Deprescribing in older people

Deprescribing is the process of discontinuing drugs that are either potentially harmful or no longer required.

It can be achieved in older people and may be associated with improved health outcomes without long-term adverse effects.

The risk of drug withdrawal effects can often be mitigated by carefully monitoring and gradually tapering the dose.

Deprescribing should ideally be a shared decision-making process between the patient and the prescriber.

Why deprescribe? Older people living with multiple chronic diseases often have a high risk of adverse health events which can be modified by medicines. For these people, the quality use of medicines includes starting new drugs, adjusting doses and discontinuing those that are no longer beneficial. Despite the great potential benefit they can derive from medicines, these patients are at high risk of experiencing medicine-related harm. Using more drugs than is clinically indicated can increase this risk.

Polypharmacy, defined as the concomitant use of five or more medicines,¹ is associated with an increased risk of adverse outcomes such as hospital admissions, falls and premature mortality.^1,2 It is also expensive for patients. The number of older Australians affected has increased by over 50% since 2006 to nearly one million.³ This rising prevalence and the associated concerns about poorer health outcomes have led to increasing attention on inappropriate polypharmacy.

Deprescribing addresses the harms associated with inappropriate polypharmacy. It is a patient-centred process involving the discontinuation of one or more drugs that are potentially harmful or no longer required.⁴

Many drugs are indicated to delay mortality so prescribers may be reluctant to discontinue them. Despite this concern, a systematic review of deprescribing found no change in mortality overall in randomised studies (odds ratio (OR) 0.82, 95% confidence interval (CI) 0.61–1.11).⁵ However, mortality was significantly decreased in non-randomised studies (OR 0.32, 95% CI 0.17–0.60).⁵ The review also found that patient-specific interventions significantly reduced mortality in randomised studies, but generalised educational interventions aimed at upskilling practitioners to alter prescribing behaviour did not change mortality. This evidence indicates that reducing polypharmacy may be achieved without perceivable adverse impacts on mortality and with clinically important benefits for some patients. Other reviews have investigated the impact of deprescribing in specific drug classes and specific settings (such as aged-care facilities and hospitals). This research generally suggested that deprescribing is safe (Table 1).^5-11

Medicines should be reviewed regularly to ensure that each drug is effective for that individual and therapy remains consistent with their care goals. Treatment should also be underpinned by a current and valid diagnosis.¹² A significant event like a fall, or an admission to hospital or a residential care facility, should prompt a thorough medicine review.¹² A review should also be triggered by increasing frailty or a decline in either their cognitive function or ability to manage activities of daily living.¹²

Falls

Older people are at a significantly increased risk of falls. This is exacerbated by both polypharmacy and certain drugs such as psychotropics, cardiovascular drugs and anticholinergics.^1,13 A New Zealand study found that deprescribing sedative and anticholinergic drugs significantly reduced the number of falls each person experienced.¹⁴ Providing older people with written information supporting discontinuation has been shown to be an effective strategy to improve sedative discontinuation.¹⁵ Although our systematic review suggested that deprescribing does not alter the risk of having a first fall, it reduces the number of subsequent falls for an older person who has already fallen.⁵ Another review found that deprescribing interventions based on a medicine review resulted in a relative risk reduction of 24% (OR 0.76, 95% CI 0.62–0.93)⁷ in the number of people who fell.

Adverse effects

Older people are more susceptible to adverse effects due to increased frailty, poor homeostatic reserve and age-related changes in pharmacokinetics and pharmacodynamics.¹⁶ It can be a challenge to detect adverse effects in older people, particularly in those with cognitive impairment who may not be able to articulate their concerns. It is not uncommon for an adverse effect to be identified as a new symptom or condition, which can lead to a prescribing cascade (see an example in the Box). In this example, the prescribers did not consider the possibility of an adverse effect when evaluating the new symptoms. The cascade has been described in a study that found that older people who are prescribed cholinesterase inhibitors are at increased risk of subsequently being prescribed an anticholinergic drug (adjusted hazard ratio 1.55, 95% CI 1.39-1.72).¹⁷ The cascade could also occur in the alternate order – a new anticholinergic drug could contribute to confusion or delirium. If this is misdiagnosed as dementia, it could result in the prescription of a cholinesterase inhibitor.

The prevalence of polypharmacy in older people increases the likelihood that more than one drug contributes to the same adverse effect (e.g. oxycodone and oxybutynin both resulting in constipation and dry mouth).

End-stage diseases

In older people with a severe life-limiting condition, such as advanced dementia or end-stage organ failure, the potential benefit of preventive medicines may not be realised due to the person’s short life expectancy and may not be the goal of their treatment. For example, 2–5 years of statin use is generally required to reduce the risk of stroke or myocardial infarction.¹⁸

Managing preventive medicines can be challenging in the context of life-limiting illness or frailty. For example, although at least 15% of older Australians live with diabetes,¹⁹ little evidence is available on the effects of discontinuing drugs for diabetes. A recent review identified only two low-quality controlled studies of deprescribing these drugs.¹¹ Tight glycaemic control (glycated haemoglobin (HbA1c) <7%) may be appropriate in those who have sufficient life expectancy to benefit from the reduced risk of microvascular complications. However, for frail older people, intensive therapy increases the risk of hypoglycaemia without a mortality benefit. De-intensification of therapy is therefore often appropriate.²⁰ In both studies, there was no significant difference in HbA1c between the group that discontinued diabetes drugs and those that continued.¹¹

Drugs may sometimes be discontinued in older people with limited or no adverse effects.⁵ In other cases, the symptoms of the underlying condition may reappear or withdrawal effects may occur. A review did not find significant harms when antihypertensives, benzodiazepines and psychotropics were discontinued in older people.²¹

