Pill pushers: pharmaceutical companies are emphasizing marketing - and downplaying responsible medicine.

Pharmaceutical companies are emphasizing marketing--and downplaying responsible medicine

Recently, while scanning the "buy" pages of a prominent Wall Street analyst's report, I came across these rather remarkable words: "We are recommending that our clients take another look at Abbott Laboratories' new drug, Depakote. There are an estimated 1.2 to 1.6 million manic depressives in the United States, and as a result, we believe manic depression can create a $1 billion market opportunity."

It's easy to forgive the analyst's somewhat tacky excitement. Pharmaceuticals, after all, are one of the steadiest performers in today's investment portfolios. Our mutual funds are engorged with Lilly and Pfizer and Glaxo and Abbott; so, too, are our pension plans and college trust accounts. In fact, never before have so many Americans benefited from the financial side of the drug industry. More and more, our individual economic fates are bound up with theirs. As is, increasingly, our health. America is now more than ever a pill-centric society. This is partly the result of rising health costs, partly because of managed care, and partly because of our penchant for self-help. Whatever the impetus, though, the sentiment is always the same: We don't want to wait to be diagnosed with GERD, the meta-heartburn of the '90s; we just want the Zantac--now. As my own doctor said recently, "Those ads that say `Ask Your Doctor Now,' really mean `Tell your doctor to give you X--or else."' Studies show that most of us know our pharmacist better than our internist.

As a result, the disinclination to rein in pharmaceutical giants has never been greater. (Witness, for example, the weird grassroots support for last year's bid to privatize the FDA--a screwball idea that even the Gingrichians ultimately rejected.) Yet just the opposite should be true. As America's health system becomes increasingly owned and operated by the pill companies, the ways of drug firms ought to be under more, not less, scrutiny. It's an unfashionable idea, but it's true: If there was ever a case for greater government involvement, pharmaceuticals carry the brief.

Consider the strange career of Depakote, our "billion-dollar market opportunity." Like many of today's most popular concoctions, Depakote began life with smaller ambitions; for years valproic acid was but another effective, unsexy bullet in the medical arsenal against epilepsy. Then, in 1990, as Prozac proved that psychiatric drugs could create new mass markets, Abbott decided to re-register the drug as a treatment for bipolar disease, the diagnostic term for manic depression. The company filed the requisite forms with the FDA and began clinical trials. But instead of waiting for the agency to render a decision about Depakote's efficacy--as is required by federal law--Abbott began hyping away. According to papers recently released through the Freedom of Information Act, the FDA not only caught Abbott using a medical education program on bipolar disease to promote Depakote illegally, it also cited the company for using the classes to collect information about attending doctors' prescribing habits. Who funded the class? Not Abbott's educational arm, but--surprise!--the Depakote product manager.

Abbott's exercise is a lesson in modern pharmorealpolitik. While it is illegal for a manufacturer to promote a drug for unapproved uses, doctors are legally permitted, within reason, to prescribe what they will. The drug companies know this and have exploited the loophole ruthlessly.

Over the past few years, the FDA has issued dozens of warning letters to pharmaceutical giants for promoting so-called "off-line" uses. Last summer, for example, Pfizer, maker of the antidepressant Zoloft, received a warning from the FDA for illegally promoting the drug as a treatment for "Premenstrual Dysphoric Disorder," a form of depression that accompanies PMS for a small percentage of women. Evidence for the claim was deemed insuffficient. The FDA thought the practice of off-line promotions so widespread at Pfizer that it directed its eight-page warning letter to the company's chairman, William Steere, instead of to its head of regulatory affairs, who would normally get such letters. By doing so, the agency was making a crucial point: Often, only the head of a drug company truly controls its sales culture. Not that Pfizer is the only culprit. So endemic is the practice of drug firms hyping unsupported product claims the facts don't support that, in 1994, FDA Commissioner Mary K. Pendergast was moved to (uncharacteristically) straightforward language. "Promotion of unapproved uses by company sales representatives," she told a congressional panel, "is a major problem"

