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How do we avoid harming the elderly with prescription drugs?

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.

Conclusion

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.

 

Posted in: Pharmaceuticals

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22 thoughts on “How do we avoid harming the elderly with prescription drugs?

  1. nybgrus says:

    There has been more and more push for geriatrics in medicine, from what I have seen. In my medical school for instance, we have specific lectures on it in the first two years and programs to help entice students to pursue geriatrics in GME. I think this is a good thing myself. I also think that the increasing computerization of medicine accompanied by more robust – and more accepted use of – guidelines will also help this. First is the development of them – which is what you have written about. Next is creating a crop of physicians who will be more willing to accept them. While not as accepted as I would like, I think my generation of physician will be more willing to change prescribing practices based on a review of guidelines. The impediment is the older generation of physicians whining in our ears about how such-and-such is taking away our autonomy and clinical judgement and how they’ve never once in their 27 billion years of practice had a problem with [XXX] and now all of a sudden some pencil-pushers are changing the rules. Of course they chalk this up to trying to cut costs and not the scientific process. But these voices are less and less and I think more and more of my colelagues are already vaccinated against this sort of thought process. Perhaps the generation of physician after me (i.e. those that I would be teaching as an attending) will be ready to more fully embrace such thoughts. As Atul Gawande said in a recent TED talk – not even cowboys operate like cowboys anymore. We just need to catch up.

    Oh, and BTW, will all the lurkers here who like to comment that this blog only ever snipes at CAM and their favorite woo-du-jour take note of this article please? There are many like it and I find them extremely useful and informative.

  2. Woody says:

    Excellent article. As a geriatric subspecialist, one of the first things I do is review the (often extensive) medication list and identify any psychoactive medications that would increase risk of confusion or imbalance as well as medications that in combination may cause excessive lowering of blood pressure and therefore put the patient at risk for syncope (fainting). Streamlining the medications for elderly patients is almost always a good thing.

    That said, I have a few pet peeves about some of the comments in your post:

    “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.”

    While it is true that cholinesterase inhibitors and memantine have limited efficacy for treating the cognitive symptoms of dementia, they do have a measurable benefit. In some patients they can have a substantial benefit. Also, they are considered standard of care for the treatment of dementia, so not offering them or stopping them without providing justification would be difficult to defend.

    “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.”

    This is a tough one, as I agree that antipsychotics are overprescribed, especially in the nursing home population. There in fact is a published black box warning discouraging their use in elderly patients with dementia. My problem with your statement and that published warning is that no alternative management strategy is provided. Elderly demented nursing home residents that are agitated and aggressive must be managed, or they will harm other residents or themselves due to their behavioral symptoms.

    1. Scott Gavura says:

      @ Woody:
      Thanks for your comments. With respect to the cholinesterase inhibitors, I’m more pessimistic about whether the effects are clinically meaningful, particularly in those with greater disease severity. I do agree that they are a standard of care, however. I also recognize the clinical challenge in determining the real-world effectiveness of this class of drugs.

      I agree that agitation in the elderly can be real and that antipsychotics can be used appropriately, particularly in the nursing home setting. What does concern me is the widespread use of antipsychotics in the ambulatory population, particularly in the absence of a clear reason for use, or when used solely as night-time sedation.

      Due to the number of products on the list I didn’t go into therapeutic alternatives for any of the products, as each one could justify a separate post.

  3. lizditz says:

    Scott as a lay reader on the lower end of “elderly” I thank you.

    I have some questions: what counts as “elderly”? I’m eligible for AARP; does that make me “elderly”?

    Do risks increase with age only, or are there other factors to consider?

    And finally: what is the lay reader to make of this, either in regards to their own medical care, or with respect to an elderly person they may be caring for (parents or an older spouse)?

    1. Scott Gavura says:

      @lizditz – The current iteration of the Beers list is written with those >65 yrs in mind. Risks increase with age due to a number of factors, including multiple medical conditions and multiple medications. For lay readers, I’d recommend reviewing some of the resources I linked to which are written expressly for families and caregivers. It can be the starting point for patient advocacy and a dialogue with your health care professionals about the goals of treatment.

  4. awesome articles on geriatric health :) Thumbs up

  5. Woody says:

    Then we are essentially in agreement. Once the dementia progresses into late stages, the benefits of cholinesterase inhibitors and memantine are marginal at best, and it is appropriate to consider discontinuation, though family members not infrequently are reluctant to withdraw treatment.

    Using antipsychotics strictly as a sleep aid is courting disaster, in my opinion, given the potential for serious adverse effects. I also see them used as “augmentation” in conjunction with SSRIs and other antidepressants, but often at doses that make me nervous, to say the least. I am not sure if such “augmentation” therapy is well-studied – I haven’t reviewed the literature on the topic.