The risk of harm can be mitigated by gradually tapering medicines and carefully monitoring for withdrawal effects. It is often not possible to tell if a condition is a current problem while symptom-relieving drugs are used (e.g. proton pump inhibitors to manage reflux, or analgesics to manage pain). For these drugs, discontinuation should be trialled rather than considered definitive. If symptoms recur, restarting the medicine at a lower dose may be sufficient to manage this.²¹

Reappearance of the original disease or symptoms

Many older people are prescribed antihypertensives to reduce their risk of cardiovascular events. This needs to be carefully balanced with the potential for harms (e.g. dizziness, falls).²² A study of frail older people found that deprescribing antihypertensives resulted in an immediate increase in blood pressure, although this reverted to baseline within nine months.²³ Another study found that systolic blood pressure increased by 7 mmHg (95% CI 3–12) after discontinuing antihypertensives.²⁴ Blood pressure should be routinely monitored during the first year after deprescribing to identify increases that may occur.²²

For symptom management, proton pump inhibitors are recommended for 2–8 weeks, yet they are commonly continued for prolonged periods.¹⁰ Stopping them may result in rebound hyperacidity, or lack of symptom control,¹⁰ especially during the first two weeks. A study that deprescribed proton pump inhibitors during hospital admissions found that 57% were still discontinued after three months.²⁵ Tapering the dose may reduce the risk of rebound symptoms, particularly if the initial dose is high. Proton pump inhibitors, H₂ antagonists or antacids (e.g. Mylanta) can be used as needed to relieve rebound symptoms.

The fracture risk in people with osteoporosis may be reduced using denosumab or bisphosphonates. Bisphosphonates can be discontinued after 3–6 years in many people without altering fracture risk.^5,26 For example, a six-year study of zoledronic acid suggested treatment could be stopped after six annual infusions, with treatment effects maintained for at least three years.²⁶ Unlike bisphosphonates, denosumab is not incorporated into the bone matrix so the effect on bone resorption is not maintained after treatment is discontinued. Discontinuing denosumab therefore results in rapid bone loss and the fracture risk reverts to baseline levels.^27,28 Periodic monitoring may identify changes in bone mineral density after a bisphosphonate has been discontinued.

Withdrawal symptoms

Discontinuing drugs can result in withdrawal symptoms. People taking long-term benzodiazepines are likely to be physiologically dependent. A withdrawal syndrome can include anxiety, irritability, insomnia and myoclonic jerks. One study demonstrated that 38% of people reported withdrawal symptoms when discontinuing benzodiazepines and Z-drugs (zopiclone and zolpidem).²⁹ This highlights the importance of slowly tapering medicines to minimise withdrawal symptoms.³⁰ This also increases the likelihood of the medicine being successfully deprescribed.

It is important to involve patients and their carers in the decision to discontinue medicines when possible.⁴ Most older people are willing to stop one or more drugs if their doctor says they can.³¹ A person may be reluctant to do this if they believe a drug is still necessary or that they may derive future benefit from it.³² Patients may be concerned about relapse or withdrawal symptoms,³² but are more willing to have a medicine deprescribed if they know they can restart it if required.³³ Inadequate time with the prescriber to discuss discontinuation, and lack of guidance on how to stop a medicine (e.g. is tapering needed, what monitoring and follow-up will occur), is another barrier.³² This highlights the importance of providing additional information about the risks and benefits of medicine use to facilitate an older person’s willingness to deprescribe. For example, those who received a brochure that described harms from Z-drugs and suggested alternative options were significantly more likely to discontinue the medicine than those who received usual care.¹⁵

There are many tools to assist clinicians to deprescribe medicines in older people.³⁴ Implicit tools such as the deprescribing algorithm (Table 2)^35-38 outline approaches for reviewing an older person’s medicine list to identify targets for deprescribing. These tools require application by a health professional. Explicit tools provide criteria-based guidance on how to approach the deprescribing of specific drugs – an example of medicine-specific guidelines is shown in Table 3.

Referring an older person for a Home Medicines Review or a Residential Medication Management Review by a pharmacist can assist the process. The pharmacist can help to identify targets for deprescribing and develop a plan for tapering doses. Deprescribing advice from pharmacists has been shown to reduce inappropriate prescribing in older people.³⁹ It is important to ensure that medicine changes are communicated with the older person’s community pharmacist so they can assist in implementing the change. This is particularly important if the pharmacist prepares a dose administration aid for the older person.

After identifying deprescribing targets, it is necessary to consider the order in which to deprescribe medicines. Often it is useful to deprescribe medicines with limited noticeable withdrawal effects first to reassure the person that the process is tolerable (Table 4).^35,37,40-45 It is usually advisable to limit deprescribing to just 1–3 medicines at a time. However, it is important to make sure they do not have overlapping indications so it is clear which medicine is responsible if withdrawal effects occur.³⁵

In the deprescribing process, the potential benefits and risks of continuing and discontinuing medicines are considered for the individual. Deprescribing to reduce polypharmacy can be achieved with potential benefits for mortality, quality of life and cognition. While some medicines can be deprescribed without noticeable effects, others are associated with predictable drug withdrawal symptoms. These medicines require more careful deliberation, tapering and monitoring if they are to be discontinued. Deprescribing medicines that are no longer indicated reduces the risk of drug-related harm and is an essential part of the quality use of medicines.

Conflict of interest: none declared

Acknowledgement: Kathleen Potter drafted Table 4 in collaboration with Christopher Etherton-Beer.