America the pharmaceutical

In drugs we trust — but should we?

By RUTHANN RICHTER

John Hersey

Two decades ago, children who failed to grow got a big boost with the creation of a synthetic version of the human growth hormone. Suddenly they could look ahead to normal heights and normal lives. Google HGH today and see what the drug has become. It’s an all-purpose elixir for aging baby boomers. The drug supposedly sharpens the mind, builds muscles, revives potency and even turns the user into a “Superman.”

For better and worse, we are a society steeped in drugs. Nearly half of all Americans — 123 million people — now routinely take some kind of prescription drug, according to a 2004 report from the federal Centers for Disease Control and Prevention. And with the aging of the population and the growing prevalence of chronic disease, more Americans are swallowing multiple medications; 17 percent (and more than half of those over age 65) has a regimen that includes three drugs or more, with many people taking drugs for longer periods of time — sometimes their entire lives. And this is just the tip of the iceberg, as drugs will increasingly permeate our lives, experts say.

“People are normalizing the taking of drugs. They’re not thinking of themselves as patients. And people are not thinking of drugs as we used to — as potentially dangerous medications. A lot of people think of drugs in the same way as they do vitamins,” says Joseph Dumit, PhD, an assistant professor in the science, technology and society program at Massachusetts Institute of Technology who studies the pharmaceutical industry.

We’ve become a drug-saturated society for many reasons. Biological advances have made it possible to save or prolong lives and minimize suffering, while at the same time satisfying public craving for pharmacologic solutions to all of life’s travails. Drug promotion, especially direct-to-consumer advertising, also has helped stock our medicine cabinets, as have national clinical guidelines suggesting use of drugs to manage problems such as high cholesterol, high blood pressure, diabetes and asthma. And the medicalization of certain conditions, such as menopause, that were once considered part of the normal course of human experience has added to our society’s drug habit.

Our affair with drugs is a love-hate relationship. Americans clamor for the newest and best in medications, and the pharmaceutical industry obliges with ever-new technologies. There’s no doubt that as a society we have benefited. Terrence Blaschke, MD, professor of medicine and of molecular pharmacology, likes to show a slide listing dozens of medications approved since he graduated from medical school in 1968 — chemical agents that have had a dramatic impact on people’s lives. Antiretrovirals, for instance, literally have lifted AIDS patients off their deathbeds. “Today we have roughly 20 drugs on the market and a number in the pipeline with a new mechanism of action,” says Blaschke, who specializes in HIV. “Fifteen years ago we had nothing for these patients.”

It’s not all good

But drugs also can cause unintended harm and come at great cost to society — economically, socially and environmentally. Americans shelled out more than $200 billion for prescription medications in 2004, four times what they spent a decade ago, according to the National Health Statistics Group. By 2014, that figure is expected to reach $521 billion, the group reports. In 2004, prescription drug costs accounted for 11.4 percent of our nation’s health-care bill and were the fastest growing component of the national health-care budget.

Many Americans now struggle to keep up with the rising cost of medications, an issue that opinion polls show is tops on people’s minds. Drug costs are at the center of much political debate, fueling a nationwide movement to legalize the importing of lower cost drugs from Canada and other countries. Patients feel the economic strain, as prescription drug spending represents the largest share of their out-of-pocket health-care expenses. In a survey released in February 2005 by the Kaiser Family Foundation, 78 percent of adults said they believe prescription drugs had had a positive impact on people’s lives, but 70 percent also said they believe drug companies put profits before people, and 59 percent thought drugs added to medical costs because they are so expensive.

“Rightly or wrongly, drug companies are now the No. 1 villain in the public’s eye when it comes to rising health-care costs,” says Kaiser Foundation president Drew Altman. “People want to rein in the cost of prescription drugs, and just about anything we poll on with that aim gets public attention.”

Consider, for instance, heart patient Sandy Wiggins of Redwood City, Calif., who puts $200 a month of his own money toward medications to help strengthen his heart, lower his cholesterol and his blood pressure and keep his blood sugar levels under control.

