Deprescribing: the most important health intervention you’ve never heard of?

Last year I spent a couple of months working as a physician in a geriatric hospital, i.e. a hospital that specializes in taking care of elderly people. One thing that struck me particularly was the large number of medications each patient was on. I don’t think it would be much of an exaggeration to say that the average patient had ten or more medications that they were taking on a daily basis.

This condition, of taking many different medications, is known as polypharmacy. It is a big problem. And a growing problem. In the US, 31% of older adults were taking 5 or more medications per year in 2006. Five years later, that number had increased to 36% . In a Swedish population study, 17% of adults were taking five or more drugs per day in 2006. This had increased to 19% in 2014. Among people over 90 years old, 80% were taking five or more drugs per day.

But, you might say, surely they needed those drugs? After all, they were prescribed the drugs by a doctor for a reason. And older people generally have more underlying conditions, and therefore need more drugs.

All of this is true, to a point, but the reality is more complicated. The first problem concerns how scientific studies of drugs are carried out. Most of the time, studies look at a group that has a single condition, for example heart disease, and exclude people with co-morbidities like lung disease or diabetes. Additionally, studies usually exclude people over a certain age.

These two things together mean that there is very little data on what happens when you give medications to people with several underlying conditions, and there is also very little data on what happens when you give medications to the elderly. So, on balance, we often don’t know whether we’re helping or harming the patient. We extrapolate from data that really applies to a different patient – a younger, healthier patient.

The second problem is that studies on medications are generally done in patients with functioning kidneys and a functioning liver. The kidneys and liver are the organs that metabolize and excrete drugs from the body. If people have kidney disease or liver disease, they will not be able to metabolize and excrete medications as effectively as healthy people, which means there is an increased risk of getting toxic levels of the medication in the body. And while a doctor might check a patient’s kidney function when putting them on a medication, there is often no follow-up to ensure that the medication is still appropriate as their kidney function inevitably declines with age.

The third problem is that patients, and especially elderly patients, see lots of different doctors. And one doctor usually doesn’t want to stop a medication that another doctor has started. The reason for this is that the second doctor generally doesn’t have full information on why the drug was started, and so doesn’t want to take the patient off a medication that they might “need”. This leads to patients accumulating medications over their years of life.

When I look in patient charts, it’s not uncommon for them to be taking medications that they’ve been taking for ten or more years. Oftentimes, these drugs have since fallen out of favor because new data has come to light showing that the harms outweigh the benefits. Often, the patients themselves have no idea why they’re taking a drug, they just keep taking it obediently because at some point a doctor told them they should be on it.

One example of this phenomenon is baby aspirin (low dose aspirin). A lot of older adults without any underlying heart conditions take this drug to prevent heart attacks, even though evidence that has come out in recent years has shown that the harms clearly outweigh the benefits. As a doctor, it’s often impossible to find the original chart explaining why the patient was put on a drug, especially if they were put on it several years ago. So you keep them on it, because that’s easier than taking the “risk” of taking them off the drug.

The fourth problem is that there are very few studies looking at what happens when you take combinations of drugs, even though that is commonly the reality. There are plenty of dangerous synergies that happen when people are taking multiple drugs. I’ll give two examples:

A lot of elderly people have atrial fibrillation. This is a disorder of the heart that is connected with an increased risk of stroke. You can decrease the risk by taking a blood thinner, like warfarin (a.k.a. coumadin). The problem is that lots of people with atrial fibrillation also have anxiety issues, and so they are put on sertraline (a.k.a zoloft). On it’s own, sertraline has a very mild anti-coagulant effect, but in combination with other drugs there can be a significantly increased risk of bleeding. Say the patient also has some joint pain, and so they are also prescribed paracetamol (a.k.a. tylenol, acetaminophen). On it’s own, paracetamol has no effect on bleeding risk, but in combination with warfarin there is a significantly increased risk of bleeding.

Each of these three drugs on its own might be ok, but in combination, there is a heavily increased risk of bleeding. This can take the form of an intracranial hemorrhage, or a bleeding stomach ulcer, which can both be rapidly fatal. And in reality, drugs are used in combination more often than not. There are few if any studies showing at which point different combinations become more harmful than helpful.

