Multimorbidity and polypharmacy – considerations

Most of the evidence to support treatments is based on “single-condition-single-treatment” clinical trials.

This is frustrating in a world where the reality for many people is multiple long-term conditions and polypharmacy.

Applying the evidence we do have requires clinical judgement and careful thought about an individual’s priorities and preferences.

This is a complex task. There are excellent educational resources and guidelines available, some of which are listed and linked to below to help with this. They are well worth spending some time to digest (if you haven’t done so already) and will help you apply the evidence presented on this website.

There are no easy, “correct” answers, but here are some broad principles to get started:

Can we assume treatment benefits are likely to be the same for someone with multiple long-term conditions as they are in the clinical trials?

It is probably reasonable to assume that the benefits of a treatment will be applicable to those with other long-term conditions (that were not necessarily present in the trial populations) unless there is a physiological reason to think this is not the case. The alternative point of view – to not offer treatment to someone with another long-term condition (because there is no direct evidence) – risks denying them a valuable benefit.

However, where a co-morbidity reduces someone’s life expectancy or affects functional ability, their chance of benefiting from a treatment may change. It may be appropriate to consider questions such as:

  • How likely is it that this person will live long enough to benefit from preventive treatment?
  • How likely are they to die from another condition?
  • Will they be able to experience a symptomatic benefit from treatment? For example:
    • a theoretical improvement in cardio-respiratory symptoms if their mobility is limited by neurological or musculoskeletal disease.

How is the risk of treatment harms affected by multimorbidity and polypharmacy?

Multimorbidity and polypharmacy inevitably increase the chance of treatment-related harm.

Firstly, treatment burden increases. The effort of managing complex medication regimes is considerable (in addition to the emotional costs of taking lots of pills) and this burden falls on patients, carers and people across the healthcare system.

  • ‘When clinicians issue medicines, they prescribe work, and this work affects many people …’ 5

Medication regimes which are too big and complex for an individual, run the risk that some or all treatments may not be taken correctly, thereby losing their intended benefits. Might someone be better off taking fewer pills (ideally the most important for them) effectively rather than many ineffectively?

Secondly, drug interactions and cumulative side effects are a common problem. Data about the exact chances of side effects or harms in a particular complex situation will not be available, but we can draw on clinical knowledge and resources to think about these. For example:

  • Multiple drugs which lower blood pressure or heart rate will increase risk of giddiness, falls etc.
  • Many drugs have anti-cholinergic properties which can accumulate in an “anti-cholinergic burden”.
  • Combinations of drugs which affect renal function can increase the risk of acute kidney injury.

Resources on the management of polypharmacy, including medicines optimisation and deprescribing, provide lots of valuable pointers to help minimise these risks. See the list below.

Certain long-term conditions will increase the risk of particular side effects. For example, an autonomic neuropathy associated with diabetes would increase the risk of syncope and might lead to a decision to prescribe fewer blood-pressure lowering drugs.

Shared decision making is a key component of good care in multimorbidity – see the next section.

Structured Medication Reviews are defined by NICE as:

‘a critical examination of a person’s medicines with the objective of reaching an agreement with the person about treatment, optimising the impact of medicines, minimising the number of medication related problems and reducing waste.’ 6

These (ideally multidisciplinary) reviews are a great opportunity to learn about how long-term treatments are affecting your patient, and reconsider their benefits and harms. These may change over a patient’s life course as a result of changes in their health profile and priorities.

Advice about how to conduct them is included in the resources below.


References and resources

1)NICE Multimorbidity Guideline (2016)

  • Recommendations on identifying multimorbidity, assessing frailty, tailoring the approach to care.

2)NHS Scotland Polypharmacy website

  • A rich resource for healthcare professionals and public. Strategies (“7 step”) for medication review, common drug interactions, deprescribing strategies, prescribing in frailty, NNTs and more.

3)Royal Pharmaceutical Society Polypharmacy Guidance 2019

  • Comprehensive review of polypharmacy including professional guidance and tools to support practice.

4)NICE Medicines Optimisation Guideline 2015

  • Recommendations on practical aspects such as communication with patients and between organisations, medicines reconciliation, self management plans and more.

5)Royal College of General Practitioners e-learning module: Multimorbidity and Polypharmacy 2022

  • Interactive module (105 minutes) which considers pragmatic aspects as well deeper questions about what drives decision making in practice. Based on recent research, it unpacks power dynamics and knowledge imbalances that affect us all – clinicians and patients.

6)National Institute for Health and Care Excellence (NICE) (2016) Medicines Quality Standard [QS120]