Socrates once declared that medicine "acts as both remedy and poison" and that "this charm, this spellbinding virtue, this power of fascination, can be—alternately or simultaneously—beneficent or maleficent." Modern America clearly appreciates the benefits. Today, a full 61 percent of adults use at least one drug to treat a chronic health problem, a nearly 15 percent rise since 2001. More than 1 in 4 seniors gulp down at least five medications daily. The trend has multiple causes: a spike in diabetes, heart disease, and arthritis related to obesity; revised medical guidelines that treat high blood sugar, hypertension, and high cholesterol sooner; and a multibillion-dollar push by pharmaceutical companies to speak directly to consumers about the payoff in trusting our hearts to Lipitor, say, or taking Boniva to help stop bone loss.
Therapeutic advances have, no question, proved lifesaving for many. Heart disease deaths have dropped steadily over the past 15 years, for example, thanks in large part to cholesterol-lowering statins and clot-busting drugs administered during heart attacks and strokes. But a growing chorus of experts worries that one unintended effect of all the pharmacological success is that many people may be blithely taking drugs they don't need, potentially setting themselves up for severe consequences. Clinical trials that prove a medicine safe and effective may demonstrate nothing about long-term risks or whether it benefits elderly folks or people with multiple health issues; usually new drugs are tested for just three or so years in a few thousand middle-age adults with a single particular problem. Given that a drug's serious side effects might show up only after months or years on the market, someone whose dangerous heart disease can't be controlled by existing meds has a much clearer incentive to try a new drug than people with a mild condition. Consider Vioxx, the blockbuster arthritis drug withdrawn from the market in 2004 after researchers estimated that it caused between 88,000 and 139,000 heart attacks during the five years it was prescribed.
"As we treat lower-risk populations, a drug has to be safer" to justify its use, says Steven Nissen, head of cardiology at the Cleveland Clinic. His 2007 study showing a link between the diabetes drug Avandia and heart attacks, along with a similarly damning study published in June by Food and Drug Administration researchers, has led many experts to call for the drug to be pulled off the market; the FDA decided last month to severely restrict access to the drug, allowing prescriptions only for those whose diabetes can't be controlled with other medications. Doctors shouldn't be prescribing any drug without considering whether a patient's personal risks exceed his or her clear benefits, Nissen says. And patients should be asking: How will this drug help someone with my medical history? What are the possible side effects? Has it been shown to prevent clinical events like a heart attack or bone fracture?
Nissen and other experts have loudly criticized the FDA for the way it monitors the safety of drugs after they've arrived on pharmacy shelves. While the agency often requires ongoing studies, drug companies decide how the research will be conducted—and they have a history of reaching positive results. An August study in the Annals of Internal Medicine found that 85 percent of industry-sponsored trials showed a drug worked well, compared to 50 percent of government-funded trials. "Companies often lack an interest in addressing safety questions after a drug is approved," says Bruce Psaty, a professor of medicine and epidemiology at the University of Washington.
In the case of Avandia, the FDA wanted a post-approval safety trial of how it works when used along with the drug metformin, as it would normally be prescribed. But manufacturer GlaxoSmithKline decided instead to compare Avandia's effectiveness in lowering blood sugar against metformin and another drug; Avandia was found to work best. Other GSK research has shown that users are no more likely to have strokes or heart attacks compared with those who took other diabetes medications, though FDA medical team leader Thomas Marciniak recently re-analyzed that data and called the study "inadequately designed." GSK spokesperson Mary Anne Rhyne told U.S. News that the study "was conducted according to good clinical practices and the data are reliable."
[What Now for the Diabetes Drug Avandia?]
Too much, too soon? Health reform will be a godsend to uninsured diabetics who have struggled to pay for daily medications or have stopped taking them because of cost. But it's also apt to fuel an upsurge in the reliance on drugs to control blood sugar. Diabetes drugs accounted for 16.7 percent of the growth in drug spending in 2009, according to Medco Health Solutions, a company that provides prescription drug benefits. Yet, given the potential heart risks and the fact that the drugs have not been shown to actually lower the risk of heart disease (which accounts for most diabetes deaths), many experts urge emphasis first on losing weight and exercise. For one thing, it's unclear whether diabetics always benefit from drugs to drive down their blood sugar levels. The American Diabetes Association recommends a hemoglobin A1C level of below 7 percent, and many doctors prescribe multiple medications to bring even moderately high levels down. But research suggests that a level of about 7.5 percent is associated with the lowest rate of heart problems and deaths.
Overmedicating is a particular problem for seniors, more than half of whom take three or more medications per day. "The drug-drug interactions can be worse than the disease," says John Morley, director of geriatric medicine at the St. Louis VA Medical Center. And too often, he adds, "doctors seem to suspend common sense" when devising a treatment plan. For example, they prescribe Aricept for Alzheimer's patients and then treat a frequent side effect, urinary incontinence, with an anticholinergic like Enablex or Ditropan whose side effects include delirium, confusion, and memory loss. A current concern among public health experts is the use of antipsychotics in nursing homes to treat anxiety, confusion, and irritability, all frequently triggered by other medications. Some 22 percent of Massachusetts nursing home residents taking antipsychotics in 2009 didn't have conditions that called for these sedative-like drugs, according to a March government report. Using antipsychotics for this inappropriate purpose "has led to fatalities," says Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research.
The trend toward treating mild conditions with strong drugs is evident in younger people, too. Millions with mild heartburn, for example, regularly rely on proton pump inhibitors intended for tough cases despite a recent FDA warning about an increased risk of hip, wrist, and spine fractures. "About 60 to 70 percent of people taking these drugs shouldn't be on them," says San Francisco Public Health Director Mitchell Katz. Antidepressants "have migrated from useful, effective treatments for those with major depression to unnecessary treatments for those who are just a little down in the dumps," says Jerry Avorn, a professor of medicine at Harvard Medical School and author of Powerful Medicines. This is despite recent evidence showing that, while the drugs may be life-transforming for people with major depression, they work no better than a placebo for mild or moderate cases. Commercials that invite you to try a pill if "you feel alone" have fueled consumer demand, and studies have shown that patients' requests for medication influence what physicians prescribe.
No panacea. Ads for Fosamax, Boniva, and Actonel have certainly helped generate multibillion-dollar-a-year demand for the osteoporosis treatments. And indeed, the bisphosphonate medications have helped many women avoid major fractures in the hip and spine, a leading cause of death in the over-65 population. But even the National Osteoporosis Foundation, which previously recommended using the drugs for prevention in women with osteopenia, or mild bone loss, now agrees that a pullback is in order; its newer guidelines exclude most women with osteopenia.
In those with full-blown osteoporosis, the drugs' benefits far outweigh their risks, says Steven Cummings, who directs the San Francisco Coordinating Center, a nonprofit research group. "For every 1,000 patients that we treat for 10 years, we'll prevent 100 major fractures," he estimates. But "those without osteoporosis really shouldn't take bisphosphonates." They'll gain little if any benefit, and may put themselves at risk for rare but serious side effects like thigh fractures and osteonecrosis of the jaw, a painful bone deterioration.
Several planned changes to the drug safety system may help doctors and patients make wiser treatment choices. In 2007, Congress granted the FDA stronger powers to check on post-marketing studies yearly and issue harsh fines if promises to conduct them aren't kept. The agency also plans to install a surveillance system by 2012 that periodically scans 100 million anonymous electronic medical records for adverse drug effects; experts say this might have detected Vioxx's problems years earlier. Psaty, who served on an Institute of Medicine panel that criticized the system a few years ago, says he's hopeful the new approach will prove both safe and effective.