“Why is Mr X on statins?” asked the palliative consultant.
“He has been on statins for a long while given his poor cholesterol profile, even before he was referred to us,” the palliative registrar replied.
“What is his prognosis?” the consultant continued.
“So why is he still on statins? Does it improve his prognosis?” questioned the consultant.
It was this very conversation I heard during a rotation at a palliative care hospital, which provoked my thoughts on the concept of “deprescribing.” It is a relatively foreign concept to most practitioners, and perhaps unsurprisingly shunned by pharmaceutical companies for obvious commercial reasons. To begin, medical students are rarely exposed to this term in medical school, especially in palliative care. It is essentially a process aimed at optimizing a patient’s treatment regime by stopping medications deemed to be unnecessary or inappropriate. Although there has been an increasing body of literature amongst the geriatric population, it is a dearth in the palliative setting.
Most, if not all consultations routinely end off with a sentence that sounds somewhat similar to the following, “I will be prescribing to you this list of medications….” Evidently, medical practitioners, and medical students alike, are often most keen about the medications they prescribe to their patients. Just as how soldiers utilize weapons to defeat their enemies in a war, drugs are the armamentarium doctors have to cure their patients’ illnesses. Paradoxically, this opens a Pandora’s box of problems, which may manifest in the form of “Adverse Drug Reactions” (ADRs), colloquially known as “side effects.” Shockingly, ADRs are between the fourth and sixth leading cause of death in the United States, and has cost approximately 5% of the national health budget(1).
The “devil” of “deprescription” is polypharmacy – an inevitable outcome in most palliative patients who suffer from advanced disease. These patients have multiple co-morbidities, accompanied by symptoms such as pain, nausea, breathlessness, which puts them on chronic medications to prevent further complications, and to control the symptoms. As such, patients in their last year of life have a significant increase in the number of medications(2). However, despite the seemingly logical reasons behind polypharmacy in palliative patients, there are strong opposing reasons to why that should not be the case.
Pharmacologically, changes to drug pharmacokinetics happen with ageing and certain terminal illnesses, thereby affecting drug distribution, metabolism and excretion. Elderly patients have an increase in total fat mass, and a decrease in lean muscle mass and blood volume. This is similar in chronic disease patients with cachexia; they suffer from fat and skeletal muscle loss. The altered body compositions affect drug distribution, loading dose, and half-lives. This is compounded by impaired liver and kidney functions, which disrupts phase II metabolism, and clearance (3). Therefore, we should avoid stretching the physiological limits of the body in such circumstances.
Secondly, the concept of “time to benefit” (TTB) is a crucial consideration that doctors must account for. TTB is defined as the time for the drug to have its intended effect on the patient(4). This ranges from months to years. One commonly prescribed medication is statin, as evident in the conversation between the consultant and registrar in the aforementioned. The approximate TTBs for statins and zoledronic acid are two years(2), and 16 months respectively(3); this is perhaps beyond the patient’s life expectancy in palliative care, and hence will not benefit them in their twilight years. There is no reasonable justification to prescribe drugs that do not have an immediate effect on patients with a very short prognosis time.
Next, some drug classes have greater potential for ADRs in terminal care patients. The Beers criteria provides consensus-derived classification of “high” and “low” risk drugs(5). Paradoxically, the “high risk” drugs are often prescribed for the elderly, and terminally ill patients. These include cardiovascular drugs, psychotropic drugs, and non-steroidal anti-inflammatory drugs. Furthermore, ADRs can be compounded by the negative effects of polypharmacy, which has been associated with falls, hip fractures, and deaths(3). In the same vein, the risk of ADRs is greater than 80% when eight or more drugs are taken regularly (6). The high risk of drug-drug interaction has been well documented among palliative patients, especially in pain management, resulting in significant adverse consequences(7). So why put our palliative patients through times of unnecessary vulnerability and adversity for our selfish love for drugs?
Lastly, medications are not cheap. Financial costs are a huge burden of polypharmacy for both patients and the government. A Canadian study involving 248 palliative care patients revealed that inpatient hospital stays was the largest cost component (33.2%)(8). More importantly, there is a shift, in many developed countries, towards palliative care delivery from hospitals into community settings, since most patients wish to die in their own homes. The implication then, is a shift in the burden of medical costs towards patients and their families.
What are the barriers?