Here’s another example: Many elderly people take one or more blood pressure medications. These decrease the body’s ability to regulate the flow of blood to the brain, and so slightly increase the risk of fainting and falling. Many elderly people also have trouble sleeping, for which they are often prescribed bensodiazepines. Benzos make you a bit groggy, and thereby also increase your risk of falling, especially if you have to get up to pee in the middle of the night (as many older people do). On top of this, many older people have pain issues for which they are prescribed opioids, which also increase the risk of falling. Each of these drugs on their own might not be too bad, but taken together they heavily increase the risk of falls, which are a leading cause of death and disability in the elderly.

Not only is there not a lot of research on these dangerous synergies, but doctors are often unaware of them. I am willing to bet that most doctors don’t know that it’s a bad idea to combine warfarin and paracetamol, since that is a combination I see frequently in patients. Obviously, the more drugs you’re taking, the bigger the risk of dangerous interactions. Like I wrote above, it’s not uncommon for elderly people to be taking ten drugs or more. I don’t even want to think about how many dangerous interactions they are being exposed to with those kinds of cocktails.

There is another problem, which contributes to polypharmacy, and that is that many drugs are hard to stop once you start. Opioids (like oxycontin) and bensodiazepines (like valium) are the most obvious examples – both are highly addictive. Other drugs, like proton pump inhibitors (for example omeprazole), that are used to treat gastritis and acid reflux, are hard to stop because the body tries to compensate for the fact that its ability to produce stomach acid is blocked, so the moment you take the pedal off the brakes, the body overcompensates and produces lots of stomach acid, and the patient gets more symptoms than ever. Rather than wait these symptoms out, many people go straight back on the proton pump inhibitor, and stay on it for life.

The problem of polypharmacy has been getting increasing attention in recent years, especially among physicians specializing in treating the elderly population. The proposed solution to the problem is deprescribing, which is, simply put, the opposite of prescribing. Instead of adding to the list of medications a patient takes, you remove drugs.

A meta-analysis was published in the British Journal of Clinical Pharmacology in 2016 seeking to quantify the extent to which deprescribing can decrease mortality. It included 10 randomized controlled trials with a total of 3,151 patients. The average age of the patients was 74 years. The average follow-up period was 10 years, and the authors reported no conflicts of interest.

One oddity about this review was that it included both interventions in which patients actually had the number of drugs they were taking decreased (8 trials with a total of 1,906 patients), and also interventions where health care providers were educated about the benefits of deprescribing, and how to go about it (2 trials with a total of 1,245 patients). To me, the first is a deprescribing intervention, and the second is an educational intervention, and it’s very weird to put both together under the umbrella of a deprescribing intervention.

Luckily, the two types of intervention were analyzed separately in terms of effect on mortality, so we have that information. But they were lumped together in all other analyses (for example when looking at quality of life, or when determining if the effect size varies between age groups), so unfortunately, we don’t have access to that information.

Why is this a problem? Because it’s pretty obvious that an indirect intervention where you’re talking to doctors about deprescribing is going to have a much weaker effect than a direct intervention where you’re actually deprescribing drugs from patients. So any analysis which lumps together education about deprescribing with actual deprescribing interventions is going to show a weaker effect than is actually there. I’ve tried to understand what the investigators were thinking, but can’t come up with a good answer. The only thing I can come up with that makes any sense was that they wanted the review to fail to find benefit. But more likely they just weren’t thinking things through properly.

Anyway, let’s look at the results.

When looking at the overall results for the ten randomized studies, there was an 18% reduction in the odds of dying. However the difference was not statistically significant. But, like I said, this overall result includes the studies which were only educating health care providers about deprescribing.

So let’s look instead at what the results were when only studies that actually implemented deprescribing in patients directly are included. Overall, in that situation, there was a 38% reduction in the odds of dying over the ten year follow-up period! That difference was highly statistically significant.

For the sake of completeness, we will look also at what the results are if we just take the studies that educated health care providers. In that scenario, there was a 20% increase in the odds of dying. However, the increase was not statistically significant. Basically, teaching stuff to doctors either does nothing at all, or makes them more likely to kill their patients!

So what can we conclude from all this?

