When John D. Abramson was practising family medicine in Hamilton, Mass., he prided himself on how conscientiously he selected the drugs that he prescribed. He closely followed pharmaceutical research. He kept track of the latest medical guidelines. And he maintained his distance when company salespeople, with promotional pitches at the ready, appeared at the practice that Abramson shared with several colleagues during the 1980s and 1990s. He typically didn't speak to pharmaceutical sales agents, although he did let them leave behind free samples of drugs that their companies sold.

Abramson knew that the companies wanted him and his colleagues to prescribe new and often expensive drugs rather than their older, less costly alternatives. But he saw no harm in stockpiling the freebies and banding them out to patients who were without health insurance and unable to buy drugs on their own.

"I thought I was being Robin Hood," Abramson says. Before long, however, he grew so familiar with administering the free drugs that he found himself writing prescriptions for the same substances for insured patients, whose coverage would then pay for the medications. For pharmaceutical companies, Abramson's behavior meant new customers. "That's what they wanted," he says. "They were playing me like a violin."

Abramson left medical practice nearly 4 years ago to write Overdosed America: The Broken Promise of American Medicine (2004, HarperCollins), which trains a critical eye on pharmaceutical companies' influence on medical research and practice. He now teaches at Harvard Medical School.

At least two pharmaceutical marketing strategies converge to alter doctors' prescribing habits. On one hand, sales representatives target physicians with visits and samples, and ads tout drugs in journals. On the other, mass media advertisements urge people to ask their doctors about specific brand-name medications. This direct-to-consumer (DTC) advertising, which is not permitted in Europe and strictly limited in Canada, has in the past decade grown into a multibillion-dollar industry in the United States.

Pharmaceutical companies and some health researchers say that promotional activities make doctors and patients better aware of available treatments. Other researchers and consumer advocates counter that the ads and giveaways goad doctors into giving patients drugs that may be unnecessarily expensive or sub-optimal in effect.

If nothing else, says internist Richard L. Kravitz of the University of Caiifornia, Davis, the consequence of drug promotions is that the medicines that are most profitable for drug companies end up being overprescribed.

ASK THE DOCTORS Eighteen actors were dispersed to physicians' offices by Kravitz and his colleagues during 2003 and 2004. Such actors are known in the medical literature as standardized patients; they aren't sick, but they're trained to describe certain realistic sets of symptoms. Medical schools use standardized patients to test students' diagnostic skills.

Kravitz had a different test in mind. He and his fellow investigators instructed the actors not only to fake specific symptoms but also, in some cases, to ask for a particular drug or a general class of drugs. The researchers wanted to know how physicians would respond to supposedly media-driven inquiries. The researchers recruited 152 family physicians and general internists practicing in San Francisco, Sacramento, Calif., or Rochester, N.Y. Each participating doctor was told that he or she would be sent two standardized patients during the next year. But the doctors weren't told the study's purpose or how to identify the fake patients.

The actors then scheduled appointments with the physicians. Once in a participating doctor's office, some of the fake patients described symptoms of major depression, a long-lasting mood disorder that's often treated with antidepressant medications. Other standardized patients complained of symptoms of a less serious psychiatric ailment, which is called adjustment disorder with depressed mood. This condition generally disappears within months without medication.

When standardized patients faking major depression didn't specifically request an antidepressant, 31 percent received a drug prescription. However, when others claimed that a television show about depression had encouraged them to seek drug treatment, 76 percent received a prescription of some kind.

In those two groups, about 6 percent of the actors who received a prescription got one for paroxetine (Paxil), one of several drugs in a class frequently used to treat major depression.

However, when members of a third group reporting identical symptoms asked specifically for Paxil, saying that they had seen it advertised on television, more than half the resulting prescriptions were for that drug.

In standardized patients who reported symptoms of adjustment disorder and didn't raise the subject of antidepressant drugs, just 1 in 10 got any medication. But nearly half of the actors who asked for medication got it. Most who asked for Paxil walked out with a prescription for that drug, while most who made a nonspecific request were prescribed some other antidepressant.

Ads aren't necessarily having a wholly negative influence, Kravitz and his colleagues note. "Direct-to-consumer advertising may have competing effects on quality, potentially both averting underuse and promoting overuse" of prescription drugs, the researchers conclude in the April 27 Journal of the American Medical Association.

"It's probably promoted use of expensive, brand-name medications, which are more likely to be heavily promoted ... than less expensive generic alternatives," Kravitz says.

Other studies support the notion that DTC ads translate into prescriptions. One 2003 investigation found that people visiting doctors' offices in Sacramento, were twice as likely to request a new prescription, and twice as likely to receive one, as were similar patients in Vancouver, British Columbia. The U.S. patients were nearly six times as likely as were their Canadian counterparts to have recently seen ads for most of the half-dozen prescription drugs that the study examined, reported a team of Canadian and U.S. researchers, including Kravitz.

In a more recent survey of 643 U.S. physicians, many attributed a double-edged effect to pharmaceutical ads. Nearly three-quarters of the doctors said that they believe that DTC ads inform people about medicines that might help them, and two-thirds of the doctors said that ads improve dialogue. One quarter of the ad-initiated doctor-patient conversations lead to diagnoses of treatable problems that might have gone undetected, the doctors report.

On the other hand, four-fifths of the survey respondents said that ads encourage patients to seek unnecessary treatments and don't fully convey the therapies' risks. Joel S. Weissman of Harvard Medical School and his colleagues posted the results of the survey on the Web site of Health Affairs in April 2004.

The pharmaceutical industry says that it recognizes its responsibility to be candid about drug benefits and risks. "Our communication with patients should really be thought of as direct-to-consumer education;' said Johnson & Johnson's chief executive officer William C. Weldon at a March meeting of the Pharmaceutical Research and Manufacturers of America (PhRMA) in Washington, D.C. "The framework we call DTC advertising may inadvertently minimize the importance and power of medicines and their risks," he said.

In the months since the PhRMA meeting, where Weldon was elected to head the trade association's board of directors, companies such as Johnson & Johnson and AstraZeneca have introduced new television ads that include recitations of circumstances in which patients shouldn't use the companies' products. Last week, PhRMA'S board gave preliminary approval to a set of advertising principles that encourage ads that "reflect balance between risks and benefits."

The new advertising trend has a backdrop of recent concerns about drug safety. Since last September, when the sudden recall of the pain medication Vioxx raised congressional concerns (SN: 2/5/05, p. 90), the Food and Drug Administration has sent numerous warning letters to drug manufacturers.

In April, for example, FDA ordered an ad for the impotence drug Levitra off the air because the agency said that it neglected to explain potential side effects. Another letter went to AstraZeneca in December, warning the London-based company that newspaper ads about Crestor contained "false and misleading" statements about risks associated with that cholesterol-lowering drug.