Advertisement

Recent Hospitalization and Initiation of Antiepileptics Among Persons With Alzheimer’s Disease

  • Jenna Elo
    Affiliations
    School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland

    Kuopio Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, Finland
    Search for articles by this author
  • Anna-Maija Tolppanen
    Affiliations
    School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland

    Kuopio Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, Finland
    Search for articles by this author
  • Marjaana Koponen
    Affiliations
    School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland

    Kuopio Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, Finland

    Center for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia
    Search for articles by this author
  • Miia Tiihonen
    Affiliations
    School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland

    Kuopio Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, Finland
    Search for articles by this author
  • Sirpa Hartikainen
    Correspondence
    Address correspondence to Sirpa Hartikainen, MD, PhD, School of Pharmacy, University of Eastern Finland, PO Box 1627, 70211 Kuopio, Finland.
    Affiliations
    School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland

    Kuopio Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, Finland
    Search for articles by this author
Published:November 17, 2022DOI:https://doi.org/10.1016/j.jamda.2022.10.009

      Abstract

      Objectives

      Antiepileptic drugs (AEDs) are frequently prescribed for persons with Alzheimer’s disease (AD), but little is known on factors associated with AED initiation in this population. We investigated whether recent hospitalization is associated with AED initiation in persons with AD.

      Design

      Nested case-control study in the nationwide register-based Medication use and Alzheimer’s disease (MEDALZ) cohort.

      Participants and Settings

      The MEDALZ cohort includes 70,718 persons diagnosed with AD during 2005-2011 in Finland. Altogether 6814 AED initiators and 6814 age-, sex-, and time since AD diagnosis-matched noninitiators were included in this study. Matching date was the date of AED initiation.

      Methods

      AED purchases were identified from the Prescription Register and hospitalizations from the Care Register for Health Care. Recent hospitalization was defined as hospitalization ending within 2 weeks before the matching date. Association between recent hospitalization and AED initiation was assessed with conditional logistic regression.

      Results

      The most frequently initiated AEDs were pregabalin (42.9%) and valproic acid (32.2%). A bigger proportion of AED initiators (36.9%) than noninitiators (5.3%) were recently hospitalized [odds ratio (OR) 10.5, 95% CI 9.22-11.9]. Dementia was the most frequent discharge diagnosis among AED initiators (29.1%) and noninitiators (27.9%). Among AED initiators, the next most frequent diagnosis was epilepsy (20.6%). Musculoskeletal diagnoses and use of analgesics including opioids was more common among gabapentinoid initiators compared with other AED initiators.

