Antipsychotics: Use as Directed

Antipsychotic medication is effective for people who are psychotic—period. It’s been used for other conditions, such as the behavioral symptoms of dementia, and it turned out not to work. It’s been used for delirium, a type of confusion that often arises in older people or people nearing the end of life, especially in the hospital, and many doctors swear it’s the only medication that helps this distressing and dangerous disorder. But a new study from Australia suggests that antipsychotic medication doesn’t work for delirium either. 

The specific situation the Australian doctors looked at was delirium in the setting of patients with advanced illness, either patients on an inpatient palliative care service or patients enrolled in a hospice facility. Out of well over 1000 patients with delirium, they were able to identify 247 who were both eligible and willing to enter the study. This group, with a mean age of 75, were randomized to risperidone (a commonly used antipsychotic), haloperidol (another commonly used antipsychotic), or placebo. Patients were also given unspecified non-medicinal treatment, presumably things like a sitter (someone to stay with them) or relaxation techniques such as massage. They were also given subcutaneous midazolam, a very short acting anti-anxiety medication under the skin, for extreme agitation. The results? Patients receiving either risperidone or haloperidol had more severe symptoms of delirium than those treated with placebo. They also, not surprisingly, had more Parkinsonian symptoms, the main side effect of these antipsychotic medications, and were more likely to die.

This is a disturbing result. Not only did antipsychotics fail to help, but they also seemed to make matters worse. Now maybe there’s something different about Australians, or maybe the specific environment they were in—a palliative care service or hospice, though neither is clearly described—makes generalization to the American general hospital impossible. Or maybe people with delirium and advanced illness are somehow different from people with delirium who don’t have an advanced illness. And conceivably, other antipsychotics such as quetiapine or olanzapine are different. More likely, antipsychotics are simply a bad choice in the treatment of delirium.

Antipsychotic medications are remarkable medications—for the treatment of psychosis in psychiatric conditions such as schizophrenia and bipolar disorder. But maybe we should stop using them for anything other than these indications.

Make No Bones About It

For some time, I’ve tried to find an up-to-date list of the medications most commonly prescribed to older people. Sounds like a simple question, but getting an answer has been surprisingly challenging. Most of the available data is ten years old and that’s a long time in an era when medications go off patent, new medications are introduced, and advertising campaigns affect medication use. Much of the information is for the population as a whole—but kids really are very different from octogenarians in their pill-taking. So I was pleased to find an article in JAMA Internal Medicine this week called “Changes in Prescription and Over-the Counter Medication and Dietary Supplement Use Among Older Adults in the United States, 2005 vs 2011.” This nationally representative sample of community dwelling older adults got its information from in-person interviews. It over-sampled certain populations to try to make sure its interviewees were truly representative. And the results are revealing.

The main finding is that fully 87.7 percent of adults over 65 (excluding those in institutions) took at least one prescription drug regularly in 2010-2011, up slightly 2005-2006. Moreover, 35.8 percent of the population take at least five prescription drugs a day (up significantly from 2005, when the rate was 30.6 percent. Lastly, there’s been a 50 percent increase in the number of people taking vitamins or supplements.

The Big Ten medications are pretty much what you would expect, though the actual percentages are a bit surprising. In first place is over-the-counter aspirin (40.2 percent); simvastatin, a cholesterol-lowering medication, is in second place (22.5 percent), and atorvastatin, another statin (formerly sold exclusively as Lipitor, before it lost patent protection) is number ten. The number three, four, six, and seven spots are taken by the anti-hypertensives, lisinopril (19.9 percent), hydrochlorothiazide (19.3 percent), metoprolol (14.9 percent), and amlodipine (13.4 percent) respectively, although it’s worth pointing out that these drugs can be used for other purposes besides lowering blood pressure—hydrochlorothiazide is a diuretic that may be used to treat heart failure, metoprolol is a beta-blocker often used to treat angina, and amlodipine is a calcium-channel blocker that can also be used in coronary artery disease. 

The remaining three drugs on the list are levothyroxine, a thyroid replacement medication, in fifth place, metformin, a drug used to treat diabetes, in eighth place, and omeprazole, a proton-pump inhibitor used for ulcers and acid reflux in the ninth spot. We are left wondering what all this means: are older people getting too many drugs? Not enough drugs? Are they getting the right medications?

Descriptive statistics cannot answer whether some patients are getting medicines they don’t need (though I’m pretty sure that’s the case) and others aren’t getting medicines from which they might benefit (probably also the case).  I think they do tell us something about the effectiveness of the strategies used to promote medications. When medications are categorized by type, statins are actually taken by just over 50 percent of older people (simvastatin and atorvastatin, drugs number 2 and 10 in the list of individual agents are not the only statins available) and anti-hypertensives by just over 65 percent of the elderly. What this tells me is that the combination of direct-to-consumer advertising, drug detailing to physicians, and  professional society guidelines--the methods used to promote statins and anti-hypertensives,at least when new drugs in each of these classes appeared on the scene--really works to change behavior. It doesn’t prove anything, but it’s awfully suggestive.

