Increased All-Cause Mortality by Antipsychotic Drugs: Updated Review and Meta-Analysis in Dementia and General Mental Health Care

Ralph, Stephen John; Espinet, Anthony

doi:10.3233/adr-170042

Cited by 121 publications

(127 citation statements)

References 92 publications

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“…This was also true for Māori with dementia (HR:3.62, 95% CI: 0.79, 16.7) although did not reach statistical significance, probably due to smaller sample size and therefore reduced number of death events (n = 7). It is well established that antipsychotics increase the risk of mortality in people with dementia . The reason that this risk might be increased in Pacific Islanders and Māori may be due to their pre‐existing increased risk of stroke and cardiovascular events; however, these factors should be controlled for in our analysis as the final model included adjustment for comorbidity.…”

Section: Discussionmentioning

confidence: 99%

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Predictors of mortality in Māori, Pacific Island, and European patients diagnosed with dementia at a New Zealand Memory Service

Cullum

Varghese

Coomarasamy

et al. 2020

Int J Geriat Psychiatry

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Background As the economic impact of dementia on health and social care increases, governments require disease‐specific epidemiological data that will help inform spending and policy decisions. The aim of this study is to examine predictors of mortality in dementia in consecutive referrals to a New Zealand (NZ) memory service that includes Māori, Pacific Islander, and NZ European patients. Methods Date of birth, sex, ethnicity, living situation, cognitive function, dementia subtype, dementia severity, physical comorbidity, and medication data were collected from electronic health records. The resulting data set was linked to administrative data on mortality and last hospital contact dates to allow time‐dependent survival analyses. Results The risk of death in people with dementia was increased by age (adjusted HR per year 1.08, 95%CI:1.05‐1.12) and lower cognitive score at baseline (adjusted HR for severe impairment:2.54, 95% CI:1.25‐5.16), and was reduced by cholinesterase inhibitors (adjusted HR:0.54, 95% CI:0.34‐0.88). Compared to NZ Europeans (HR:1.19, 95% CI:0.63‐2.25), antipsychotics increased the risk of death three‐fold in Māori (adjusted HR:3.62, 95% CI:0.79‐16.7) and Pacific Islanders (adjusted HR:2.54, 95%CI:1.10‐5.85). Conclusions Further research is required to elucidate the mechanisms underlying the survival rates in Māori and Pacific Islanders living with dementia in NZ,and their increased risk of death if antipsychotics are used.

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Section: Discussionmentioning

confidence: 99%

“…It is well established that antipsychotics increase the risk of mortality in people with dementia. 30 The reason that this risk might be increased in Pacific…”

Section: Antipsychotic Medicationmentioning

confidence: 99%

Predictors of mortality in Māori, Pacific Island, and European patients diagnosed with dementia at a New Zealand Memory Service

Cullum

Varghese

Coomarasamy

et al. 2020

Int J Geriat Psychiatry

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“…A type of medication called antipsychotics may be prescribed to treat hallucinations, aggression and agitation. However, research has shown that some antipsychotics are associated with an increased risk of stroke and death in individuals with dementia 47,48 . The decision to use antipsychotics must be considered with extreme caution.…”

Section: Overview Of Alzheimer's Diseasementioning

confidence: 99%

“…However, research has shown that some antipsychotics are associated with an increased risk of stroke and death in individuals with dementia. 47,48 The decision to use antipsychotics must be considered with extreme caution. The FDA has ordered manufacturers to label such drugs with a "black box warning" about their risks and a reminder that they are not approved to treat dementia symptoms.…”

