When it comes to drug claims, skepticism is healthy

June 20, 2008   Chris Kresser

I’m preparing for an upcoming presentation in September called “The (Hidden) Truth About Antidepressants”, so I will be writing frequently about issues related to the definition, cause and treatment of depression in the weeks to come.

Much of what I write may challenge your current beliefs and contradict what you’ve heard about depression and antidepressants. My hope is that today’s post about the influence of the pharmaceutical industry on doctors, researchers and patients will inspire you to re-examine what you’ve been told so far and approach everything you hear in the future with a “healthy skepticism”.
The truth is that all of our beliefs about depression have been tainted, quite intentionally, by the more than $20 billion spent each year by pharmaceutical companies to promote their drugs (an amount greater than the gross domestic product of all but 70 of the world’s richest nations). In 2000, the pharmaceutical industry had a combined lobbying and campaign contribution budget of $200 million – larger than any other industry (Wayne & Peterson, 2001). The industry has 625 registered lobbyists, more than there are members of congress (Wayne & Peterson, 2001). The industry also underwrites about 70% of clinical drug trials in the United States (DeAngelis et al., 2001).

Consumer Reports has detailed the marketing strategies used by drug companies, including:

• giving free samples and information to doctors
• advertising in medical journals
• using “ask your doctor” media advertisements aimed directly at the consumer (the U.S. and New Zealand are the only two countries that allow this)
• sponsoring promotional dinner meetings with substantial gifts or even cash provided for attendees
• paying consultants to speak at scientific meetings where it is possible to circumvent FDA guidelines that require disclosure of side effects
• funding only those research projects that have a high likelihood of producing favorable results for a particular drug company’s product
• terminating negative studies before they are ready for publication
• not publishing studies with negative results
• offering to pay journalists to cover their products
• helping to fund patient advocacy and other public interest groups so the consumer group appears to be publicly carrying the banner of a particular drug

How can we possibly rely on information that is so inexorably intertwined with corporate interests?

Corporations have very little motivation to share information that could harm sales of their products, as they are required by law to maximize profits for their shareholders. On the contrary, they have much incentive to do everything in their power to suppress such information. Several studies have shown that researchers who produce data that is contrary to the interests of the pharmaceutical industry risk legal, professional, or even personal attack – directly or indirectly financed by the industry. (Bosley, 2002; Healy, 2002; Monbiot, 2002).

As researcher David Antonuccio points out in his excellent article Antidepressants: A Triumph of Marketing over Science?:

“Company-sponsored experts, whether they are researchers or educators, are by definition company employees. They will be retained only if they offer consistently favorable treatment to the company’s products. It could be argued that their efforts on behalf of antidepressants often fit more properly under the rubric of marketing or advertising, not science or education.”

Clinical trials are the basis of approval of new drugs by the FDA, but their reliability is seriously in doubt because of three major flaws: conflicts of interest on the part of investigators; inappropriate involvement of research sponsors in their design and management; and publication bias in disseminating their results. (Quick, 2001)

The situation has become so dire that in September of 2001 the editors of 13 leading medical journals published a joint editorial in which they said:

“Research contracts should give the researchers a substantial say in trial design, access to the raw data, responsibility for data analysis and interpretation, and the right to publish”

Huh? Wouldn’t you expect researchers to have these rights already? In many cases, they don’t.
The editor of the prestigious New England Journal of Medicine argued in a separate editorial that the editors didn’t go far enough in their rebuke:

“The entire system of clinical investigation is driven by profit. We are seeing the corruption of a system of research that used to have high ideals and be clearly in the public interest.”

The conflicts of interest between researchers and drug companies is bad enough. But what’s even more distressing is that many doctors do not even read the research to learn about the drugs they are prescribing. Jerry Avorn, a Harvard Medical School professor and drug researcher is a leading authority on how physicians are educated about new drugs. He acknowledges that most physicians have only minimal knowledge about drug studies. Instead, Dr. Avorn has this to say about where most physicians get their knowledge about drugs:

“Pharmaceutical marketing is about the most important source of knowledge about new drugs for most physicians, and a major form of continuing education as well.”