“Sometimes I wonder if the medical profession isn’t driven by pharmaceutical companies,” he says. “Sometimes it appears to me, when a pharmaceutical company knows they have something that works, boy do they charge you for it.

“For me, it’s $200 or death.”

Wiggins is fortunate: He has insurance that covers a portion of his drug costs. But one of the flaws of our health-care system is that it doesn’t provide equitable access to drugs. Millions of people have no insurance at all, or their coverage doesn’t include a pharmacy benefit. So while some patients have access to drugs they need, others go without.

“People are having to make a choice between eating and paying the rent or buying medications,” says David Katzenstein, MD, professor of medicine and HIV specialist. “It’s rather tragic if you need these medications to alleviate a problem or stay alive. So I think access to essential medications is a problem in the United States,” as well as in other, poorer countries around the globe.

Pharmaceuticals also have become a major environmental concern, joining the growing list of chemical contaminants in the water. In recent years, a number of compounds, such as Prozac (an antidepressant), Premarin (a hormone therapy), estrogens (active ingredients in birth control pills) and some antibiotics, have been detected at low levels in rivers and in water supplies in North America and in Europe. These drugs are excreted by people into wastewater treatment systems, which aren’t designed to break down these chemical compounds.

Of particular concern are the so-called endocrine disruptors, substances like estradiol (a type of estrogen), that may interfere with the body’s hormonal system, says Linda Giudice, MD, PhD, the Stanley McCormick Memorial Professor and chief of the division of reproductive endocrinology and infertility. The presence of these drugs in water supplies is most troubling because they may have an effect on human fertility and the growth of the developing fetus, Giudice says.

Engineering professor Richard Luthy, PhD, an expert in water pollution, says these compounds have been detected near some wastewater discharge areas, where they have been shown to cause damage in fish species even at very low concentrations.

“There’s no doubt these endocrine disruptors produce changes in wildlife at the point of discharge,” says Luthy, the Silas H. Palmer Professor and chair of the Department of Civil and Environmental Engineering. “If it’s not good for fish and amphibians, it may not be good for us, and we should be thinking about that.”

John Hersey

So how have we become a society hooked on drugs? The SSRIs (serotonin reuptake inhibitors), a class of psychiatric drugs initially developed as a remedy for depression, are a good example of how drugs can enter — and take over — our lives. When Prozac, the first in this line of drugs, burst on the scene in 1988, it completely changed the landscape of psychiatric treatment by offering a less toxic alternative for treatment of depression, says depression researcher Alan Schatzberg, MD, professor and chair of psychiatry and behavioral sciences. Armed with drugs that were safer, easier to use and better tolerated, psychiatrists also were able to treat patients who had milder forms of the disease, as well as anxiety, he says. Soon SSRIs — drugs such as Celexa, Lexapro, Luvox, Paxil and Zoloft — became all pervasive, as psychiatrists began prescribing them for a host of then off-label indications, such as obsessive-compulsive disorder, panic disorder and premenstrual dysphoric disorder, which have now all become approved indications.

By 2000, 7 percent of adult Americans were on antidepressants, and 57.6 million annual doctor or hospital visits in 2001-02 were related to antidepressant use, according to the CDC. Moreover, with these new drugs available, many psychiatrists abandoned psychotherapy — time spent talking out issues with patients — for drug treatment alone.

“Things shifted pretty dramatically in the late 1980s and early 1990s,” Schatzberg says. “Many practitioners now use pharmacologic agents routinely where they might not have 20 years ago.”

The surge in the SSRI market also played into the growing public appetite for so-called “lifestyle drugs.” These life-enhancing drugs can help lift spirits, improve our sex lives, help us sleep, calm stomachs and boost brainpower. They include substances like Viagra to improve erectile function in men, Modafinil and Aricept to enhance brain function in healthy people and the SSRIs, when prescribed as a chemical solution to the discomforts of daily living. Cardiologist Stanley Rockson, MD, while cheering the advent of many vitally needed medicines, bemoans how consumers look to drugs for answers rather than take responsibility for their own health.