      Conclusions and Implications

      Recent hospitalization was significantly related to AED initiation. Initiations of AED might have been related to common symptoms in persons with AD like neuropathic pain, epilepsy, and neuropsychiatric symptoms.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of the American Medical Directors Association
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Bialer M.
        Why are antiepileptic drugs used for nonepileptic conditions?.
        Epilepsia. 2012; 53: 26-33
        • Spina E.
        • Perugi G.
        Antiepileptic drugs: indications other than epilepsy.
        Epileptic Disord. 2004; 6: 57-75
        • Lackner T.E.
        Strategies for optimizing antiepileptic drug therapy in elderly people.
        Pharmacotherapy. 2002; 22: 329-364
        • Ortinski P.
        • Meador K.J.
        Cognitive side effects of antiepileptic drugs.
        Epilepsy Behav. 2004; 5: 60
        • Sarycheva T.
        • Lavikainen P.
        • Taipale H.
        • et al.
        Antiepileptic drug use and the risk of stroke among community-dwelling people with Alzheimer disease: a Matched Cohort Study.
        J Am Heart Assoc. 2018; 7: e009742
        • Maximos M.
        • Chang F.
        • Patel T.
        Risk of falls associated with antiepileptic drug use in ambulatory elderly populations: a systematic review.
        Can Pharm J (Ott). 2017; 150: 101-111
        • Taipale H.
        • Lampela P.
        • Koponen M.
        • et al.
        Antiepileptic drug use is associated with an increased risk of pneumonia among community-dwelling persons with Alzheimer's disease-Matched Cohort Study.
        J Alzheimers Dis. 2019; 68: 127-136
        • Sarycheva T.
        • Lavikainen P.
        • Taipale H.
        • et al.
        Antiepileptic drug use and mortality among community-dwelling persons with Alzheimer disease.
        Neurology. 2020; 94: e2099-e2108
        • Zaccara G.
        • Perucca E.
        Interactions between antiepileptic drugs, and between antiepileptic drugs and other drugs.
        Epileptic Disord. 2014; 16: 409-431
        • Jankovic S.M.
        • Dostic M.
        Choice of antiepileptic drugs for the elderly: possible drug interactions and adverse effects.
        Expert Opin Drug Metab Toxicol. 2012; 8: 81-91
        • Bell J.S.
        • Lönnroos E.
        • Koivisto A.M.
        • et al.
        Use of antiepileptic drugs among community-dwelling persons with Alzheimer's disease in Finland.
        J Alzheimers Dis. 2011; 26: 231-237
        • Sarycheva T.
        • Taipale H.
        • Lavikainen P.
        • et al.
        Incidence and prevalence of antiepileptic medication use in community-dwelling persons with and without Alzheimer's disease.
        J Alzheimers Dis. 2018; 66: 387-395
        • Beagle A.J.
        • Darwish S.M.
        • Ranasinghe K.G.
        • et al.
        Relative incidence of seizures and myoclonus in Alzheimer's disease, dementia with lewy bodies, and frontotemporal dementia.
        J Alzheimers Dis. 2017; 60: 211-223
        • Scarmeas N.
        • Honig L.S.
        • Choi H.
        • et al.
        Seizures in Alzheimer disease: who, when, and how common?.
        Arch Neurol. 2009; 66: 992-997
        • Amatniek J.C.
        • Hauser W.A.
        • DelCastillo-Castaneda C.
        • et al.
        Incidence and predictors of seizuresn patients with Alzheimer's disease.
        Epilepsia. 2006; 47: 867-872
        • Cheng C.H.
        • Liu C.J.
        • Ou S.M.
        • et al.
        Incidence and risk of seizures in Alzheimer's disease: A nationwide population-based cohort study.
        Epilepsy Res. 2015; 115: 63-66
        • Zelano J.
        • Brigo F.
        • Garcia-Patek S.
        Increased risk of epilepsy in patients registered in the Swedish Dementia Registry.
        Eur J Neurol. 2020; 27: 129-135
        • Kales H.C.
        • Gitlin L.N.
        • Lyketsos C.G.
        When less is more, but still not enough: why focusing on limiting antipsychotics in people with dementia is the wrong policy imperative.
        J Am Med Dir Assoc. 2019; 20: 1074-1079
        • Gerlach L.B.
        • Kales H.C.
        • Kim H.M.
        • et al.
        Trends in antipsychotic and mood stabilizer prescribing in long-term care in the U.S.: 2011-2014.
        J Am Med Dir Assoc. 2020; 21: 1629-1635.e8
        • Gerlach L.B.
        • Maust D.T.
        • Kales H.C.
        • et al.
        Evaluation of antipsychotic reduction efforts in patients with dementia in Veterans Health Administration Nursing Homes.
        Am J Psychiatry. 2022; 179: 544-552
        • Hakala A.
        • Tolppanen A.M.
        • Koponen M.
        • et al.
        Does recent hospitalization increase antipsychotic initiation among community dwellers with Alzheimer's disease?.
        J Am Med Dir Assoc. 2021; 22: 1543-1547.e3
        • Tarvainen A.
        • Hartikainen S.
        • Taipale H.
        • et al.
        Association of recent hospitalisation with antidepressant initiation among community dwellers with Alzheimer's disease.
        Int J Geriatr Psychiatry. 2021; 36: 1075-1084
        • Tolppanen A.M.
        • Taipale H.
        • Koponen M.
        • et al.
        Cohort profile: the finnish medication and Alzheimer's disease (MEDALZ) study.
