaques, atheromatous debris was most frequently seen, whereas fibrosis was rare. Homogeneous echolucent plaques showed a high proportion of cholesterol and/or recent haemorrhage. Thrombosis at the plaque surface was often seen in "completely echolucent" plaque type (each P<0.001). Carotid B-mode ultrasonography is able to predict the histopathological components and the texture of carotid plaques.     

Identifying the core competencies of mental health telephone triage

Aims and objectives. The primary aim of this study was to identify the core competencies of mental health telephone triage, including key role tasks, skills, knowledge and responsibilities, in which clinicians are required to be competent to perform safe and effective triage. Background. Recent global trends indicate an increased reliance on telephone‐based health services to facilitate access to health care across large populations. The trend towards telephone‐based health services has also extended to mental health settings, evidenced by the growing number of mental health telephone triage services providing 24‐hour access to specialist mental health assessment and treatment. Mental health telephone triage services are critical to the early identification of mental health problems and the provision of timely, appropriate interventions. In spite of the rapid growth in mental health telephone triage and the important role these services play in the assessment and management of mental illness and related risks, there has been very little research investigating this area of practice. Design. An observational design was employed to address the research aims. Methods. Structured observations (using dual wireless headphones) were undertaken on 197 occasions of mental health telephone triage over a three‐month period from January to March 2011. Results. The research identified seven core areas of mental health telephone triage practice in which clinicians are required to be competent in to perform effective mental health telephone triage, including opening the call; performing mental status examination; risk assessment; planning and action; termination of call; referral and reporting; and documentation. Conclusions. The findings of this research contribute to the evidence base for mental health telephone triage by articulating the core competencies for practice. Relevance to clinical practice. The mental health telephone triage competencies identified in this research may be used to define an evidence‐based framework for mental health telephone triage practice that aims to improve the quality, consistency and accuracy of telephone‐based mental health triage assessment.