“What I find immensely gratifying about the world of pharmacology is its incisive ability, when used appropriately, to solve problems,” says Rockson, professor of cardiology. “What I dislike — the abuse of it — is the way it feeds our culture’s desire for lack of accountability for one’s health and well-being.

“What our society wants is to solve the problem by simply going to the drugstore. We want a lack of accountability for our weight and our appearance and all these things for which somebody’s supposed to have a magic solution in a bottle. That’s the pitfall of the whole drug realm.”

The kids conundrum

The drug culture seduces children as well as adults. The number of school-age children on stimulants — drugs like Ritalin, Adderall, Stratera and Concerta — doubled between 1995 and 2002, according to CDC figures. Physicians prescribe them for attention-deficit hyperactivity disorder in children. Some worry that they are prescribing them too often — mistaking performance or behavior problems in school for ADHD, for which there is no simple lab test, Schatzberg, the psychiatry chief, says.

“Just because kids don’t do well in school doesn’t mean they have attention-deficit disorder,” he notes.

David Magnus, PhD, director of the Stanford Center for Biomedical Ethics, says he believes use of stimulants is part of the trend toward medicalization of conditions once considered a normal part of life.

“Before Ritalin, almost no one had ADHD. Then suddenly everybody’s got it. We used to call this childhood — kids being distracted and having too much energy,” says Magnus, associate professor (teaching) of pediatrics. “Now we have a drug that makes them act more like adults. I’m sure for a percentage of children this drug is useful. But I’m also sure that the marketing of drugs is heavily influencing the creation of these disease categories and decisions about who belongs in them.”

Nowhere is the issue of drug use more controversial than in psychotropic medications for children. Between 1995 and 2002, the number of youngsters on antidepressants skyrocketed from 1.1 million to 3.1 million, with some arguing that doctors prescribed them cavalierly to children who weren’t properly diagnosed or carefully monitored. After studies linked the medicines to a slight increase in suicidal behavior, the U.S. Food and Drug Administration in October 2004 issued a stringent safety warning on antidepressant use in children. Primary care providers and psychiatrists since have become more cautious in prescribing the drugs, balancing their risks to young patients with the potential benefits. Schatzberg says he’s concerned now that some children might go untreated, leading to an increased risk of suicides.

“It’s OK to warn people to be conservative,” he says, “though I think that warning should not be at the expense of those kids who actually need the medication. That would be the downside.”

The drug du jour, please

One pitfall of the drug realm is the overuse phenomenon, in which a drug intended and approved for a narrow group of individuals becomes much more broadly applied, harming patients and increasing national drug costs. The Cox-2 inhibitors, enmeshed in recent controversy, are a good example of this behavior, also referred to as “therapeutic creep,” says Randall Stafford, MD, PhD, associate professor of medicine with the Stanford Prevention Research Center.

The Cox-2 inhibitors — drugs like Vioxx and Celebrex — were originally developed to avoid the gastrointestinal problems caused by nonsteroidal inflammatory painkillers like ibuprofen. But millions of patients who had no GI problems ended up using Cox-2 drugs unnecessarily, paying six times the cost of simple drugs like ibuprofen and unwittingly exposing themselves to potential heart risks, Stafford and his colleagues reported in a study in January 2005 in the Archives of Internal Medicine.

“One clearly sees in the Cox-2 inhibitor an example where people took these drugs because they wanted to be taking the newest thing but had an unreasonable expectation that the newest drugs would be the best drugs,” Stafford says. “We don’t just desire drugs but we desire newer drugs, and that has the implication of not using older drugs that may be just as effective and adds to the cost of health care without adding any significant benefit.”

Stafford says hormone therapy is another example of therapeutic creep, as the hormones estrogen and progestin, specifically designed to relieve postmenopausal symptoms, became widely used by women who had few or no symptoms at all. Women who previously persevered through this phase of life without intervention became lulled by the popular media and promotional campaigns into thinking they could drink from the fountain of youth by taking hormone therapy, notes Marcia Stefanick, PhD, chair of the steering committee for the Women’s Health Initiative — the federally funded long-term investigation of strategies to prevent disease in postmenopausal women.

