Photo kindly provided by JOSHUA COLEMAN on Unsplash

​    Several times on my first day in a geriatrics ward, I was told the legend of the fast-tracked EOL (End of Life) patient who made a miraculous recovery from the process of ‘active dying’, after all their regular medications had been struck off their drug charts. Let’s call them Snow White, who gratefully accepted an apple from the kindly farmer’s wife only for it to put her in a very deep sleep.
 
    Almost every known medication has at least four documented common side effects. Patients taking a cocktail of drugs are exposed to multiple sets of these side effects, as well as additional ones arising from adverse drug interactions. Common consequences include diarrhea, flatulence, nausea, headache, postural hypotension, hyponatraemia, altered taste, decreased appetite, and fatigue. Now imagine having all of them together, at the same time. Any healthy medical student on this regime would probably feel close to death too.
 
    This is not an exaggeration. In fact, I conjured up this list by consulting the BNF for ‘common or very common’ side effects for drugs that could reasonably be prescribed to John Smith, a 60-year old male patient with metabolic syndrome who has just tipped into diabetes, with a few other comorbidities:
 
    1. A statin for high blood cholesterol
    2. An ACE inhibitor and furosemide for blood pressure
    3. Metformin and a gliptin for his diabetes
    4. Omeprazole, a relic from an episode of GORD 8 years ago
    5. Prazosin for benign prostate hyperplasia
    6. Sertraline for signs of depression.

  This man is hardly an exceptional patient: John almost certainly can be found somewhere in your extended family.
 
About Polypharmacy
    Polypharmacy refers to the prescription of multiple medications to manage or treat complex health conditions and multiple comorbidities. The prevalence of polypharmacy within the UK is increasing. In Scotland, the proportion of patients prescribed 5 or more medications doubled to 20.8% from 1995 to 2010, and the proportion prescribed 10 or more medications tripled to 5.8%. Similarly, in England, national dispensing data from 2001 to 2011 shows a 64% increase in the number of medications dispensed in primary care from 2001 to 2011.
 
   This may be attributed to several factors, principally our aging population and the increasing prevalence of multi-morbidity, where patients live with several long-term conditions, often compounded by disability and/or frailty. As the population ages, there are more elderly patients with multiple chronic conditions and comorbidities. Management guidelines frequently recommend the use of multiple drugs that act synergistically, based on robust evidence, and there are more available treatments and drug classes for common conditions. This leads to increased prescribing for chronic conditions such as diabetes. Furthermore, many of these problems are detected earlier, meaning that pharmacological treatment commences earlier in life for patients. This is in addition to the medical management of risk factors, where asymptomatic people are treated with preventative interventions to reduce their future risk of mortality and disease. Polypharmacy may also be caused and worsened by prescription cascades. This occurs when a drug prescribed to treat a health condition has side effects, which are then managed by prescribing a second drug, and so on. A common example of this is prescribing omeprazole to mitigate the risk of a stomach ulcer caused by NSAIDs.
 
   As well as these inevitable factors, many drugs are continued in patients who previously derived a benefit, but who may no longer do so - for example where the long-term mortality or morbidity benefits are unlikely to manifest in their limited life expectancy.
 
   It is important to note that not all polypharmacy is problematic. Polypharmacy is appropriate when there is robust evidence supporting their concurrent use to improve a patient’s quality of life and extend their life, for instance in heart failure or for controlling cardiovascular risk factors. However, there is strong evidence that increased numbers of medicines are associated with adverse effects, including a greater risk of medication errors, drug interactions and adverse drug reactions, and impairing medication adherence. In elderly patients, where complex medication regimes are the most prevalent, cognitive impairments, visual impairments and loss of dexterity are common. This makes medication adherence harder, and both the risks and dangers of medications may increase if they are not administered as clinically intended.
 
Polypharmacy in the community
   Elderly people are often prescribed numerous medications to treat various health conditions and comorbidities, and control their risk factors for cardiovascular diseases. The patient may visit a specialty clinic for each condition, and be admitted onto any one of the related specialist wards.
 
   Distributing the responsibility of a single patient’s care to multiple specialty teams ensures the patient receives the best treatment for each of their organ systems, but not necessarily for their holistic wellbeing. Upon discharge, the patient is returned to the care of their GP, who is then tasked with untangling why their patient has been burdened with all these prescriptions. Often, patients leave the hospital with more routine prescriptions than they had upon admission. According to a CQC report, details of medicines prescribed in secondary care sent to GPs are commonly incomplete or inaccurate. As a result, the safest, simplest way to act in a patient’s best interest may well be to not alter what the specialists have prescribed.
 
