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This could be a big deal: the overuse of psychotropic medications for advanced Alzheimer’s patients

I received the following email, entitled “A research lead (potentially bigger than the opioid epidemic,” from someone who wishes to remain anonymous:

My research lead is related to the use of psychotropic medications in Alzheimer’s patients. I should note that strong cautions have already been issued with respect to the use of these medications in the elderly (e.g. https://www.mind.uci.edu/alzheimers-disease/articles-of-interest/medications-to-avoid-for-patients/). As a practical matter, however, at present agitated and aggressive behaviors are considered a common symptom of advanced Alzheimer’s and therefore the use of these drugs as chemical restraints is common even by the most conservative physicians. Furthermore, as the medical profession is very diverse many physicians have not updated their practice and are far from cautious in prescribing these medications to the elderly. Indeed, chemical restraints are the norm in nursing home practice, so it is my belief that psychotropic medications are ubiquitous in nursing homes.

A family member is an active medical professional (a physician assistant who works as a front-line health care provider in a family practice office in rural America), so I have some insight into how a conservative medical practitioner will behave. I have observed two things: first, when a symptom is in the list of potential symptoms for a disease that has been diagnosed in the patient, there is a strong presumption that the symptom is caused by the disease. Second, when a symptom is a side effect of a medication (particularly one prescribed by another doctor), there is a presumption that the need for the medication outweighs the side effect.

A combination of close familiarity with my mother’s symptoms/behavior on and off a variety of drugs and my knowledge of the ubiquitous bank gaming of regulatory controls in financial markets leads me to wonder whether the drug companies aren’t playing the same kind of game. In particular the addition of “behavioral and psychological symptoms of dementia” (BPSD) to the criteria for the diagnosis of late-stage Alzheimer’s is as far as I can tell of very recent vintage. (I believe they were introduced with the DSM-5 in 2013.) BPSD are symptoms treated by psychotropic medications. These same medications are also commonly used to treat mild sleep and anxiety disorders in the general population.

The problem with all the psychotropic medications is that they are used to treat the same behaviors that they can also cause as side effects, including irritability, anxiety, “disinhibition” which maps into a willingness to hit out at or behave abusively to others, aggressiveness, and self-harm. In sufficiently high doses, however, the patient is heavily sedated and they are very effective chemical restraints.

My suspicion is that the introduction of BPSD into the definition of common symptoms of Alzheimer’s has developed as a result of the ubiquitous use of psychotropic medications in this population. That is, as far as I can tell the studies that have found BPSD to be common in Alzheimer’s are population-based studies that did not control for the use of medications that have as side effects BPS behaviors. Successfully bringing BPSD into the clinical definition of Alzheimer’s is hugely profitable for the drug companies that now have physician’s biases – to attribute symptoms to the disease that has already been diagnosed, rather than to the drug that may cause it as a side effect – working on their side.

In short, what I would really like to see is a careful statistician’s review of the studies that find that BPSD are common symptoms of Alzheimer’s and an analysis of whether sufficient controls for the use of medicines that have as side effects the same symptoms have been implemented. (With psychotropic medications, the length of use is an important factor because they build up in the system. Thus long-term use has different effects from short-term use. Long-term prescriptions are not a good proxy for long-term use, since refill/renewal of shorter term prescriptions is common practice.)

I don’t know anything about this, but I ran it by an expert on eldercare who said that, yes, this is a big deal. So I’m posting this in the hope that someone will look into it more carefully. As you can see from the discussion above, there are statistical entry points to this one, and it touches on some interactions between causal inference and decision analysis.

27 Comments

  1. Janet says:

    FDA has black box warning on use of these medications in elderly, and there are already some health services researchers studying related issues (e.g., Singh RR1, Nayak R2, Impact of FDA Black Box Warning on Psychotropic Drug Use in Noninstitutionalized Elderly Patients Diagnosed With Dementia: A Retrospective Study. J Pharm Pract. 2016 Oct;29(5):495-502. doi: 10.1177/0897190015579451. Epub 2015 Apr 27. https://www.ncbi.nlm.nih.gov/pubmed/25917167).

    I would still not be surprised if they are still overused despite black box warning and under-studied relative to the number of people affected.