“We had a drug that seemed to be the answer to women’s health. We really hit a point where the medical community was putting everybody on hormones without evidence it was good for everybody,” says Stefanick, professor of medicine at the Stanford Prevention Research Center. By 2002, the WHI halted that trend, as it revealed that millions of women on hormones had put themselves at risk for breast cancer, heart attack, stroke and blood clots. A year later, the WHI reported that women on hormones, many of whom were taking the drugs in the mistaken belief it would help prevent Alzheimer’s, were actually doubling their risk of dementia.

We get the message

Critics say consumer-targeted drug ads also have encouraged overuse and misuse. Stafford believes that was the case with Vioxx, which according to his research was the most heavily advertised drug in 2000, with promotional expenditures of $161 million. Spending on consumer-targeted drug ads generally reached $2.5 billion in 2000 and grew threefold between 1996 and 2000, Harvard researchers reported in the New England Journal of Medicine in February 2002. In a survey of family physicians, 71 percent said they believed these ads pressured doctors into prescribing drugs they wouldn’t ordinarily have recommended.

Rockson, the cardiologist, agrees that consumer ads contribute to overuse but says they can play a positive role as well by encouraging patients to become partners in their care.

“It may be that a patient comes in and says, ‘I was watching TV and I heard about this drug Vytorin and it sounds like a good thing, and you haven’t checked my cholesterol in six months. Should we check it?’ That’s not a bad thing if it keeps everybody honest and focused on a problem. If it becomes a deciding factor, then I think it’s a problem. Because I think choosing a lipid-lowering drug isn’t quite like choosing a shampoo,” he says.

The lipid-lowering drugs, especially the so-called statins, are another example of a technological innovation that’s exploded in the marketplace, aided by advertising as well as by government guidelines that promote their use. The statins work by blocking an enzyme involved in the formation of low-density lipoprotein or LDL, the so-called bad cholesterol that can contribute to clogged arteries and serious heart problems. These drugs first gained popularity after the 1994 publication of a landmark trial that showed they reduced death rates in high-risk heart patients by a staggering 42 percent.

Since 1988, the National Cholesterol Education Panel of the National Institutes of Health has continually lowered its recommended threshold for ideal LDL levels in patients. In 2004, it brought it down to its lowest level yet — 70 milligrams per deciliter for high-risk patients. That has greatly expanded the number of candidates for these drugs.

As a result, the statins today are the world’s best-selling medications. In 2004, Lipitor topped the list with worldwide sales of $10.75 billion, according to IMS Health, an independent health-care information firm. The drugs are expensive, with Lipitor retailing for about $2 a pill. But studies have shown they actually save money over the long haul by reducing the need for patients to be hospitalized and undergo expensive procedures such as bypass surgeries or angioplasties, Rockson, the cardiologist, notes. The cost is justified, he believes, because the drugs have such strong preventive power.

Buckle your seat belts

So where will our penchant for drugs take us?

Paul Saffo, a director at the Institute for the Future in Palo Alto, says it’s just the beginning — that the lure of drugs and their ability to reshape our bodies and minds is just too great to resist. For instance, there will come a day when all the controversy over steroid use in athletes will seem an artifact of history, he says.

“In a decade or so, in the next Olympics or the one after, there are going to be athletes sponsored by steroid makers,” Saffo predicts. “Now it seems shocking. But we’ve already crossed the line where steroids for wrestlers are not only socially acceptable but expected.

“It will be like smoking,” he adds. “If you’re an adult, you can make a smart choice. Parents will be saying to their children, ‘Johnny, I know you want to be on first-string football, but you have to wait until you’re 18 before you can take anabolic steroids.’ It’s absolutely inevitable when it’s this easy and ubiquitous. So this is just the tip of iceberg, especially when we get into mass-customized pharmaceuticals. Everybody is just going to take it for granted.”

Drugs in America. As American as… . Well, you know the rest.

 

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