  6. evilrobotxoxo says:

    As a psychiatrist who treats some geriatric patients, my comment is that the use of antipsychotics is complicated in general, and in the elderly in particular; however, you can’t make blanket statements about the entire class of meds. I agree that using antipsychotics for insomnia is a bad idea in general, but to be fair people really only use seroquel for that purpose, and at the typical doses of 25-50 mg it’s more an antihistamine (and 5HT2A antagonist) than anything else. Schizophrenics on Seroquel typically get 800-1200 mg daily. However, there is still some risk of metabolic side effects even at low doses, and I agree that it’s generally a bad idea unless there are contraindications to other classes of sleep meds (e.g. bipolar pts with comorbid substance abuse) or if there is a second reason to be using it (e.g. insomnia in treatment-refractory depression). But I agree that Seroquel is used as a sleeping pill way too often because it works really well, and people are focused more on effectiveness in the present than on metabolic risk in the future.

    On the topic of antipsychotic augmentation for depression, that’s a complicated issue because “antipsychotics” is simply the name we give D2 antagonists, but the more selective D2 antagonists (e.g. haldol) are not generally effective as augmentative agents to SSRIs. In other words, you’re using other off-target effects of the meds for augmentation. Abilify is a functionally selective partial agonist at D2, so when people use that as an augmentative agent in depression, they’re probably depending on the activation of D2 (and possibly the partial agonism at 5HT1A). You could probably do the same thing with a combination of pramipexole (D2/D3 agonist) and buspirone (5HT1A partial agonist), and both of those have some evidence as augmentation strategies for SSRIs, as Abilify does. Seroquel has some legitimate evidence supporting its use for augmentation in major depression, but this is probably due to its active metabolite norquetiapine, which is (among other things) a selective norepinephrine reuptake inhibitor. So it works, but it’s unclear whether that would be more effective than simply augmenting with Wellbutrin, which doesn’t cause all the metabolic side effects. Given the side effect burden, I think antipsychotic augmentation probably should not be a first-line strategy for unipolar depression unless psychotic features are present.

    Regarding antipsychotics in the elderly in general, there are obviously lots of circumstances where they’re overused, but to be frank I think that you have to approach most cases of dementia-related psychosis in the elderly from a palliative perspective, where life extension is less important than restoration of functional status (to whatever extent this is possible).

  7. DavidRLogan says:

    Great article and comments. Thanks everyone.

  8. trrll says:

    Since when is reserpine an alpha agonist?

  9. Alia says:

    Thanks for the article. We’re coping with such a situation at the moment, with my father-in-law, who’s currently on so many medications it’s hard to keep track of them. Well, he’s got many co-existent health problems but still, some of his medications are used solely to manage side effects of other medications. The problem is exacerbated by the fact that he visits several specialists who do not have contact with one another.

  10. evilrobotxoxo says:

    @trrll: nice catch about the reserpine; I missed that.

    @Scott Gavura: thanks, this is an interesting article on an important topic. One thing I was thinking about is generalizing this topic. In a sense, the goal is not to avoid harming the elderly, but to avoid harming patients who are susceptible to adverse drug effects, and old age is probably the most common strong predictor of susceptibility. However, it’s obviously not the only predictor, and I wonder how much better we could do if we were to take other factors into account. For example, I do something that is probably not evidence-based, but I think all clinicians do it: if I see two patients who are both 70 years old, but one is healthy and strong-looking, but the other looks weak and frail, I’ll be more cautious with prescribing meds to the frail-looking one. Is frail appearance a valid predictor or not? Who knows? I’ve had young, healthy patients in their 20s and 30s who’ve suffered medication side effects that textbooks will tell you occur almost exclusively in the elderly, so obviously nothing is 100%. But at the same time, it doesn’t make sense to throw clinical judgment out the window and treat all “elderly” patients the same because of a number.

    As a second, unrelated point, the list says that tricyclic antidepressants (TCAs) should not be used in the elderly. It’s true that TCAs are rarely used as antidepressants today, but they are commonly used in very low doses for treatment of peripheral neuropathies, and I think that should fall into a separate category of things that are more acceptable. I think the basis of TCAs being contraindicated in the elderly is the fact that they’re much more strongly anticholinergic than SSRIs and other antidepressants, but there was recently a large study showing that elderly pts on TCAs had lower overall mortality rates than pts on SSRIs. As usual, things are complicated, I guess.

  11. wales says:

    Thanks for this helpful article, it’s something we all need to be aware of.

  12. nybgrus says:

    I think the basis of TCAs being contraindicated in the elderly is the fact that they’re much more strongly anticholinergic than SSRIs and other antidepressants

    As a student, I also find them scary to prescribe because of how much they interact with basically everything. They are P450 metabolized, and old people like to drink grapefruit juice. They have cardiotoxic effects because they can act like Class 1A antiarrhythmics… and old people tend to be on cardiac meds. They also inhibit sodium and calcium channels… and old people tend to be on calcium channel blockers. And on and on…

    But even as sole therapy (which, as we’ve pointed out really isn’t called for in general) accumulation in elderly can be an issue. Unless there is something I don’t know about, we don’t have test for liver function to scale dosages for hepatically metabolized drugs like we can for renally cleared drugs. So you really don’t know how well the elderly liver is clearing the drug. Elderly people are also prone to dehydration, loss of muscle and fat mass, and sub-clinical UTI which can all affect volume of distribution. And the problem with TCA overdose is that it is not really reversible.