  2. Anoneuoid says:

    This is a common pattern in biomedical research (not that it isn’t elsewhere as well) from what I have seen. It is all about gaming definitions (that are constantly changing), running flawed (eg unblinded, p-hacked, “compare two groups”) studies to perpetuate funding and giving treatments that cause the same symptoms as the disease.

    The only thing that will get rid of these practices is if people (or maybe just the FDA?) start demanding they come up with quantitative models that make precise predictions, then compare tests those hypotheses (rather than the default nil null) to alternatives, including the mundane ones like “researcher bias caused the results”.

  3. Z says:

    I’ve seen something like this process play out with my wife’s grandfather who has dementia but not Alzheimers. He was given chemical restraints which agitated him, necessitating/justifying stronger chemical restraints. It did seem to severely impact his quality of life.

    I’m curious about the email writer’s criteria for ‘bigger than the opioid epidemic’. Maybe it impacts a larger population, but it’s a population with low quality of life and life expectancy even in the absence of drug abuse.

    • Dzhaughn says:

      It is ridiculous to compare this to the “opioid epidemic.” There are no good options for treating dementia, and there is high variance in any treatment, high variance in any estimate of the quality of outcome, and those estimates lack a convincing connection to the patients quality of life.

      In contrast, there are lots of good options for dealing with the challenges of adult life, including pain. And the outcome of using increasing levels of opioids has a low-variance, clearly bad outcome.

      • Phil Koop says:

        “There are no good options for treating dementia”

        Well, there’s this one: https://en.wikipedia.org/wiki/Hogewey.

        • Z says:

          I love the idea of that place. While the entire thing may not be scalable, the basic concept of providing an environment where they can go about their lives and are not constantly reminded that they have a problem seems replicable.

          I read about a place (in Arizona?) with a similar approach. One feature of that place was that they provide a bus stop for residents with the urge to escape. I think the bus drives in a loop and drops them back off at the facility after about 15 minutes, by which time they’ve forgotten why they left and cooled off.

        • Martha (Smith) says:

          +1 to Hogewey.

          I’ve also heard of some memory care facilities that provide safe looped paths for patients who are inclined to wandering (as many with Alzheimer’s are).

        • Dzhaughn says:

          Sounds nice, but only relative to competing institutions. Better to be at home with an understanding family.

          I would not describe either of those as a “treatment” as opposed to managing life with the condition.

          • Martha (Smith) says:

            Unless/until there is a real “treatment” for Alzheimers and other dementias (i.e., reducing the severity of the condition, or reversing it entirely), managing life with the condition is the best that can be done.

  4. Keith O'Rourke says:

    I do think richer data sources are becoming available for this type of issue with entry points for academics on the horizon.

    https://healthpolicy.duke.edu/events/ninth-annual-sentinel-initiative-public-workshop

  5. The problems with psychotropic drugs extend far beyond their overuse in the elderly. Investigative journalist Robert Whitaker has written two excellent books on the harmful effects of antipsychotics, antidepressants, and other psychiatric medications. See Anatomy of an Epidemic: Magic Bullets, Psychiatric Drugs, and the Astonishing Rise of Mental Illness in America. Whitaker argues that while some psychiatric drugs can be useful under certain circumstances, they tend to be greatly over-used — and they can also exacerbate the very problems that they are designed to treat.

    • jrkrideau says:

      Careful when mentioning Whitaker. I believe the executive committee of the American Psychiatric Association start gibbering at the name.

      Irving Kirsch’s work on anti-depressants and placebos is not all that encouraging either but I’d like to have a better look at his methodology or rather have a really good methodologist look at it. A major meta-analysis of four anti-depressant drugs by Kirsch et al. is at doi; 10.1371/journal.pmed.0050045

      • UK says:

        Yes, and maybe that’s because the APA itself is exactly the organization crammed with people on the payroll of pharma business. No wonder they don’t like Whitaker, being the guy questioning their add-on incomes! You may critize him in his interpretations of the evidence regarding drugs or in any other way, but saying he is wrong BECAUSE the APA is “gibbering” is just ridiculous. And regarding Kirsch, Whitaker also cites him and this meta-analysis (I only have the epub-version from whitaker, so no page, but after 37% of content in the book):

