Diseases
Stroke Risk Increases Risk for Memory Loss
Jan 19th
A recent study in Neurology found a link between the risk of having a stroke and future development of memory loss or cognitive decline. The link was strongly tied to high blood pressure. The study, called REGARDS, involved 23, 752 older adults, average age 64, and followed them for 4 years. In those with a higher risk of stroke at the start of the study they had a higher incidence of cognitive issues. For every 10mmHg increase in systolic blood pressure (the upper number) there was a 4.1% increase in the risk of developing cognitive issues.
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.
Bisphosphonates may cause bone & joint pain: A new prescribing cascade?
Oct 24th
FDA reported in 2008 and 2009, with health alerts to providers and consumers, that bisphosphonates (Fosamax, Actonel, Boniva and Reclast) can cause bone and joint pain that lead to the prescribing of analgesics. The act of treating a side-effect from a drug with another drug is called a “prescribing cascade”, and is known to increase the risk for further adverse effects. In this case, one should always ask if the bisphosphonate is the cause of the pain by looking back to when the pain started, to see if it started after the bisphosphonate was started. Keep in mind, pain can start anytime after having started the bisphosphonate, yet FDA reported on average about 90 days after initiation of therapy. Here’s the link from the FDA on this alert from 2008: http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm124165.htm Here’s the link for the 2009 alert: http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm124165.htm
Pain is one of the geriatric syndromes known to cause impaired mobility, reduce quality of life, contribute to falls, increase the risk for depression, and lead to adverse drug events when analgesics of all types are prescribed to manage the pain. As with all geriatric syndromes, the pain may be assumed to be a “normal part of aging” and lead to inappropriate treatment. NSAIDs are known to cause gastrointestinal bleeding, hypertension, precipitate heart failure and cause kidney damage. NSAIDS can interact with warfarin and increase the risk of bleeding. Opiates can increase the risk of falls and also that of delirium. So if a bisphosphonate is the cause of bone and joint pain, followed by the prescribing of analgesics, this is a prescribing cascade that is worthy of attention.
If you suspect bone or joint pain from a bisphosphonate, consideration should be made to hold the bisphosphonate and reevaluate for symptoms of pain. This should occur ONLY after having a discussion with your physician. For health care practitioners, prescribing cascades are a very real problem in geriatric medicine and careful consideration should be made to ensure unnecessary drug treatment does not occur by assuming the drug to be the cause until proven otherwise.
Prolia (denosumab): Another Option For Those At High Risk For Fracture
Oct 10th
So far in the arsenal of bone health drugs used to treat osteoporosis we have, Evista (raloxifene); bisphosphonates such as Fosamax (alendronate), Actonel (risedronate), Boniva (ibandronate), and Reclast (zoledronic acid); Forteo (teripartatide); and Miacalcin (calcitonin). All have their established efficacy and their associated adverse effects. Evista is not that effective and causes hot flashes and has the risk for thromboembolism. Forteo is effective at increasing bone density and reducing fracture risk, but use is limited to two years. The bisphosphonates carry the largest amount of controversy with them, those being: osteonecrosis of the jaw; renal failure with IV administration of Reclast; and atypical fractures of the femur. There are also concerns with use beyond 5 years, not knowing if the drugs are safe and still yet effective. Miacalcin (calcitonin) is not as effective as the bisphosphonates but has minimal side-effects and can be useful as an adjunct in those with back pain from vertebral crush fractures. Now I will be the first one to state that we rely too heavily upon the use of drugs to reduce the risk of a fracture, and the most effective fracture risk-reduction strategy, especially in the old-old population, is fall risk-reduction (fall prevention). The approach needs to be multi-factorial, looking at a comprehensive assessment for fall risk factors, and engaging the person to address those risk factors, whether they be poor balance, medications, home safety issues, leg weakness, etc. But for those with high-fracture risk due to low bone density, where drug treatment is justified, along with the multi-factorial approach to reducing fall risk, there is now Prolia.
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.