  13. evilrobotxoxo says:

    @nybgrus: interactions aside, most of the things you’re discussing with TCAs are relevant only in overdose, though it’s true that the therapeutic index is much lower than the SSRIs, and you’re also correct that you have to be more careful from a cardiac perspective. However, it’s not true that you don’t know how well people are clearing the drug because it’s easy to measure plasma levels of TCAs, and they correlate well with effectiveness (at least for nortriptyline). That said, I certainly don’t think TCAs should be first-line antidepressants in the elderly (or anyone else), and non-specialists probably shouldn’t be prescribing TCAs in the high dose ranges used for antidepressant effect. Also, while you’re correct that prescribing TCAs is more complicated than prescribing SSRIs/SNRIs/NDRIs/etc, there isn’t good evidence that this translates into any increase in mortality among the elderly, and as I mentioned before, a recent study suggests that TCAs might actually be safer than SSRIs (which can increase risk of GI bleeds).

  14. nybgrus says:

    @evilroboto:

    I realize you can test blood levels… but is that done? Is it covered by insurance? If you give an elderly patient a TCA do you routinely check their blood levels to titrate the dose?

    All I am saying is that it seems that as stand-alone therapy it is reasonable to use a TCA… though even then you admit it shouldn’t be a first line therapy. And my point was that in elderly people we can very easily overdose them to experience the side effects I mentioned before. And many elderly people are on other medications so the point rapidly becomes moot… at least from what I can see.

  15. evilrobotxoxo says:

    @nybgrus: yes, I routinely check TCA levels, at least for some TCAs. When I say “overdose,” I mean intentional overdose, i.e. suicide attempt. My only point is that I don’t think TCAs are as dangerous as you seem to think they are, unless we’re talking about intentional overdose, which is obviously not a concern to be dismissed in patients suffering from depression.

  16. nybgrus says:

    @evil:

    Ok. I really didn’t know that TCA levels were checked outside of OD. Though it still seems I’d rather leave their prescription to experts such as yourself.

    I have a follow up question then. Lets say you prescribe the TCA – because I as the PCP am not comfortable with it. But then I need to add to my patient’s drug regimen for BP control. And now lets say that my pt has developed a-fib because of a stretched out atrium from the chronic HTN, so I refer to a cardiologist who also adds an antiarrhythmic. How should I/we and you handle these changes in meds vis-a-vis the TCA? Assume for arguments sake that for whatever reason we needed to use heart/BP meds that were more likely to cause interaction problems.

    Should we first have the patient consult you before starting the meds? Should we start them and refer to you? I’m just asking what would be a “best practice” way of handling this amongst many specialists.

    I’m also thinking about insurance coverage – psychiatry is typically poorly covered and I believe it is quite possible that there will be instances where a f/u visit with you after my med changes may not be covered. How many TCA level checks are covered? Would you like the patient to be on the new meds for a while and draw a level before seeing you?

    Sorry if these are stupid questions. I’m just trying to get a model for ways to manage drug regimens across disparate specialties in my head as a rough approximation.

  17. evilrobotxoxo says:

    @nybgrus: it’s a complicated question. IIRC, they don’t normally use antiarrhythmics to treat new onset AFib, they usually rate control the ventricle and try cardioversion, then just anticoagulate and rate control if that fails. Also, AFib is not a contraindication for TCAs. But imagine that the pt developed some sort of AV node conduction problem or ventricular dysrhythmia or whatever, and you were concerned about the TCAs. If it’s an emergency, the PMD does whatever they think is appropriate, but otherwise it’s usually best for the MDs to talk on the phone and agree on a plan. In most cases, I’d probably switch the pt from TCAs to something else. There are enough other options now that psychiatrists rarely use TCAs.

    As far as insurance coverage goes, that’s a complicated question. It’s not like the insurance company has to approve of each individual visit, it’s that they usually reimburse a certain number of visits per year, and that number is not always enough. I haven’t had problems with pts having to pay out of pocket for routine labs.

  18. nybgrus says:

    Thanks evilroboto. I’m realizing this is more complex an issue than could (or should) be hashed out here. I have a better understanding now and will just keep my ears perked up as I continue my education to get a better foundation on it.

    Thanks!

  19. Nybgrus, this is a good read:

    http://www.aafp.org/afp/2002/0715/p249.html

    You will hear the words “Cardizem drip” until your ears bleed while on your medicine rotation!

  20. nybgrus says:

    danke!

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