Tag: older adults

04/27/21

Death, Taxes and Dementia

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Are you 55 or older and do you take an antidepressant or an antipsychotic medication? What about an antiepileptic drug? How about an antiparkinson or an antimuscarinic medication for an overactive bladder? These medications are probably anticholinergic drugs and if you use them regularly, you could be at a 50% higher risk of dementia. However, before looking at the evidence showing how anticholinergic medications could lead to dementia, we need to first understand a few things about these drugs.

Older adults with multiple co-occurring medical conditions are likely to be prescribed medications with anticholinergic properties, drugs that block the action of the neurotransmitter acetylcholine (Ach). These drugs are associated with many side-effects and are consistently shown to be associated with the later development of cognitive problems and dementia. Given the association between anticholinergic exposure and adverse effects, accurate quantification of anticholinergic burden (the cumulative effect over time) is needed to assess the risks versus benefits of prescribing these medications. There are a number of scales and measures that have been developed to assess anticholinergic burden.

“A review of published anticholinergic scales and measures” in Archives of Gerontology and Geriatrics found that the Anticholinergic Cognitive Burden (ACB) Scale was well suited to use in observational studies where anticholinergic exposure needed to quantified because it considered a large number of medications. The ACB Scale was developed by Malaz Boustani of the Aging Brain Program of Indiana University. Drugs were given a score of 1 if lab tests indicated possible anticholinergic effects, but there was no evidence of clinically relevant cognitive effects. A drug was given a score of 2 or 3 if it has established, clinically relevant anticholinergic effects.

A study by Coupland et al, “Anticholinergic Drug Exposure and the Risk of Dementia” concluded that regular use of some anticholinergic medications increased your risk of developing dementia by 50%. The researchers found significant increases in dementia risk for anticholinergic antidepressants, antiparkinson drugs, antipsychotics, antiepileptics, and urological/antimuscarinic drugs. According to Peter Simons, who reviewed the study for Mad in America, “The researchers estimated that 10% of all new dementia cases are due to the adverse effects of these medications.” The increased risk of dementia was projected from a total anticholinergic exposure equivalent to “3 years’ daily use of a single strong exposure medication at the minimum effective dose recommended for older people.” These findings were consistent with 3 other studies and the coherence of their findings provided strong evidence for the study’s reliability.

One of these studies was “Anticholinergic drugs and risk of dementia: case control study” by Richardson et al. The researchers said while middle aged and older adults are increasingly taking multiple anticholinergic drugs, the potential adverse effects of long-term use were not well understood. The researchers selected patients with a new diagnosis of dementia and compared their prescriptions of anticholinergic medications 4-20 years before the diagnosis of dementia with a matched group of patients without dementia. They found a noticeable association between an increasing anticholinergic burden over the previous 4-20 years and the occurrence of dementia. This dose-response effect was only evident for certain classes of anticholinergic drugs, antidepressants and urologicals/antimuscarinics. Significantly these relations were seen even when the drugs were used 15-20 years before the dementia diagnosis.

“The association with dementia increases with greater exposure to these types of medication,” said George Savva, who was one of the researchers. He cautioned that the study only showed an association, not a cause. “But because our research shows that the link goes back up to 15 or 20 years before someone is eventually diagnosed with early dementia symptoms, probably isn’t the case.” Fortunately, there is no apparent risk with anticholinergic drugs used to treat common conditions, like hay fever, travel sickness and stomach cramps. “The risk of dementia increased with greater exposure for antidepressant, urological, and antiparkinson drugs with an ACB score of 3.”

