Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery.

BACKGROUND: Stroke is the major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression. Recently, small trials have demonstrated that SSRIs might improve recovery after stroke, even in people who are not depressed. Systematic reviews and meta-analyses are the least biased way to bring together data from several trials. Given the promising effect of SSRIs on stroke recovery seen in small trials, a systematic review and meta-analysis is needed. OBJECTIVES: To determine whether SSRIs improve recovery after stroke, and whether treatment with SSRIs was associated with adverse effects. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (August 2011), Cochrane Depression Anxiety and Neurosis Group Trials Register (November 2011), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 8), MEDLINE (from 1948 to August 2011), EMBASE (from 1980 to August 2011), CINAHL (from 1982 to August 2011), AMED (Allied and Complementary Medicine) (from 1985 to August 2011), PsycINFO (from 1967 to August 2011) and PsycBITE (Pyschological Database for Brain Impairment Treatment Efficacy) (March 2012). To identify further published, unpublished and ongoing trials we searched trials registers, pharmaceutical websites, reference lists, contacted experts and performed citation tracking of included studies. SELECTION CRITERIA: We included randomised controlled trials that recruited stroke survivors (ischaemic or haemorrhagic) at any time within the first year. The intervention was any SSRI, given at any dose, for any period. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. In order to be included, trials had to collect data on at least one of our primary (dependence and disability) or secondary (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early) outcomes. DATA COLLECTION AND ANALYSIS: We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. For trials in English, two review authors independently extracted data. For Chinese papers, one review author extracted data. We used standardised mean differences (SMD) to estimate treatment effects for continuous variables, and risk ratios (RR) for dichotomous effects, with their 95% confidence intervals (CIs). MAIN RESULTS: We identified 56 completed trials of SSRI versus control, of which 52 trials (4059 participants) provided data for meta-analysis. There were statistically significant benefits of SSRI on both of the primary outcomes: RR for reducing dependency at the end of treatment was 0.81 (95% CI 0.68 to 0.97) based on one trial, and for disability score, the SMD was 0.91 (95% CI 0.60 to 1.22) (22 trials involving 1343 participants) with high heterogeneity between trials (I(2) = 87%; P < 0.0001). For neurological deficit, depression and anxiety, there were statistically significant benefits of SSRIs. For neurological deficit score, the SMD was -1.00 (95% CI -1.26 to -0.75) (29 trials involving 2011 participants) with high heterogeneity between trials (I(2) = 86%; P < 0.00001). For dichotomous depression scores, the RR was 0.43 (95% CI 0.24 to 0.77) (eight trials involving 771 participants) with high heterogeneity between trials (I(2) = 77%; P < 0.0001). For continuous depression scores, the SMD was -1.91 (95% CI -2.34 to -1.48) (39 trials involving 2728 participants) with high heterogeneity between trials (I(2) = 95%; P < 0.00001). For anxiety, the SMD was -0.77 (95% CI -1.52 to -0.02) (eight trials involving 413 participants) with high heterogeneity between trials (I(2) = 92%; P < 0.00001). There was no statistically significant benefit of SSRI on cognition, death, motor deficits and leaving the trial early. For cognition, the SMD was 0.32 (95% CI -0.23 to 0.86), (seven trials involving 425 participants) with high heterogeneity between trials (I(2) = 86%; P < 0.00001). The RR for death was 0.76 (95% CI 0.34 to 1.70) (46 trials involving 3344 participants) with no heterogeneity between trials (I(2) = 0%; P = 0.85). For motor deficits, the SMD was -0.33 (95% CI -1.22 to 0.56) (two trials involving 145 participants). The RR for leaving the trial early was 1.02 (95% CI 0.86 to 1.21) in favour of control, with no heterogeneity between trials. There was a non-significant excess of seizures (RR 2.67; 95% CI 0.61 to 11.63) (seven trials involving 444 participants), a non-significant excess of gastrointestinal side effects (RR 1.90; 95% CI 0.94 to 3.85) (14 trials involving 902 participants) and a non-significant excess of bleeding (RR 1.63; 95% CI 0.20 to 13.05) (two trials involving 249 participants) in those allocated SSRIs. Data were not available on quality of life, fatigue or healthcare costs.There was no clear evidence from subgroup analyses that one SSRI was consistently superior to another, or that time since stroke or depression at baseline had a major influence on effect sizes. Sensitivity analyses suggested that effect sizes were smaller when we excluded trials at high or unclear risk of bias.Only eight trials provided data on outcomes after treatment had been completed; the effect sizes were generally in favour of SSRIs but CIs were wide. AUTHORS' CONCLUSIONS: SSRIs appeared to improve dependence, disability, neurological impairment, anxiety and depression after stroke, but there was heterogeneity between trials and methodological limitations in a substantial proportion of the trials. Large, well-designed trials are now needed to determine whether SSRIs should be given routinely to patients with stroke