Deprescribing has a big impact on mortality. A 38% reduction in the odds of death is pretty huge. Especially since all you have to do to get that benefit is take fewer pills. For comparison, statins decrease the odds of death by 14% according to a meta-analysis by the Cochrane collaboration, and statins are often sold as a hugely life saving intervention. Well, the effect of deprescribing is almost three times as big.

On the other hand, just teaching doctors about deprescribing does not seem to work. To me, this makes perfect sense. Most doctors are working under significant time constraints, and so do not have the time to go through patients medication lists in detail, to decide which medications can safely be removed. Additionally, doctors face an unrelenting barrage of lobbying from pharmaceutical companies to prescribe more medications, not less.

So, the best thing you can do as an individual patient is to get educated about your medications, and to avoid being put on too many medications in the first place. Always ask your doctor why you are being put on a certain medication, what the size of the benefit that can be expected is, what potential harms there are, and how long you’re supposed to take the drug. If you’re not satisfied with the answers you get, it is perfectly within your rights to say no. It is also perfectly within your rights to say that you want to go home and do some research before deciding whether to take the drug or not. This is especially important when it comes to drugs that you are supposed to take continuously for the rest of your life, and drugs that are hard to stop once your start.

The simple fact is that a drug might well be beneficial when given on its own, but harmful when combined with several other drugs. I have a hypothesis that, on balance, when the number of drugs you take goes beyond five, the negative effects of each additional drug start to outweigh the positive effects, and that the negative effects increase exponentially with each additional drug, as the risk of interactions and dangerous synergies increases.

It is well known among doctors and nurses who care for patients in the last days and weeks of life that their symptoms often improve when the decision is taken to stop giving life prolonging treatment, and they are taken off most of their meds.

Here’s an idea for a randomized controlled trial that I would love to see done: Take a group of elderly patients who are all on 10+ drugs. Rank the drugs based on how important you think they are for each patient. In the intervention group, get rid of all drugs except the five that you have rated as most important (obviously you would have to replace the drugs you’ve gotten rid of with placebos, in order to maintain blinding). The control group continues on as before. See how many are alive in each group five years later.

My guess is that the intervention group would live significantly longer, with a significantly higher quality of life, than the control group. No pharmaceutical company would ever fund that study, for obvious reasons. It would need to be funded by the government, or by a philanthropist. So if you have several million dollars lying around and want to make a huge contribution to human health… You’re welcome for the idea.

You might also enjoy my article about whether statins save lives or my article about how aggressively high blood pressure should be managed.

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Author: Sebastian Rushworth, M.D.

I am a practicing physician in Stockholm, Sweden. I studied medicine at Karolinska Institutet (home of the Nobel prize in medicine). My main interests are evidence based medicine, medical ethics, and medical history. Every day I get asked questions by my patients about health, diet, exercise, supplements, and medications. The purpose of this blog is to try to understand what the science says and to translate the science in to a format that non-scientists can understand.

20 thoughts on “Deprescribing: the most important health intervention you’ve never heard of?”

  1. This is an excellent article, thank you again, Dr Rushworth.

    Many years ago, my ex wife, a former nurse and long-time manager in elder-care facilities once corrected me when I facetiously said that the profit-by-turnover-driven elder-care industry in New Zealand are probably motivated to reduce medications so as to free up bedspace: “Oh, no!” she said, “When we take them off their meds they live longer!”

    I never forgot that.

    I wrote this article on the topic of questioning the role medications causing dementia. I hope you don’t mind me sharing it with you and your readers:
    https://www.garymoller.com/post/is-this-the-real-cause-of-the-dementia-epidemic

  2. My grandmother was in her mid-eighties with failing health. Doctors told the family the end was near, it’s time to pay last respects. As the end approached, they ceased 19 of her 22 (!) medications. She recovered and lived for 2 more years. More health care is not always better health care.

  3. Another excellent article Sebastian, thank you. I spend a lot of time deprescribing for my elderly patients and I completely agree with your conclusions.

  4. The polypharmacy can prevail since the elderly people blinly trust their doctors. But they are ruthlessly betrayed by them.

  5. You’re right on the money with the analyses, and obviously it’s like that by design. Facts, analyses and information is an excellent way to start, which then can improve procedures in the future.