My Statin Causes Memory Loss: Now If I Could Only Remember to Tell My Physician
Sep 8th
One of my first experiences in working with older adults, in a retirement community where I could engage with them and learn from them on a day-to-day basis, started me on my journey in learning how adverse drug events (ADEs) are more common and potentially life-altering in more ways than I could have imagined. I was talking with a resident at a diabetes support group I was leading and coaching him on the need to take a statin to lower his cholesterol, since he was at high risk for a cardiovascular event such as a heart attack or stroke. He said he could not take a statin since the one he tried caused him to be “goofy and loopy” and that he experienced “memory loss”. I said, “Balderdash”! I suggested he talk with his MD about trying another statin. Weeks later, at another meeting, he expressed the same symptoms after starting a different statin. I then started to listen to him, that is I started to take his complaint seriously, that he might actually be reporting a side-effect to a medication that is real. I then returned to the office and poured through the literature. What I found was interesting, to say the least.
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.
Reclast (zoledronic acid) and actue kidney failure: FDA warning
Sep 4th
FDA updated the warning label on Reclast (zoledronic acid), used to treat osteoporosis, regarding the drug causing acute renal (kidney) failure in high-risk patients. FDA warned to NOT use Reclast in those with impaired renal function, e.g. an estimated creatinine clearance of <35ml/ml, or other evidence of renal function, such as severe dehydration in those using diuretics, or nephrotoxic (kidney- toxic) drugs. Several cases have been reported to FDA of acute renal failure requiring dialysis, and fatal outcomes with use of Reclast.
Reclast is an intravenous medication used to treat those with osteoporosis. Those who are scheduled to receive Reclast, a once-yearly intravenously administered drug, should have a discussion with their physician to find out if they are considered “at risk”.
Dangerous Heart Rhythm Disturbances from High-Dose Celexa (citalopram)
Aug 24th
The FDA released an alert today (8/24/2011) warning against the use of Celexa (citalopram), a drug used to treat depression, at doses greater than 40mg per day due to a risk of abnormal heart rhythms. The drug, at doses greater than 40mg per day, is linked with QT interval widening, a term that describes how an electrical pattern in the heart as the large chambers of the heart contract, widens can leads to premature electrical activity in the ventricles. QT interval widening is associated with possible fatal cardiac arrhythmias. People taking Celexa (citalopram) at doses greater than 40mg per day should contact their physician or practitioner that prescribed the drug.
Also of interest, is that the drug is not shown to be anymore effective for managing depression at doses greater than 40mg per day.
The link to the FDA alert is:
Antidepressant use in older adults associated with risk for negative outcomes
Aug 15th
We all know that depression left untreated is associated with higher risk for negative outcomes such as stroke, heart attack, dementia, poor self-care in those with diabetes, among others. We also know that treatment of depression improves outcomes and quality of life. However, every time we add drug therapy to the mix there is an increased risk for adverse effects from the medications themselves. A study published in the British Medical Journal this August attempts to be specific as to which class of antidepressants in older adults are more likely than others to cause certain adverse effects. You may be familiar with the older antidepressants like Elavil (amitriptyline), Pamelor (nortriptyline), Tofranil (imipramine) that we all know have significant side-effects for older adults, such as drowsiness, falls, cognitive impairment, dry mouth, constipation, urinary retention among others. You may also have the perception that newer classes of antidepressants may be “cleaner acting” and safer than the older ones. However, this study draws conclusions that are contrary to that view.
The newer class of antidepressants, which includes Prozac (fluoxetine), Zoloft (sertraline), Celexa (citalopram), Paxil (paroxetine), Lexapro (escitalopram), called SSRIs, or selective serotonin reuptake inhibitors, was associated with higher levels of risk in many areas. One or more of the drugs in this class were associated with a higher risk of falls and low serum sodium (hyponatremia) which can be serious and warranting hospitalization. Other studies have confirmed these higher levels of risk. The levels of risk varied and in some ares were modest increases in risk. What can be taken away from this study is that we can not assume that SSRIs are “cleaner acting” than older antidepressants and that they carry their own level of risk for adverse outcomes. Since non-drug interventions for the treatment of depression can be equally effective as drugs, consideration should be made for those who are older and have significant risk for falls or GI bleeding, and consider non-drug treatments, also closely monitoring for adverse effects to reduce the risk for significant adverse outcomes. Other considerations in older adults would be starting with low doses and titrating up slowly, and selecting the antidepreassant that has the best side-effect profile. Other drugs in the study that were associated with significant adverse effects were trazodone, Effexor (venlafaxine), and Remeron (mirtazapine).