   In the UK, the central role of General Practice in the organization of health services means that management of long-term prescribing is predominantly carried out in the primary care setting, which is also where repeat prescriptions are provided. Hence, GPs are in a prime position to review and reduce their patients’ prescription burdens.
 
   However, this is hardly an easy task. Although the harms of polypharmacy are well-established in cross-sectional and longitudinal studies, there is currently a lack of clear evidence about the benefits or safety of deprescribing. The evidence base for multiple interventions for several conditions in an individual patient is poor, and many clinical trials and practice guidelines do not consider polypharmacy in the context of multi-morbidity. Currently, a single-disease framework prevails in most healthcare systems, medical research and medical education, leading to a lack of training in undertaking complex medication reviews. This is likely because polypharmacy is a relatively new phenomenon, and more time is needed for research to be conducted to support clinical practice and development of guidelines. Social and structural limitations further exacerbate the issue – polypharmacy has become the norm, and some patients or families may feel disgruntled if their regular medications that have been taken for decades are discontinued, while doctors lack time to review and explain changes in routine consultations.
 
A Concerted Effort Against Polypharmacy
   We can begin to mitigate polypharmacy by picking at low-hanging fruit. For instance, GPs and doctors can start by clearly documenting the rational for prescribing a medicine, for ease of reference during future consultations. Similarly, when going over a patient’s prescription, doctors can and should question the rationale for every medication and deprescribe it if it is no longer indicated. Before prescribing new preventative medications, the time benefit of a medication should be considered in relation to the patient’s remaining lifespan – is the patient likely to benefit from the medication in their lifetime? Finally, GPs can work alongside patients to empower them to make informed choices about their treatments and the burden of pills they are expected to consume, so that the patient is fully on board with their treatment plan – a known method of improving compliance.
 
   Systemic changes would be needed to accommodate changes in practice. The duration of primary care consultations for multi-morbidity should be increased to allow sufficient time for the use of drugs to be reviewed. GPs and doctors should be trained in managing complex multi-morbidity, polypharmacy and other aspects of medicines management. Key topics might include:
​  O Whether interactions between drugs where medication is combined will undermine therapeutic benefit
    O Spotting iatrogenic symptoms to prevent prescription cascades
    O Recognising when current side-effects might outweigh future benefits  

   Outside of modifying clinical practice, public health policy and healthcare research must also catch up. There is a strong case for reviewing the way in which the quality and outcomes framework focuses on improving the treatment of single diseases rather than the needs of patients with a number of long-term conditions. Guidelines should be updated to take into account long-term conditions that commonly co-exist, such as diabetes, coronary heart disease, heart failure and COPD, and address when to stop medications. Clinical trials should be conducted to include patients with multi-morbidity and polypharmacy, taking these factors into consideration when evaluating new drugs, rather than excluding these patients from trials. Furthermore, a method to quantify the risk-benefit ratio of different drug interventions in the context of polypharmacy and in relation to real-life applications should be developed. Systems that optimize medicines use where there is polypharmacy so that people gain maximum benefit from their medication with the least harm and waste have to be developed. This may include training programmes, improved electronic decision support for clinicians and/or patients, and patient-friendly information systems.
 
   The rise of polypharmacy was driven by demographic changes, scientific progress, structural factors and public health policies. While well-intentioned, polypharmacy as a treatment comes with unexpected side effects. The solution to this, as with all other treatments and diseases, requires a concerted effort by doctors, policy makers, researchers, professional organisations, national bodies and pharmaceutical companies to change current clinical and scientific practice. Important first steps are to increase awareness levels of this phenomenon in the healthcare industry to motivate change, and immediate action can be taken by doctors and general practitioners who are battling disease on the frontline. Let us guard against unintentional harm to our patients by the same weapons that were designed to combat poor health.
 

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This report offers a comprehensive review of polypharmacy.
 
Sources:
https://www.bmj.com/content/366/bmj.l5497/rr
https://bmcfampract.biomedcentral.com/articles/10.1186/s12875-018-0856-9
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451545/
https://www.futurity.org/too-many-medications-medsafer-deprescribing-2179342-2/
https://www.kingsfund.org.uk/sites/default/files/field/field_publication_file/polypharmacy-and-medicines-optimisation-kingsfund-nov13.pdf