Here the libertine in all of us would, of course, like to say: "What's the big deal? Didn't these drugs get approval eventually?" For the most part, yes. But that doesn't mean they're without substantial problems--problems often downplayed or absent from the preapproval information most doctors receive. Depakote, for example, proved only marginally more effective than lithium, the long-standing (and cheaper) treatment for manic depression. It also displayed far more severe side effects for pregnant mothers than lithium, with resulting fetal complications including developmental delay, a small head, facial abnormalities, and a significantly increased risk of spine bifida. Similarly, Paxil--SmithKline Beecham's brand name for its antidepressant offering, paroxtine--proved to have the unforeseen side effect of severe withdrawal syndrome. As recorded both in drug trials and by physicians participating in the FDA's voluntary reporting program, patients who stopped taking paroxetine experienced symptoms including extreme anxiety, hostility, vision abnormalities, insomnia, dizziness, and diarrhea. One test subject, according to FDA files, "became preoccupied with homicidal thoughts and plans, initially directed towards acquaintances and later towards his own children. These became so intense...he contemplated suicide" In another case, a 67-year-old man who had run out of paroxetine committed suicide. Of course, as in any of these cases, direct causation is difficult to determine, but the "suspect adverse reaction report" filed in this case noted: "It was thought that [running out of paroxetine tablets] could have caused a sudden withdrawal reaction...which led to a relapse of the patient's depression, causing him to commit suicide" Clearly, Paxil should have been tested more rigorously before its release, and accompanied by a warning label alerting physicians and patients to all of the drug's severe side effects. As it is, prescribing instructions for Paxil have been revised 11 times in just three years, with withdrawal syndrome now topping the FDA's list of adverse reactions.

All right, no drug is perfect. And all of this would not be so objectionable if today's doctors had the time to perform their traditional role as gatekeeper to the national apothecary. But they don't. Physicians' prescribing habits are increasingly circumscribed by two new forces: HMOs, who increasingly push them to prescribe more drugs, and PBMs, or pharmaceutical benefit managers. These companies--many owned by the pharmaceutical firms themselves--tell physicians which drugs insurance companies will pay for. In essence, doctors have lost control of their prescription franchise. Control instead exists in the ganglia of vague arrangements between drug companies, PBMs, and HMOs. A study released in January shows one possible consequence of that: In 1996, the cost of treating the adverse reactions to pharmaceuticals topped $4 billion.

In the U.S. health care system, two of the biggest trends are self-diagnosis and self-treatment, fueled in no small part by the most important movement in pharmaceuticals--the conversion of prescription drugs to over-the-counter status. There is, of course, some curative in this trend. After years of believing everything doctors told them, Americans have taken back some power. Good for them. But as "empowering" and "nurturing" as the self-care movement may be, it still depends on one basic notion: that the information we all get about, say, Paxil, is legitimate--that it has jumped all the hurdles erected to protect us, that the information is unbiased and clear, and that we're not being offered the product until the FDA has deemed it safe and effective.

Sadly, anyone who has actually studied today's ubiquitous drug advertising knows that obfuscation and legalism long ago replaced clarity. The recent campaign for the prescription skin cream Renova promises "A Tube of Truth" Effexor, yet another antidepressant, promises, "There is Hope--in fact, there is more than hope" The FDA has a unit specifically empowered to police drug-company hype, but that arm, the Division of Drug Marketing, Advertising, and Communications (DDMAC) is increasingly understaffed and overworked. It has a total of 29 staff members and a small budget with which to take on the legal and marketing departments of the world's biggest drug companies. Moreover, the FDA itself is under cultural and political siege. Because of its outgoing director's campaign against tobacco, the agency has taken its share of hits for being "too aggressive" and "heavy handed" The reality is just the opposite. During the Clinton years, review times for new drug applications dropped dramatically. And the drug companies have a new weapon designed to cow the FDA from becoming more vigilant: Because of laws passed in the early 1990s, the agency must report progress in reducing review times, or face cuts in its funding.

How then to guard the consumer, once quaintly known as "the patient"? Three notions come to mind. One is to ramp up the DDMAC; if self-prescription is the key to saving health care bucks, then let's make sure we at least get good information upon which to base our decisions. The second is to call for full and prominent disclosure of drug company hype; if Lilly, for example, is caught promoting Prozac as a cure for bunions, make it pay for a campaign of corrective ads. Lastly, we might think about spending more money to educate students about pharmaceutical drugs. Health curriculums could be revamped; the venerable Physicians Desk Reference could even be abridged for the laity. Such ideas would likely find support in America's beleaguered medical community. As one doctor wrote me recently, "Perhaps there should be a requirement that drug companies underwrite a neutral informational spot for every promotional spot they fund"

That would be a radical idea--but perhaps no more radical than calling manic depression "a billion-dollar market opportunity."

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