http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm293623.htm

http://elderdrugs.com/2011/09/my-statin-causes-memory-loss-now-if-i-could-only-remember-to-tell-my-physician/

http://elderdrugs.com/2011/07/simvastatin-zocor-new-warnings-from-fda/

http://elderdrugs.com/2011/07/statin-use-in-older-adults-benefit-or-unnecessary-risk/

http://www.goldenliving.com/healthcare-news-events/gl-press-releases/press.aspx?assetId=bf1f968b-74d4-41eb-8262-04ec546b9e0a

“Two factors, polypharmacy and polyprescribers, appear to be strongly associated with the increased exposure of elderly patients to drug-drug interactions (DDIs) and potentially inappropriate medications (PIMs).”

It has been known for awhile that the number of drugs taken by an older adult are linearly correlated with the risk for an ADE. We also know that when multiple prescribers are involved there is a tendency for one prescriber to not work from an updated med-list and not necessarily update the primary care provider, thereby leading to possible duplicate therapies and additive side-effect potential from multiple medications. One other factor that we need to consider is the filling of prescriptions at more than one pharmacy. Without an accurate medication history it is not possible for the dispensing pharmacist to detect potentially serious DDIs or duplicate therapies. One other thought is that the authors define polypharmacy as just taking multiple medications. However, it may be best to consider the definition to be the use of multiple medications whereas not all of the medications are appropriate nor have an adequate monitoring plan thereby increasing the risk for serious harm. Many people can take multiple medications but do just fine and not experience an ADE, because the drugs selected for use are not PIMs or there is an adequate monitoring plan in place.

“Many drugs adversely affect older patients by leading to falls, fractures, and functional and cognitive decline, and sometimes to unnecessary and costly hospitalizations and nursing home placements.”

If 20-25% of ADEs lead to hospitalization in the older adult population, then it stands to reason that preventing 50% of these ADEs can significantly lower costs. If the cumulative evidence is applied to reduce medication utilization AND minimize the risk for ADEs, then it is modeled to predict significant reduced health care expenditures on the drug side of the equation in addition to reducing costs by reducing health care system utilization.

“The addition of each new drug to a treatment regimen increases the risk of an ADE. For instance, in an ambulatory care setting in 2003, Gandhi et al. determined that the mean numbers of ADEs per patient increased by 10% for each additional medication.”

Oh so true! Some data are reflected to state: “If you take 5 to 8 medications you are at 50% risk for an ADE, and if you take more than 8 medications you are at 100% risk for an ADE.” This is where the key principle stated here by the authors is clearly reflected in the data. The more the drugs = the greater the risk. So, in effect aren’t we then being driven to determine where we can minimize medication use? Doron Garfinkel published in Archives of Internal Medicine in October 2010 about using specific criteria to safely eliminate almost 50% of medications taken by 72 older adults in the 80-something plus cohort. Function and overall well-being improved, as did measures of cognition, yet with no harms noted.

“The manifestation of ADEs in elderly patients may not be obvious because the effects can be similar to problems frequently experienced by elderly persons, such as increased frequency of falls, excessive sedation, increased confusion, urinary retention, decreased oral intake, or general failure to thrive. These manifestations, when not recognized as drug-related, can result in the physician’s prescribing another medication to mitigate the ADE.”

Also known as the “prescribing cascade”, where a drug is added to treat the side-effect from another drug where the side-effect from the other drug was not recognized as such. This is not uncommon. Here’s an uncommon but documented scenario: I start a statin, say Zocor for high cholesterol. I then develop memory loss a few weeks later, which is assumed to be a “normal part of aging” seeing as how I’m 87. The physician, along with support form my wife, then adds Aricept (donepezil) so that I am now taking two drugs, of which it can be debated in many circumstances if the statin is needed in the first place. Aricept and similar memory health drugs are known to cause urinary incontinence in about 10-20% of users. Therefore, since I’m now peeing in my pants it’s time to add a bladder health drug, say Detrol or Ditropan. Either of these two drugs blocks the beneficial effects of Aricept, and may also cause cognitive impairment, dizziness, sedation, constipation, dry mouth, and so on. So there we have three drugs at about $5000 per year with two, for sure, not being needed, and with the third possibly also not being needed, all in an attempt to try and lower a cholesterol number in someone without any history of heart disease and limited life expectancy. You want lower costs? Then start with medication minimization.

“ADEs can be minimized and their occurrence can be managed but not totally eliminated.”

