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The excess mortality risk associated with anticholinergic burden among older patients discharged from acute care hospital with depressive symptoms

Published:November 15, 2018DOI:https://doi.org/10.1016/j.ejim.2018.11.004

      Highlights

      • Depressive symptoms may increase the risk of iatrogenic events.
      • Depressive symtpoms may influence the prognostic impact of anticholinergic drugs.
      • A prognostic interaction between anticholinergic burden and GDS score is reported.
      • Hospital physician should try to reduce anticholinergic burden at discharge.
      • This is especially relevant for vulnerable patients carrying high GDS score.

      Abstract

      Background

      The relationship between anticholinergic burden and mortality is controversial, and the impact of anticholinergic burden on prognosis may vary in presence of other conditions common in old age. We aimed at investigating the role of depressive symptoms as potential effect modifiers in the association between anticholinergic burden and 1-year mortality in older patients discharged from hospital.

      Methods

      Our series consisted of 576 older patients consecutively admitted to seven geriatric and internal medicine acute care wards in the context of a prospective multicenter observational study. Overall anticholinergic burden was assessed by Anticholinergic Cognitive Burden (ACB) score. Depressive symptoms were assessed by 15-item Geriatric Depression Scale (GDS). The study outcome was all-cause mortality during 12-months follow-up. Statistical analysis was carried out by Cox regression analysis.

      Results

      After adjusting for potential confounders, discharge ACB score = 2 or more was significantly associated with the outcome among patients with GDS > 5 (HR = 3.70; 95%CI = 1.18–11.6), but not among those with GDS ≤ 5 (HR = 2.32; 95%CI = 0.90–6.24). The association was confirmed among depressed patients after adjusting for ACB score at 3-month follow-up (HR = 3.58; 95%CI = 1.21–10.7), as well as when considering ACB score as a continuous variable (HR = 1.42; 95%CI = 1.10–1.91). The interaction between ACB score at discharge and BADL dependency was statistically significant (p < .005).

      Conclusions

      ACB score at discharge may predict mortality among older patients discharged from acute care hospital carrying high GDS score e. Hospital physician should be aware that prescribing anticholinergic medications in such a vulnerable population may have negative prognostic implications.

