For many patients, prescriptions never change – except to become more numerous – but as some experts have pointed out, doctors are all taught how to prescribe medications, not how to stop them, writes Rita Rubin in JAMA Medical News.
Among US adults aged 40 to 79, about 22% reported using five or more prescription drugs in the previous 30 days, shows data from the National Centre for Health Statistics (NCHS), part of the US Centres for Disease Control and Prevention (CDC).
People aged 60 to 79 were more than twice as likely to have used at least five prescription drugs in the previous month as those aged 40 to 59. On average, 750 older adults in the US are hospitalised daily because of adverse drug events.
“We’re all taught how to prescribe these medications. We’re not taught how to stop them,” Eric Lee, MD, a Kaiser Permanente geriatrician in Los Angeles, told JAMA. So “prescribing inertia” – the tendency to keep prescribing a drug even if the indication it originally treated no longer exists – sets in.
In recent years, though, Lee and other researchers have begun to address that knowledge gap. Although older patients, especially those with dementia, are more likely to be using multiple medications simultaneously, the topic of de-prescribing is relevant to adults of any age who have been refilling the same prescription for years.
Over time, a drug’s benefit may decline while its harms increase, Johns Hopkins geriatrician Cynthia Boyd, MD, MPH, said.
“There is a limited number of drugs for which the benefit-harm balance never changes.”
In some cases, the benefit might not even be known because the patient has aged out of the population studied in clinical trials. For instance, nearly half of multiple sclerosis (MS) sufferers are over 55, but clinical trials of disease-modifying therapies, available for three decades, excluded them. The data supporting the use of these medications over 55 are basically non-existent.
The same is true for anti-cholinergic medications, Lee, co-chair of the Southern California Permanente Medical Group High Risk Drugs in the Elderly Committee, and his co-authors noted in a recent research letter. The efficacy for many of these drugs, which include antihistamines, skeletal muscle relaxants, and antidepressants – both selective serotonin reuptake inhibitors and the older tricyclic antidepressants – “has not been demonstrated in older adults”, they wrote.
Meanwhile, the harms from continuing to use medications can be substantial, including cognitive dysfunction, impaired balance and increased risk of falls, and in patients who are pregnant, teratogenicity, University of Michigan neurologist Samuel Termin, MD, MS, said.
However, de-prescribing is not a decision to be made lightly or unilaterally.
It requires shared decision-making that considers “what patients value and what patients prioritise”, said Boyd, co-director of the US Deprescribing Research Network, funded by the National Institute on Ageing.
“You can’t do it in a cookbook kind of way,” she said. “You have to talk to the patient and the family.” Presented with the same data about the same medication, one patient might decide to stop taking it while another might prefer to continue taking it.
‘If it ain’t broke’
Not surprisingly, one of the major obstacles to de-prescribing is the concern by both patients and physicians that doing so would worsen symptoms.
“Most people think all of their medications are needed,” Boyd said.
Lee has heard that before. “They think if they don’t get a medication for the neuropathy, it’s only going to get worse.” And yet, he said, the likelihood that medications will relieve their discomfort from neuropathy “is actually quite small”.
Humans have a strong drive “to over-attribute causation”, Terman said. For example, many patients who’ve been seizure-free for years credit their medications and prefer to continue taking them. “However, it’s not that deterministic.”
In reality, two-thirds of people with epilepsy become seizure-free with anti-epileptic drugs, and only about a third relapse after they stop taking them. Experiencing a seizure after stopping medication doesn’t change patients’ prognosis, and they can simply resume taking the drug, he said.
Guidelines, like a 2021 American Academy of Neurology (AAN) practice parameter, endorse that patients who’ve been long free of seizures consider stopping anti-seizure medications. These patients might be seizure-free without the drugs, but that’s unknowable if they keep taking the meds, the AAN practice parameter notes.
Yet clinicians don’t routinely raise the possibility of discontinuing anti-seizure medications, Terman and his co-authors found in a recent retrospective cohort study of patients with epilepsy at the University of Michigan and at two Dutch centres.
Of all patients who were seizure-free for at least a year, they found documentation of any discussion about discontinuing anti-seizure medication for only about half of them. That proportion increased to about two-thirds for patients who’d been seizure-free for at least two years.
Giving up?
Prescribers worry that advising patients to consider stopping a medication they’ve taken for years might be misinterpreted as giving up on them, research suggests.
When the patient has dementia, family and informal caregivers might perceive de-prescribing as “withdrawing care”, wrote Joshua Niznik, PharmD, PhD, a University of North Carolina geriatrics services researcher, and co-authors recently.
They interviewed a dozen prescribers – caring for older people with dementia in nursing homes – about de-prescribing bisphosphonates for osteoporosis. Such patients are often excluded from randomised trials of fracture prevention medications, resulting in a dearth of evidence about how the drugs might benefit or harm them.
Yet de-prescribing of bisphosphonates in older nursing home patients occurs infrequently, Niznik said. They found most nursing home residents with dementia who were prescribed bisphosphonates were at least 80.