Yes, this is true. Prevention estimates range from 26% to 95%. The estimate I have seen most frequently and that makes most sense is that about 50% of ADEs can be prevented. That might cut the mortality rate of this “man-made disease” in half. By the way, the mortality rate from ADEs  makes it the 5^th leading cause of death by disease. It can climb to number one in about 10 years if there is no change in how we practice our respective health care professions of medicine, pharmacy, nursing, psychiatry, and all the others involved in the medication-use process. Oh, and don’t forget the person at the center here, the one who is paramount in helping solve this problem. If we listen to complaints, respond to them with our intuitive expertise, and the evidence, we can mitigate or prevent a large number of these ADEs. Many self-reported ADEs by the patient go untreated or ignored, yet I know of two studies that showed how fairly accurate people are at detecting an ADE, but not all types.

“Pharmacists are a critical part of this process, in ensuring proper medication use in the elderly through medication counseling, medication therapy management services, and use of drug utilization evaluations to ensure that medications are being prescribed and monitored appropriately. Pharmacists can also work in conjunction with physicians to decrease ADEs by obtaining an accurate medication and medical history, aligning medications with disease states, identifying medications that may be treating side-effects of another medication, and ensuring medication reconciliation at every care transition if new medications are ordered or existing orders are rewritten. Prescribers should avoid prescribing inappropriate medications for the elderly if possible and use drug therapy only when it is essential, helping to ensure maximum therapeutic benefit, minimal side-effects and overall compliance.”

Many parts in the above paragraph may be correct. However, I don’t see where the reimbursement system incentivizes pharmacists to do all of the above, especially in the community where 95% of older adults reside. We would need to change the incentive in our health care system to reward quality and outcomes while reducing cost. However, that’s much further in the future. Right now every community pharmacy outside of a health care system is incentivized by “profit per prescription” in order to survive, which is alright but not linked to the appropriate incentive to reward quality outcomes in preventing and mitigating ADEs. However, in some health systems  there are pharmacists placed at the appropriate portal, reviewing and reconciling medications and making just such an impact. But we need this done en masse throughout our communities, because if we continue to do business as usual we’ll get the same results.

One additional method that may be hugely impacting is utilizing the most comprehensive, and sensitive, medication screening tool at the point of prescribing. Almost 50% of ADEs start at the point of prescribing, not even considering how many start there because of the absence of an adequate monitoring plan, which is estimated at 40%. But I must make a point, in that you need the expertise that can help design that tool in order for it to make an impact. This then segues into the term I threw out there before, called “intuitive expertise”. A wonderful article in NY Times, October 23, 2011 written by Daniel Kahneman, speaks to the concept of “being an expert”. I don’t want to get into the details as I’ve gone on long enough, but I know this guy is right on. He knows when someone who proclaims to be an expert is NOT an expert. Quoting Daniel, “Many people exercise their judgment with evident confidence, sometimes priding themselves on the power of their intuition. In a world rife with illusions of validity and skill, can we trust them? How do we distinguish the justified confidence of experts from the sincere overconfidence of professionals who do not know they are out of their depth?”

What I find amusing about Daniel Kahneman’s article is that he studied the success of professional investors of large mutual funds and showed how those overconfident, overbearing and bullish fund managers were no better than average in their returns. But by the way he heard these fund managers speak you’d think they were the real experts. In closing, I quote the author: “True intuitive expertise is learned from prolonged experience with good feedback on mistakes.” I find that learning about ADEs in older adults requires years of experience, with listening to and observing older adults, and pouring through the literature to eventually establish validity. Some of the methods of study design and statistical methods used in the published literature are filled with errors and come to incorrect conclusions, thereby misleading health care professionals and the lay people. For example, one can reference a “study” that concluded calcium supplements are associated with an increased risk of death. Then a year later another study finds that other supplements, but not calcium, are associated with a higher risk of death. Or, two studies come to the opposite conclusion regarding SSRI’s (Prozac, Zoloft, etc) and the risk for GI bleeding. Do you know which conclusions are correct, if any?