      Keywords

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      References

        • Landi F.
        • Dell'Aquila G.
        • Collamati A.
        • Martone A.M.
        • Zuliani G.
        • Gasperini B.
        • et al.
        Anticholinergic drug use and negative outcomes among the frail elderly population living in a nursing home.
        J Am Med Dir Assoc. 2014; 15: 825-829
        • Pasina L.
        • Djade C.D.
        • Lucca U.
        • Nobili A.
        • Tettamanti M.
        • Franchi C.
        • et al.
        Association of anticholinergic burden with cognitive and functional status in a cohort of hospitalized elderly: comparison of the anticholinergic cognitive burden scale and anticholinergic risk scale: results from the REPOSI study.
        Drugs Aging. 2013; 30: 103-112
        • Ruxton K.
        • Woodman R.J.
        • Mangoni A.A.
        Drugs with anticholinergic effects and cognitive impairment, falls and all-cause mortality in older adults: a systematic review and meta-analysis.
        Br J Clin Pharmacol. 2015; 80: 209-220
        • Bostock C.V.
        • Soiza R.L.
        • Mangoni A.A.
        Associations between different measures of anticholinergic drug exposure and Barthel Index in older hospitalized patients.
        Ther Adv Drug Saf. 2013; 4: 235-245
        • Ness J.
        • Hoth A.
        • Barnett M.J.
        • Shorr R.I.
        • Kaboli P.J.
        Anticholinergic medications in community-dwelling older veterans: prevalence of anticholinergic symptoms, symptom burden, and adverse drug events.
        Am J Geriatr Pharmacother. 2006; 4: 42-51
        • Myint P.K.
        • Fox C.
        • Kwok C.S.
        • Luben R.N.
        • Wareham N.J.
        • Khaw K.T.
        Total anticholinergic burden and risk of mortality and cardiovascular disease over 10 years in 21,636 middle-aged and older men and women of EPIC-Norfolk prospective population study.
        Age Ageing. 2015; 44: 219-225
        • Mangoni A.A.
        • van Munster B.C.
        • Woodman R.J.
        • de Rooij S.E.
        Measures of anticholinergic drug exposure, serum anticholinergic activity, and all-cause postdischarge mortality in older hospitalized patients with hip fractures.
        Am J Geriatr Psychiatry. 2013; 21: 785-793
        • Fox C.
        • Richardson K.
        • Maidment I.D.
        • Savva G.M.
        • Matthews F.E.
        • Smithard D.
        • et al.
        Anticholinergic medication use and cognitive impairment in the older population: the medical research council cognitive function and ageing study.
        J Am Geriatr Soc. 2011; 59: 1477-1483
        • Vetrano D.L.
        • La Carpia D.
        • Grande G.
        • Casucci P.
        • Bacelli T.
        • Bernabei R.
        • et al.
        Anticholinergic medication burden and 5-year risk of hospitalization and death in nursing home elderly residents with coronary artery disease.
        J Am Med Dir Assoc. 2016; 17: 1056-1059
        • Gutierrez-Valencia M.
        • Martinez-Velilla N.
        • Vetrano D.L.
        • Corsonello A.
        • Lattanzio F.
        • Ladron-Arana S.
        • et al.
        Anticholinergic burden and health outcomes among older adults discharged from hospital: results from the CRIME study.
        Eur J Clin Pharmacol. 2017; 73: 1467-1474
        • Dauphinot V.
        • Faure R.
        • Omrani S.
        • Goutelle S.
        • Bourguignon L.
        • Krolak-Salmon P.
        • et al.
        Exposure to anticholinergic and sedative drugs, risk of falls, and mortality: an elderly inpatient, multicenter cohort.
        J Clin Psychopharmacol. 2014; 34: 565-570
        • Luukkanen M.J.
        • Uusvaara J.
        • Laurila J.V.
        • Strandberg T.E.
        • Raivio M.M.
        • Tilvis R.S.
        • et al.
        Anticholinergic drugs and their effects on delirium and mortality in the elderly.
        Dement Geriatr Cogn Dis Extra. 2011; 1: 43-50
        • Kumpula E.K.
        • Bell J.S.
        • Soini H.
        • Pitkala K.H.
        Anticholinergic drug use and mortality among residents of long-term care facilities: a prospective cohort study.
        J Clin Pharmacol. 2011; 51: 256-263
        • Lattanzio F.
        • Corica F.
        • Schepisi R.
        • Amantea D.
        • Bruno F.
        • Cozza A.
        • et al.
        Anticholinergic burden and 1-year mortality among older patients discharged from acute care hospital.
        Geriatr Gerontol Int. 2018; 18: 705-713
        • Lattanzio F.
        • Onder G.
        • La Fauci M.M.
        • Volpato S.
        • Cherubini A.
        • Fabbietti P.
        • et al.
        Anticholinergic burden is associated with increased mortality in older patients with dependency discharged from hospital.
        J Am Med Dir Assoc. 2018 Jul 23; (pii: S1525-8610(18)30332-3 [Epub ahead of print])https://doi.org/10.1016/j.jamda.2018.06.012
        • Prina A.M.
        • Cosco T.D.
        • Dening T.
        • Beekman A.
        • Brayne C.
        • Huisman M.
        The association between depressive symptoms in the community, non-psychiatric hospital admission and hospital outcomes: a systematic review.
        J Psychosom Res. 2015; 78: 25-33
        • Pierluissi E.
        • Mehta K.M.
        • Kirby K.A.
        • Boscardin W.J.
        • Fortinsky R.H.
        • Palmer R.M.
        • et al.
        Depressive symptoms after hospitalization in older adults: function and mortality outcomes.
        J Am Geriatr Soc. 2012; 60: 2254-2262
        • Onder G.
        • Penninx B.W.
        • Landi F.
        • Atkinson H.
        • Cesari M.
        • Bernabei R.
        • et al.
        Depression and adverse drug reactions among hospitalized older adults.
        Arch Intern Med. 2003; 163: 301-305
        • Aalto U.L.
        • Roitto H.M.
