Is the best medicine no medicine at all? Sometimes. My past posts have emphasized that the appropriateness of any drug depends on an evaluation of benefits and risks. There are no completely safe interventions, and no drug is free of any side effects. Our choice is ideally informed by high-quality data like randomized controlled trials, with lots of real-world experience so we understand a drug’s true toxicity. But when it comes down to a single patient, treatment decisions are personalized: we must consider individual patient characteristics to understand the expected benefits and potential harms. And in a world with perfect prescribing and drug use, harms wouldn’t be eliminated, but they would be minimized. Unfortunately, we’re not there yet. There is ample evidence to show that the way in which prescription drugs are currently used causes avoidable harms to patients.
The art and science of medicine is a series of interventions to improve health. In making these treatment decisions, we strive to minimize iatrogenic harm — that is, harms caused by the intervention itself. High up on the list of of avoidable harms are adverse events related to drug treatments. Audits of adverse events are astonishing and shameful. Studies suggest 28% of events are avoidable in the community setting, and 42% are avoidable in long-term care settings. That’s a tremendous amount of possible harm resulting from treatments that were prescribed to help. And the group that is harmed the most? The elderly.
The Hazards of Aging
One of the early lessons of pharmacology is that “Children are not little adults” and “Seniors are not older adults.” That is, we cannot assume our understanding of how a drug works in a healthy adult is automatically applicable to either the young or the old. Systems for eliminating drugs may not have developed (in the young), or may have declined (in the elderly) so the usual dose of a drug may be much lower. Children and the elderly have different physical characteristics, too. There’s a different ratio of fat to muscle compared to adults, affecting how drugs are distributed throughout the body. In the elderly, the net effect is that drugs are usually not excreted as quickly, increasing the risk of accumulation and toxicity.
But that’s not all that happens. As we age, our odds of having medical issues increases significantly — and along with it, the likelihood we’ll be prescribed one or more drugs for each illness. Despite the fact that drug use is exceptionally prevalent in the elderly, our knowledge of the risks and benefits in this group can be limited. Few clinical trials deliberately include the elderly, or those on multiple medications with several medical conditions. The effects and side effects in this group may not be as well known. Add in other medications, and you increase the risk of drug-drug interactions Combine this with the normal effects of aging, like decreased mobility, vision impairment, and hearing problems, and you’ve got patients already disadvantaged if drugs exacerbate these conditions.
While all drugs have the potential to harm, some are demonstrably worse than others, particularly in the elderly. Mark Beers, a geriatrician, published a list of of potentially inappropriate medications (PIMs) in 1991. His list focused on nursing home patients, and over the next decade expanded it to include those that were potentially inappropriate for anyone over the age of 65. They key word, of course, is “potentially”. There are no hard and fast rules about appropriateness of any drug, as a unique set of patient circumstances (e.g., allergies, other medications) can mean that a potentially inappropriate medication is the most appropriate one. But some drugs are rarely appropriate, and that’s what the “Beers List” included.
There were multiple criticisms of the list when it was published. The methodology was essentially expert opinion — not based on systematic evaluations of harms. But, the list has been used extensively, and cited in hundreds of papers, linking the use of PIMs to poor consequences for patients including adverse events, hospitalization and death. The list has also stimulated further research, which has confirmed that some PIMs are directly associated with harms.
The list has been updated several times, and the most recent version was published earlier this year.
The Beers List
The most recent version of the list was derived based on a literature search followed by voting by experts and finally, an expert panel discussion. 53 drugs made the list and were categorized as follows:
- never appropriate
- potentially inappropriate, depending on other diseases/conditions
- use with caution drugs — safety and effectiveness data are still emerging
So what drugs should be avoided? I’ll refer you to the full paper [PDF] or you can jump just to the entire list. Here’s some of the bigger categories of drugs that generally should be avoided in the elderly:
- Antihistamines and other drugs that block acetylcholine (e.g., Benadryl), which can cause blurred vision, confusion, and constipation.
- Antiparkinson drugs used to treat the side effects of antipsychotics, which are both ineffective and cause further side effects.
- Antispasmodics (e.g., dicyclomine), an old class of drugs with little demonstrated efficacy yet considerable side effects.
- Some drugs to treat blood clots (e.g., ticlopidine) which have been superseded by better tolerated, more effective drugs.
