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Deprescribing in Palliative Care: An Overview

Bradi L. Frei, PharmD MSc BCOP BCPS
Professor, Pharmacy Practice
Feik School of Pharmacy
University of the Incarnate Word
San Antonio, TX

Deprescribing is the practice of discontinuing potentially inappropriate prescription and nonprescription medications, including complementary and alternative medicine (CAM), in patients when the possible risks outweigh the benefits. Potentially inappropriate medications (PIMs) are largely referred to as medications lacking evidence-based indications, medications with treatment risks that may outweigh their benefits, medications associated with significant adverse reactions, and those that may potentially interact with other medications or diseases.1 This practice was initially developed for use in geriatric patients who had significant polypharmacy and limited life expectancy, but it has slowly been adopted in palliative care and oncology. Deprescribing has many benefits, including reducing medication costs, minimizing adverse drug effects, improving patients’ quality of life, improving adherence to beneficial medications, and decreasing the burden of polypharmacy in the last months of life.

Polypharmacy, frequently defined as taking five or more prescriptions concurrently for the treatment of one or more coexisting diseases, is common in older cancer patients.2 Polypharmacy in this setting can be appropriate if the additional medications are indicated and are benefiting the patient, but each added medication should be thoroughly assessed for benefits and risks. Trends in prescription drug use was evaluated by Kantor and colleagues with the National Health and Nutrition Examination Survey from 1992 to 2012.3 A significant increase in polypharmacy was seen over the years in all adult age and ethnic groups.3 During the 2011–2012 period, 39% of adults aged 65 years and older reported polypharmacy.

Cancer, often diagnosed in older patients, is difficult to treat, and the management of cancer symptoms and the adverse effects of treatment further complicate that treatment. The prevalence of polypharmacy at time of diagnosis in older acute myelogenous leukemia (AML) patients has been reported as 38%, with a median of four prescription medications prescribed.4 Several other clinical trials report an average of four to nine prescription medications per patient with 50%–69% of patients reporting use of CAM.4-6 Milic and colleagues reported that 37% of metastatic breast cancer patients were taking 10 or more tablets per day.7

The impact of polypharmacy in oncology patients has been evaluated in several studies. Woopen and colleagues analyzed prospective ovarian cancer trials to evaluate the influence of polypharmacy on grade 3/4 toxicity, prior discontinuation of chemotherapy, and survival.8 Increased medication use was associated with overall grade 3/4 toxicity (p < .001) and hematological (p < .001) and nonhematological (p < .001) toxicities. However, increased medication use was not associated with early discontinuation of chemotherapy (p = .196) or with overall survival (p = .068). In addition, Elliot and colleagues conducted a retrospective analysis of newly diagnosed AML patients (N = 150) and demonstrated that the total number of prescription medications at baseline was associated with increased 30-day mortality.4 The authors suggest that the increase in mortality could be caused by comorbidities and poorer health rather than resulting from an effect of polypharmacy. However, although an increased number of medications has been associated with chemotoxicity in some studies, overall results have been inconsistent, and many of the trials have not shown any adverse effects of PIMs. It is possible that some of the supportive care medications that could be classified as PIMs still have benefit to mitigate adverse effects from treatment in older patients.1

Several studies have described the common medications taken by patients near the end of life. Woopen and colleagues conducted a meta-analysis of three ovarian cancer trials (N = 1,213) and reported that the most frequent medications taken by the patients, besides those prescribed for symptomatic relief, were beta blockers (17.4%), diuretics (13.4%), and angiotensin-converting enzyme inhibitors (11%).8 Medications appropriate for deprescribing may seem evident in some cases, but others may have some positive attributes despite the negative ones. In addition, some prescribers may be reluctant to discontinue certain medications (e.g., proton pump inhibitors [PPIs] and statins) because of fear of adverse effects or other complications. PPIs are a mainstay in treating many acid-related disorders. Strong data support the short-term use of PPIs to control dyspepsia and gastroesophageal reflux disease (GERD). Because dyspepsia and other acid-related disorders can decrease a patient’s quality of life, the use of PPIs could be viewed as appropriate. However, long-term use of PPIs has been associated with hypergastrinemia, hypochlorhydria, idiosyncratic reactions, and pharmacokinetic interactions. Each of these can lead to health problems such as malabsorption of nutrients and tissue dysplasia.

Deprescribing of PPIs has been recommended for adults who are symptom-free after completion of a minimum 4-week PPI treatment for GERD.9 Kutner and colleagues conducted a randomized unblinded clinical trial that included 381 patients with limited life expectancy to evaluate the effects of statin deprescribing.10 Forty-eight percent of the patients had cancer. The primary outcome of death within 60 days was not different between the two groups (p = .36). Very few cardiovascular events occurred during the trial, with no difference between groups. Quality of life was statistically better in the group that discontinued statin use. Deprescribing was associated with cost savings of $3.37 per day and $716 per patient.

