Drug-related problems and deprescribing in older adults

The population of older adults in Canada is growing rapidly. In 2008, adults aged 65 and older made up 14% of the population and this number is expected to rise to more than 27% by 2050.[1] Clinicians caring for older adults must be comfortable balancing quality of life with length of life when managing multiple comorbidities (also known as multimorbidity). Managing multimorbidity often requires several medications for each clinical condition,[2] and the polypharmacy that can result (defined in some articles as more than six regularly scheduled prescription medications) is associated with a number of negative effects, including adverse drug reactions, falls, fractures, decreased medication compliance, malnutrition, functional impairment, hospitalization, and death.[3-6] Inappropriate medication use encompasses both overprescribing and underprescribing.

Overprescribing often occurs when multiple specialists care for the same patient, each focusing on a single organ system. In addition, physicians may unintentionally contribute to polypharmacy by adhering strictly to clinical practice guidelines (CPGs), which are frequently based on trials that either exclude or underrepresent frail older adults with multimorbidity.[7] This means the recommendations may not apply to older adults, and may even cause harm. An older patient may respond differently to the same dose of the same medication given to a younger patient because of age-related changes in pharmacokinetics. The classic parameters of absorption, distribution, metabolism, and excretion are all affected by changes in the gastrointestinal tract, increased fat-to-water ratio, and reduced hepatic and renal function.[8] To avoid toxic effects as a patient ages, medication use may need adjusting to account for the patient’s changing pharmacokinetic profile. 

Appropriate prescribing relies on starting medications that are indicated, but also discontinuing medications when they are no longer indicated or have fallen out of alignment with the patient’s goals of care. Reducing medications (also known as deprescribing) can produce several positive outcomes, including improved quality of life and decreased risk of adverse drug effects.[9]

Evidence for deprescribing
A recent comprehensive review of the evidence for deprescribing was performed by Scott and colleagues.[10] They summarized drug withdrawal trials, as well as studies of interventions for reducing inappropriate medications. While a number of trials demonstrated safety and feasibility of drug discontinuation, there is a paucity of high-quality evidence reporting on patient-centred clinical outcomes. 

The literature thus far shows some positive effects on a number of different outcomes. A systematic review in 2008 showed that withdrawal of psychotropic drugs and benzodiazepines reduced the number of falls and improved cognition and psychomotor functioning.[11] Furthermore, a randomized controlled trial in 2009 demonstrated a reduction in mortality when antipsychotics were withdrawn in nursing home patients with dementia.[12] A 2013 Cochrane review showed that inpatient medication reviews led by physicians, pharmacists, and other health care professionals resulted in a 36% reduction in emergency department visits from 30 days to 1 year following discharge.[13] A nonrandomized controlled trial conducted in nursing homes and nursing departments used an algorithm to identify and stop potentially inappropriate medications or shift to other more appropriate medications.[14] There was a reduction in mortality and referral to acute care, and staff reported decreased agitation, increased alertness, and a reduction in disability. A follow-up study using the same algorithm showed that 88% of community dwelling patients reported global improvement in health when polypharmacy was addressed.[15] A recent unblinded, randomized pragmatic clinical trial showed that patients with life expectancy of less than 1 year could safely discontinue statins, and that discontinuation was associated with better quality of life, use of fewer nonstatin medications, and a reduction in medication costs.[16] 

Deprescribing is an area of active research as clinicians come to realize the importance of having a parallel plan to re-evaluate and limit the duration of use each time a new medication is prescribed. There are many ongoing trials that will add evidence for deprescribing by focusing on relevant patient outcomes such as hospital admission, mortality, falls, sleep quality, cognitive function, independence in activities of daily living, and quality of life.[17] In addition, a Canadian study is currently under way to develop guidelines for discontinuation of certain classes of drugs, including proton pump inhibitors, benzodiazepines, and antipsychotics.[18] A follow-up process for evaluating the effect of applying these guidelines is also planned. A local British Columbia program, Call for Less Antipsychotics in Residential Care (CLeAR), is focusing on reducing inappropriate use of antipsychotics in residential care homes and has already reported on some positive outcomes.[19]

Barriers to deprescribing
Prescribing medications comes more naturally to most physicians than deprescribing medications. This may stem from the fact that medical schools provide little to no training on the subject of deprescribing. As well, there are a number of barriers to reducing medication use, and studies surveying the views of patients and physicians have shed some light on why deprescribing can be difficult. 

A study published in the BC Medical Journal in 2014 surveyed family physicians in Vancouver and found they were reluctant to deprescribe medications that were prescribed by a specialist or another practitioner. Survey results also indicated that many physicians felt they lacked the skills and knowledge to deprescribe in a safe and effective manner. Other barriers cited were organizational factors, fear of causing an adverse effect, and concern that patients would feel the physician had given up on them.[20] Another study found that physicians were uncomfortable stopping medications because this often requires discussing the patient’s limited life expectancy, which is difficult to do.[21] This problem is especially apparent when trying to stop a medication that is only prescribed for primary prevention. In addition, many physicians feel compelled to prescribe according to current CPGs. A systematic review in 2013 looked at articles exploring the views of patients and care providers.[22] If a patient had noticed an improvement when a medication was first started, the patient was less likely to accept stopping the medication later, even if it was no longer indicated.