As a result of hearing this PT’s comment I searched the literature again and looked at falls through a different lens, the one that views the null hypothesis of drugs not causing falls. In an article published in 2003 in Pharmacy & Therapeutics, the authors stated: “Beta- blockers do not contribute to falls”. Perhaps they needed to know about the systemic effects of beta blocker eye drops because Australian data have proven timolol eye drops to be the number one risk factor for falls in patients with glaucoma. (One must also understand that any drug that can cause bradycardia or hypotension can cause a fall.) The authors also stated that “Chronic therapy with blood pressure lowering medications rarely cause falls.” They referred to older studies and meta-analyses from the 1990′s, clearly older evidence that conflicts with more recent data.  I found other references that state medications are key contributors to falls, and that is also backed by years of professional experience where changes in antihypertensive medications eliminated dizziness and reduced the incidence of falls. Dr. James Cooper, PharmD, has shown that medications play a key role in causing falls, as reviewed in Medication Interventions for fall prevention in the older adult, Pharmacy Today, 2009 where he referred to his research in reducing the incidence of falls in nursing home residents by 70%. The literature is replete with references showing that alterations in medications reduces the incidence of falls in older adults, and I could fill a few pages with those validated studies.

I am fascinated by the conflicting “evidence” in the literature, and it is now beginning to amuse me. It also shows me that years of reviewing the literature, combined with clinical experience, helps paint a clearer picture that precludes any conclusions from a meta-analysis or retrospective database review that implies cause and effect after “adjusting for confounding factors”. If I followed the advice in some of the literature over the last couple of years I would: Adhere to a complex medication regimen that causes me to be cognitively impaired, dizzy and  to fall down the stairs breaking a hip, all because someone said non-adherence causes falls. I would have also stopped taking my calcium, because it is associated with higher risk of death, for which I then might be at greater risk of fracture. I would also have stopped taking a multivitamin with iron and become anemic, thereby further contributing to my risk of falling by causing weakness, and last but not least, I would be typing this post from my nursing home room.

If you don’t know where to look then you won’t know where to find the truth. It’s also wise to work as a team addressing all the identifiable risk factors for falls.

Prolia (denosumab) is a monoclonal antibody which is very effective at increasing bone density, at least as effective as bisphosphonates and Forteo. It is easily administered by a subcutaneous injection (fatty tissue under the skin) twice a year. Many of the side-effects seen with bisphosphonates are not there, and the complexity of taking an orally administered bisphosphonate clearly disappears with an injection. The drug-drug interaction between proton pump inhibitors, e.g. Prilosec and others, is non-existent, which otherwise render bisphosphonates ineffective. It also doesn’t have the risk for renal failure, as is seen with Reclast injection. There are some data that suggest eczema and serious skin infections may occur, and more needs to be known about that. However, Prolia has been on the market, for other uses and other names for about 8 years. So the safety data are quite well established. For those that have very low bone density, and are at high fall and fracture risk, Prolia just might be a very reasonable alternative, to combine with an effective fall prevention strategy.

UWDC partnered with the Pharmacy Society of Wisconsin (PSW) and geriatric pharmacists to develop a Geriatric Toolkit to be used by PSW’s Wisconsin Pharmacy Quality Collaborative (WPQC) pharmacists when conducting comprehensive medication reviews (CMRs). The participating WPQC pharmacists were trained on how to use the toolkits and learned how to perform CMRs in older adults with the intent of identifying risk for ADEs, including falls, and probable ADEs. They then learned how to develop a medication action plan to address these ares of risk in order to prevent unnecessary harm or loss of independence of older adults.

This initiative is a unique model in which multiple providers across the health care spectrum of delivery were brought together to collaborate and define a process, whereby an interdisciplinary effort could be made available to seniors throughout the county. For more information on the initiative, go to: www.safeandhealthyaging.org

Falls, for example, can be caused by a number of risk factors such as medications, leg weakness, protein malnutrition, vitamin D deficiency and urinary incontinence, all of which can be altered with a little knowledge and effort. If we are protein malnourished we can always eat more protein, and that combined with the proper exercise regimen can improve our leg strength. We can also do balance exercises that help reduce our risk of falling, along with altering some of those medications known to cause falls, such as blood pressure medications, medications for insomnia among many others. Incontinence can be managed with behavioral modifications thereby avoiding medications that can affect our memory and cause falls. Vitamin D deficiency, known to be associated with poor balance, falls, and memory loss in some, can be corrected with the right replenishment of vitamin D. All of these are easy to identify when screened for and easily altered to improve function and quality of life. We all know our body’s organ systems decline with aging but we can slow down that decline and alter the trajectory with these interventions.

