Associations between off-label low-dose olanzapine or quetiapine and cardiometabolic mortality

Berge, Jonas; Abri, Paul; Andell, Pontus; Movahed, Pouya; Ragazan, Dragos C.

doi:10.1016/j.jpsychires.2021.11.023

Cited by 10 publications

(16 citation statements)

References 39 publications

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“…Cardiometabolic risk factors with use of low-dose quetiapine have been investigated in smaller cohort studies 32,33 and in one nationwide database study 34 , but the evidence of cardiovascular risk/safety has been insufficient 35,36 . The only nationwide database study 34 found increased risk of cardiovascular death with 6-12 months of cumulative exposure, but pooled low-dose quetiapine with low-dose olanzapine, providing no specific evidence for the risks associated with quetiapine.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the common and increasing use of low-dose quetiapine as an anxiolytic or hypnotic [3][4][5][6]31 , no study has investigated its long-term cardiovascular safety in a nationwide setting with long follow-up as the present analysis. Cardiometabolic risk factors with use of low-dose quetiapine have been investigated in smaller cohort studies 32,33 and in one nationwide database study 34 , but the evidence of cardiovascular risk/safety has been insufficient 35,36 . The only nationwide database study 34 found increased risk of cardiovascular death with 6-12 months of cumulative exposure, but pooled low-dose quetiapine with low-dose olanzapine, providing no specific evidence for the risks associated with quetiapine.…”

Section: Discussionmentioning

confidence: 99%

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Use of low‐dose quetiapine increases the risk of major adverse cardiovascular events: results from a nationwide active comparator‐controlled cohort study

et al. 2022

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At standard doses used for schizophrenia or bipolar disorder, quetiapine has been associated with weight gain and increased levels of triglycerides, to tal cholesterol and lowdensity lipoprotein (LDL) cholesterol, which are risk factors for cardiovascular morbidity and mortality. However, this drug is also commonly used offlabel at low doses for anxiolytic or hypnotic purposes, and its cardiovascular safety at these doses is unknown. We aimed to assess the risk of major adverse cardiovascular events with use of lowdose quetiapine compared to use of Zdrug hypnotics in a nationwide, active comparatorcontrolled cohort study. The cohort included new users of either drugs in Denmark from 2003 to 2017, aged 1885 years, without history of ischemic stroke, myocardial infarction, cancer, and severe mental illness. The main outcome was the occurrence of major adverse cardiovascular events, defined as nonfatal myocardial infarction or ischemic stroke, or death from cardiovascular causes. Selective serotonin reuptake inhibitors (SSRIs) were used as an alternative comparator in sensitivity analyses.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Use of low‐dose quetiapine increases the risk of major adverse cardiovascular events: results from a nationwide active comparator‐controlled cohort study

et al. 2022

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“…and cardiovascular (cardiomyopathy, myocarditis, tachycardia, hypotension, prolonged QT interval, etc.) symptoms, although more serious consequences, including death, have been reported 3–6 …”

Section: Introductionmentioning

confidence: 99%

Cardiac adverse events associated with quetiapine: Disproportionality analysis of FDA adverse event reporting system

et al. 2023

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Objective Quetiapine, an atypical second‐generation antipsychotic drug, is approved for treatment of schizophrenia, bipolar disorder, and depression. Due to the limitations of clinical trials, the association between quetiapine and rare cardiac adverse events (AEs) is still unclear. This study is to evaluate quetiapine‐associated cardiac AEs through data mining of FDA Adverse Event Reporting System (FAERS). Methods Reporting odds ratio (ROR) was used to quantify the signals of quetiapine‐related cardiac AEs from the first quarter (Q1) of 2018–2022 Q1. Serious and nonserious cases were compared, and signals were prioritized using a rating scale. Results A total of 1004 cases of quetiapine‐associated cardiac AEs were identified, with 31 signals being detected, among which 13 AEs were identified as new and unexpected signals. Besides, nine and 22 cardiac AEs were identified as moderate and weak clinical priority. The median TTO for moderate and weak clinical priority signals were 0 and 4 days, respectively. All of the cardiac AEs had early failure type characteristics, suggesting that most of the patients developed cardiac AEs in a few days after quetiapine treatment, and that the risk of cardiac AEs occurrence would be gradually decreased over time. Conclusion Our study provided valuable evidence for health‐care professionals to mitigate the risk of quetiapine‐associated cardiac AEs based on an extensive analysis of a real‐world, large‐sample FAERS database, and prioritize cardiac AE signals.

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“…Quetiapine is an atypical antipsychotic, approved in most countries for the treatment of schizophrenia, bipolar disorder, and in a few countries adjunctive therapy with antidepressants for major depressive disorder (AstraZeneca, 2020; FDA, 2020; Pringsheim & Gardner, 2014). However, quetiapine is frequently prescribed ‘off‐label’, most commonly for insomnia, anxiety, and agitation at doses of 100 mg or less (Berge et al, 2022; Carton et al, 2015; Gjerden et al, 2017; McKean & Monasterio, 2012). Daily doses of quetiapine for its approved indications range between 150 and 800 mg/day (AstraZeneca, 2020; FDA, 2020) following a 4–8 day low‐dose run‐in titration period (Brett, 2015; Drug Utilisation Sub‐Committee, 2013; Lee, Pilgrim et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Effects of the antipsychotic quetiapine on sleep and breathing: a review of clinical findings and potential mechanisms

Fauska,

Bastiampillai,

Adams

et al. 2023

Journal of Sleep Research

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SummaryQuetiapine is an antipsychotic medication indicated for schizophrenia and bipolar disorder. However, quetiapine also has hypnotic properties and as such is increasingly being prescribed at low doses ‘off‐label’ in people with insomnia symptoms. Pharmacologically, in addition to its dopaminergic properties, quetiapine also modulates multiple other transmitter systems involved in sleep/wake modulation and potentially breathing. However, very little is known about the impact of quetiapine on obstructive sleep apnoea (OSA), OSA endotypes including chemosensitivity, and control of breathing. Given that many people with insomnia also have undiagnosed OSA, it is important to understand the effects of quetiapine on OSA and its mechanisms. Accordingly, this concise review covers the existing knowledge on the effects of quetiapine on sleep and breathing. Further, we highlight the pharmacodynamics of quetiapine and its potential to alter key OSA endotypes to provide potential mechanistic insight. Finally, an agenda for future research priorities is proposed to fill the current key knowledge gaps.

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Associations between off-label low-dose olanzapine or quetiapine and cardiometabolic mortality

Cited by 10 publications

References 39 publications

Use of low‐dose quetiapine increases the risk of major adverse cardiovascular events: results from a nationwide active comparator‐controlled cohort study

Use of low‐dose quetiapine increases the risk of major adverse cardiovascular events: results from a nationwide active comparator‐controlled cohort study

Cardiac adverse events associated with quetiapine: Disproportionality analysis of FDA adverse event reporting system

Effects of the antipsychotic quetiapine on sleep and breathing: a review of clinical findings and potential mechanisms

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