RESUMO
BACKGROUND: Patients experiencing significant agitation or perceptual disturbances related to delirium in an intensive care setting may benefit from short-term treatment with an antipsychotic medication. Some antipsychotic medications may prolong the QTc interval, which increases the risk of potentially fatal ventricular arrhythmias. In this targeted review, we describe the evidence regarding the relationships between antipsychotic medications and QTc prolongation and practical methods for monitoring the QTc interval and mitigating arrhythmia risk. METHODS: Searches of PubMed and Cochrane Library were performed to identify studies, published before February 2023, investigating the relationships between antipsychotic medications and QTc prolongation or arrhythmias. RESULTS: Most antipsychotic medications commonly used for the management of delirium symptoms (eg, intravenous haloperidol, olanzapine, quetiapine) cause a moderate degree of QTc prolongation. Among other antipsychotics, those most likely to cause QTc prolongation are iloperidone and ziprasidone, while aripiprazole and lurasidone appear to have minimal risk for QTc prolongation. Genetic vulnerabilities, female sex, older age, pre-existing cardiovascular disease, electrolyte abnormalities, and non-psychiatric medications also increase the risk of QTc prolongation. For individuals at risk of QTc prolongation, it is essential to measure the QTc interval accurately and consistently and consider medication adjustments if needed. CONCLUSIONS: Antipsychotic medications are one of many risk factors for QTc prolongation. When managing agitation related to delirium, it is imperative to assess an individual patient's risk for QTc prolongation and to choose a medication and monitoring strategy commensurate to the risks. In intensive care settings, we recommend regular ECG monitoring, using a linear regression formula to correct for heart rate. If substantial QTc prolongation (eg, QTc > 500 msec) is present, a change in pharmacologic treatment can be considered, though a particular medication may still be warranted if the risks of discontinuation (eg, extreme agitation, removal of invasive monitoring devices) outweigh the risks of arrhythmias. AIMS: This review aims to summarize the current literature on relationships between antipsychotic medications and QTc prolongation and to make practical clinical recommendations towards the approach of antipsychotic medication use for the management of delirium-related agitation and perceptual disturbances in intensive care settings.
RESUMO
BACKGROUND: Physical activity is increasingly recognized as an important modifiable factor for depression. However, the extent to which individuals with stable risk factors for depression, such as high genetic vulnerability, can benefit from the protective effects of physical activity, remains unknown. Using a longitudinal biobank cohort integrating genomic data from 7,968 individuals of European ancestry with high-dimensional electronic health records and lifestyle survey responses, we examined whether physical activity was prospectively associated with reduced risk for incident depression in the context of genetic vulnerability. METHODS: We identified individuals with incident episodes of depression, based on two or more diagnostic billing codes for a depressive disorder within 2 years following their lifestyle survey, and no such codes in the year prior. Polygenic risk scores were derived based on large-scale genome-wide association results for major depression. We tested main effects of physical activity and polygenic risk scores on incident depression, and effects of physical activity within stratified groups of polygenic risk. RESULTS: Polygenic risk was associated with increased odds of incident depression, and physical activity showed a protective effect of similar but opposite magnitude, even after adjusting for BMI, employment status, educational attainment, and prior depression. Higher levels of physical activity were associated with reduced odds of incident depression across all levels of genetic vulnerability, even among individuals at highest polygenic risk. CONCLUSIONS: Real-world data from a large healthcare system suggest that individuals with high genetic vulnerability are more likely to avoid incident episodes of depression if they are physically active.