CMAJ Review CME Deprescribing for older patients Christopher Frank MD, Erica Weir MD MSc See related editorial at www.cmaj.ca/lookup/doi:10.1503/cmaj.122099 and articles at www.cmaj.ca/lookup/doi:10.1503/cmaj.122012 and www.cmaj.ca/lookup/doi:10.1503/cmaj.130523 he principles that guide optimal prescribing outcomes related to medications than other older Competing interests: None for older patients1,2 (Box 1) include depre- patients. They are also more likely to have limited declared. scribing medications that are no longer indi- life expectancy than well older people of similar This article has been peer T 17 cated, appropriate or aligned with evolving goals of age. Medication lists tend to lengthen as patients reviewed. care. Deprescribing is a relatively new term that age, and there are few guidelines to inform medi- Correspondence to: focuses attention on the sometimes overlooked step cation management in the context of polyphar- Christopher Frank, frankc in medication review of stopping medications to macy, multiple morbidities and age-related @providencecare.ca improve outcomes and decrease risks associated changes to pharmacokinetics and pharmacody- CMAJ 2014. DOI:10.1503 with polypharmacy in older people.3–5 These risks namics (Box 1). All prescribers contributing to the /cmaj.131873 include nonadherence,6 adverse drug reactions,7 medication list need to be alert to “prescribing functional and cognitive decline,8 and falls.9,10 In inertia”18 (the tendency to automatically renew a Canada, more than 50% of older people living in medication even when the original indication is long-term care facilities and 27% of those living in no longer present) and should view polypharmacy the community take more than five medications a as an impetus to deprescribe when appropriate. day.11 Although frailty12 should be a catalyst for Any patient interaction can be an opportunity deprescribing, the principles and practice of depre- for critical medication review. Certain transitional scribing apply to all older patients and, if integrated events in the care of older patients provide identi- early into care, may play a role in preventing frailty. fiable opportunities. For example, medication In this article, we describe an approach to errors tend to occur during transfers between care deprescribing based on principles, practice and settings.19,20 To reduce this risk, facilities routinely available evidence. We reviewed evidence from undertake systematic reconciliations of medica- systematic reviews and randomized controlled tri- tion lists between sites; this is an opportunity for als on the impact of deprescribing (Box 2). Most deprescribing. Similarly, changes in the overall of the studies failed to measure clinical outcomes health of a patient that affect life expectancy, such relevant to the care of older patients, such as as the diagnosis of a terminal cancer or progres- improved functioning. The quality of the evidence sion of dementia or clinical frailty,17 signal the was limited by small samples, short study dura- need for medication review to identify drugs that tions and heterogeneous study designs.13–15 None- are unlikely to provide meaningful benefit to the theless, we found evidence16 that a substantial individual in their remaining time.21 proportion of older patients can tolerate careful dosage reduction or withdrawal of certain classes Can deprescribing medications of medications without harmful consequences and with possible improvement in quality of life, espe- improve clinical outcomes? cially if the goals of care shift from disease- specific targets to improvements in symptom It is well recognized that medications can cause management and function. harm in older patients, and there is growing rec- When and for whom is Key Points deprescribing appropriate? • The same principles that guide prescribing for older patients guide deprescribing for this patient group. • Identify drugs that are no longer indicated, appropriate or align with Although all older people taking prescribed drugs goals of care. may benefit from a medication review with a • Engage the patient, family and other health care providers in the process. deprescribing lens, those who are frail12 are the • Develop a tapering/discontinuation plan and monitor adverse main target of this approach. Frail patients tend to outcomes and benefits. take more medications and have more adverse © 2014 Canadian Medical Association or its licensors CMAJ, December 9, 2014, 186(18) 1369 Review ognition that careful adherence to disease-specific Drugs that are no longer indicated guidelines in frail patients can result in increased A systematic review of 31 trials involving older risks of drug interactions and adverse reactions.22 adults, published in 2007, examined the benefits Despite this context, the evidence to support and harms of withdrawing medications felt to be deprescribing as a broad strategy to improve no longer indicated.16 The studies focused on the clinical outcomes in older patients is weak. complete withdrawal of one of four classes (ben- According to three recent reviews,13–15 most of zodiazepines, antihypertensives, diuretics for the trials studying deprescribing failed to mea- indications other than heart failure and antipsy- sure clinical outcomes relevant to the care of chotics). Although the included studies were older patients, such as improved functioning, and limited by small samples and short durations, the were limited by small samples and short study results showed that a substantial proportion of durations. Although many of the interventions participants could tolerate withdrawal of one of involved pharmacists, the engagement between these classes and experienced benefits of reduced the pharmacist and prescriber was not adequately risk of falling (e.g., psychotropic medication described,14 and few studies incorporated patient withdrawal, hazard ratio 0.34, 95% confidence perspectives. Heterogeneity in study design, interval 0.16–0.74)23 and improvement in total sample selection, choice of outcome measure memory test scores (e.g., benzodiazepine with- and intervention made it difficult to synthesize drawal, p < 0.004).24 results and draw conclusions. These results are borne out in current clinical Nonetheless, when the evidence about depre- practice. It is almost conventional wisdom that ta- scribing is organized by the intentions to stop pering benzodiazepines25 can improve cognition drugs that are no longer indicated, that are no and reduce the risk of falls. The recent changes in longer appropriate or that no longer align with clinical practice guidelines to relax targets for goals of care, deprescribing appears to be poten- blood pressure (e.g., 150/90 mm Hg)26,27 and tially helpful without causing substantial harm, if blood glucose (hemoglobin A1C concentration done well. < 7.5%)28 in older patients is informed by the trade-off between the risk of vascular events with Box 1: Principles to guide prescribing and deprescribing the risk of falling because of orthostatic hypoten- medications in older patients1,2 sion29 or hypoglycemia. Likewise, there is evi- Pharmacokinetics: what the body does to the drug; what factors dence that a systematic approach to reduce the determine the concentration of the drug at the target receptor or organ prescribing of antipsychotics for behavioural Absorption: little change due to aging alone, but it can be affected by symptoms of dementia when stable allows many medications and conditions common in older people people to be off medications for sustained periods Distribution: increased fat:water ratio with aging; protein binding may be of time or indefinitely.30 affected by malnutrition or medical conditions Metabolism/excretion: decrease in some liver metabolism with aging may Drugs that are no longer appropriate affect different drugs differently; decrease in renal excretion with aging A recent Cochrane review31 concluded that sys- may affect drugs dependent on kidneys for excretion tematic medication reviews involving a pharma- Pharmacodynamics: what the drug does to the body; what factors affect whether medication will have a greater or lesser affect with same serum cist working closely with the physician and the concentration patient or caregiver results in a substantial reduc- Prescribing tips tion in inappropriate prescribing, either through • Remember that medications may cause illness medication substitution or discontinuation. The results from these studies do not clarify whether • Know the patient and his or her current medications (and how they are taken) improving appropriateness of prescribing im- • Consider nonpharmacologic therapy proves clinical outcomes; however, this associa- • Know the pharmacology of the prescribed drugs tion may be inferred from the evidence about • Keep drug regimens simple • Establish treatment goals at the time of prescription Box 2: Evidence for this review • Strive for a diagnosis before prescribing; if a therapeutic trial is done, stop medications if treatment goals are not reached We included published systematic reviews that were known to us. We then searched the • Encourage the patient to be a responsible medication user and to databases Embase and MEDLINE using the terms participate in his or her medication management “deprescribing” and “drug withdrawal” to • Consider the patient’s current medications and medical conditions before identify additional systematic reviews as well as adding or changing new medications reports of randomized controlled trials