Also worth exploring is the dramatic increase in the percent of older people who take supplements. The authors of the study assert that this occurred although there is “no evidence of any clinical benefit.” I think this is a distortion. There may be little evidence of clinical benefit for some of the supplements, such as omega 3 fatty acids, but the story for vitamin D and calcium is both messier and more illuminating.

Over the years, Vitamin D has gone from being clearly necessary for strong bones, to very useful in preventing falls, to a dangerous poison, to a useless additive, and back again. Just what do we know as of 2016? We know that vitamin D is essential to human beings and we get it from sun exposure or from diet, although not many foods other than the ones such as milk to which we now add it naturally contain Vitamin D. Actually, that’s not quite accurate either, as what we get from the sun and from food is a pre-cursor of the active form of vitamin D that we need to make bones, and we rely on our kidneys and livers to perform the transformation. We also know from the National Health and Nutrition Examination Study that at least as of 2005-2006, 42 percent of adults had vitamin D levels below 20 ng/ml, which just about all authorities regard as too low. We also know that people who take megadose vitamin D as part of a fad diet, sometimes taking as much as 100 times the recommended daily dose, can get poisoned by such quantities.

The big question remains whether taking supplementary vitamin D—on the order of 800 units a day (not the tens of thousands of units taken by fad dieters)—prevents falls and fractures. Falls and fractures cost over $28 billion in older people, and that’s just the direct costs; it doesn’t include the pain and suffering and the loss of functioning and independence. The data on the efficacy of vitamin D are a mixed bag, with some studies showing strong evidence that it helps and a few failing to show any benefit at all. Putting all the conflicting evidence together, the American Geriatrics Society recommends, based on the preponderance of evidence, that all older adults, whether living in the community or in an institution, take vitamin D supplements of at least 1000 units together with calcium. Judging by the JAMA Internal Medicine article, we have a long way to go to reach this target: while 35 percent of older people do take a multivitamin (which includes 400 units of vitamin D), just under 16 percent take vitamin D alone.

The back story here is that vitamin D is cheap. No drug company is promoting vitamin D. In addition to being cheap, vitamin D has virtually no side effects (unless it is taken at hundreds of times the recommended dose). And it just might work. We should think about the ways that the consumption of cardiac medications have changed—and the ways that these changes have been achieved. We might learn something about how our system operates and how we can change the attitudes and behavior towards therapy that has a good chance of helping without breaking the bank.

Where is the lamp beside the golden door?

According to the New York Times, fewer than 2000 Syrian refugees have been accepted for resettlement to the United States. Of these, half are children and one-quarter are over age 60. So the refugee crisis, of which Syrians are a significant part, affects older people as well as the young and the middle-aged. As we hear more and more strident calls to keep out these refugees, ostensibly because they might be terrorists, when in fact they are seeking to escape from those same terrorists who roam their native lands, we would do well to remember an earlier refugee crisis. It’s a crisis I’m all too familiar with, as my parents—then ages 13 and 14—were among those who left Germany in the winter of 1939, at first merely to escape persecution, later to escape death. It would be 8 years before they finally found refuge in the United States, where they have lived productive lives for the past 68 years.

By the summer of 1942, tens of thousands of European Jews had already been rounded up by the seemingly unstoppable Germans and incarcerated in ghettoes, enslaved as forced laborers, or sent to extermination camps. Those who remained in Holland, Belgium, and France were on the run. One of the only countries to run to was Switzerland, an oasis of neutrality in war-torn Europe. But in August, the Swiss government sealed its borders to refugees, invoking the time-honored allegation that further Jewish immigration was a threat to the peace and stability of their society. In December of 1942, the government clamped down further, ordering that every refugee over the age of 16 be turned away at the border. In the coming months, the Swiss police would send about 25,000 people to almost certain death.

It was not the first time that the world had turned its back on Jewish refugees. In the summer of 1938, just days after the American Independence Day holiday, representatives from 32 countries gathered at the majestic Hotel Royale in the French lake-side resort of Evian-les-Bains to discuss the plight of the millions of European Jews who wished to immigrate to avoid discrimination, persecution, and worse. For over a week, the delegates convened to express their concern--but did nothing.