While the deprescribing process is not without its risks and barriers, these hurdles are not insurmountable.
From the clinical perspective, there is the risk of withdrawal reactions. A retrospective study showed that 26% of medication stoppage led to either adverse withdrawal reactions(9) or disease progression. This has been shown in Alzheimer disease patients, who suffer a decline in cognitive scores after deprescribing donepezil. However, it is arguable whether this indeed has a negligible impact on palliative patients with very short prognosis (ie. weeks and months). Moreover, this can be circumvented if drugs are deprescribed gradually over a period of time instead of sudden stoppage.
Interestingly enough, doctors can face resistance from patients when deprescribing, especially after a perceived improvement in starting a medication. Although there are no clinical indications, benefits are often psychological in nature, which gives them mental comfort and hope in cure (10). Lastly, both doctors and patients suffer from poor support. The former lacks proper support guidelines and knowledge to deprescribe. Although the Beers criteria provides guidelines for safer prescriptions in elderly patients, they may not be readily applied to palliative patients. Consequently, on the receiving end, patients do not receive enough time and support from their doctors to discuss deprescription.
Way forward for doctors & medical students
What is the way forward? Guidelines such as the Beers criteria, and the Screening Tool of Older Person’s Prescriptions (STOPP) / Screening Tool to Alert doctors to Right Treatment (START) criteria, should be modified to include the palliative population. It must be recognized that palliative patients suffer from a completely different set of distressing symptoms and complications. Furthermore, education courses and workshops can be conducted for doctors to increase awareness and knowledge. Ultimately, these efforts must be supported by scientific research, which unfortunately has a disproportionate emphasis in investigating methods and reasons to start drug treatment; there is conversely little effort done to study discontinuing.
While there are no set rules and guidelines thus far, doctors must still continue to frequently reassess their patients’ drug regimen, and actively consider discontinuation of drugs in palliative patients when necessary, bearing in mind the individuality of every patient’s circumstances. I would propose that a few key aspects to consider include life expectancy, goals of care, TTB, and symptom management.
Ultimately, the appreciation of such a concept should start in medical school. Medical students should not route-learn pharmacology merely in terms of drug classes, pharmacokinetics, pharmacodynamics, and drug mechanisms. Instead, learn the ‘why’s and ‘when’s of giving, and stopping a drug.
“Primum non nocere”. We are taught to practice by this very principle of “doing no harm”; it defines our profession. But just when medications are often, always, the first to come to our minds when treating harm, we must bear in mind that it is itself a source of harm.
1. Bain KT, Holmes HM, Beers MH, Maio V, Handler SM, Pauker SG. Discontinuing medications: a novel approach for revising the prescribing stage of the medication-use process. Journal of the American Geriatrics Society. 2008;56(10):1946-52.
2. Akinbolade O, Husband A, Forrest S, Todd A. Deprescribing in advanced illness. Progress in Palliative Care. 2016;24(5):268-71.
3. Hardy JE, Hilmer SN. Deprescribing in the Last Year of Life. Journal of Pharmacy Practice and Research. 2011;41(2):146-51.
4. Holmes HM, Hayley D, Alexander G, Sachs GA. Reconsidering medication appropriateness for patients late in life. Archives of Internal Medicine. 2006;166(6):605-9.
5. American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. Journal of the American Geriatrics Society. 2015;63(11):2227-46.
6. Currow DC, Stevenson JP, Abernethy AP, Plummer J, Shelby-James TM. Prescribing in palliative care as death approaches. Journal of the American Geriatrics Society. 2007;55(4):590-5.
7. Bernard SA, Bruera E. Drug interactions in palliative care. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2000;18(8):1780-99.
8. Dumont S, Jacobs P, Fassbender K, Anderson D, Turcotte V, Harel F. Costs associated with resource utilization during the palliative phase of care: a Canadian perspective. Palliative medicine. 2009;23(8):708-17.
9. Reeve E, Shakib S, Hendrix I, Roberts MS, Wiese MD. The benefits and harms of deprescribing. The Medical journal of Australia. 2014;201(7):386-9.
10. Reeve E, To J, Hendrix I, Shakib S, Roberts MS, Wiese MD. Patient barriers to and enablers of deprescribing: a systematic review. Drugs & aging. 2013;30(10):793-807.
“Why is Mr X on statins?” asked the palliative consultant.