        • Finne-Soveri H.
        • Kautiainen H.
        • Pitkala K.
        Use of anticholinergic drugs and its relationship with psychological well-being and mortality in long-term care facilities in Helsinki.
        J Am Med Dir Assoc. 2018; 19: 511-515
        • Tosato M.
        • Settanni S.
        • Antocicco M.
        • Battaglia M.
        • Corsonello A.
        • Ruggiero C.
        • et al.
        Pattern of medication use among older inpatients in seven hospitals in Italy: results from the CRiteria to assess appropriate medication use among elderly complex patients (CRIME) project.
        Curr Drug Saf. 2013; 8: 98-103
        • Pahor M.
        • Chrischilles E.A.
        • Guralnik J.M.
        • Brown S.L.
        • Wallace R.B.
        • Carbonin P.
        Drug data coding and analysis in epidemiologic studies.
        Eur J Epidemiol. 1994; 10: 405-411
        • Lesher E.L.
        • Berryhill J.S.
        Validation of the geriatric depression scale–short form among inpatients.
        J Clin Psychol. 1994; 50: 256-260
        • Boustani M.A.
        • Campbell N.L.
        • Munger S.
        • Maidment I.
        • Fox G.C.
        Impact of anticholinergics on the aging brain: a review and practical application.
        Aging Health. 2008; 4: 311-320
        • Campbell N.L.
        • Boustani M.A.
        • Lane K.A.
        • Gao S.
        • Hendrie H.
        • Khan B.A.
        • et al.
        Use of anticholinergics and the risk of cognitive impairment in an African American population.
        Neurology. 2010; 75: 152-159
        • Carnahan R.M.
        • Lund B.C.
        • Perry P.J.
        • Pollock B.G.
        • Culp K.R.
        The Anticholinergic Drug Scale as a measure of drug-related anticholinergic burden: associations with serum anticholinergic activity.
        J Clin Pharmacol. 2006; 46: 1481-1486
        • Rudolph J.L.
        • Salow M.J.
        • Angelini M.C.
        • McGlinchey R.E.
        The anticholinergic risk scale and anticholinergic adverse effects in older persons.
        Arch Intern Med. 2008; 168: 508-513
        • Folstein M.F.
        • Folstein S.E.
        • McHugh P.R.
        "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician.
        J Psychiatr Res. 1975; 12: 189-198
        • Mintzer J.
        • Burns A.
        Anticholinergic side-effects of drugs in elderly people.
        J R Soc Med. 2000; 93: 457-462
        • Collamati A.
        • Martone A.M.
        • Poscia A.
        • Brandi V.
        • Celi M.
        • Marzetti E.
        • et al.
        Anticholinergic drugs and negative outcomes in the older population: from biological plausibility to clinical evidence.
        Aging Clin Exp Res. 2016; 28: 25-35
        • Corsonello A.
        • Pedone C.
        • Incalzi R.A.
        Age-related pharmacokinetic and pharmacodynamic changes and related risk of adverse drug reactions.
        Curr Med Chem. 2010; 17: 571-584
        • Leon C.
        • Gerretsen P.
        • Uchida H.
        • Suzuki T.
        • Rajji T.
        • Mamo D.C.
        Sensitivity to antipsychotic drugs in older adults.
        Curr Psychiatry Rep. 2010; 12: 28-33
        • Kurzen H.
        • Wessler I.
        • Kirkpatrick C.J.
        • Kawashima K.
        • Grando S.A.
        The non-neuronal cholinergic system of human skin.
        Horm Metab Res. 2007; 39: 125-135
        • Razani-Boroujerdi S.
        • Behl M.
        • Hahn F.F.
        • Pena-Philippides J.C.
        • Hutt J.
        • Sopori M.L.
        Role of muscarinic receptors in the regulation of immune and inflammatory responses.
        J Neuroimmunol. 2008; 194: 83-88
        • Lampela P.
        • Lavikainen P.
        • Garcia-Horsman J.A.
        • Bell J.S.
        • Huupponen R.
        • Hartikainen S.
        Anticholinergic drug use, serum anticholinergic activity, and adverse drug events among older people: a population-based study.
        Drugs Aging. 2013; 30: 321-330
        • Georgakis M.K.
        • Papadopoulos F.C.
        • Protogerou A.D.
        • Pagonari I.
        • Sarigianni F.
        • Biniaris-Georgallis S.I.
        • et al.
        Comorbidity of cognitive impairment and late-life depression increase mortality: results from a cohort of community-dwelling elderly individuals in rural greece.
        J Geriatr Psychiatry Neurol. 2016; 29: 195-204
        • Park S.H.
        • Kim D.
        • Cho J.
        • Jin Y.
        • Lee I.
        • Lee K.
        • et al.
        Depressive symptoms and all-cause mortality in Korean older adults: a 3-year population-based prospective study.
        Geriatr Gerontol Int. 2018; 18: 950-956
        • Dagyte G.
        • Den Boer J.A.
        • Trentani A.
        The cholinergic system and depression.
        Behav Brain Res. 2011; 221: 574-582
        • Landi F.
        • Russo A.
        • Liperoti R.
        • Cesari M.
        • Barillaro C.
        • Pahor M.
        • et al.
        Anticholinergic drugs and physical function among frail elderly population.
        Clin Pharmacol Ther. 2007; 81: 235-241
        • Zia A.
        • Kamaruzzaman S.
        • Myint P.K.
        • Tan M.P.
        Anticholinergic burden is associated with recurrent and injurious falls in older individuals.
        Maturitas. 2016; 84: 32-37
        • Hajek A.
        • Brettschneider C.
        • van den Bussche H.
        • Luhmann D.
        • Oey A.
        • Wiese B.
        • et al.
        Impact of falls on depressive symptoms among the oldest old: results from the AgeQualiDe study.
        Int J Geriatr Psychiatry. 2018 Oct; 33: 1383-1388
        • Salahudeen M.S.
        • Duffull S.B.
        • Nishtala P.S.
        Anticholinergic burden quantified by anticholinergic risk scales and adverse outcomes in older people: a systematic review.
        BMC Geriatr. 2015; 15: 31