Section: Signs Of Alzheimer's or Other Dementias Typical Age-relatedmentioning

confidence: 99%

2020 Alzheimer's disease facts and figures

2020

Alzheimer's & Dementia

1,962

653

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This article describes the public health impact of Alzheimer's disease (AD), including incidence and prevalence, mortality and morbidity, use and costs of care, and the overall impact on caregivers and society. The Special Report discusses the future challenges of meeting care demands for the growing number of people living with Alzheimer's dementia in the United States with a particular emphasis on primary care. By mid‐century, the number of Americans age 65 and older with Alzheimer's dementia may grow to 13.8 million. This represents a steep increase from the estimated 5.8 million Americans age 65 and older who have Alzheimer's dementia today. Official death certificates recorded 122,019 deaths from AD in 2018, the latest year for which data are available, making Alzheimer's the sixth leading cause of death in the United States and the fifth leading cause of death among Americans age 65 and older. Between 2000 and 2018, deaths resulting from stroke, HIV and heart disease decreased, whereas reported deaths from Alzheimer's increased 146.2%. In 2019, more than 16 million family members and other unpaid caregivers provided an estimated 18.6 billion hours of care to people with Alzheimer's or other dementias. This care is valued at nearly $244 billion, but its costs extend to family caregivers’ increased risk for emotional distress and negative mental and physical health outcomes. Average per‐person Medicare payments for services to beneficiaries age 65 and older with AD or other dementias are more than three times as great as payments for beneficiaries without these conditions, and Medicaid payments are more than 23 times as great. Total payments in 2020 for health care, long‐term care and hospice services for people age 65 and older with dementia are estimated to be $305 billion. As the population of Americans living with Alzheimer's dementia increases, the burden of caring for that population also increases. These challenges are exacerbated by a shortage of dementia care specialists, which places an increasing burden on primary care physicians (PCPs) to provide care for people living with dementia. Many PCPs feel underprepared and inadequately trained to handle dementia care responsibilities effectively. This report includes recommendations for maximizing quality care in the face of the shortage of specialists and training challenges in primary care.

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“…Although the reasons are not well defined, antipsychotic medications are also associated with increased mortality in vulnerable populations receiving off-label prescriptions including children [12] and older adults [13][14]. Clinical data indicate that schizophrenic patients are more susceptible to infections [15]; the role of medications, per se, on the increased susceptibility to infections in this population has not been clearly delineated.…”

Section: Introductionmentioning

confidence: 99%

The antipsychotic medication, risperidone, causes global immunosuppression in healthy mice

et al. 2019

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Atypical antipsychotic medications such as risperidone are widely prescribed for diverse psychiatric indications including schizophrenia, bipolar disorder and depression. These medications have complex pharmacology and are associated with significant endocrine and metabolic side effects. This class of medications also carries FDA black box warnings due to increased risk of death in elderly patients. Clinical reports indicate that patients treated with these medications are more susceptible to infections; however, the underlying mechanisms/pharmacology are unclear. We have previously reported that risperidone and it's active metabolite distributes to the bone marrow in clinically relevant concentrations in preclinical species, leading us to hypothesize that the hematopoietic system may be impacted by these medications. To test this hypothesis, using proteomic and cytokine array technology, we evaluated the expression of genes involved in inflammatory and immune function following short term (5 days) and longer term (4 weeks) treatment in healthy animals. We report that low-dose risperidone treatment results in global immunosuppression in mice, observed following 5 days of dosing and exacerbated with longer term drug treatment (4 weeks). These data are consistent with increased susceptibility to infection in patients administered these medications and have profound implications for the increasing off-label prescribing to vulnerable patient populations including children and the elderly.

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Increased All-Cause Mortality by Antipsychotic Drugs: Updated Review and Meta-Analysis in Dementia and General Mental Health Care

Cited by 121 publications

References 92 publications

Predictors of mortality in Māori, Pacific Island, and European patients diagnosed with dementia at a New Zealand Memory Service

Predictors of mortality in Māori, Pacific Island, and European patients diagnosed with dementia at a New Zealand Memory Service

2020 Alzheimer's disease facts and figures

The antipsychotic medication, risperidone, causes global immunosuppression in healthy mice

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