Although Richardson et al did not find the risk of dementia increased with exposure to antipsychotics, it should be noted that several antipsychotics, including Thorazine, Zyprexa, Trilafon, Seroquel, Mellaril, and Stelazine have an ACB score of 3. The antidepressants amitriptyline (Elavil) and paroxetine (Paxil) have an ACB score of 3 and were among the five most commonly prescribed drugs in the study. Less popular antidepressants with an ACB score of 3 included Anafranil, Tofranil, Sinequan, and Surmontil. Antidepressants with an ACB scores of 1 (Wellbutrin, Luvox, Effexor, Trazodone), were associated with dementia, but the association was greater when these antidepressant prescriptions were given close to the timing of the dementia diagnosis.  Abilify, an antidepressant and Effexor, an antidepressant, were given a score of 1 in a 2012 update to the ACB Scale.

The organization Health in Aging Foundation, created by the American Geriatrics Society, adds some additional medications that older adults should be wary of. There is a helpful Tip Sheet on its HealthinAging.org website, “Ten Medications Older Adults Should Avoid or Use With Caution.” The noted medications expand the adverse side effects for older adults from certain medications beyond just the risks for cognitive decline and dementia. They also underscore some of the warnings given above. For instance, the caution against antipsychotics was in bold: “If you are NOT being treated for psychosis, use antipsychotics WITH CAUTION.” Antipsychotics are commonly used to treat behavioral problems in older adults with dementia, where they increase the risk of stroke and even death.

Avoiding medications for anxiety (such as benzodiazepines) or insomnia such as Sonata (zaleplon), Ambien (zolpidem) and Lunesta (eszopiclone) was suggested. These drugs increase the risk of falls and can cause confusion. “Because it takes your body a long time to get rid of these drugs, these effects can carry into the day after you take the medication.” Muscle relaxants such as Flexeril (cyclobenzaprine; ACB score of 2), Robaxin (methocarbamol, ACB score of 3) and Soma (carisoprodol) can leave you feeling groggy and increase your risk of falls as well. “Plus, there is little evidence that they work well.” Women should avoid estrogen pills and patches prescribed for hot flashes and other menopause-related symptoms, as they can increase the risk of breast cancer and blood clots.

Psychiatric Times published a literature review, “Benzodiazepine Use and the Risk of Dementia,” that evaluated the evidence benzodiazepine use may increase the risk of dementia in older adults. They found 15 studies that assessed the association between benzodiazepine use and the development of dementia. Of the 15 studies, 8 showed a positive association between benzodiazepine use and dementia. The authors said given the prevalence of benzodiazepine use among older adults, the association between benzodiazepines and the development of dementia is a major cause of concern.

A study among older adults in the province of Quebec, Canada published in the BMJ, “Benzodiazepine use and risk of Alzheimer’s disease: case-control study,” found that benzodiazepine use was associated with an increased risk of Alzheimer’s disease. “The risk of Alzheimer’s disease was increased by 43-51% among those who had used benzodiazepines in the past.” There was a dose-effect relationship between benzodiazepine use and increased risk of Alzheimer’s disease in older people treated previously for more than three months. There was also a higher risk with long-acting formulas.

These medication concerns overlap an existing and growing problem as Americans grow older. In the United States, the number of Americans 65 and older was projected to nearly double from 53 million in 2018 to 95 million by 2060. That age group’s share of the total population is supposed to rise from 16% to 23%. The aging baby boomer generation may also fuel a 50% increase in the number of Americans requiring nursing home care. “Demand for elder care will also be driven by a steep rise in the number of Americans living with Alzheimer’s disease, which could more than double by 2050 to 13.8 million, from 5.8 million today.” So, an increase of older adults living with Alzheimer’s disease (not counting those with dementia) of over 200% is expected by 2050.

The word at this point seems to be that the influence of anticholinergic medications on the rates of dementia in older adults cannot be proven with certainty. Yet the evidence suggests there is a relationship. Maybe by 2050 we will have found a cure for dementia and Alzheimer’s; maybe not. However, there was a Dutch study suggesting that dementia and Alzheimer’s disease may not be an inevitable part of aging. Dr. Richard Isaacson, the director of the Alzheimer’s Prevention Clinic at Weill Cornell Medicine and New York-Presbyterian Hospital told ABC News that dementia and Alzheimer’s tend to have multifactorial conditions. This means “that a mix of genetics, age, environment, lifestyle behaviors and medical conditions that coexist together and can lead a person toward or away from cognitive decline.”