Bisphosphonates accumulate in the bone and then are slowly released over time, meaning patients can take a drug holiday for a year with no ill effect, Niznik said. But what if a patient isn’t expected to live more than a year?
“What makes the most sense is grounding it in what matters to this person the most, making it clear you’re invested in their best interests” he said.
Niznik is trying to spread the word that if older people with dementia stop taking bisphosphonates or medications to treat type 2 diabetes, hypertension, or high cholesterol, they won’t quickly decline or have a rebound effect.
Trade-offs
Some patients want to take as few medications as possible, but others “cling to their medications for some source of security”, Niznik said.
Another recent article in JAMA Network Open backed him up. In it, researchers focused on why people aged 65 or older disagreed with a de-prescribing recommendation.
The scientists had asked study participants, who lived in Australia, the Netherlands, the UK, and the US, to read a hypothetical vignette about a 76-year-old woman who took 11 medications. In one version, her primary care physician recommended she stop taking a statin for primary prevention of heart disease and stroke, and in the other version, a proton pump inhibitor for indigestion.
The physician cited a lack of benefit, a potential for harm, or both. A substantial proportion of the participants who disagreed with the physician’s recommendation expressed concerns about what might happen if the medication were stopped, like a worsening of symptoms and health.
Broaching the subject
Besides patients’ concerns that symptoms might worsen, there’s another main obstacle to deprescribing: physicians are reluctant to stop a medication that another physician prescribed.
“Prescribers could be choosing the path of least resistance because of system-level barriers such as healthcare system fragmentation, deference to colleagues’ clinical decision-making, time required to co-ordinate care with other clinicians, and adequate time for shared decision-making with patients,” Boyd said.
In a retrospective analysis of 2014 data for Medicare beneficiaries with epilepsy, Terman and his co-authors found that the patients filled a median of 12 different prescriptions written by a median of five different prescribers.
Boyd said while primary care physicians considered the financial impact of continuing or discontinuing medications to be the least important barrier, it might actually provide a more palatable way of starting a discussion about deprescribing.
Studies show that up to two-thirds of patients said they spent a lot on their prescriptions or that the prospect of paying less would play a role in their willingness to deprescribe. “This is an area we need to further investigate,” Boyd said.
University of Colorado neurologist John Corboy, MD, MA, said he plants the seed for possibly stopping MS treatment when patients hit 55, at which point evidence of benefit is scant. Considering the average age at onset of MS symptoms is 30, he said, 55-year-old patients may have been taking disease-modifying medications for a quarter of a century.
He led a recently published randomised multicentre trial designed to help inform patients with MS and their physicians about the risk of new disease activity if they discontinue or continue disease-modifying therapies for two years. “The reality is we didn’t know what was going to happen except for our own personal anecdotal experience,” he said.
Only patients 55 or older, who’d been relapse-free for at least five years and had had no new lesions seen on magnetic resonance imaging (MRI) in at least three years, were eligible for the study.
The study found that discontinuation might be associated with a small increased risk of clinically silent new brain lesions on MRI scans. However, Corboy said “more people at the end of the study were satisfied being off drugs than being on drugs”.
He and his co-authors also recently reported the results of an extension trial that enrolled about 30% of the original participants, some randomised to discontinuation, some to continuation. None had relapsed or been found to have a new brain lesion during the original 24-month trial.
After an average of 40 months since entering the original trial, none of the participants had relapsed, and only two who’d discontinued their disease-modifying therapy and one who’d continued it had new brain lesions.
Not all or nothing
In some cases, stopping medication or maintaining the status quo isn’t the only option.
For example, Lee said, instead of taking an anti-cholinergic drug daily for urge incontinence, patients might find they can take it only as needed, such as when they’re going to a party.
And instead of discontinuing an anti-seizure medication, they could switch to a newer drug that’s associated with less cognitive dysfunction or reduce the dose of the drug they’ve been taking.
Even if patients decide that deprescribing is the best option, non-pharmacological alternatives, such as using cognitive behavioural therapy instead of benzodiazepines to treat insomnia, can help ease the transition. (Due to increased risk of cognitive impairment, delirium, falls, fractures, and motor vehicle crashes, the widely prescribed benzodiazepines are on the American Geriatrics Society’s list of medications older adults should avoid.)
In some cases, complementary and integrative health approaches like mindfulness meditation and yoga might represent another non-drug option. The National Centre for Complementary and Integrative Health has provided funding to the US Deprescribing Research Network for pilot trials of such approaches to facilitate deprescribing of benzodiazepines.
As data around deprescribing emerge, clinicians need help putting the findings into practice. “There is not enough content about this in medical school,” Boyd said.
She said guidelines should be providing summaries of the evidence needed when making recommendations to specific patients.
JAMA Network article – Deprescribing in Epilepsy (Open access)
See more from MedicalBrief archives:
US opioid prescription guidelines ‘wrongly implemented’
1.3m UK asthma sufferers skip doses because of prescription charges
Pharma company settles prescription kickback suit in US
Questions of over-prescription
Experts flag dangers of anti-psychotics for dementia patients