        “Finally, in 2008, Irving Kirsch, a psychologist at the University of Hull in the United Kingdom, found that in the trials of Prozac, Effexor, Serzone, and Paxil, symptoms in the medicated patients dropped 9.6 points on the Hamilton Rating Scale of Depression, versus 7.8 points for the placebo group. This was a difference of only 1.8 points, and the National Institute for Clinical Excellence in Britain had previously determined that a three-point drug-placebo difference was needed on the Hamilton scale to demonstrate a “clinically significant benefit.” It was only in a small subgroup of patients—those most severely depressed—that the drugs had been shown to be of real use. “Given these data, there seems little evidence to support the prescription of antidepressant medication to any but the most severely depressed patients, unless alternative treatments have failed to provide benefit,” Kirsch and his collaborators concluded.”

        So, I do not think Whitaker does a bad job in citing Kirsch (it corresponds to exact the same conclusions in the article). And I do not know if there is ANY association or consortium of doctors around that is more intertwined with pharma money than psychiatrists. Psychotropic drugs are VERY often blogbuster drugs in sales, so no wonder…

        Reading Whitaker does more good to the interested reader than beliefing in the “integrity” of the APA as far as I can tell!

        • jrkrideau says:

          Sorry UK.
          I think you misinterpreted my first two sentences. The verb ” gibbering” was not intended to be complimentary.
          but saying he is wrong BECAUSE the APA is “gibbering”

          Well no, I was saying exactly the opposite. I think I read some of Whitiker’s work four or five years ago and I am not sure how correct he is on various points but he has done good work in pointing out that the emperor has no clothes in many cases.

          I certainly was not saying Whitiker was wrong. I was saying that his criticisms are really affecting the American Psychiatric Association to the point that they seem to be reduced to incoherent gibbering when commenting on his work. This is all to the good.

          Belief in the integrity of the American Psychiatric Association? Well it must have some. On the other hand, the infighting and general fiasco of the DSM-V process did not give me a warm and fuzzy feeling.

  6. GBL says:

    As a physician who deals with this on an almost daily basis, I wasn’t expecting this topic to pop up on this blog :)

    As you can all expect this issue is incredibly complex, and I don’t know of a physician who is not aware of the risks involved with medicating the elderly, especially the demented elderly. Here’s a small list of the common issues, in no particular order. Keep in mind that my practice is based around hospitalized patients, so I may be biased a bit:
    1) There are many types of dementia, of which Alzheimer and vascular dementia are the most common, and all respond differently to the different classes of medications. They all have a different natural history and respond differently to the different medications we have depending on how advanced they are. FUrther, it’s usually impossible to be truly sure what kind of dementia someone has.

    2) Delirium, especially healthcare associated delirium is a real issue in this population. One of the most common speech I make to families is about how being in a hospital make elderly go crazy (I don’t use the word crazy with families of course). And the more aggressive you are in terms of therapy (even if warranted, such as for an infection), the worse their delirium becomes. And then you’re stuck in a vicious cycle for which anti-psychotics become the only option.

    3) There is absolutely a tendency for physicians not to reassess the need for previously prescribed medications. This becomes especially true after a patient is discharged after requiring anti-psychotics in hospital for delirium. They sometimes stay on those medications for a long time without reassessment.

    4) Chronic pain is a big deal. Most elderly patient live with pain on a daily basis e.g. osteoarthritis, diabetes associated neuropathies, spinal stenosis, osteoporotic fractures, none of which are indications for opioids. Unfortunately, opioids work. Not for a long time, and they carry side-effects, but they work. Especially in an elderly population for which tylenol has barely no effect, anti-inflammatories (e.g. advil) are contraindicated (gastrointestinal bleed and renal failure!), and other adjuncts medications have such potent anticholinergic effect that they usually end up precipitating delirium (e.g. tricyclics antidepressants, NSRIs, cannabinoids, pregabalin/gabapentin). When you factor in that in the elderly pain is a frequently under-recognized cause of delirium, you can imagine how problematic this becomes.

    5) Families and patient themselves often fail to realize that the patient is indeed demented, or even delirious. It’s not that they are oblivious to it, it’s just that they have naturally developped ways to adapt to the disease at home in such a way that they are not aware how profound the problem is. And given that the most successful non-pharmacologic strategies for treatment of delirium or dementia related agitation involve heavy family collaboration, it sometimes become unavoidable to prescribe anti-psychotics.

