Withdrawing Treatment and Deprescribing - Synthesis

Withdrawing Treatment and Deprescribing - Synthesis


There are few guidelines to support decision-making around the withdrawal of active treatment, and deprescribing of long-term chronic disease medications, making this a difficult topic. Cessation of non-essential or inappropriate medications (deprescribing) is not the same as withdrawal of treatment or the decision not to initiate curative or potentially life prolonging treatments. [1] The evidence often includes the discussion of the four ethical principles used in medical decision making: beneficence, non-maleficence, respect for patient autonomy and justice. [2] Deprescribing or rationalising medicines describes the structured tapering or stopping of medications.

Consultative discussions amongst the health professionals, the person and their close relatives is the starting point for discussions around deprescribing or withdrawing treatment. Whenever possible, withdrawal of treatment discussions should be part of the discussion process at the initiation of treatment, so there is clarity about what may need to occur if the treatment is no longer effective. When a person does not have the capacity to participate in these discussions, an advance care directive may describe the person’s wishes and preferences at end of life and who they have nominated as their substitute decision-maker. [2]

Polypharmacy, defined as five or more medications, is common in both palliative and aged care settings. [3,4] As a person enters the last months of life, the deprescribing of medications that no longer provide benefit, that cause adverse effects or are burdensome to the person, needs to be considered following conversations with the person and family. [4] These discussions may be in response to a change in the goals of care, a change in the person’s clinical presentation or entry to a residential aged care facility (RACF). Home Medication reviews (HMRs) and residential medication management reviews (RMMRs) may offer an opportunity for GPs to work in partnership with pharmacists to develop a plan. [5]

Quality Statement

This synthesis utilised evidence from reviews and other evidence resources: eight systematic reviews [1,6-12] and eleven lower-level reviews. [2-4,13-20] This was supplemented with articles describing tool validation studies and consensus guidelines [21-28] and evidence from a palliAGED topic page. [5] Six papers/resources dealt with withdrawal of treatment or deprescribing in a palliative care and aged care context [2,7-9,12,21] while others had a focus on palliative care [1,10,13,25], aged care [23], or cancer care. [24] Others were not specific to a cohort or setting. [3,6,11,14,22]

The overall quality of the systematic review evidence was good with approach searches and methods for extraction and analysis. No meta-analyses were completed.

Evidence Synthesis

Withdrawal of life-sustaining treatment

As there are no evidence-based guidelines for the withdrawal of treatment, it is useful to refer to the goals of palliative care: to relieve a person’s symptoms and suffering, not to intentionally hasten or postpone death. [25] In one Canadian article by van Beinum et al., [14] it was recommended in the ICU setting that all health professionals involved with a person, meet to discuss the person’s progress so that when discussions begin regarding the withdrawal of treatment, all health professionals are giving the same message to the person and the family. Ideally, involvement of palliative care specialists should be considered sooner rather than later as they provide additional support to the family/carer.

Withdrawal of life supporting treatment, e.g. ventilators or dialysis, often generate strong emotional responses from families. In an American article by Melhado et al. [11] substitute decision-makers who were kept informed on the progress of their relative with open and clear communication with the health professionals found it easier to support the withdrawal process. And in older patients, futility of treatment was often the reason for withdrawing treatment.

When dealing with neurocritical (life-threatening diseases of the nervous system - the brain, spinal cord and nerves issues), the involvement of palliative care staff is most effective when engaged early so as to build a trusting relationship with the person and their family. [13]

There were no specific systematic reviews or articles regarding the withdrawal of nutrition and hydration. However, Therapeutics Guidelines: Palliative Care version 4, makes it very clear that from an ethical and legal perspective, medically-assisted nutrition and hydration are considered medical treatments. [25] These guidelines also state that medically assisted nutrition (e.g. enteral feeds, parenteral nutrition) or medically assisted hydration can lead to problems associated with fluid overload, including lower limb oedema, cerebral oedema, respiratory secretions (and noisy breathing) and gastrointestinal secretions (with vomiting). [26] Therefore, there is no requirement for these to be administered to a person who is dying unless they provide relief of symptoms. Health professionals may need to support family/carers in this process due to cultural, emotional and social factors as many families find it distressing to withhold or withdraw such treatment.

Withdrawal of cancer treatment

The relationship between the oncologist and person is usually very strong with the oncologist often the main health professional involved. It can be difficult for the oncologist to move from a curative role to that of a counsellor when a person is requiring palliative care. Discussions are often started by the oncologist who guides the process. Clinical factors such as disease response and progression as well as the burden of side effects are the main considerations to begin the discussions to withdraw treatment. [10] The review by Clarke et al. [10] states that the patient-doctor relationship was a key part of decision-making concerning the withdrawal of anticancer drugs towards the end of life. This adds growing support to the body of knowledge on the importance of ‘trust’ and ‘rapport’ in shared healthcare decision-making.

The Australian OncPal deprescribing guideline was developed to support deprescribing of unnecessary or futile medications in palliative cancer individuals. [19,24] It helps by reducing costs, potential side effects and the burden of polypharmacy.