A few months later, on what would become known as Kristallnacht, synagogues were torched throughout Germany, Jewish businesses destroyed, and 30,000 people arrested for the crime of being Jews. In response, a democratic US Senator and a Republican representative introduced a bill that would have admitted 20,000 Jewish refugee children to the United States. But public opinion was resoundingly against immigration on the grounds that it could be harmful to American citizens, and the bill died an early death. 

When the United States entered the war, virtually all immigration to this country ceased. But already that fateful fall, the State Department had deliberately put barriers in the way of Jewish refugees. Even accessing the limited quotas in place as of the xenophobic Immigration Act of 1924 became increasingly difficult. Consulates abroad were instructed to “delay” and “effectively stop” the trickle of immigrants arriving in the United States by resorting to administrative devices to “postpone and postpone and postpone the granting of the visas.”

After World War II was over, the member states of the newly established United Nations recognized the callous cruelty of their behavior towards refugees. Committed to mending their ways, they drew up the Declaration of Human Rights (1948), which asserted that everyone has the right to “seek and to enjoy in other countries asylum from persecution.” This was followed in 1951 with the “Convention Relating to the Status of Refugees” which defined refugees and delineated their rights. In 2001, dozens of countries reaffirmed their commitment to the rights of refugees, acknowledging that “many persons still leave their country of origin for reasons of persecution and are entitled to special protection on account of their position.”

In light of this history, the current attempts by state governors, including Charlie Baker of Massachusetts, to close their hearts and barricade the gates to refugees is both tragic and intolerable. We must not confuse the persecuted with their persecutors. We need to remember the words engraved on the Statue of Liberty, a gift to us from France, from the poem, “The New Colossus” by Emma Lazarus:

Give me your tired, your poor,

Your huddled masses yearning to breathe free,

The wretched refuse of your teeming shore.

Send these, the homeless, tempest-tossed, to me:

I lift my lamp beside the golden door.

Medicare: the Great Facilitator

On July 30, 1965, President Lyndon Johnson signed Medicare (and Medicaid) into law. In the last fifty years, it has evolved further—adding coverage for those with disabilities, regardless of age, ditto for those with advanced renal disease; adding a hospice benefit, a prescription drug benefit; and creating a private, managed care alternative (most recently known as Medicare Advantage plans). Along the way, it has stimulated changes in the way health care is delivered to its now 40 million members by introducing prospective payment for hospital care (resulting in shorter hospital stays and the burgeoning of the post-acute industry), by promoting the integration of care across multiple sites (office, hospital, nursing home) through the creation of Accountable Care Organizations, and by beginning to pay for quality rather than volume (incentivizing physicians, for example, to prevent readmissions after patients have been discharged from the hospital). So what do we know about the impact of Medicare on patients’ health and well-being? The most recent issue of the Journal of the American Medical Association is devoted almost entirely to the effects of Medicare. The results? Older patients (and others covered by Medicare) are doing better than ever.

Mortality for patients enrolled in Medicare fell from 5.3% in 1998 to 4.4% in 2013, a sizable drop. Now just because Medicare patients did better doesn’t mean that Medicare caused the improvement. The great improvement in mortality at the beginning of the twentieth century was attributable primarily to better public health—things like clean water and improved sanitation—rather than to medical interventions, as Rene Dubos explained in his seminal  1959 book, Mirage of Health. More recently, Michael Marmot has persuasively argued that longevity is affected by the position in the social hierarchy, by which he means relative position in the pecking order, not just income or education. So while medical care does matter—there has been a marked decline in mortality from heart disease, due at least in part to new medications and coronary care units, not just to better nutrition and exercise—it’s rarely the whole story. And there’s good reason to believe that while Medicare didn’t cause the recent fall in the death rate directly, it did facilitate the decline by paying for hospital care, medications, and outpatient treatments.

Other trends are similarly impressive. Hospitalization, at least among patients enrolled in fee-for-service Medicare (we unfortunately do not collect data on patients enrolled in Medicare Advantage programs except whether they die), also declined: from 35 hospitalizations/10,000 person-years to 27 from 1999 to 2013. Hospital length of stay fell also, from a median of 5 days down to 4. And fewer people end up in the hospital during their last month of life. All this while Medicare expenditures per person fell from $3250 to $2800.

As with mortality, these other trends are associated with enrollment in Medicare but cannot be assumed to be caused by the Medicare program. But what is clear is that, as I argued in my paper, How Medicare Shapes the Way We Die, Medicare is the great facilitator. It affects what we die of, where we die, when we die, and how we die. In particular, it helps determine the procedures we have, the drugs we take, and the diseases we suffer from. It achieves this by providing a stimulus to inventors to innovate and device manufacturers to produce machines and physicians to promote them, just because the inventors, manufacturers, and physicians were guaranteed to be handsomely reimbursed for their work.  The new data suggest that Medicare does the same for the way we live when we are old. Here’s to the next fifty years!