Other barriers to deprescribing that have been identified include lack of physician time and support, fear of withdrawal reactions, previous poor experiences with cessation of medications, and nonspecific fears about the consequences.[22] Although deprescribing continues to gain attention, there is still a significant lack of awareness regarding the impact polypharmacy has on older adults.[23] 

Overcoming these barriers to de-prescribing may start with improving physician education about the harms of polypharmacy and developing clear guidelines for deprescribing. CPGs should be transparent when recommendations are based on trials that have not included older patients with multimorbidity. In the future, more trials will need to include older patients with multimorbidity and more CPGs will need to take age and comorbidities into account. Some recent CPGs already do this. For instance, the Canadian Diabetes Association 2013 guidelines recommend a target HbA1c level of 7.1% to 8.5% for patients with limited life expectancy, a higher level of functional dependency, and multiple comorbidities.[24] 

Despite physician fears that de-prescribing will cause adverse effects, studies have shown the opposite is often true—that deprescribing can be done safely for multiple classes of drugs and may improve global health.[11,15] Although patients have concerns about deprescribing, a study showed that more than 90% of patients would be willing to cease a medication if a physician said this was possible.[25] 

Guiding principles and steps for deprescribing
Less than half of physicians surveyed in BC reported that they use a consistent approach to reducing polypharmacy.[20] This is probably rooted in the lack of clinical guidelines on deprescribing. In 2012, the American Geriatric Society (AGS) published a set of guiding principles for managing patients with multimorbidity[26] that are relevant to the topic of deprescribing, and should be considered during each encounter with an older adult affected by polypharmacy:
•    Elicit and incorporate patient preferences into medical decision making.
•    Interpret and apply the medical literature specifically to older adults with multimorbidity, while recognizing the limitations of the evidence base.
•    Frame clinical management decisions within the context of risks, burdens, benefits, and prognosis.
•    Consider treatment complexity and feasibility when making clinical management decisions. 
•    Choose therapies that optimize benefit, minimize harm, and enhance quality of life.

While a number of review articles describe deprescribing protocols or algorithms, mostly derived from expert consensus methods, there is little evidence of clinical outcomes for the application of any such protocols. Nevertheless, a structured approach to deprescribing is still recommended, as a lack of process has been identified as a barrier to addressing polypharmacy. 

The patient-centred deprescribing process described here involves five steps that can be repeated at regular intervals as necessary (Figure).[27] 

Step 1: Comprehensive medication history
A meticulous history of the patient’s medical background should be obtained at the outset. All of the patient’s medications, including over-the-counter medicines and supplements, should be reviewed to obtain a best possible medication history. The most effective way is to have the patient or the patient’s caregiver bring all medications to an appointment for a “brown bag” review.[28] This will facilitate an accurate assessment of medication use and help establish whether the patient is following dosing instructions or if blister-packing the medications or another intervention is needed to improve adherence. The patient’s awareness of all medical conditions being treated and the indications for each medication should be ascertained. Lack of awareness is quite common, especially if the patient has any cognitive impairment, and could contribute to problems with following dosing instructions. It is essential to gather background on the patient’s social environment and functional and cognitive capabilities, and the supports currently in place. These are all factors that will determine the feasibility of continuing with current medication regimens, as well as the feasibility of proceeding with any proposed interventions for prescribing or deprescribing medications.

Step 2: Identify potentially inappropriate medications
Once a best possible medication history has been obtained, the physician can determine which medications might be targeted for discontinuation. A particular drug may be selected for deprescribing for several reasons: 
•    The original indication for using the drug no longer applies. 
•    The patient feels the drug is causing an adverse effect.
•    Drug-drug interactions are occurring. 
•    Drug-disease interactions are occurring.
•    The drug is inappropriate given the patient’s life expectancy. 
•    Use of the drug no longer aligns with the goals of care for the patient.

To determine whether a medication can be stopped, the physician should follow the AGS guiding principles on managing multimorbidity and consider patient preferences, evidence for the medication, the patient’s prognosis, and the feasibility of continuing or withdrawing the medication.26 The physician must also determine whether a medication is likely to provide any benefit in the context of the patient’s estimated life expectancy. The time horizon to benefit is the time needed to accrue an observable, clinically meaningful risk reduction for a specific outcome.[26] For instance, for primary prevention the time horizon to benefit for statin therapy is approximately 2 years.[16] Thus, in a patient with limited life expectancy, statins for primary prevention are unlikely to provide any meaningful benefit, and can be selected for cessation. This applies to many other classes of medication, including bisphosphonates for osteoporosis. A patient may also choose to focus more on quality of life and relief of symptoms and less on preventing disease progression, or vice versa. A patient’s personal preferences and unique wishes must always be considered. 

