Antipsychotic Drug Use and the Risk of Venous Thromboembolism in Elderly Patients With Dementia

Schmedt, Niklas; Garbe, Edeltraut

doi:10.1097/jcp.0b013e3182a412d5

Cited by 30 publications

(32 citation statements)

References 44 publications

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“…An increased risk of venous thromboembolism associated with antipsychotic medication has previously been reported in an UK population-based nested case–control study, with older people at particular risk [39], and also in older people with dementia in a German nested case–control study [40]. Our study supports this finding in older people with dementia; inactivity-related venous stasis may not be the only mechanism involved—enhanced platelet aggregation and raised anticardiolipin antibodies may also be important factors [41].…”

Section: Discussionmentioning

confidence: 96%

Risk of Adverse Outcomes for Older People with Dementia Prescribed Antipsychotic Medication: A Population Based e-Cohort Study

et al. 2017

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IntroductionOver recent years there has been growing evidence of increased risk of mortality associated with antipsychotic use in older people with dementia. Although this concern combined with limited evidence of efficacy has informed guidelines restricting antipsychotic prescription in this population, the use of antipsycotics remains common. Many published studies only report short-term outcomes, are restricted to examining mortality and stroke risk or have other limitations. The aim of this study was to assess adverse outcomes associated with the use of antipsychotics in older people living with dementia in Wales (UK).MethodsThis was a retrospective study of a population-based dementia cohort using the Welsh Secure Anonymised Information Linkage databank. The prior event rate ratio (PERR) was used to estimate the influence of exposure to antipsychotic medication on acute cardiac events, venous thromboembolism, stroke and hip fracture, and adjusted Cox proportional hazard models were used to compare all-cause mortality.ResultsA total of 10,339 people aged ≥65 years were identified with newly diagnosed dementia. After excluding those who did not meet the inclusion criteria, 9674 people remained in the main cohort of whom 3735 were exposed to antipsychotic medication. An increased risk of a venous thromboembolic episode [PERR 1.95, 95% confidence interval (CI) 1.83–2.0], stroke (PERR 1.41, 95% CI 1.4–1.46) and hip fracture (PERR 1.62, 95% CI 1.59–1.65) was associated with antipsychotic use. However, there was no long-term increased mortality in people exposed to antipsychotics (adjusted hazard ratio 1.06, 95% CI 0.99–1.13).ConclusionsThe increase in adverse medical events supports guidelines restricting antipsychotic use in this population.Electronic supplementary materialThe online version of this article (doi:10.1007/s40120-016-0060-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 96%

Risk of Adverse Outcomes for Older People with Dementia Prescribed Antipsychotic Medication: A Population Based e-Cohort Study

et al. 2017

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“…APD users generally deteriorated more rapidly in physical health and died earlier. The only German studies to have investigated the impact of APDs on health outcomes among dementia patients focused on venous thromboembolism ( 4 ) and death ( 14 ), whereas the latter study compared single APDs with risperidone. Our study extends these results by using dependency on LTC and NH admission as outcomes which may be considered as measures of different degrees of physical limitations.…”

Section: Discussionmentioning

confidence: 99%

“…In the past years, SGAs have increasingly replaced FGAs because of their higher efficacy and fewer extra pyramidal symptoms. However, there are concerns about the safety of both FGAs and SGAs, indicating an elevated risk of death, cerebrovascular events ( 2 , 3 ), and thromboembolism ( 4 ). In addition to these specific events, little is known about the impact of APDs on disability-related outcomes.…”

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confidence: 99%

The Impact of Antipsychotic Drugs on Long-term Care, Nursing Home Admission, and Death in Dementia Patients