- Nitrofurantoin, an antibiotic used to treat bladder infections, despite the availability of safer alternatives.
- Alpha-1 blockers (e.g., terazocin) for hypertension, when better tolerated, more effective drugs exist.
- Alpha-agonists (e.g., reserpine) a old group of drugs now rarely used to treat high blood pressure, because better, safer alternatives exist.
- Some drugs used to treat heart arrythymias (e.g., amiodarone) which are often unnecessary
- The drug digoxin when used at high doses to treat heart failure.
- Older antidepressants called “tricyclics” which have significant side effects (and are rarely used today, as a result).
- Antipsychotics, both older drugs (e.g., haloperidol) and the newer ones (e.g., risperidone), a wildly overused group of drugs which increase the risk of stroke.
- Barbituates like phenobarbital, an old group of drugs dating back a few decades which cause tolerance and dependence.
- The sedative class called the “benzos” like diazepam (Valium). They all increase the risk of falls, congnitive impariment, and motor vehicle accidents.
- The “non-benzo” sleeping drugs such as zolpidem (Ambien) which largely have the same side effects as the benzos.
- Hormones such as testosterone (potential for cardiac problems, and rarely necessary) “dessicated” thyroid (safer alternatives exist) and estrogens like Premarin (few documented benefits in this population).
- The narcotic meperidine (Demerol) as it has a toxicity that’s unique to narcotics — safer choices exist.
- Almost all non-steroidal anti-inflammatory drugs (NSAIDs) (e.g., ibuprofen) due to the high risks of stomach ulceration.
- Muscle relaxants like methocarbamol which have unclear efficacy but a documented side effect profile which may increase the risk of falls.
While the list covers many of the drugs that come to mind when you think about side effects, there are several products on the list which are rarely prescribed to anyone — elderly or not — so why they’re still included is unclear. At the same time, there’s no mention of the entire class of narcotic drugs which are often used inappropriately for pain control while raising the risk of tolerance to its effects. There’s also the drugs used to treat Alzheimer’s disease, the cholinesterase inhibitors, which lack convincing efficacy data yet continue to be used widely to treat dementia. Overall, the list focuses heavily on harms while it seems to give a pass to drugs that lack convincing evidence of efficacy. From my personal perspective, no side effect is justified if the drug doesn’t work. So most over-the-counter treatments for coughs and colds should also be on the list, given they have little evidence of efficacy and don’t affect the underlying illness.
I’m not the only one that would modify the list, or seek to improve upon it. There are several others French version, a Norweigan version, the Zhan criteria, the STOPP (Screening Tool of Older Persons’ potentially inappropriate Prescriptions) tool, and one called the Drug Burden Index. Still, the Beers list remains the most well-know and understood. With its 2012 update, the authors have made a significant effort to put the list into practice, creating a number of resources. There’s a summary for patients and caregivers (PDF), and nicely, a summary of how to talk to healthcare providers if you or a family member is taking a drug on the list. There’s even an app for the Beers list.
Another criticism of the Beers list is that long lists can distract from the real drivers of hospitalization: A study looking at preventable hospitalizations found that warfarin (Coumadin) alone causes one-third of hospitalizations, while insulin, antiplatelet drugs, and oral diabetes medications cause another third, with other “high risk” drugs making up a minority of admissions. While this study focused on admissions, and not overall harms, it suggests that focused efforts to more effectively manage diabetes and antithromibic medications may be most effective in reducing drug harms.
Some physicians and geriatricians call for more efforts at deprescribing or “drugectomies” as a means of reducing drug-related harms in the elderly: Ruthlessly discontinuing drug therapies if the expected clinical benefits are small. The approach involves a careful consideration of each drug, confirming that it’s still medically appropriate and necessary, while considering patient preferences and overall quality of life. As data emerges suggesting these approaches look promising, we may see more standardized approaches to deprescribing in the future.
Screening tools like the Beers list can be helpful and empower patients and caregivers to check for potentially inappropriate medications. The elderly are already at risk – drugs which increase the risk of harms should always be questioned. However, all treatments are ultimately individualized, so there are no absolute rules. Importantly, all drugs have the potential to harm: not just the ones on the Beers list. There is good evidence to suggest that prescribing and drug use in the elderly can be significantly improved. Until we more carefully consider the patient-specific benefits and risks of medications, there will continue to be substantial and avoidable drug-related harms.