What I recommend is to go to the National Institute of Aging web site at: www.nihseniorhealth.gov or www.nia.nih.gov, and go to the Publications section, Age Pages, and search for the condition that affects you or your loved one. The brochures can be printed in PDF format or can be read on line with altering text size for those with low vision. It’s a great way to continue your life-long learning and age well. One other point is that medications themselves can cause geriatric syndromes which are assumed to be a normal part of aging. A medication review with an experienced pharmacist can help identify medications associated with geriatric syndromes and help you age in place. Don’t subscribe to the stereotype that falls, urinary incontinence and memory loss are always a normal part of aging. They may not be in your case!

In this study the most frequently reported symptoms were: gastrointestinal problems, fatigue, dizziness, problems with balance, rash or itching, which all accounted for 55% of reported symptoms. But what did the researchers miss because they were not knowledgeable about the unexpected adverse effects of some medications? Just about any complaint that an older adult has can be medication-related. Think of all the adverse effects I’ve discussed on this site such as: urinary incontinence, muscle aches, memory loss, poor balance and falls, insomnia, among many others, all assumed to be age-related complaints. In summary, if you are experiencing what you think to be medication-related symptoms, have your medications reviewed in order to determine if a medication is affecting your function or quality of life so you can avoid unnecessary discomfort or harm.

When you suspect a medication may be causing a problem, don’t let it go but persist in finding out what’s going on. There is a strong likelihood that you are experiencing an ADE that can impact your function and quality of life. When looking at falls and ADEs, there are a number of strategies that can be employed to help reduce your risk of a fall, one being reducing medication use altogether, lowering doses of blood pressure medications when you experience dizziness, staying away from drugs that are strongly associated with falls such as benzodiazepines, which are drugs like Valium (diazepam), Ativan (lorazepam), Xanax (alprazolam), and other drugs even as apparently innocuous such as Tylenol PM (acetaminophen & diphenhydramine) and Benadryl (diphenhydramine). Even these over-the-counter (OTC) medications are known to contribute to falls. There is more to know about the relationship between falls and medications and this is only an introduction to set you in the right direction. Keep in mind that any changes in your medication regimen should be done only under the supervision of an experienced medical professional who is well versed in this area. That’s it for now, stay well and stay upright!

Explanation
Based on observation, and verification in the literature, it is clear that medications can be the cause of many problems instead of the cure. The literature shows that adverse drug events hasten decline in older adults by precipitating geriatric syndromes, such as falls, memory loss, incontinence, among others. These types of ADEs I call “soft ADEs”, as opposed to the usually reported ADEs of GI bleeding, electrolyte imbalances, hypoglycemia, and others. “Soft-ADEs” are instances where a side-effect of a medication can cause or worsen a geriatric syndrome, which alone can affect another area of function. The development of the drug-induced syndrome can also lead to the prescribing of additional medication for symptom management which can cause another geriatric syndrome, when in fact what is needed is an adjustment of the current medication regimen by withdrawing the drug, altering the dose, or finding a cleaner acting drug. The BBPP© model simplifies the complexity of the interrelationship between geriatric syndromes in relation to medications commonly used in older adults.

Here’s how it works
Falls is a geriatric syndrome and a leading cause for loss of independence in older adults. There are many risk factors in play so one approach is not enough to effectively lower risk. To some degree there is an over-reliance on bone health drugs to prevent fractures when in fact preventing falls is more effective at reducing fracture risk. We also know that taking a medication that causes cognitive impairment can contribute to or cause falls. Examples are Tylenol PM, antihistamines, Valium-like drugs (benzodiazepines), or in rare instances statins. Using statins as an example, they are now validated to be a risk factor for falls due to the muscle weakness and pain that exist as side-effects in some individuals. Statins can also cause memory loss and what may happen is Aricept may be prescribed to someone we think has dementia when it can actually be medication-induced. However, Aricept can cause urinary incontinence thereby increasing fall risk. A drug for incontinence is then often prescribed which antagonizes the beneficial effects of Aricept and can cause further cognitive impairment. Incontinence also leads to social isolation which also is a risk factor for depression. Depression also leads to memory loss issues even in those without dementia. So you can see that medication use can affect several different areas such as Bones (falls), Brains (memory loss, depression), Pee (urinary incontinence) and Pain (muscle pain), and all caused by medications.

This was a brief overview of the BBPP© concept that teaches you to 1) If you have issues with BBPP©, always suspect your medications until proven otherwise, 2) Don’t over-rely on medications to manage your health risk, and 3) Understand that many of our organ systems are interrelated and taking a medication can affect more than one system leading to functional decline or loss of independence. If you are taking more than four medications and have concerns with your ability to function, please consider a comprehensive medication review to rule out medications as the cause of your problems.