Abstract
Objectives
We aimed to investigate whether sedative medications are associated with adverse outcomes
in people with dementia, and whether specific characteristics of these medications
predict a higher risk of harm.
Design
Retrospective cohort study.
Setting and Participants
15,210 patients diagnosed with dementia between 2008 and 2017 in South London.
Methods
From recorded medications at dementia diagnosis, we ascertained those with drowsiness
listed as a side effect (termed “sedative” hereafter) and subdivided them by frequency
and strength of sedation, receptor profile, half-life, and whether they were psychotropics.
Multivariable Cox regression models were applied to determine risk of mortality and
emergency hospitalization, and generalized estimating equations to investigate cognitive
decline. Final models were adjusted for 19 potential confounders, including measures
of physical and mental health, functioning, and central anticholinergic burden.
Results
At diagnosis, 70.4% of patients with dementia were receiving at least 1 sedative medication.
Median survival time was 4.0 years and median time to first hospitalization 1.4 years.
After controlling for potential confounders, receipt of any sedative medication at
dementia diagnosis was associated with accelerated cognitive decline and a higher
hospitalization risk, but only medications with a cautionary warning yielded an increased
mortality hazard. Medications acting through γ-aminobutyric acid agonism, psychotropic
sedatives, and those with a short half-life were associated with a higher risk of
mortality. γ-aminobutyric acid agonists, N-methyl-d-aspartate receptor antagonists, and nonpsychotropic sedatives were associated with
an increased hospitalization risk. α1 antagonist, antihistamines, N-methyl-d-aspartate receptor antagonists, psychotropic sedatives, and those with the shortest
or longest half-life were associated with accelerated cognitive decline.
Conclusions and Implications
Receipt of any sedative agent was associated with hospitalization and accelerated
cognitive decline. Differences in hazard appear to exist between frequency and strength
of sedation, receptor profiles, half-life, and prescribing indication. These differences
should be taken into consideration in medication reviews at the time of dementia diagnosis.
Keywords
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References
- Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study.Lancet. 2012; 380: 37-43
- Polypharmacy in people with dementia: associations with adverse health outcomes.Exp Gerontol. 2018; 106: 240-245
- Medication appropriateness tool for co-morbid health conditions in dementia: consensus recommendations from a multidisciplinary expert panel.Intern Med J. 2016; 46: 1189-1197
- Anticholinergic effect on cognition (AEC) of drugs commonly used in older people.Int J Geriatr Psychiatry. 2017; 32: 650-656
- Impact of high risk drug use on hospitalization and mortality in older people with and without Alzheimer's disease: a national population cohort study.PLoS One. 2014; 9: e83224
- Risk of death associated with new benzodiazepine use among persons with Alzheimer disease: a matched cohort study.Int J Geriatr Psychiatry. 2018; 33: 583-590
- Hypnotics and the occurrence of bone fractures in hospitalized dementia patients: a matched case-control study using a national inpatient database.PLoS One. 2015; 10: e0129366
- Sedative load and mortality among residents of long-term care facilities: a prospective cohort study.Drugs Aging. 2009; 26: 871-881
- The problems of anticholinergic adverse effects in older patients.Drugs Aging. 1993; 3: 335-348
- Neuromodulatory and neurotoxic effects of sedative agents.in: Ely E.W. Stevens R.D. Sharshar T. Brain Disorders in Critical Illness: Mechanisms, Diagnosis, and Treatment. Cambridge University Press, 2013: 150-159
- The South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLAM BRC) case register: development and descriptive data.BMC Psychiatry. 2009; 9: 51
- Cohort profile of the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Case Register: current status and recent enhancement of an Electronic Mental Health Record-derived data resource.BMJ Open. 2016; 6: e008721
- Encyclopedia of Language & Linguistics: Sca-Spe.Elsevier, 2006
- Antipsychotic use in dementia: the relationship between neuropsychiatric symptom profiles and adverse outcomes.Eur J Epidemiol. 2021; 36: 89-101
- British National Formulary.69th ed. BMJ Group and Pharmaceutical Press, 2015