Deprescribing Process

The geriatric literature describes several models for deprescribing, and a few models appear in oncology and palliative care literature. Scott and colleagues described a five-step process for eprescribing (Table 1 - see PDF).11 The first step in deprescribing is to perform medication reconciliation, including over-the-counter medications and medications used in CAM. The patient should be interviewed to determine the indication for the use of each medication; contacting the patient’s other providers to help determine the indication may also be necessary. After a determination has been made about which medications are to be discontinued, a decision can be made about which medications to stop first. When prioritizing drugs for discontinuation, the provider should choose to stop medications that have the greatest risk of harm and the least benefit, followed by those easiest to discontinue and then those that the patient is most willing to discontinue. Medications should be discontinued one at a time. The provider and patient should develop a written plan for discontinuation, including tapering instructions and a plan for follow-up and monitoring for any adverse effects of discontinuation. The provider should fully document the reasons for, and outcome of, discontinuation. Shared decision making is important in this process because deprescribing can have a psychological impact on both patients and caregivers. Deprescribing medication could be interpreted as having “given up on the patient” or believing that “the patient will soon die.” Other patients and caregivers may embrace having fewer medications and decreased medication costs.

(Table 2 - see PDF) lists common medication classes that are recommended to be tapered when they are being discontinued. A general rule of thumb when tapering is to decrease the dose by 50% for a prespecified amount of time and then decrease by 50% again or permanently discontinue the medication if a subsequent decrease is not feasible with the available dosage options. Tapering may take a week or up to several months depending on the medication and patient response. However, only one medication should be tapered or discontinued at a time.11

Tools for Deprescribing Medications

Several tools can help determine which medications should be discontinued; a list of available resources is given in (Table 3 - see PDF). The Beers Criteria, an explicit list of PIMs that are usually best avoided in older adults, is published by the American Geriatrics Society on a 3-year update cycle, with the most recent update published in 2019.12 In addition, the Medication Appropriateness Index (MAI) was developed in 1992 to identify PIMs by asking 10 questions that incorporate a 1–3 rating option depending on the appropriateness. The higher the score, the more likely it is that the medication is inappropriate for the patient. MAI is one of the few tools that also considers drug-drug interactions.13 The National Comprehensive Cancer Network (NCCN) Guidelines for Older Adult Oncology provides a list of medications that are commonly used for supportive care and that are a concern in older cancer patients. The guideline provides recommendations and alternative options for commonly prescribed supportive care medications.14 The Screening Tool of Older Persons’ Prescriptions (STOPP) criteria note the medications that increase the risk of falls and those with a high chance of adverse events (drug-drug and drug-disease interactions are included).15 These are explicit criteria for determining optimal prescribing and can be applied to most patients. The Drug Burden Index was developed to measure the cumulative exposure to medications with anticholinergic and sedative effects in older adults and its impact on physical and cognitive function.16

The MedStopper online tool (MedStopper.com) incorporates data from the Beers Criteria, STOPP, and the Drug Burden Index.17 The tool allows multiple medications to be entered along with the associated indication. Of note, not all common indications are currently listed. For example, when warfarin, an anticoagulant, is entered, no deep vein thrombosis treatment or prevention indication is given. Also, no nausea or vomiting indication option is provided for prochlorperazine, a common antiemetic. However, an “unknown” indication option is available in these situations. Smiley and frowny faces indicate the extent to which the medicine may improve symptoms, may reduce risk for future illness, or may cause harm. The recommendations can be modified for frail or fit patients. The tool is very user-friendly and provides analysis of the medications, including suggestions for deprescribing and tapering. The analysis can be printed to aid the provider when discussing deprescribing with patient and caregivers. The smiley and frowny faces and colors can be easily understood by most patients, and reports are available in both English and French.

Additional information and decision aid tools on deprescribing can be found at www.deprescribing.org.18 The website was developed and is supported by a pharmacist and physician who work with older patients and are concerned about the risks associated with medications at the Bruyère Research Institute (Ottawa) and Université de Montréal. The available information includes webinars and other educational tools about deprescribing for healthcare professionals.

Barriers to Deprescribing

Although deprescribing has many benefits for patients, some barriers for the process exist, including a reluctance to cease medications prescribed by specialists, the perception of inability to change patients’ attitudes, and the belief that a strong indication for a medication existed. Djatche and colleagues surveyed 160 Italian physicians concerning their attitudes about deprescribing in elderly patients who were not primarily cancer patients.19 The majority of physicians surveyed were primary care physicians, and only 5% were hematology specialists. Seventy-eight percent of the physicians were comfortable deprescribing preventive medications in elderly patients, and 40% of physicians reported hesitance in discontinuing medications prescribed by other prescribers. One in four physicians reported lack of time and difficulty engaging the patient or caregiver as barriers to deprescribing.

In 2013, Reeve and colleagues published a study evaluating attitudes about deprescribing for patients with multiple comorbidities.20 Of the 100 Australian participants, 92% reported being willing to stop one or more medications if possible. In a separate study, Reeve and colleagues evaluated 1,981 United States Medicare beneficiaries using the Patients’ Attitudes Towards Deprescribing Questionnaire.21 Ninety-two percent of participants reported being willing to stop taking one or more of their medications if their physician agreed. Overall, more than two-thirds of participants wanted to reduce the number of medications they were taking.