Nerius

Johnell

García-Ptacek

et al. 2017

The Journals of Gerontology: Series A

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BackgroundBehavioral and psychological symptoms of dementia are commonly treated with antipsychotic drugs (APDs), which have been associated with adverse health effects. We examine the effect of APDs on long-term care (LTC), nursing home (NH) admission, and death of dementia patients.MethodsWe used health claims data of the largest German health insurer from 2004 to 2010 and followed newly-diagnosed dementia patients aged 60 years and older into LTC, NH, and until death. Cox proportional hazards models were estimated to explore whether the risk of these outcomes differed between patients receiving haloperidol, melperone, risperidone, or quetiapine.ResultsIn a cohort of 6,930 dementia patients who were initially free of LTC dependency, APD users generally faced a twofold increased risk of LTC relative to nonusers. Quetiapine was the exception, showing a comparatively lower risk (HR = 1.64; CI = 1.35–1.98). Among 9,950 dementia patients initially living in private homes, the risk of moving into a NH was generally increased by about 50% among APD users relative to nonusers. Risk of death (N = 10,921) was significantly higher for haloperidol-, melperone-, and risperidone- but not for quetiapine users (HR = 0.91; CI = 0.78–1.08). The excess mortality associated with haloperidol and melperone was greater among patients living in private households.ConclusionsIn our study, APDs appeared to accelerate adverse health outcomes in German dementia patients. Differentiating between the effect of antipsychotic drug use among dementia patients residing in private households and in NHs, we found that excess mortality for haloperidol and melperone users was higher in private settings.

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“…21 cases and 15 controls used AP All Diagnosis of DVT or PE within 180 days after surgical treatment Yes Univariate analysis p = 0.3, not included in the regression analyses Elderly patient populations Kleijer et al, 2010 [ 42 ] Time-matched, nested, case–control study The PHARMO Institute’s record linkage system, The Netherlands 1998–2008 112,000 new users of AP 1032 cases (367 DVT, 342 PE and 323 outpatients) and 4125 controls ≥ 60 VTE diagnosis or start of treatment with LMWH in combination with vitamin K antagonists No? aOR, SGA: 0.9 (0.7–1.1) vs. FGA Schmedt and Garbe, 2013 [ 43 ] Case–control study The German pharmacoepidemiological research database (GePaRD), Germany 2004–2007 73,000 patients with dementia 1028 cases and 4109 controls ≥ 65 Hospitalisations due to VTE No aOR, AP: 1.2 (1.0–1.5) FGA: 0.89 (0.6–1.2) SGA: 0.94 (0.7–1.2) FGA and SGA: 1.6 (1.2–2.3) Deceased patient populations Walker et al, 1997 [ 11 ] Case–control study The US national registry of clozapine recipients and National death register, USA 1991–1993 67,000 current and former clozapine users 396 deaths in 85,399 person-years; 19 deaths due to PE, 18 used AP 10–54 Fatal PE Not stated RR for current clozapine use compared with previous use = 5.2 Parkin et al, 2003 [ 44 ] Case–control study Coroner’s records (cases) and GP records (cases and controls), New Zealand 1990–1998 All residents in New Zealand aged 15–59 years 62 cases and 243 GP-based controls ...…”

Section: Early Studiesmentioning

confidence: 99%

Venous Thromboembolism During Treatment with Antipsychotics: A Review of Current Evidence

et al. 2018

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This article summarises the current evidence on the risk of venous thromboembolism (VTE) with the use of antipsychotics. An increasing number of observational studies indicate an elevated risk of VTE in antipsychotic drug users. Although the use of certain antipsychotics has been associated with VTE, current data can neither conclusively verify differences in occurrence rates of VTE between first- and second-generation antipsychotics or between individual compounds, nor identify which antipsychotic drugs have the lowest risk of VTE. The biological mechanisms involved in the pathogenesis of this adverse drug reaction are still to be clarified but hypotheses such as drug-induced sedation, obesity, increased levels of antiphospholipid antibodies, enhanced platelet aggregation, hyperhomocysteinaemia and hyperprolactinaemia have been suggested. Risk factors associated with the underlying psychiatric disorder may at least partly explain the increased risk. Physicians should be aware of this potentially serious and even sometimes fatal adverse drug reaction and should consider discontinuing or switching the antipsychotic treatment in patients experiencing a VTE. Even though supporting evidence is limited, prophylactic antithrombotic treatment should be considered in risk situations for VTE.

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Antipsychotic Drug Use and the Risk of Venous Thromboembolism in Elderly Patients With Dementia

Cited by 30 publications

References 44 publications

Risk of Adverse Outcomes for Older People with Dementia Prescribed Antipsychotic Medication: A Population Based e-Cohort Study

Risk of Adverse Outcomes for Older People with Dementia Prescribed Antipsychotic Medication: A Population Based e-Cohort Study

The Impact of Antipsychotic Drugs on Long-term Care, Nursing Home Admission, and Death in Dementia Patients

Venous Thromboembolism During Treatment with Antipsychotics: A Review of Current Evidence

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