  6. My late mother-in-law was on about 10 different drugs when she was diagnosed with dementia, most likely due to too high a dose of statins, a vitamin B12 deficiency due to antacids and PPIs and a vitamin D deficiency due to her being elderly and never going outside (probably added to by the aluminium toxicity from her annual flu vaccinations, before aluminium was removed). When I had a good look at her medications, it seemed to me that each one was prescribed for a side-effect of the previous one, going back to the very first drug. Although some of the side-effects were uncommon or rare, from my observations, she did seem to be someone who was quite sensitive to drugs and therefore may well have been in the minority when it came to the known drug adverse reactions. The trouble was that her doctors dismissed those more “uncommon” AEs as if nobody every reacted to drugs in that way, that her new symptoms were just due to some other condition and therefore required a new drug! When drugs are tested they often start with those who are already healthy and are then tested on different cohorts. But many adverse reactions that occur once a drug is let loose on the public aren’t fed back to the regulators and so they remain in the “uncommon” or “rare” category and so doctors don’t realise that more people fall into that category.

    My late father-in-law, on the other hand, was prescribed drugs to deal with his inoperable but slow-growing brain tumour. It was never recognised that the drug built up in his system and so he ended up being rushed into hospital on several occasions with issues that were due to toxicity of the drug. This happened many times, yet nobody appeared to have learned from it.

  7. My old boy is 90. When he had a stroke in Nov 2018 at 88 he was given equilis. It gave him stupendous nose bleeds and the sh*ts. He refused the medication after a while and has been fine since. I am 73. We take no medication now and no flu jabs.

    1. Hi Floyd,
      I would include supplements in general, but not vitamins and minerals. The reason for this is that they are widely available in food, necessary for our bodies to function, and we have evolved to function with them over many millions of years. Having said that, very high doses of vitamins and minerals can be toxic.

  8. My appreciation to Gary Moller for his posting. And heartfelt thanks to Sebastian Rushworth and all medics like him who are at last now finally speaking out in large numbers. Whether or not it will save humanity remains to be seen. I would like to draw readers’ attention to the valuable ‘RxISK’ website of Dr. David Healy, without which over the years I would have gone insane as I have been in a personal lockdown for four years, as carer for my husband. My husband who finally died a few weeks ago with aggresive vascular dementia, the seeds of which were initially sown some 12 years ago & vehemently denied by a succession of drug-dispensing GPs
    This, if I may include the url, was just the beginning of our death-by-doctors story, and there are untold millions like us.
    https://rxisk.org/nearly-invisible-drug-traffic-accidents/

  9. Moyra,

    What a beautifully written and eloquent article you have written. My heart goes out to you when imagining what you have been through.

    I want to thank you for sharing your experience with us and for Dr’s Like Sebastian Rushworth giving the world his unbiased analysis and commentary. It is only by doing so that change for the better will come about.

    My plan is to write an article for my readers about this topic so I can share your story.

    You might like this one as well:
    https://www.garymoller.com/post/2019/04/02/stress-among-care-givers

  10. Thank you for this, Dr. Rushworth. This is a terrible problem which will not be addressed, since industry owns the levers of political power as well as medical guideline committees, certainly in the U.S. and likely elsewhere. And they clearly own the public health apparatus worldwide. In the U.S. properly prescribed prescription drugs kill more than 100,000 yearly, putting them on par with stroke as the fourth leading cause of death. From my mid-forties to mid-sixties I was on as many as three BP drugs (ACE inhibitor, beta blocker, and diuretic). At 55 I trained for and ran a marathon. But the beta blocker caused dangerous positional hypotension. I began to do my own research, and for six or seven years I have been drug free except for a few precautionary courses of antibiotics prescribed by a doctor and a dentist I trust. I now believe that BP drugs cause more harm than good except when the BP is very high. The Sidney Port paper published in The Lancet (January 15, 2000, vol. 355, pp. 175-179) clearly shows there is no increased mortality risk from BP which is below the 70th percentile for age and sex. For my age group (65-74) mortality risk is flat from systolic 100 to 160 at 32/1,000 per year, when it begins to rise. This is based on Framingham data.

  11. The biggest entry on my book of records was a 70-year-old woman who showed me 32 different prescriptions. She was not stupid at all and only take those drugs which were approved by her feelings [about a dozen].