Physicians should be aware that a prescribing cascade can lead to polypharmacy and subsequent harm. In a prescribing cascade, the adverse effect of one medication is mistaken for the symptom of a new condition, and another medication is prescribed, placing the patient at risk of further adverse effects related to potentially unnecessary treatment.[29] For example, if the use of a calcium channel blocker leads to the development of leg edema, the physician may treat the edema by prescribing a loop diuretic. When the loop diuretic then causes hypokalemia, the physician may treat this by prescribing a potassium supplement. To avoid starting a prescribing cascade, physicians should always consider the possibility that a new symptom is the result of an adverse drug effect rather than a new condition. 

A number of tools can help identify potentially inappropriate medications. Among these are the revised 2012 Beers criteria[30] and the STOPP criteria,[31] which include lists of medications or classes of medication that can be inappropriate for older patients. Electronic medical records can also be powerful tools in the prevention of inappropriate prescribing. A review article showed that introducing electronic prescribing and computerized decision support systems helped achieve some important clinical outcomes, including lower risk of falls and reduced inappropriate prescribing.[32]

Step 3: Determine if medication can be ceased and prioritization
After identifying potentially inappropriate medications, the many attitudes and views that are barriers to deprescribing must be addressed. For instance, the fact that a medication was prescribed by another specialist or health care provider can often be an impediment to discontinuation. By involving the original prescriber,  the physician has the opportunity to elicit additional advice on the clinical situation and has a better chance of obtaining the patient’s agreement on discontinuation. Direct telephone conversations with previous prescribers are preferable to other less reliable forms of communication. 

In line with the AGS guiding principles for managing multimorbidity,[26] patient preference must be considered and both the patient and caregiver need to be on board with any plan. This can only be achieved if their concerns and fears are acknowledged and addressed. This is especially important when there is a psychological investment in a particular medication, which is often the case with narcotics and sedatives. If the patient has had a poor experience with drug cessation previously, the reasons need to be explored and a plan should be developed that differs from the one tried previously.

Patients should be medically stable at the time of drug cessation, unless the drug targeted for discontinuation is already causing instability. If the patient is medically stable, any change in symptoms is more likely to be caused by the drug cessation, and less likely to be caused by the dynamics of an intercurrent disease.[33] 

Once medications are identified for withdrawal, they should be prioritized and the medication most likely to be causing the most significant symptoms or the most harm should be withdrawn first.

Step 4: Plan and initiate withdrawal
A deprescribing protocol based on a number of studies recommends withdrawing one medication at a time,[10] even though some withdrawal trials have successfully stopped multiple medications at once.[14] While there is no evidence that one method is more efficacious than another, it may be most practical to withdraw medications in a sequential manner.[10] This means that as each drug is withdrawn, any change seen in the patient’s clinical status is more likely to be the result of withdrawing that particular drug.

Some drugs require tapering, especially opioids, steroids, and medications affecting the cardiovascular and central nervous systems.[33] In fact, some patients fear withdrawal effects even when discontinuing medications not known to cause these.[22] Thus, it may make sense to use a tapering regimen for all drugs, even those not known to cause withdrawal symptoms.

Step 5: Monitoring, support, and documentation
Patient monitoring is essential, given that one of the barriers to deprescribing identified by patients is lack of physician time and support.[22] Some deprescribing trials have employed telephone interviews for follow-up,[15] which seems to be an acceptable method of monitoring after a deprescribing intervention. The monitoring step is an iterative one that usually requires multiple sessions with the patient to check for the consequences of drug discontinuation, including rebound effects, withdrawal symptoms, and the return of symptoms that previously indicated a need for the medication. The physician should determine if the patient is experiencing a positive effect from discontinuation, and should be prepared to restart the medication if the patient experiences withdrawal effects or the return of previous symptoms. 

Proper documentation of the discontinuation process must take place, and the results should be communicated to relevant colleagues to ensure that another health care provider does not restart the medication or use the same withdrawal technique that was tried in the past and failed. Good communication practices are also needed to prevent medication reconciliation errors during transitions in care, such as when a patient is admitted to acute care or discharged back into the community. 

Summary
Evidence is mounting that deprescribing can be done safely, and can result in clinically meaningful patient outcomes. To address polypharmacy, the focus should shift from asking if the patient is taking too many medications to asking whether the patient is taking appropriate medications tailored to specific patient needs and goals. The American Geriatric Society guiding principles for the care of older adults with multimorbidity can be helpful. When determining the appropriateness of a particular medication, the physician should consider patient preferences, evidence for the medication, the patient’s prognosis, and the feasibility of continuing or withdrawing the medication. Life expectancy and time horizon to benefit should both be considered as well, and the deprescribing process should be implemented accordingly, with appropriate monitoring, support, and documentation. The concerns and fears of the patient should always be addressed, and there should be frequent assessment and communication with the patient, caregivers, and other health care providers. 

Competing interests
None declared.

This article has been peer reviewed.

Dr Lai is a subspecialty resident in the Division of Geriatric Medicine at the University of British Columbia. Dr Fok is a clinical instructor in the Division of Geriatric Medicine at the University of British Columbia and a staff geriatrician and internist at Vancouver General Hospital.