The authors list several limitations to their observational study and suggest further research in this area should be done to confirm their findings. Also of interest is that several other studies have linked SSRIs with a higher increase in risk for GI bleeding. This study concluded the opposite, that SSRIs are not associated with an increased risk for GI bleeding.The authors do state that the limitations of possible selection bias and adjusting for multiple confounding variables may explain their findings. In other words, perhaps the conclusions are not quite right.
Here’s a link to the abstract of that study.
Treating Other Conditions May Stave Off Alzheimer’s
Apr 21st
Referring to yet another NY Times article that refers to a study in China, researchers measured a 40% lower risk of developing Alzheimer’s in those treated for diabetes, hypertension or high cholesterol. In the study of 837 Chinese residents with mild cognitive impairment, 50% of those with cardiovascular risk factors developed Alzheimer’s disease over a 5 year period as compared to 36% without these risk factors. Those with risk factors who were treated experienced a 40% risk reduction. The study was published in the journal Neurology.
Neurology has also published studies that focus on reducing the risk of developing Alzheimer’s disease by treating diabetes. Researchers refer to diabetes in this subset of the population as Type 3 diabetes where it is strongly linked with “neuroaging”, a premature aging of the brain due to the metabolic and cardiovascular effects of diabetes. Also some time ago I read an Italian study that showed how nursing home admissions for Alzheimer’s disease were greatly reduced in those with hypertension when treated with an antihypertensive drug ramipril. What this says is that cardiovascular damage from these conditions is strongly linked to the development of dementia. It also suggests that if we can identify these risks then we can intervene with established treatments to slow the progression to full-blown dementia thereby aging in place.
Theories abound but what’s important is to understand the role of these risk factors and their potential for leading to dementia if left untreated. My observation in a large older adult cohort is that isolated systolic hypertension is rampant in as many at 33% of this population yet remains untreated. When you get screened for these risk factors, the next step would be to choose appropriate treatment and monitor that treatment in order to prevent adverse events from occurring. Please feel free to scan my previous posts on diabetes and neuroaging, isolated systolic hypertension and others on dementia.
Does vitamin B-12 supplementation protect against Alzheimer’s disease?
Nov 28th
A recent article in Neurology, October 2010, studied the risk of Alzheimer’s disease over a 7-year period showing that those with the highest levels of vitamin B-12 in their blood had the lowest risk of developing Alzheimer’s disease. In addition to measuring vitamin B-12 levels they measured a marker of Alzheimer’s disease risk called homocysteine, and the active form of B-12, holotranscobalamin. Those that had the highest levels of holotranscobalamin had the lowest levels of homocysteine. For each measurable increase in homocysteine levels there was a 16% increased risk of Alzheimer’s disease, whereas each measurable increase in the active form of B-12 (holotranscobalamin) reduced risk 2%. Summary: Taking vitamin B-12 reduces homocysteine levels thereby reducing risk of Alzheimer’s disease.
It has long been understood that B-12 deficiency can cause anemia, neuropathy and, if severe, memory loss which can be irreversible if left untreated. Prevention is your best best to staying healthy as you age. Make sure you take the supplements recommended for older adults to help manage risk since prevention is more efficient than reacting to a deficiency and trying to correct it before it’s too late. Check out my blog on supplements. The link is below.
http://elderdrugs.com/2010/05/supplements-what-older-adults-should-take/
Bone Health Drugs Associated with Atypical Femur Fractures
Oct 17th
The FDA just released last week another warning about the relationship between the use of bisphosphonates (Fosamax (alendronate), Actonel (risedronate), Bonvia (ibandronate)), and other drugs with femur fractures. FDA does not say the drugs absolutely caused these fractures but they are associated with people taking these drugs. More research needs to be done to determine if there is a cause and effect relationship and to what extent these drugs may actually be causing fractures they are intended to prevent. Here’s the FDA link of the most recent warning on bisphosphonates..