The takeaway seems to be we can be certain of cognitive decline from dementia or Alzheimer’s with older adults, but we can’t be certain of what causes it. Benjamin Franklin said, “in this world nothing can be said to be certain, except death and taxes.” Perhaps we can suggest in this world nothing can be certain except death, taxes and dementia.

11/24/17

“Cash Cows” for the Drug Industry

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The AARP, the American Association for Retired Persons, completed a report looking at the trends in the retail prices of prescription drugs used by older Americans between 2006 and 2015.  And the report’s findings were disturbing. Between 2014 and 2015, the retail prices of 268 widely used brand name prescription drugs increased by 15.5%, the fourth year in a row of double-digit increases. The increase was almost 130 times faster than that of inflation—15.5% to .1% for inflation. The average annual retail cost for one brand name drug was over $5,800 in 2015, almost $1,000 more than the annual cost in 2014. “For the average older American taking 4.5 prescription drugs per month, the annual cost of [drug] therapy would have been more than $26,000 for 2015—more than three times the cost seen 10 years earlier.

This was an industry-wide trend, as the prices of the identified drugs, from all 35 drug manufacturers with at least two brand name drugs assessed within the study, increased faster than the rate of general inflation in 2015. “All but one of the therapeutic categories of brand name drugs had average annual price increases over 5% in 2015. . . . The higher costs are typically passed on to the consumer in the form of higher cost sharing, deductibles, and premiums.”  These increases were far beyond the price increases for other consumer goods and services between 2006 and 2015. The following graph compares the annual price of brand name prescription drugs to rate of general inflation for the corresponding year.

The next figure illustrates how the average annual cost for widely used brand name drugs by older adults grew more than 300% from 2006 to 2015. The Medicare Part D program was first implemented in 2006. Older Americans fill an average of 4.5 prescriptions for medications per month. If they used brand name prescription drugs, their average annual retail cost for medications would be $26,132. “This annual retail cost of brand name prescription drugs exceeds the median annual income for a Medicare beneficiary ($24,150).”

It is no coincidence that these price increases for medications commonly used by older adults occurred after The “Medicare Prescription Drug, Improvement, and Modernization Act” was approved in 2003. “It expressly prohibited Medicare from negotiating bulk prescription drug prices.” But the Veterans Health Administration and the Defense Department were allowed to negotiate lower prescription drug prices. Prohibiting Medicare from negotiating bulk drug discounts seems directly related to increases in medications noted above.

The AARP Public Policy Institute found there were six specific brand name drugs with the highest percentage changes in retail price from 2006 to 2015. FIVE of them were from the same pharmaceutical company—Valeant. One mg and two mg tablets of Ativan (for anxiety) increased 2,873% and 2,080% respectively in their retail price. Cara .5% cream (certain skin disorders) increased 2,395%. Wellbutrin (for depression) increased 1,185%. Zovirax 5% cream (certain skin disorders) increased 783%. Eli Lilly’s Humulin R (U-500) 500 units/ml, an insulin drug used to treat diabetes, ONLY increased 530%.

If recent trends in brand name drug prices and related price increases continue unabated, the cost of drugs will prompt increasing numbers of older Americans to stop taking necessary medications due to affordability concerns. Continued excessive brand name drug price increases will also lead to increased cost sharing and premiums, which could ultimately make health care coverage unaffordable and lead to poorer health outcomes and to higher health care costs in the future.Given that health care reform expanded the number of people using prescription drugs, it would have been reasonable to expect smaller brand name drug price increases. Instead, brand name drug prices have accelerated substantially. Clearly, the economics of the pharmaceutical market are not working as expected.