Medication deprescribing

Polypharmacy, defined as five or more medications, is common in both palliative and aged care settings. [3,4,19] Deprescribing aims to reduce polypharmacy and improve patient outcomes. [1,7-9,12,19,21] According to the Australian Government Department of Health and Aged Care, the concurrent use of five or more medications is considered polypharmacy. [23] However, the term inappropriate polypharmacy is increasingly used and instead of number of medications considers the harms and the potential benefits of more than one medication in the management of multiple morbidities and/or a complex condition. [6] Evidence suggests that pharmacist-led medication reviews may improve prescribing appropriateness. [1,6]

The practice of deprescribing has been described as a process in which a clinician with the skills to evaluate a person’s entire medication list and to deprescribe one or more specific medications taking a person-centred approach to care considering life expectancy, symptom burden, adverse effects of medication, adverse drug events, drug-drug interactions and risks (e.g. falls). [1,4,7-9,19] Using a structured stepped process a clinician plans and supervises the identification and tapering or stopping of medications. [1,4,8,12,19] Deprescribing of inappropriate medications in older patients with life-limiting illness and limited life expectancy is complex and challenging. [12]

The Australian Government Department of Health and Aged Care has developed guiding principles for medication management in residential aged care facilities; these lack discussion on deprescribing. [23]

There is evidence that deprescribing improves medication appropriateness but little evidence that it improves health outcomes [6,12] or quality of life [8,12] in older people. A recent systematic review reports a positive but not significant change in sleep quality, bowel function, cognitive function, physical function and general health status in frail older people after a deprescribing intervention. [12] The same systematic review suggests that deprescribing interventions has the potential to bring about a cost saving but further research. [12]

The barriers and enablers to deprescribing in palliative care seem to be the same to those in general care even though they may be more compelling due to the person’s reduced life expectancy. [1,6] One important barrier is the sometimes-limited time available for GPs and other healthcare professionals to discuss goals of care and to closely monitor patients after treatment discontinuation. [1] The RACGP aged care clinical guide (Silver Book) for GPs acknowledges the role of pharmacists in providing team based palliative care for older Australians. [28] Pharmacists can provide advice on medication management including prescribing (including ‘off-label’ and anticipatory), administration, and deprescribing in line with rational use of medicines. [5] Australian pharmacists can formally review medicines, via government-funded Home Medication Review or Residential Medication Management Review. This review becomes urgent as patients lose the ability to safely and effectively swallow oral medications and medication uptake by the gastrointestinal tract becomes unreliable. [26]

It is wise to approach deprescribing as a shared decision between a person and health care providers, and to address any concerns people or carers may have related to the deprescribing process. [1,4] Deprescribing in older people with limited life expectancy may be complicated by the prevalence of cognitive impairment, involvement of family in any discussions remains important. [4,7] The use of multiple medications increases a patient’s risk of drug–drug interactions and adverse drug reactions and is an indicator of increased mortality risk among elderly people. [15] Advance care planning can provide opportunities to discuss deprescribing. [1,4]

One tool, developed in Ireland, is specific for deprescribing for frail older people at the end of life: STOPPFrail (Screening Tool of Older Persons Prescriptions in Frail adults with limited life expectancy). STOPPFrail is a list of indicators of potentially inappropriate prescribing designed to assist physicians with stopping such medications in older patients (≥65 years) who meet ALL the following criteria [21]:

  • End-stage irreversible pathology
  • Poor one-year survival prognosis
  • Severe functional impairment or severe cognitive impairment or both
  • Symptom control is the priority rather than prevention of disease progression.

This tool can be used for frail older people and those with limited life expectancy. [9]

Although rationalisation of medication or deprescribing can be a structured and stepped process, it is not always so. Some people lose the ability to swallow quite suddenly and enter the terminal phase while on drugs that can cause a withdrawal reaction if stopped suddenly e.g. antiseizure medicines. [4,19] In these circumstances, a pharmacist may be able to provide guidance as to the practicality of a tapered withdrawal, possible alternate route of administration, substitution with another medication with an appropriate formulation, and prescribing medications for symptomatic relief of withdrawal effects or recurrence of effects. [20,27]

Evidence Gaps

  • There is little evidence around processes involved in stopping anti-cancer treatments other than clinical trials. More evidence-based research is needed to support clinicians and patients in decision making regarding withdrawal of treatment. [10]
  • Among palliative specialists, there are some significant knowledge gaps about the law on withholding and withdrawing life sustaining treatment from adults who lack decision-making capacity. Steps should be taken to improve doctors’ legal knowledge in this area and to harmonise the law across Australia. [29]
  • Guidelines that incorporate deprescribing are greatly needed, particularly when counterbalancing clinical practice guidelines that recommend the initiation of preventive medication therapy without consideration of multimorbidity, advanced illness, or limited life expectancy. [16]
  • For end-of-life situations, very little rigorous research has been conducted on reducing inappropriate medications in frail older adults or those approaching end of life. [2,12,18]
  • Future studies need to consider the variable illness trajectories. For example, typically, in cancer there is a steady progression and usually a clear terminal phase, while in people with dementia or frail older people, the progression is often a prolonged, gradual decline. [12]
  • The potential cost saving after a deprescribing intervention needs to be established. [12]
  • Multimorbidity and polypharmacy are common with ageing, with protocols for stopping medication in these circumstances being scarce. [4,17]

Page updated 27 August 2021

  • References

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