Medication-related harm: a geriatric syndrome

Abstract

The WHO Global Patient Safety Challenge: Medication Without Harm recognises medication-related harm (MRH) as a global public health issue. Increased life-expectancy coupled with multimorbidity and polypharmacy leads to an increased incidence of MRH, especially in older adults: at a cost of approximately £400 million to the National Health Service (NHS) in England. Harm from medicines has long been recognised by geriatricians, and strategies have been developed to mitigate harm. In general, these have focused on the challenges of polypharmacy and appropriateness of medicines, but impact on the quality of life, clinical and economic outcomes has been variable and often disappointing. The problem of MRH in older adults will continue to grow unless a new approach is adopted. Emerging evidence suggests that we need to take a broader approach as described in our conceptual model, where well-recognised physiological changes are incorporated, as well as other rarely considered psychosocial issues that influences MRH. Parallels may be drawn between this approach and the management of geriatric syndromes. We propose there must be a greater emphasis on MRH, and it, of itself, should be considered as a geriatric syndrome, to bring the spotlight onto the problem and to send a clear signal from geriatric experts that this is an important issue that needs to be addressed using a co-ordinated and tailored approach across health and social care boundaries. This requires a more proactive approach to monitor and review the medicines of older adults in response to their changing need.

Key points

• Avoidance of MRH has focused on inappropriate polypharmacy with limited impact on clinical outcomes.

• MRH shares the key criteria of a geriatric syndrome.

• Multiprofessional and multidimensional assessment and intervention may reduce MRH.

Introduction

Harm from medicines is on the rise [1], especially in older adults. Increased life expectancy coupled with multimorbidity frequently leads to polypharmacy and an increased risk of medication-related harm (MRH) [2, 3]. To this, add frailty, multiagency care within and across health and social care, and MRH seems almost inevitable. Strategies to mitigate MRH have considered these drivers so that polypharmacy and age-related alterations in drug handling are the focus of potentially inappropriate medicines (PIMs) criteria [4, 5] and risk prediction models [2], while transitions of care are addressed by medicines reconciliation and review. However, the impact on the quality of life, clinical and economic outcomes of such interventions is variable and often disappointing [6, 7]. The scale of MRH suggests that it should now be thought of as a global public health issue [8].

Geriatricians have long recognised the scale and importance of MRH in older adults [9]: latrogenesis was added as a 5th pillar to Isaacs’ Geriatric Giants. A modern equivalent, the Geriatric 5Ms recognises medicines as a priority point of geriatric expertise and details some important considerations: polypharmacy, deprescribing, optimal prescribing, adverse medication effects and medication burden [10]. While this is helpful, MRH remains problematic. An increasing older population means an increasing number of patients at the risk of MRH and potentially resulting in more hospital admissions and GP visits, costing the NHS in England an estimated £400 million annually [11]. More importantly, the healthcare burden on these individuals is tangible, and reduces the quality of life of those approaching the end of life.

Emerging evidence reminds us that in frail older adults, even ‘appropriate’ medicines can present as a situational challenge and be harmful due to multiple reserve deficits impairing mechanisms to deal with even a minor side-effect [12, 13]. Existing systems employed to reduce MRH fail to recognise this vulnerability, and the instability of an individual. It is now time to place a greater emphasis on MRH, and we propose that it should, of itself, be considered as a geriatric syndrome, to bring the spotlight onto this problem and to send a clear signal from geriatric experts that this is an important issue that needs to be addressed using a coordinated and tailored approach across health and social care boundaries. This requires a more proactive approach to monitor and review the medicines of older adults, in accordance with the patient journey.

Multifactorial MRH—a biopsychosocial model

To develop such an approach, it is important to rehearse the factors responsible for MRH, and the complex interplay that exists between them. Many are well recognised e.g. physiological changes, whereas others are rarely considered e.g. psychosocial issues (Figure 1).

The pathophysiological pathway includes: age-related physiological changes that influence drug handling [14] and age-related changes that impact on drug action so that for specific medicines, the risk of harm is likely to outweigh any potential benefit [4, 5]. In frail older adults, different, but often linked, mechanisms impact on the loss of physiological reserve, the rate and chronology of which is subject to individual variation. A depletion of this reserve may increase the risk of MRH, as seen in frailty, with or without multimorbidity.

Psychosocial factors also contribute to MRH. This may be through their influence upon medicines adherence [15] or, as with physiological reserve, a depletion in the excess capacity means that a minor insult causes significant harm. Reduction in functional ability, social support, cognition, mood or financial circumstances may all contribute to the depletion of psychosocial reserve. As an example, poor health due to disease resulting in impaired physiological function and the addition of a new medicine can reduce mood, and thus psychosocial reserve, and vice versa.

MRH: a geriatric syndrome?

So, does MRH satisfy the requirements of a geriatric syndrome? Tinetti and colleagues defined geriatric syndromes as ‘multifactorial health conditions that occur when the accumulated effect of impairments in multiple systems renders an older person vulnerable to situational challenges’ [16]. According to this proposition, three criteria must be met for MRH to be considered as a geriatric syndrome.