    Here, doctors may have fears on changing or stopping a medical prescription.
    For me that’s not only a mark of ignorance (or stupidity) but also a mark of disrespect for a person that’s ill.
    Here its is not forbidden to ask a colleague [by letter or phone] to clearly understand the reason of a medical prescription. And, usually, finishing with an agreement.

    Here is almost a rule to prescribe a ‘prazol’ [PPI] to protect the patient’s stomach from the other drugs! That’s plainly stupid. And as a disgrace doesn’t come alone, the PPI is prescribed in the morning and at night.
    Even when correctly prescribed for a G-E reflux, every one must know that HCl secretion is bigger over the night. And that a bottle drains easier when recumbent.
    First, elevate the head of the entire bed by 12-15 cm. Second, take the PPI when you go to bed. It is not so difficult.

    I feel that the epidemics of Dementia to the selling of statins. All started at the 1980 decade. I only have prescribed a statin four times. All four cases sufered secondary effects. For me, any unwanted effect is a signal that the drug (any drug) is not good for that person.
    In my medical youth the only Dementia was caused by cerebral vascular disease and Syphilis.
    Over the years I realized that those with high cholesterol levels are very intelligent and die peacefully (and healthy) older than 90.

    As usual, I’m opened to any question.

  12. It’s refreshing to read that you are sceptical about statins and aware of the adverse effects. So many doctors seem to be in denial! My late mother-in-law developed dementia in her early 70s just after I met my husband. I had a look at her medications (about 10 of them), when they’d first been prescribed and what the potential AEs might be (but not being able to know what the combination of those drugs might produce, of course!) It became obvious that the cascade of prescription drugs came about due to the AEs of the previous ones. Some of the AEs listed were “rare” or “uncommon” but we all know that post-marketing surveillance of drugs is pretty poor, so those that were rare or uncommon during the trials may not be so rare or uncommon. Plus she was very sensitive to drugs generally, so may well have been one of those people to whom those AEs occur more rarely – after all, they must exist!

    We noticed that her memory issues seemed to worsen after her statin drug (may have been coincidence, but led me to look into it further) plus she was on the highest possible dose for an adult, despite her being a slight female. I then found out about the memory problems being associated with statins, but also the nutritional deficiencies that occur due to PPIs, particularly B12, which was something she was found to be severely deficient in, and is also linked with dementia. Vitamin D status was also so low as to be almost non-existent but the GP seemed to have no idea that any of those factors may have contributed to her condition.

    I discovered, from Professor Chris Exley’s research, that aluminium is likely to be a huge contributor to Alzhemer’s Disease and one thing she had always taken was Aludrox, which contains aluminium. I believe that the more modern antacids are made without aluminium, thankfully. One thing Exley pointed out was that the yellow colouring used in the drug Aricept is made from an aluminium salt…

    Sadly it’s too late now for us to have helped her, but at least we’ve informed ourselves about how to avoid dementia!

  13. Anglosvizzera, thankyou for your message. I am sorry to hear about what has happened to your mother -n-law. Hopefully talking about your experience will help others avoid this kind of catastrophe.

    I’m looking at the ingredients of Aricept that is sold here in New Zealand and can’t find aluminium. Can you do a double-check for us, thank you?
    https://www.medsafe.govt.nz/Consumers/cmi/a/Aricept.pdf

  14. Thanks for your reply. I had a quick look to see what colourings are used for Aricept but they don’t seem to contain aluminium. I remember Exley mentioning it in a video a couple of years ago, so perhaps it’s been changed.

    However, on the UK medicines site, there are 7 pages of pharmaceutical drugs that do contain “aluminium lake”. I don’t know if you will be able to access the site in NZ but here’s my search within it:

    https://www.medicines.org.uk/emc/search?fullText=true&createFilters=True&filters=attributes%5Bspc%5D&q=%22aluminium%20lake%22

  15. I can recommend ‘Too Many pills’ by James le Fanu (himself a doctor).
    Also, I have been asthmatic all my life and have had salbutamol for 40 odd years (I had a brief time on steroid inhaler but decided to struggle without it). I’ve just read James Nestor’s book ‘Breath’ which primarily focuses on nose breathing (instead of mouth), taping the mouth when sleeping (small piece of micropore tape) and humming when breathing through nose to release more nitric oxide (and get more oxygen into the cells). I haven’t used an inhaler for over 2 months, and I don’t need one for my weekly football game.

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