Overall, research does not support the hypothesis that barriers toward deprescribing are prevalent among patients. Physicians are open to deprescribing, but they are reluctant to deprescribe medications initiated by another prescriber. The research pertaining to deprescribing statin medications and PPIs initiated by a specialist or during hospitalization provides helpful guidance for some cases,9,10 but further research and education may be needed to increase comfort with deprescribing, especially in cancer patients, in other situations.

Deprescribing medications is an important part of the care of all patients, including cancer patients, near the end of life. Medications once taken to ensure long-term health are often no longer a beneficial choice and may have more health risks than benefits. Oncology and palliative care pharmacists are in an ideal position to help in the deprescribing process because they are aware of the patient’s prognosis and medications. Deprescribing can decrease the burden of polypharmacy, decrease medication costs, and reduce possible adverse drug reactions and interactions. For these reasons, deprescribing is an appropriate step for patients near the end of life.

References

  1. Sharma M, Loh KP, Nightingale G, Mohile SG, Homes HM. Polypharmacy and potentially inappropriate medication use in geriatric oncology. J Geriatr Oncol. 2016;7:346-353.
  2. Lees J, Chan A. Polypharmacy in elderly patients with cancer: clinical implications and management. Lancet Oncol. 2011;12:1249-1257.
  3. Kantor ED, Rehm CD, Haas JS, Chan AT, Giovannucci EL. Trends in prescription drug use among adults in the United States from 1999-2012. JAMA. 2015;314:1818-1831.
  4. Elliot K, Tooze JA, Geller R, et al. The prognostic importance of polypharmacy in older adults treated for acute myelogenous leukemia (AML). Leuk Res. 2014;38:1184-1190.
  5. Cashman J, Wright J, Ring A. The treatment of co-morbidities in older patients with metastatic cancer. Support Care Cancer. 2010;18:651-655.
  6. Sokol KC, Knudsen JF, Li MM. Polypharmacy in older oncology patients and the need for an interdisciplinary approach to side-effect management. J Clin Pharm Ther. 2007;32:169-175.
  7. Milic M, Foster A, Rihawi K, Anthoney A, Twelves C. ‘Tablet burden’ in patients with metastatic breast cancer. Eur J Cancer. 2016;55:1-6.
  8. Woopen H, Richter R, Ismaeel F, et al. The influence of polypharmacy on grade III/IV toxicity, prior discontinuation of chemotherapy and overall survival in ovarian cancer. Gynecol Oncol. 2016;140:554-558.
  9. Helgadottir H, Bjornsson ES. Problems associated with deprescribing of proton pump inhibitors. Int J Mol Sci. 2019;20:E5469.
  10. Kutner JS, Blatchford PJ, Taylor DH Jr, et al. Safety and benefit of discontinuing statin therapy in the setting of advanced, life-limiting illness: a randomized clinical trial. JAMA Intern Med. 2015;175:691-700.
  11. Scott IA, Hilmer SN, Reeve E, et al. Reducing inappropriate polypharmacy: the process of deprescribing. JAMA Intern Med. 2015;175:827-834.
  12. 2019 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2019;67:674-694.
  13. Hanlon JT, Schmader KE. The medication appropriateness index at 20: where it started, where it has been, and where it may be going. Drugs Aging. 2013;30:893-900.
  14. National Comprehensive Cancer Network. Older Adult Oncology (Version 1.2019). http://www.nccn.org/professionals/physician_gls/pdf/senior.pdf. Accessed: December 29, 2019.
  15. O’Mahony D, O’Sullivan D, Byrne S, O’Connor MN, Ryan C, Gallagher P. STOPP/START criteria for potentially inappropriate prescribing in older people: version 2. Age Ageing. 2015;44:213-218.
  16. Hilmer SN. Calculating and using the drug burden index score in research and practice. Expert Rev Clin Pharmacol. 2018;11:1053-1055.
  17. MedStopper. MedStopper deprescribing resource. Available at http://medstopper.com/. Accessed December 29, 2019.
  18. Bruyere. Optimizing medication use. Available at http://deprescribing.org/. Accessed: December 29, 2019.
  19. Djatche L, Lee S, Singer D, Hegarty SE, Lombardi M, Maio V. How confident are physicians in deprescribing for the elderly and what barriers prevent deprescribing? J Clin Pharm Ther. 2018;43:550-555.
  20. Reeve E, Wiese MD, Hendrix I, Roberts MS, Shakib S. People’s attitudes, beliefs, and experiences regarding polypharmacy and willingness to deprescribe. J Am Geriatr Soc. 2013;61:1508-1514.
  21. Reeve E, Wolff JL, Skehan M, Bayliss EA, Hilmer SN, Boyd CM. Assessment of attitudes toward deprescribing in older Medicare beneficiaries in the United States. JAMA Intern Med. 2018;178:1673-1680.
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