Criterion 1: is highly prevalent in older adults, especially frail older people. Studies from the last decade suggest a high incidence of older adults experiencing MRH in both the acute healthcare setting and the community; ranging from 11.5 to 26% experiencing inpatient ADRs [17, 18], and 30–51.2% post-discharge MRH [11, 19], with 36% frail older adults experiencing MRH after hospitalisation compared with 25% non-frail older adults [12].

Criterion 2: is a unified manifestation of multiple causations [20],that do not occur in the same combination in each person or in the same person on repeated occasions. Prospective observational studies have identified multiple associations with MRH events. There has been a focus on polypharmacy, which is associated with geriatric syndromes and the development of prefrailty from a robust state; and specific risk medicines, such as psychoactive and hypotensive medications due to their association with falls. As suggested in our biopsychosocial model (Figure 1), the physiological and psychosocial factors contribute to MRH. Crucially, the influence of each factor is likely to differ for different individuals and for the same individual at different points in time. The multiplicity of factors, and variation in the contribution of each to MRH in an individual, prevents population level precise prediction of MRH [2].

Criterion 3: is associated with multimorbidity, poor outcomes and other geriatric syndromes. Older adults are four times as likely as younger adults to be hospitalised due to ADR, with 16.6% of hospitalisations associated with ADRs in adults >65 years old [23]. MRH due to non-adherence is associated with 1 year all-cause mortality [24]. MRH is associated with frailty [12, 25]and, through shared risk factors such as polypharmacy, can lead to falls, cognitive impairment and functional decline. This, in turn, leads to increasing frailty with poor outcomes such as disability, hospitalisation and death.

Overcoming the challenges to improve practice

We have presented MRH in older adults as a complex construct, and like other geriatric syndromes, an integrated approach is required to improve outcomes. Motivation to undertake a whole system change, involving health and social care, which uses clinician’s judgement to support medicines prioritisation based upon patient preference and need, and not driven by guidelines and incentives, is required: a difficult, but not insurmountable challenge.

Choosing Wisely, Realistic Medicine and the Comprehensive Geriatric Assessment (CGA) already promotes such an approach: looking beyond medicines and disease, to focus on prioritising individual patient aims. However, even the medicines review the component of the CGA concentrates on inappropriate medicines. More work is required on mitigating harm from appropriate medicines which, despite the anticipated risk of adverse effects, are necessary to delay disease progression and alleviate symptoms. Lessons may be drawn from the Pharm2Pharm study, which reduced MRH admissions in older adults by over a third, and the majority of which were due to appropriate medicines. This study considered medicines management issues in the context of health literacy, cultural practices and social service issues over a 12-month period after hospital discharge, and engaged with the patient and prescriber during follow-up to identify and resolve problems [13]. This approach facilitated the management of the changing instability and the vulnerability of the individual over time.

The lack of an agreed definition of MRH is problematic as it impairs both recognition, documentation and targeted intervention. We believe any definition must include both ADR and non-adherence as approaches exist to identify both. Common agreement would allow coding for MRH events to be undertaken in a robust manner and standardise outcome measures when the impact of interventions tested. Furthermore, it would facilitate the communication of MRH across settings to raise the awareness of potential problems in that individual, but also in the wider population. Clinicians and academics should work to agree a definition.

The multiple causation of MRH impedes the identification of a casual pathway: attempts to determine the underlying causes may prove futile and sometimes harmful [20]. Unlike other geriatric syndromes, which despite having a relatively non-specific pathophysiology, are recognisable; MRH often masquerades as another syndrome, e.g. falls, and so can be misclassified. In light of this and the incidence of MRH in older adults, it should be considered a differential diagnosis in all older adults. It would also help if we no longer considered older adults as having an atypical response to medication; but rather they are responding typically.

Recognising MRH as a geriatric syndrome will raise the awareness of the multidimensional nature of the problem, which may, of itself, be a powerful force for change and lead to multiprofessional and multi-agency engagement to identify patients at greatest risk, and not to delegate the responsibility solely to pharmacists.

Interventions may then be aligned, for example through intensification of work on the ‘stubbornly elusive’ risk prediction model [26], ensuring that future models include a frailty index. It may also promote more selective use of PIMs criteria, as supported in AGS Beer’s Criteria Seven Key Principles which state that those with a low risk of falls have a different risk benefit profile to those with a high risk of falls, and while this does not mean that drugs should be used indiscriminately, the risk benefit balance is different.

Finally, building upon the conclusions of others, MRH assessment and intervention need to move from a unidimensional medicines focus to a multidimensional assessment, with a toolkit of interventions available to generate an individual care plan [27–29] containing ‘packages of medicines care’. These should embrace the early detection of MRH and the optimisation of medicines use.

Conclusion

MRH in older adults is a public health issue, which will continue to grow unless a new approach is adopted to improve medicines outcomes in older adults. MRH shares the key criteria of a geriatric syndrome: a syndrome that is highly prevalent, increases in incidence with age, is multifactorial, with these factors not occurring in the same combination in each person or in the same person on repeated occasions, and is associated with adverse outcome including other geriatric syndromes. As demonstrated in other geriatric syndromes, a multifaceted individually targeted intervention that responds to the changing need of the patient may reduce MRH.

Declaration of Conflicts of Interest

None.

Declaration of Funding

None.

References