There are now over 90,000 pharmaceutical reps walking the halls of medical offices around the U.S. Since there are less than 600,000 office-based doctors in the U.S. today, there is approximately one full-time drug rep for every six physicians. The drug reps bring free food for office staff, free samples for distribution to patients, free pens, free textbooks and other free gifts. They are also sometimes authorized to provide free vacations for physicians who would enjoy spending a weekend with other physicians in places like Hawaii or the Caribbean hearing the latest “research” on the effectiveness of a drug. In 2006, the pharmaceutical industry spent $2 billion on these types of events alone.
Does all of this advertising and promotion actually influence doctors? You bet it does. A government report found that in just one year the most heavily advertised drugs had prescription increases of 25% (U.S. General Accounting Office, 2002). There is even a formula that generally applies to drug advertising: each dollar spent on advertising increases sales by $4.

Even more discouraging than the influence of drug companies on doctors is the influence of patients who’ve been subjected to drug company advertising on doctors! A study published in the Journal of the American Board of Family Practitioners reported that 49% of patient requests for drugs or other requests prompted by “direct-to-consumer” advertising were not clinically appropriate. Yet 7 out of 10 times, physicians gave into the requests. (And that is by their own admission; there is likely a percentage of physicians who do not want to admit they write prescriptions or order tests on the basis of patient requests.)
The influence of advertising on doctors and patients is particularly relevant in the case of antidepressants. By a wide margin the largest amount spent on advertising by drug companies was on antidepressant promotion – a whopping $367 million dollars per week!(U.S. General Accounting Office, 2002) In fact, it appears that DTC advertising may be the single most effective way a drug company can increase the number of people who are diagnosed with depression and then will begin taking antidepressants (Donohue, 2004).

I could go on, but I think you get the point. As consumers and patients we simply cannot rely on profit-driven drug companies to give us accurate information about their products. And unfortunately, because of the massive conflicts of interest that exist between researchers, physicians and the pharmaceutical industry – we cannot necessarily rely on our doctors or even scientific studies to show us the way.

Luckily for us, there are still studies being done by independent researchers and those brave enough to risk the ire of the drug companies that we can turn to for honest, unbiased data. Unsurprisingly, these studies often have very different results than those sponsored by the industry. Thanks to the Freedom of Information Act, some researchers have even been able to access the studies done by the drug companies that they never published (obviously the ones that were least favorable to their drugs).

When these independent and unpublished studies are analyzed, a very different picture of depression and the efficacy of antidepressants begins to emerge.

Contrary to popular belief:

1. There is no evidence that depression is caused by a “chemical imbalance” (which is the rationale behind prescribing antidepressants).
2. Recent meta-analyses of the research data show that antidepressants have no clinically meaningful advantage over placebo. Therefore, the term “antidepressant” is a misnomer and should be abandoned.
3. Poor study design may account for the small degree of superiority shown over placebo
4. Claims that antidepressants are more effective in more severe conditions have little evidence to support them.
5. Antidepressants have not been shown to affect the long-term outcome of depression or suicide rates.
6. It is now recognized that SSRIs (the most widely used class of antidepressants) increase the risk of suicidal behavior in children and adolescents, and there is legitimate concern that the same is true for adults.
7. Given doubt about their benefits and concern about their risks, current recommendations for prescribing antidepressants should be reconsidered.

You might be shocked by some of these statements. Though I was already very skeptical about antidepressants before beginning this research, I myself have been blown away by the complete lack of evidence supporting the theory that depression is a biological disease and the very strong evidence that antidepressants are no more effective than placebo.

I’ll be writing in more detail about several of the points to come in the coming weeks, so please stay tuned!
==============================================================
Read the complete article here.