        BMJ Open. 2016; 6: e012100
        • McKhann G.
        • Drachman D.
        • Folstein M.
        • et al.
        Clinical diagnosis of Alzheimer's disease.
        Neurology. 1984; 34: 939
        • American Psychiatric Association
        Diagnostic and Statistical Manual of Mental Disorders: DSM-IV.
        4th ed. American Psychiatric Association, Washington, DC1994
        • WHO. Collaboration Center for Drug Statistics Methodology
        The anatomical therapeutic chemical classification system.
        https://www.whocc.no/atc_ddd_index/
        Date accessed: March 5, 2022
        • Finnish Medical Society Duodecim
        Finnish Current Care Guidelines for The Progression of Alzheimer’s Disease. Duodecim.
        https://www.kaypahoito.fi/nix00516
        Date accessed: March 5, 2022
        • Yeh Y.C.
        • Ouyang W.C.
        Mood stabilizers for the treatment of behavioral and psychological symptoms of dementia: an update review.
        Kaohsiung J Med Sci. 2012; 28: 185-193
        • Ballard C.
        • Corbett A.
        Agitation and aggression in people with Alzheimer's disease.
        Curr Opin Psychiatry. 2013; 26: 252-259
        • Cohen-Mansfield J.
        • Thein K.
        • Marx M.S.
        • et al.
        Efficacy of nonpharmacologic interventions for agitation in advanced dementia: a randomized, placebo-controlled trial.
        J Clin Psychiatry. 2012; 73: 1255-1261
        • Lyketsos C.G.
        • Lopez O.
        • Jones B.
        • et al.
        Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study.
        JAMA. 2002; 288: 1475-1483
        • Sampson E.L.
        • White N.
        • Leurent B.
        • et al.
        Behavioural and psychiatric symptoms in people with dementia admitted to the acute hospital: prospective cohort study.
        British Journal of Psychiatry. 2014; 205: 189-196
        • Wettermark B.
        • Brandt L.
        • Kieler H.
        • Bodén R.
        Pregabalin is increasingly prescribed for neuropathic pain, generalised anxiety disorder and epilepsy but many patients discontinue treatment.
        Int J Clin Pract. 2014; 68: 104-110
        • Tassone D.M.
        • Boyce E.
        • Guyer J.
        • Nuzum D.
        Pregabalin: a novel gamma-aminobutyric acid analogue in the treatment of neuropathic pain, partial-onset seizures, and anxiety disorders.
        Clin Ther. 2007; 29: 26-48
        • Snyder M.J.
        • Gibbs L.M.
        • Lindsay T.J.
        Treating painful diabetic peripheral neuropathy: an update.
        Am Fam Physician. 2016; 94: 227-234
        • Forsgren L.
        • Beghi E.
        • Oun A.
        • Sillanpää M.
        The epidemiology of epilepsy in Europe – a systematic review.
        Eur J Neurol. 2005; 12: 245-253
        • Finnish Medical Society Duodecim
        Finnish Current Care Guidelines for Epilepsies (adult). Duodecim.
        https://www.kaypahoito.fi/hoi50072
        Date accessed: March 5, 2022
        • Bruun E.
        • Virta L.J.
        • Kälviäinen R.
        • Keränen T.
        Choice of the first anti-epileptic drug in elderly patients with newly diagnosed epilepsy: a Finnish retrospective study.
        Seizure. 2015; 31: 27-32
        • Baillon S.F.
        • Narayana U.
        • Luxenberg J.S.
        • Clifton A.V.
        Valproate preparations for agitation in dementia.
        Cochrane Database Syst Rev. 2018; 10: CD003945
        • Tariot P.N.
        • Schneider L.S.
        • Cummings J.
        • et al.
        Chronic divalproex sodium to attenuate agitation and clinical progression of Alzheimer disease.
        Arch Gen Psychiatry. 2011; 68: 853-861
        • Taipale H.
        • Koponen M.
        • Tanskanen A.
        • et al.
        High prevalence of psychotropic drug use among persons with and without Alzheimer's disease in Finnish nationwide cohort.
        Eur Neuropsychopharmacol. 2014; 24: 1729-1737
        • Ferlazzo E.
        • Sueri C.
        • Gasparini S.
        • Aguglia U.
        Challenges in the pharmacological management of epilepsy and its causes in the elderly.
        Pharmacol Res. 2016; 106: 21-26
        • Denic A.
        • Glassock R.J.
        • Rule A.D.
        Structural and functional changes with the aging kidney.
        Adv Chronic Kidney Dis. 2016; 23: 19-28
        • Sarkis R.A.
        • Dickerson B.C.
        • Cole A.J.
        • Chemali Z.N.
        Clinical and neurophysiologic characteristics of unprovoked seizures in patients diagnosed with dementia.
        J Neuropsychiatry Clin Neurosci. 2016; 28: 56-61
        • Sund R.
        Quality of the Finnish Hospital Discharge Register: a systematic review.
        Scand J Public Health. 2012; 40: 505-515
        • Solomon A.
        • Ngandu T.
        • Soininen H.
        • Hallikainen M.
        • Kivipelto M.
        • Laatikainen T.
        Identification of AD cases from the applied data sources Alzheimer & Dementia. 10. 2014: 303-309
        • Rikala M.
        • Hartikainen S.
        • Sulkava R.
        • Korhonen M.J.
        Validity of the Finnish Prescription Register for measuring psychotropic drug exposures among elderly finns: a population-based intervention study.
        Drugs Aging. 2010; 27: 337-349