Pathophysiology and management of Akathisia 70 years after the introduction of the chlorpromazine, the first antipsychotic

OBJECTIVE: Akathisia is among the most troubling effects of psychiatric drugs as it is associated with significant distress on behalf of the patients. and it limits treatment adherence. Though it most commonly presents during treatment with antipsychotic drugs which block dopamine D2 receptors. Akathisia has also been reported during treatment with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), stimulants, mirtazapine, tetrabenazine and other drugs. MATERIALS AND METHODS: This article was designed as a narrative review on akathisia with a focus on its clinical presentation, pathophysiology and management. A PubMed search for akathisia was conducted which returned 8481 articles. RESULTS: Akathisia is experienced as severe restlessness commonly accompanied by dysphoria and purposeless movement which relieves subjective tension. It has been attributed to an imbalance between dopaminergic and noradrenergic neurotransmission in the basal ganglia. Acute akathisia commonly resolves upon treatment discontinuation but tardive and chronic akathisia may persist after the causative agent is withdrawn and prove resistant to pharmacological treatment. Even drugs which induce no other extrapyramidal side effects (such as clozapine, quetiapine, aripiprazole and cariprazine) may induce akathisia. A high index of suspicion should be maintained in patients with motor disabilities, drug-induced parkinsonism and those under mechanical restraint. Propranolol and low-dose mirtazapine are the most thoroughly studied pharmacological interventions for akathisia, though benzodiazepines, voltage- gated calcium channel blockers (gabapentin. pregabalin) and opioids may be effective. CONCLUSIONS: Pharmacological management may pose a challenge in chronic akathisia. Rotation between different pharmacological management strategies may be optimal in resistant cases. Discontinuation of the causative drug and use of b-blockers, mirtazapine, benzo-diazepines or gabapentinoids for symptomatic relief is the basis of management

Association between Atrial Fibrillation and Cognitive Impairment in Individuals with Prior Stroke: A Meta-Analysis and Meta-Regression Analysis

Background and Purpose - Atrial fibrillation (AF) is the most common chronic arrhythmia. Dementia and cognitive impairment (CI) are major burdens to public health. The prevalence of all 3 entities is projected to increase due to population aging. Previous reports have linked AF with a higher risk of CI and dementia in patients without prior stroke. Stroke is known to increase the risk for dementia and CI. It is unclear if AF in patients with history of stroke can further increase the risk for dementia or CI. Our purpose was to evaluate the impact of AF on risk for dementia or CI among patients with history of stroke. Methods - Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed. Pubmed, Scopus, and Cochrane central were searched. The outcomes of interest were dementia, CI, and the composite end point of dementia or CI. A random-effect model meta-analysis was performed. Meta-regression analysis was also performed. Publication bias was assessed with the Egger test and with funnel plots. Results - Fourteen studies and 14 360 patients (1363 with AF) were included in the meta-analysis. In the meta-analysis of adjusted odds ratio, AF was associated with increased risk of CI (odds ratio, 1.60 [95% CI, 1.20-2.14]), dementia (odds ratio, 3.11 [95% CI, 2.05-4.73]), and the composite end point of CI or dementia (odds ratio, 2.26 [95% CI, 1.61-3.19]). The heterogeneity for the composite end point of dementia or CI was moderate (adjusted analysis). The heterogeneity for the analysis of the end point of CI only was substantial in the unadjusted analysis and moderate in the adjusted analysis. The heterogeneity for the end point of dementia only was moderate in the unadjusted analysis and zero in the adjusted analysis. Conclusions - Our results indicate that an association between AF and CI or dementia is patients with prior strokes is possible given the persistent positive associations we noticed in the unadjusted and adjusted analyses. The heterogeneity levels limit the certainty of our findings. © 2020 Lippincott Williams and Wilkins. All rights reserved

Atrial Fibrillation Is Associated with Cognitive Impairment, All-Cause Dementia, Vascular Dementia, and Alzheimer’s Disease: a Systematic Review and Meta-Analysis

Background: Atrial fibrillation (AF) is a risk factor for cognitive impairment and dementia in patients with stroke history. However, the association between AF and cognitive impairment in broader populations is less clear. Objective: To systematically review and quantitatively synthesize the existing evidence regarding the association of AF with cognitive impairment of any severity and etiology and dementia. Methods: Medline, Scopus, and Cochrane Central were searched in order to identify studies investigating the association between AF and cognitive impairment (or dementia) cross-sectionally and longitudinally. Studies encompassing and analyzing exclusively patients with stroke history were excluded. A random-effects model meta-analysis was conducted. Potential sources of between-study heterogeneity were investigated via subgroup and meta-regression analyses. Sensitivity analyses including only studies reporting data on stroke-free patients, vascular dementia, and Alzheimer’s disease were performed. Results: In total, 43 studies were included. In the pooled analysis, AF was significantly associated with dementia (adjusted OR, 1.6; 95% CI, 1.3 to 2.1; I2, 31%) and the combined endpoint of cognitive impairment or dementia (pooled adjusted OR, 1.5; 95% CI, 1.4 to 1.8; I2, 34%). The results were significant, even when studies including only stroke-free patients were pooled together (unadjusted OR, 2.2; 95% CI, 1.4 to 3.5; I2, 96%), but the heterogeneity rates were high. AF was significantly associated with increased risk of both vascular (adjusted OR, 1.7; 95% CI, 1.2 to 2.3; I2, 43%) and Alzheimer’s dementia (adjusted HR, 1.4; 95% CI, 1.2 to 1.6; I2, 42%). Conclusion: AF increases the risk of cognitive impairment, all-cause dementia, vascular dementia, and Alzheimer’s disease. Future studies should employ interventions that may delay or even prevent cognitive decline in AF patients. © 2021, Society of General Internal Medicine