Systemic markers of inflammation are independently associated with S100B concentration: results of an observational study in subjects with acute ischaemic stroke

<p>Abstract</p> <p>Background</p> <p>Vascular dysfunction and brain inflammation are thought to contribute to the pathophysiology of cerebral injury in acute stroke. However acute inflammation and vascular dysfunction may simply be markers of an acute phase response to cerebral injury, reflecting the size of the cerebral lesion. We aimed to determine if systemic markers of vascular dysfunction and inflammation are independently associated with concentrations of the astroglial protein S100B, a marker of brain injury, in participants with acute ischaemic stroke.</p> <p>Methods</p> <p>Fifty-seven men and women recruited within 96 hours of acute ischaemic stroke at two tertiary hospitals participated in this cross sectional observational study. Clinical, imaging (stroke lesions area measured with perfusion CT) and laboratory data were the independent variables and co-variates. The outcome variable was serum S100B concentration, analysed by multivariate regression.</p> <p>Results</p> <p>High sensitivity-CRP (<it>B </it>= 0.41) and lesion area (<it>B </it>= 0.69) were independently associated with S100B concentration (R²= 0.75, p < 0.01). Other variables with significant univariate associations with S100B concentration were not independently associated with S100B concentration in the final multivariate model.</p> <p>Conclusion</p> <p>The degree of systemic inflammation is associated with S100B concentration in acute ischaemic stroke, independent of the size of the ischaemic lesion.</p

Piracetam for Acute Ischemic Stroke

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The effect of homocysteine-lowering with B-vitamins on osteoporotic fractures in patients with cerebrovascular disease: substudy of VITATOPS, a randomised placebo-controlled trial

10.1186/1471-2318-13-88BMC Geriatrics131

Systemic vascular function, measured with forearm flow mediated dilatation, in acute and stable cerebrovascular disease: a case-control study

BACKGROUND Acute ischaemic stroke is associated with alteration in systemic markers of vascular function. We measured forearm vascular function (using forearm flow mediated dilatation) to clarify whether recent acute ischaemic stroke/TIA is associated with impaired systemic vascular function. METHODS Prospective case control study enrolling 17 patients with recent acute ischaemic stroke/TIA and 17 sex matched controls with stroke more than two years previously. Forearm vascular function was measured using flow medicated dilatation (FMD). RESULTS Flow mediated dilatation was 6.0 ± 1.1% in acute stroke/TIA patients and 4.7 ± 1.0% among control subjects (p = 0.18). The mean paired difference in FMD between subjects with recent acute stroke and controls was 1.25% (95% CI -0.65, 3.14; p = 0.18). Endothelium independent dilatation was measured in six pairs of participants and was similar in acute stroke/TIA patients (22.6 ± 4.3%) and control subjects (19.1 ± 2.6%; p = 0.43). CONCLUSIONS Despite the small size of this study, these data indicate that recent acute stroke is not necessarily associated with a clinically important reduction in FMD.This study was funded by the Centre for Training in Clinical Cerebrovascular and Cardiovascular Research, a National Health and Medical Research Council funded Centre of Clinical Research Excellence

Affective disorders, psychosis and dementia in a community sample of older men with and without Parkinson's disease

Background: Dementia and affective and psychotic symptoms are commonly associated with Parkinson's disease, but information about their prevalence and incidence in community representative samples remains sparse. Methods: We recruited a community-representative sample 38173 older men aged 65-85 years in 1996 and used data linkage to ascertain the presence of PD, affective disorders, psychotic disorders and dementia. Diagnoses followed the International Classification of Disease coding system. Age was recorded in years. Follow up data were available until December 2011. Results: The mean age of participants was 72.5 years and 333 men (0.9%) had PD at study entry. Affective and psychotic disorders and dementia were more frequent in men with than without PD (respective odds ratios: 6.3 [95%CI = 4.7, 8.4]; 14.2 [95%CI = 8.4, 24.0] and 18.2 [95%CI = 13.4, 24.6]). Incidence rate ratios of affective and psychotic disorders were higher among men with than without PD, although ratios decreased with increasing age. The ageadjusted hazard ratio (HR) of an affective episode associated with PD was 5.0 (95%CI = 4.2, 5.9). PD was associated with an age-adjusted HR of 8.6 (95%CI = 6.1, 12.0) for psychotic disorders and 6.1 (95%CI = 5.5, 6.8) for dementia. PD and dementia increased the HR of depressive and psychotic disorders. Conclusions: PD increases the risk of affective and psychotic disorders, as well as dementia, among community dwelling older men. The risk of a recorded diagnosis of affective and psychotic disorders decreases with increasing age

