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/

The upper number of blood pressure, also called systolic, is very important in older adults as it tends to rise with age, which was another risk factor from this study that was correlated with stroke risk. In my experience with helping older adults it is common to find isolated systolic hypertension, occurring in about 30% over the age of 80. Isolated systolic hypertension is where the upper number is elevated but the lower (diastolic) number is normal. Treatment of this type of high blood pressure is very effective at preventing strokes in which only 13-18 people need to be treated to prevent one stroke. What is also important to note is that “silent strokes”, in which you have very small strokes that go undetectable but contribute to cognitive decline, can be reduced by better management of your high blood pressure.

My advice, pay attention to your blood pressure and if that upper number is higher than 140, see your doctor and start a conversation. Also keep in mind that self-monitoring of your blood pressure and sharing those recordings with your doctor is more likely to catch high blood pressure, and is also known to be more accurate than the occasional blood pressure check in the doctor’s office.

“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?

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

One study was an accumulation of case reports of people who had experienced memory loss, amnesia, or other similar cognitive changes from taking a statin. Although case reports are not as strong as large, double-blinded, randomized trials, I started to believe there may be something to this reported adverse effect. As time has gone by there have been more studies on statins, with some saying there is no association with memory loss, and others stating a valid argument that there may be a problem in some individuals. One study struck particularly hard when it reported that several people had the diagnosis of Alzheimer’s disease removed from their medical record when the cause of their memory loss was verified as being from their statin. So let’s see, we can be falsely diagnosed with dementia all because of a drug, and worse yet, health care providers may not listen to the complaint nor believe that this association is real. What a shame.

Two studies I frequently refer to are based on patient reported symptoms of adverse drug events (side-effects warranting medical attention) and validate that people are fairly accurate in recognizing when an adverse effect is occurring. The first study, Adverse Drug Reactions in Elderly Patients as a Contributing Factor for Hospital Admission, BMJ Vol. 315, Oct. 25, 1997, measured that people are good at recognizing non-severe ADEs, but not severe ADEs, such as gastrointestinal bleeding. That would make sense, since a GI bleed can be without symptoms until it reaches the point at which life is in danger. However, when someone’s cognitive function is altered soon after starting a medication, that association is rather obvious. We need to listen and observe. In the above study, the measured sensitivity in people detecting ADEs was 0.70 and the specificity was 0.85, those numbers at the level found in many screening tools health care providers rely upon.

Referring to the second study, Patient Reported Medication Symptoms in Primary Care, Archives of Internal Medicine, Vol. 165, Jan. 24, 2005, researchers measured that physicians in this study, which included four primary care practices, failed to change therapy in 48 cases of patient-reported symptoms and that this resulted in 31 ADEs (65% of 48 cases). Also of interest is that patients reported medication-related symptoms to the physicians only 69% of the time. So what can be gleaned from these studies is that we need to take seriously any change in function or how we feel as possibly being related to a medication, and act accordingly.

The concept that there is a strong probability that an ADE is being experienced based on reported symptoms is one principle used in the Naranjo Adverse Drug Reaction Probability Scale (Naranjo Scale). The strength of the probability that an ADE is occurring is strengthened as various criteria are met. For example, if the ADE starts soon after drug initiation, then there are assigned points. If the ADE subsides after the drug is stopped, there are more points assigned. If the ADE reappears after the drug is restarted, there are more points assigned. And there are other criteria, when met, that further increase the probability that and ADE is occurring. The final outcome is that an ADE is either definite, probable, possible or doubtful. This is what we have to work with in verifying likelihood of ADEs. What’s paramount in feeding this screening tool is the patient-reported symptoms, or those observed or measured. So where else can we find patient-reported symptoms of memory loss?

I sometimes visit the website www.askapatient.com. The reason I do is as stated above- I wish to listen and gather information so I can get as close to the truth as is possible. The website gives me a large number of people that are reporting adverse effects, or medication-related symptoms, that I can measure in terms of incidence, although there are limitations to these data. First about this website- People go to this site and report their experience under the specific drug name, whether it be positive, neutral or negative, on a scale of 1 to 5, 5 being the best experience. they can also enter their comments about their experience. This is where I went into two statins on this site, simvastatin and Lipitor, and searched the pages for “memory loss”.

There were 819 patient reviews for simvastatin and of those, 97 (11.84%) reported memory loss as a symptom. That doesn’t mean that is the incidence of memory loss because most everybody on this site has experienced a side-effect of some type and many do not report memory loss as an issue with statins. When searching Lipitor I found 996 reports and 122 (12.25%) had reports of memory loss. What does this mean? Can all these people be wrong? According to the literature, a large number are probably correct. In fact, many of these reports had people stopping the drug with memory loss resolving, kind of like strengthening the case as in the Naranjo Scale as stated above. When referring to other “studies”, since the incidence of memory loss from statins is probably “rare”, about 1% or less, studies that are not powered high enough, that is to say, with enough participants, are most likely not going to detect memory loss, but it appears that this may be a real problem.

So what to do? In geriatric pharmacy practice we play the role of “Colombo” the detective and suspect a drug as guilty until proven otherwise. Hence, it is appropriate to suspect a statin as causing memory loss until we prove otherwise. The potential negative outcome of not performing that due diligence is permanently altering someone’s life beyond their worst nightmare- being diagnosed with Alzheimer’s disease.

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.

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.