Andy Slavitt, when he was the acting administrator for the Centers for Medicare & Medicaid Services, told the pharmaceutical industry in November of 2016 at a conference that increased medication costs were pervasive. Total prescription drug spending in 2015 was $457 billion, 16.7% of health care spending. Mylan’s Epipen was not even in their top twenty list for high price increases for 2015. Specialty drugs (like hepatitis C drugs) were a big part of the cost increase. They accounted for 31.8% of spending, while representing only 1% of prescriptions. Out of the 20 drugs with the highest per-unity cost increases in Medicaid, seven were generic drugs. Those increases were not to recoup drug development expenditures. See “Pharma’s not Getting the Message” for more on this topic.

The NYT reported there has been a sharp rise in polypharmacy, the use of three or more psychotropic drugs, with older adults. Almost half of these patients DID NOT have a diagnosis for mental health or pain disorder on record. Dr. Maust, a geriatric psychiatrist and lead author of the study, told Psychiatric News: “This begs the question of why physicians are exposing patients to all the risks of these medications, but not for the diagnoses they are intended to treat.” He thought the pattern suggested some inappropriate prescribing. Dr. Dilip Jeste, a geriatric neuropsychiatrist and past president of the American Psychiatric Association, said he was stunned to hear “that despite all the talk about how polypharmacy is bad for older people, this rate has doubled.” Over 90 percent of the office visits examined in the study occurred outside the psychiatric setting.

The AARP Public Policy Institute reported that 65% of adults over the age of 65 reported using 3 or more prescription drugs in the past 30 days. Ninety percent reported using one prescription drug in the past 30 days, while 39% said they used five or more. See the following figure from “Prescription Drug Abuse Among Older Adults.”

Disturbingly, this study looked at polypharmacy with medications noted within the Beers Criteria, named after its originator with the American Geriatrics Society twenty years ago. The Beer Criteria lists dozens of medications and their mutual interactions that are potentially harmful when prescribed to older adults. “Geriatric medical organizations have long warned against overprescribing to older people, who are more susceptible to common side effects of psychotropic drugs, such as dizziness and confusion.” The Psychiatric News article linked above has a chart of the Beer’s list of CNS medications, their potential risks and alternative clinical recommendations. The classes of medications examined in the study include: antipsychotics, benzodiazepines, sedative hypnotics for sleep (like Ambien), antidepressants (tricyclics and SSRIs) and opioids. An article in the Journal of the American Geriatrics Society on the 2015 updated Beers Criteria is available here.

Data reported by the AARP Public Policy Institute in “Prescription Drug Abuse Among Older Adults” also noted that older adults has several unique risk factors making them particularly susceptible to misuse of prescription drugs. Misuse is defined here as “the use of prescription drugs in a way a doctor did not direct.” First, older adults use more prescription drugs than any other age group. They also have higher rates of pain, anxiety, and sleep disorders. There could be memory problems that interfere with taking medications at the right time and in the right doses. The high rates of polypharmacy can also lead to potentially dangerous drug interactions.

Age-related physiological changes can also increase the potential for prescription drug abuse. Changes in metabolism, weight, and body fat can affect how a medication works in the body, increasing the potential for misuse and abuse and potentially dangerous side effects. The combination of alcohol and medications can bring about particularly adverse reactions among older adults, as their bodies detoxify and eliminate medications and alcohol more slowly.

Recommendations to prevent drug misuse with older adults include: regular reevaluation of drug dosages to help compensate for physiological changes and declining drug metabolism. Monitor for any inappropriate prescribing of prescription medications. Use of the Beer Criteria discussed above would be helpful. here Because patients often see multiple healthcare providers and obtain multiple prescriptions, keep an eye on a patient’s entire regimen of prescription and nonprescription drug use.

It seems hard to deny that pharmaceutical companies corralled older adults over the past twenty years and branded them as “cash cows” for the drug industry.