Prevalence of mental disorders among older Australians: Contrasting evidence from the 2020–2021 National Study of Mental Health and Wellbeing among men and women and the Health In Men Data Linkage Study

Objective: To determine the prevalence of common mental disorders among older Australians included in the Health In Men Data Linkage Study and compare those with the results of the 2020–2021 National Study of Mental Health and Wellbeing (NSMHW). Method: We used longitudinal record linkage to estimate the prevalence of mental disorders from age 65 years in a random sample of 38173 Australian men aged 65–85 years living in the Perth metropolitan region. Outcome was the proportion of participants affected by depressive episodes or dysthymia, bipolar disorder, anxiety disorder, psychotic disorder and alcohol use disorder. Results: Prevalence estimates for participants aged 65–69, 70–74, 75–79, 80–84 and ≥85 years were 0.9%, 2.0%, 3.6%, 5.8% and 12.6% for depressive, 0.2%, 0.3%, 0.4%, 0.4% and 0.7% for bipolar, 0.1%, 0.5%, 1.3%, 2.2%, 6.9% for anxiety, 0.2%, 0.4%, 0.5%, 0.4% and 0.6% for psychotic and 1.2%, 1.7%, 2.1%, 2.2% and 4.2% for alcohol use disorders. Conclusions: In contrast to the NSMHW, our data indicate that the prevalence of depressive and anxiety disorders increases with age, particularly among the older old. We conclude that the NSMHW should not be relied upon to guide planning or policies to address the mental health needs of older Australians

Lacunar infarcts, depression and anxiety symptoms one year after stroke

Background: Mood disorders are frequent after stroke and are associated with poorer quality of life. Previous studies have reported conflicting results as to stroke subtype in the incidence of poststroke mood disorders. We explored the relationship between subcortical ischemic stroke subtype (lacunar) and presence of such symptoms at 1 year after stroke. Methods: Anonymized data were accessed from the Virtual International Stroke Trials Archive. Stroke subtypes were classified according to the Trial of Org 10172 in Acute Stroke Treatment classification. Depression and anxiety symptoms were assessed using Hospital Anxiety and Depression Scale. We investigated independent predictors of depression and anxiety symptoms using a logistic regression model. Results: Data were available for 2160 patients. Almost one fifth of the patients developed both anxiety and depression at 1-year follow-up. After adjusting for confounders, the lacunar subtype was least associated with both anxiety (odds ratio [OR] = .61; 95% confidence interval [CI] = .46-.80) and depression symptoms (OR = .71; CI = .55-.93) versus other stroke subtypes. Conclusions: Lacunar strokes have a weaker association with presence of anxiety and depression symptoms compared with other subtypes

Non-vitamin K oral anticoagulants for secondary stroke prevention in patients with atrial fibrillation

The aims of this article are to review the evidence regarding the use of non-vitamin K oral anticoagulants (NOACs) for secondary stroke prevention as compared to vitamin K antagonists in patients with atrial fibrillation (AF) and in patients with embolic strokes of uncertain source (ESUS), and when to initiate or resume anticoagulation after an ischaemic stroke or intracranial haemorrhage. Four large trials compared NOACs with warfarin in patients with AF. In our meta-analyses, the rate of all stroke or systemic embolism (SE) was 4.94% with NOACs vs. 5.73% with warfarin. Among the patients with AF and previous transient ischaemic attack or ischaemic stroke, the rate of haemorrhagic stroke was halved with a NOAC vs. warfarin, and the rate of major bleeding was 5.7% with a NOAC vs. 6.4% with warfarin. There was no significant difference in mortality. In a trial comparing apixaban with aspirin in patients with AF, the rate of stroke or SE was 2.4% at 1 year with apixaban vs. 9.2% at 1 year with aspirin and the rates of major bleeding were 4.1% with apixaban vs. 2.9% with aspirin. Data from registries confirmed the results from the randomized trials. Initiation or resumption of anticoagulation after ischaemic stroke or cerebral haemorrhage depends on the size and severity of stroke and the risk of recurrent bleeding. Two large trials tested the hypothesis that NOACs are more effective than 100 mg aspirin in patients with ESUS. Neither trial showed a significant benefit of the NOAC over aspirin. In the meta-analysis, the rate all stroke or SE was 4.94% with NOACs vs. 5.73% with warfarin and the rate of haemorrhagic stroke was halved with a NOAC. The four NOACs had broadly similar efficacy for the major outcomes in secondary stroke prevention