Shocking News

Much has been written lately about over-treatment of older patients. Only rarely does anyone suggest that older patients are getting too little treatment, but a new study in JAMA does just that. The reality isn't quite so clear.

The treatment is the implantable cardioverter defibrillator (ICD) and the patients are people over the age of 65 who have had a heart attack and are found afterwards to have a weak heart (defined as an ejection fraction less or equal to 35%). These patients are at risk of sudden death, of an irregular heart rhythm such as ventricular tachycardia, and the ICD is designed to deliver an electric shock if that happens, effectively bringing the patients back from death. By looking at the National Cardiovascular Data Registry, which keeps track of heart attack patients, the authors of the article found that only 8.1% of “eligible” patients actually received an ICD. As a result, they claim, the 92% of patients who didn’t get an ICD were more likely to die than their counterparts who did.

This is a surprising finding in light of the persuasive and cogent argument made by Sharon Kaufman in her recent book, Ordinary Medicine: Extraordinary Treatments, Longer Lives, and Where To Draw The Line. Kaufman makes the case that many high tech treatments come to be seen by physicians and patients as normal and necessary once Medicare agrees to pay for them. The end result for many marginally beneficial, burdensome, and expensive treatments, including the ICD, is that patients just can’t say no. If that's true, why are so few older people getting an ICD? 

Now it wouldn't be the first time that ageism or misinformation prevented older people from getting beneficial treatment. Many years ago, patients who were over a certain age were precluded from receiving clot-busting drugs (thrombolytic therapy) because it was widely assumed that in older age groups, the risks outweighed the benefits. It turned out that clot-busting drugs were actually more beneficial in older patients, basically because their heart disease tended to be severe which meant they stood to gain a great deal from treatment. Elevated systolic blood pressure was likewise once assumed to be normal in the geriatric population, or even desirable in order to improve blood flow to the brain. Studies eventually showed that elevated systolic blood pressure, even in older patients, predisposed to stroke and other unfortunate outcomes, and warranted treatment—though the recommendations about just how much blood pressure should be lowered have evolved over time. Is the ICD implantation rate just another case of bias or ignorance at work?

Dr. Robert Hauser of the Minnesota Heart Institute, writing an editorial published alongside this article, blames our fragmented health care system. He speculates that primary care physicians may not realize that their patients were supposed to get an ICD. The fact that there's supposed to be a 40-day waiting period between the onset of the heart attack and implantation of the ICD contributes to the problem. Hauser suggests that the primary care physician is so frazzled and overburdened that he is apt to neglect to send his patient to a cardiologist. Is this the explanation?

It can’t be the whole story. While patients who saw a cardiologist after hospital discharge were more likely to wind up with an ICD than patients who didn’t, only 30% of the patients who saw a cardiologist had an ICD implanted. Recall that 100% of them were, technically speaking, “candidates” for an ICD. So what else is going on?

Hauser hints at another explanation: “It is possible that some older patients may refuse ICD treatment for personal reasons or because comorbidities such as endstage kidney disease or advanced frailty were considered in the decision regarding ICD implantation.” He doesn't accept this explanation as sufficient, rightly recognizing that patients are very likely to accept whatever technological intervention their physician recommends and that shared decision-making, if it takes place at all, is apt to reflect the physician’s preferences as well as the patient’s. So the problem, if it is a problem, must lie with doctors, too. Physicians are not systematically and emphatically recommending ICD implantation to their older patients. Even the most technologically sophisticated academic medical centers only implanted ICDs in 16% of their eligible older patients. But is this a problem that needs fixing, like under-treatment of heart attacks with clot busters and inadequate treatment of high blood pressure in the past?

Dr.  Hauser believes it is, saying “even though the use of ICD for primary prevention may not seem to make as much sense for an 80 year old patient as it does for a patient in his 50s or 60s, an older patient at risk for sudden cardiac death should have the same opportunity to choose potentially lifesaving therapy.” But the benefits of ICD in those over 80 are far from clear. The studies include very few people in this age group. What data there is indicates that there is little if any survival benefit. Moreover, ICDs implanted in older people fire erroneously half the time. That means they deliver a very unpleasant electric shock to the hapless patient. In addition, if the ICD does work as intended, what that means is the abolition of sudden death. 

Maybe, just maybe, the low rate of ICD implantation in older people is a refreshing instance of massive civil disobedience—of both patients and doctors refusing to abide by prevailing clinical guidelines. We all have to die of something. An ICD virtually guarantees that the something will involve a protracted period of decline and suffering. If you had to choose between cancer, Alzheimer’s disease, and sudden death, which would you pick?