    6) Fragmentation of care is a serious issue. Where I live, and I suspect in most parts of North America, there is definitely a lack of access to medical experts trained in the above. Not only physicians (actually we may be the least important here), but also nurses, physiotherapists, social workers, etc. Patients with advanced dementia often do not qualify for full palliative care (this is usually reserved for end-stage cancer), and are stuck being managed by multiple physicians of different specialties, or by multiple acute care providers who don’t know much about them and won’t follow them for long. Geriatricians can be quite helpful, but are in great shortage.

    I don’t think we need to invoke big pharma to explain the over-prescription of anti-psychotics in this population. It certainly doesn’t help, but the problem is much more deeply rooted.

    Dementia and delirium are just extremely difficult diseases to manage.

    • Z says:

      (2) happened to my wife’s grandfather. He went to the hospital for something relatively minor, entered the cycle described in (2), and then wasn’t allowed to leave because of symptoms that were results of either (2) or just being 96 years old. I believe he would have been much better off if he were discharged sooner, but rigid rules about when patients are allowed to be discharged (probably motivated by liability fears) prevented that.

    • gdanning says:

      This is a very interesting and thoughtful comment. Thank you.

      I was wondering if you could expand on one thing: You say that “[f]amilies and patient themselves often fail to realize that the patient is indeed demented, or even delirious. It’s not that they are oblivious to it, it’s just that they have naturally developped ways to adapt to the disease at home in such a way that they are not aware how profound the problem is.” When I read that, I think to myself, “if they have adapted to it, is the problem really that profound?” I know that, in other contexts, there can be a danger of outsiders viewing as pathological a situation which, for the people involved, is perfectly functional (albeit suboptimal). Is that a concern in this context?

      • Martha (Smith) says:

        gdanning: My reaction to that quote was the same as yours. For example, my mother always had idiosyncracies — but physicians not good at respecting individual differences (including a lot of psychiatrists, I suspect) would be likely to interpret these as “pathological.” Sure, there was some dementia — but there was also just her personality and personal preferences involved.

  7. Martha (Smith) says:

    Sad to hear about the BPSD complication that fosters the inappropriate use of psychotropic medications to treat dementia.

    In the early 90’s, my mother was diagnosed not with Alzheimers but with vascular dementia of the left frontal lobe, and had to be put in a nursing home. The only home that had no waiting list was owned by an osteopathic physician who restricted which other physicians could see residents. He gave my mother Haldol, which made symptoms much worse. Eventually, she rose to the top of the waiting list of another nursing home that had very different policies. She was like a different person after a short while there.

    Good studies are definitely needed here!

    It sounds like the

  8. I have personal experience here…and wrote about it for Time.com
    More study needed…it is epidemic.
    http://time.com/4513741/end-of-life-care-concerns/

    • Martha (Smith) says:

      Thanks for the link, and writing the article. The good nursing home that my mother finally got into had things like pet therapy, and a plant-filled greenhouse-type atrium which was very pleasant and calming for residents.

  9. Gail Weatherill says:

    Ask any Tom, Dick, or Harry who works in nursing homes or has had a loved one in a nursing home, and they can affirm the enormity of this issue. As usual, it boils down to the bottom line, the almighty dollar. A pill paid for by Medicare or health insurance is cheap for nursing home owners. Their only cost is to have a “medication assistant” on hand to pop it into Granny when she gets out of hand. The alternative is expensive, at least in the short run. The proven alternative for these drugs is to have sufficient numbers of staff on duty at all times who are well trained in supporting people with dementia through times of confusion and anxiety. Plenty of vultures saw the Boomer wave coming and threw a nursing home or assisted living home on the next street corner. They recognized the cash cow that can be most profitable when personnel costs were kept low. As a registered nurse who has worked in and around long-term care for twenty years, I have seen it, lived it, and rejected it. I walked away over a year ago for advocacy work instead.

  10. Joshua Pritikin says:

    “Alzheimer’s is not an inevitable part of aging. There are certain plant foods and spices which studies indicate have the potential of preventing or slowing the disease. This includes saffron, coffee, ginger, apple juice, beans, vitamins D and B-12, whole grains and whole fruits and vegetables.” http://nutritionfacts.org/topics/alzheimers-disease/

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