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When It Comes to Drug Claims, Skepticism Is Healthy

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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!

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16 Comments

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  1. Tricyclic antidepressants, in particular amitriptyline, commonly cause substantial weight gain/fluid retention/oedema in people who take them. I consider that this, along with their other serious adverse effects, makes them very harmful drugs which should not be prescribed at all, even if, very occasionally, they provide some benefit to the patient.

  2. Thanks for your comment RM.

    While it is true that in the particular case you mention the effect could be a correlation, and not a cause, I think the weight of evidence (along with common sense) points to advertising and promotion having a significant effect on both doctors and patients.

    In 2000 $2.46 billion was spent by drug companies on DTC (direct-to-consumer) advertising, up from $791 million in 1996. During that time requests from patients for drugs they felt they need also began to rise, with one out of four patients making such requests. A survey conducted by the FDA found that 85% of physicians reported that their patients asked either “often” or “all the time” for advertised drugs.

    I think it would be difficult to argue that this is correlation, i.e. that the patient’s request for the drugs are driving the advertising increases. The patients wouldn’t even know about the drugs if it wasn’t for advertising.

    Doctors are also clearly influenced by pharmaceutical advertising and promotion. As Dr. Jerry Avorn from Harvard said in his study:

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

    If the only way most doctors are learning about these drugs is by reading promotional literature, as Avorn’s study suggests, then by definition they are being influenced by promotion. And while this does not prove that drug promotion is responsible for the rise in prescriptions beyond a shadow of a doubt, I think it’s a perfectly robust and supportable hypothesis.

    As to your second point, I was referring to the combination of unpublished and published studies. Kirsch and colleagues used the Freedom of Information Act to obtain access to the FDA database, which includes all published and unpublished studies. Using that database for their meta-analyses, they determined that antidepressants have no clinically meaningful advantage over placebo.

    For more detail on this, see my original post Placebos as effective as antidepressants”, and today’s post A closer look at antidepressants. Make sure to check out the comments on that post for further discussion.

  3. Very interesting article. I consider myself a skeptic as well, and have some differences in interpretation of some of the pieces of data you present.

    “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.”

    Correlation vs Causation… this effect could simply be driven by pharmaceutical companies advertising their most effective, and thus most prescribed, medications. In this case it would not support the conclusion that the advertising is influencing doctors. (This possibility is not mutually exclusive with yours, and I don’t think the reality is 100% one or the other.)

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

    I can’t tell if you mean when *only* the unpublished studies are analyzed, or when they are included with published studies. If the former is the case, then you’re subjecting yourself to the same sampling bias that you accuse the drug companies of (but, of course, pointing you toward the opposite conclusion).

  4. G,

    I’m grateful for your participation and support!

    I was aware of the antidepressant effect of D, but not of Dr. McCleary’s work. Thanks for pointing that out. I’ll read his articles on D’s role in the brain, and yes, I do intend to write more on the relationship between the fat soluble vitamins in the future.

    It may be a while, though. I have several more articles in the antidepressant series to write first!

    Best,
    Chris

  5. BTW… DRMcCleary.com has great commentary and thoughts regarding vitamin D’s benefits on the brain. He’s a retired pedi-neurosurgeon/author living in California. (click on ‘blog’ on the brain top-L-corner)

  6. Chris,

    Did you know that Vitamin D is an antidepressant? It ameliorates SAD (seasonal affective disorder) very well.

    I’m looking forward to your review on the relationship betw A/D/E/K2! You write so wonderfully! Keep up the strong work 🙂

    -G

  7. Hi Chris,

    I fully agree with you about the “chemical imbalance” thing; it’s incredibly dense. They try to spin it like you were born with depression and there’s nothing you can do about it but take a drug. I have a friend who’s into mood disorder research and I’ve talked to him about that meta-analysis showing no significant effect of ADs.

    First of all, he has no dog in the fight because his interest in mood disorders is purely academic. I can vouch for his lack of bias toward antidepressants. Here’s what he told me. Basically, what we call “depression” is actually a collection of related disorders. Antidepressants only work on a subset of them.

    There are “responders” and “non-responders” in any group of people who receive antidepressants. For responders, antidepressants can be very effective. When you do a meta-analysis where you’re averaging everyone with “depression” together, the effect of an antidepressant will be small or nonexistent because of the heterogeneity. So this is a problem with saying that antidepressants aren’t effective based on that analysis.

    I don’t have a problem believing that antidepressants work for some people. They certainly work in animal models of depression, where there is no placebo effect. I don’t think we should banish them from planet Earth. But I do think the fact that we use them so much points to a bigger problem that we should be addressing by other means.

  8. Thanks for the information on drug claims. I can’t beleive they spend $20 billion to promote their products! And a 25% increase in heavily advertised drug prescriptions…wow.

    We recently wrote an article on drug companies relationship with doctors at Brain Blogger. Though the Research Ethics Boards exists to protect research subjects in clinical trials by providing guidelines, sometimes healthcare companies and doctors find a way around them. Is money that big a draw that a doctor could go against his own ethics?

    We would like to read your comments on our article. Thank you.

    Sincerely,
    Kelly