- The Maudsley Prescribing Guidelines in Psychiatry.13th ed. Wiley-Blackwell, 2018
- DrugBank 5.0: a major update to the DrugBank database for 2018.Nucleic Acids Res. 2018; 46: D1074-D1082
- Improving access and use of psychotropic medicines. World Health Organization. Mental Health Policy and Service Guidance Package Web site.https://www.who.int/mental_health/policy/services/10_improving%20access_WEB_07.pdfDate: 2005Date accessed: April 22, 2020
- Mini-mental state". A practical method for grading the cognitive state of patients for the clinician.J Psychiatr Res. 1975; 12: 189-198
- The relationship between polypharmacy and trajectories of cognitive decline in people with dementia: a large representative cohort study.Exp Gerontol. 2019; 120: 62-67
- Longitudinal data analysis using generalized linear models.Biometrika. 1986; 73: 13-22
- The English indices of deprivation 2007.Communities and Local Government, 2007
- Health of the Nation Outcome Scales for elderly people (HoNOS 65+).Br J Psychiatry. 1999; 174: 424-427
- Associations of acetylcholinesterase inhibitor treatment with reduced mortality in Alzheimer's disease: a retrospective survival analysis.Age Ageing. 2018; 47: 88-94
- Factors associated with response to acetylcholinesterase inhibition in dementia: a cohort study from a secondary mental health care case register in London.PLoS One. 2014; 9: e109484
- Cardiovascular outcomes of cholinesterase inhibitors in individuals with dementia: a meta-analysis and systematic review.J Am Geriatr Soc. 2018; 66: 1805-1811
- Flexible multiple imputation by chained equations of the AVO-95 survey.TNO Prevention and Health Leiden, 1999
- The anticholinergic effect on cognition (AEC) scale-Associations with mortality, hospitalisation and cognitive decline following dementia diagnosis.Int J Geriatr Psychiatry. 2020; 35: 1069-1077
- STOPP/START criteria for potentially inappropriate prescribing in older people: version 2.Age Ageing. 2015; 44: 213-218
- American Geriatrics Society 2019 Updated AGS Beers Criteria(R) for Potentially Inappropriate Medication Use in Older Adults.J Am Geriatr Soc. 2019; 67: 674-694
- Psychiatric medication and abnormal behavior as predictors of progression in probable Alzheimer disease.Arch Neurol. 1999; 56: 1266-1272
- Hazardous benzodiazepine regimens in the elderly: effects of half-life, dosage, and duration on risk of hip fracture.Am J Psychiatry. 2001; 158: 892-898
- [Association between elimination half-life of benzodiazepines and falls in the elderly: a meta-analysis of observational studies].Yakugaku Zasshi. 2019; 139: 113-122
- Mortality risk of atypical antipsychotics for behavioral and psychological symptoms of dementia: a meta-analysis, meta-regression, and trial sequential analysis of randomized controlled trials.J Clin Psychopharmacol. 2019; 39: 472-478
- Associations of neuropsychiatric symptoms and antidepressant prescription with survival in Alzheimer's disease.J Am Med Dir Assoc. 2017; 18: 1076-1081
- Cognitive effects of atypical antipsychotic medications in patients with Alzheimer's disease: outcomes from CATIE-AD.Am J Psychiatry. 2011; 168: 831-839
- Benzodiazepines and related drugs as a risk factor in Alzheimer's Disease dementia.Front Aging Neurosci. 2019; 11: 344
- Impact of antidepressant use on the trajectory of Alzheimer's disease: evidence, mechanisms, and therapeutic implications.CNS Drugs. 2019; 33: 17-29
- Association of concomitant use of cholinesterase inhibitors or memantine with cognitive decline in alzheimer clinical trials: A meta-analysis.JAMA Network Open. 2018; 1: e184080
- Polypharmacy and Medicines Optimisation. Making It Safe and Sound.The King’s Fund, 2013
- Safe prescribing in cognitively vulnerable patients: the use of the anticholinergic effect on cognition (AEC) tool in older adult mental health services.BJPsych Bull. 2019; : 26-30
Article info
Publication history
Published online: February 02, 2022
Footnotes
A.M., D.B., R.S., and C.M. are co–first authors.
C.M., G.P., and R.S. receive salary support from the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. R.S. is an NIHR Senior Investigator and is funded by the National Institute for Health Research (NIHR) Applied Research Collaboration South London (NIHR ARC South London) at King's College Hospital NHS Foundation Trust. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care.
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© 2022 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
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