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A Systematic Review of Practice Guidelines and Recommendations for Discontinuation of Cholinesterase Inhibitors in Dementia

  • Brenna N. Renn
    Affiliations
    Veterans Affairs HSR&D Houston Center of Innovation, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX

    Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX

    Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA
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  • Ali Abbas Asghar-Ali
    Affiliations
    Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX

    Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX

    Veterans Affairs South Central Mental Illness Research, Education and Clinical Center, Houston, TX
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  • Stephen Thielke
    Affiliations
    Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA

    Veterans Affairs Puget Sound Health Care System, Seattle, WA
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  • Angela Catic
    Affiliations
    Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX

    Department of Medicine—Section of Geriatrics, Baylor College of Medicine, Houston, TX

    Veterans Affairs South Central Mental Illness Research, Education and Clinical Center, Houston, TX
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  • Sharyl R. Martini
    Affiliations
    Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX

    Department of Neurology, Baylor College of Medicine, Houston, TX
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  • Brian G. Mitchell
    Affiliations
    Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX

    Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX
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  • Mark E. Kunik
    Correspondence
    Send correspondence and reprint requests to Dr. Mark E. Kunik, MEDVAMC 152, 2002 Holcombe Blvd., Houston, TX 77030.
    Affiliations
    Veterans Affairs HSR&D Houston Center of Innovation, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX

    Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX

    Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX

    Department of Medicine—Section of Health Services Research, Baylor College of Medicine, Houston, TX

    Veterans Affairs South Central Mental Illness Research, Education and Clinical Center, Houston, TX
    Search for articles by this author
Published:October 10, 2017DOI:https://doi.org/10.1016/j.jagp.2017.09.027

      Highlights

      • Practice guidelines and textbooks were reviewed to synthesize discontinuation recommendations of cholinesterase inhibitors (ChEI) in Alzheimer's disease.
      • Published randomized controlled trials of ChEI discontinuation lack consistency; the absence of consistent findings precludes conclusions about continuing treatment.
      • Practice and textbook recommendations offer no agreement about clinical findings or situations that warrant discontinuation.
      • The top recommendation to discontinue ChEIs was a lack of response or loss of treatment effectiveness, which can be impossible to ascertain in a progressive condition.
      • Starting and stopping ChEI treatment should be individualized, based on patient and family values and preferences, to include a balanced discussion of risks and benefits.
      Cholinesterase inhibitors (ChEIs) are the primary pharmacological treatment for symptom management of Alzheimer disease (AD), but they carry known risks during long-term use, and do not guarantee clinical effects over time. The balance of risks and benefits may warrant discontinuation at different points during the disease course. Indeed, although there is limited scientific study of deprescribing ChEIs, clinicians routinely face practical decisions about whether to continue or stop medications. This review examined published practice recommendations for discontinuation of ChEIs in AD. To characterize the scientific basis for recommendations, we first summarized randomized controlled trials of ChEI discontinuation. We then identified practice guidelines by professional societies and in textbooks and classified them according to 1) whether they made a recommendation about discontinuation, 2) what the recommendation was, and 3) the proposed grounds for discontinuation. There was no consensus in guidelines and textbooks about discontinuation. Most recommended individualized discontinuation decisions, but there was essentially no agreement about what findings or situations would warrant discontinuation, or even about what domains to consider in this process. The only relevant domain identified by most guidelines and textbooks was a lack of response or a loss of effectiveness, both of which can be difficult to ascertain in the course of a progressive condition. Well-designed, long-term studies of discontinuation have not been conducted; such evidence is needed to provide a scientific basis for practice guidelines. It seems reasonable to apply an individualized approach to discontinuation while engaging patients and families in treatment decisions. 

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      Linked Article

      • Cholinesterase Inhibitor Discontinuation: The Buck Stops Here
        The American Journal of Geriatric PsychiatryVol. 26Issue 2
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          Physicians are very good at starting drug therapies; not so good at stopping them. This, in spite of the fact that our patients tell us regularly, in words and in deeds, that they don't like taking medications. But truth be told, physicians have good reasons to start and attempt to keep patients on chronic pharmacotherapies. Nowhere is this more evident than in the treatment of chronic conditions like hypertension and diabetes. But psychiatrists too have excellent evidence on the basis of which we recommend chronic pharmacotherapies, whether it is antidepressants for recurrent depression, mood stabilizers for bipolar disorder, or antipsychotics for schizophrenia.
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