Off-Label Meds: Caveat Prescriptor

In medicine we say that a drug is “indicated” for a given disorder when it has gone through rigorous testing for that condition. Typically, a drug company will perform clinical trials in which they select patients with the condition, give them the new drug, and compare them with similar patients who are given a placebo (or an established drug which is already used to treat the disease). In the US, when the FDA approves a drug, the drug company is then permitted to advertise it in magazines, journals, TV, the internet, and directly to doctors, but they must specify its “approved” use.

In the past few years, several drug companies have found themselves in trouble after accusations of marketing their drugs for off-label indications. Total fines have reached into the billions, and many companies have vowed to change their marketing practices in response.

It should be emphasized, however, that doctors use drugs off-label very frequently. This is particularly true in psychiatry, where an estimated 31% of all prescriptions are off-label. Some familiar examples include trazodone (an antidepressant) for insomnia or beta blockers (originally approved for hypertension and heart failure) for anxiety. Furthermore, some very common symptoms and conditions, such as personality disorders, impulsivity, nightmares, eating disorders, and PTSD, have no (or few) “indicated” medications, and yet we often treat them with medications, sometimes with great success. And since the FDA restricts its approvals to medications and devices, even psychotherapy—something we routinely recommend and “prescribe” to patients—is, technically, off-label.

One colleague took this one step further and explained that virtually any psychiatric drug which has been prescribed for more than 8 or 12 weeks is being used “off-label” since the studies to obtain FDA approval are generally no longer than that. Admittedly, that’s nitpicking, but it does demonstrate how the FDA approval process works with a very limited amount of clinical data.

Drug companies that deliberately market their drugs for off-label indications are indeed guilty of misrepresenting their products and deceiving doctors and consumers. But to blame them for bad patient outcomes conveniently ignores the one missing link in the process: the doctor who decided to prescribe the drug in the first place. Whether we like it or not, drug companies are businesses, they sell products, and as with everything else in our consumerist society, the buyer (in this case the doctor) must beware.

Here’s an example. A new drug came to market in February called Latuda, which has been FDA approved for the treatment of schizophrenia. Before a few months ago, most community psychiatrists (like me) knew absolutely nothing about this drug.

If a sales rep visits my office tomorrow and tells me that it’s approved for schizophrenia and for bipolar disorder, she is obviously giving me false information. This is not good. But how I choose to use the drug is up to me. It’s my responsibility—and my duty, frankly—to look at the data for schizophrenia (which exists, and which is available on the Latuda web site and in a few articles in the literature). If I look for data on bipolar disorder, I’ll find that it doesn’t exist.

That’s just due diligence. After reviewing the data, I may conclude that Latuda looks like a lousy drug for schizophrenia (I’ll save those comments for later). However, I might find that it may have some benefit in bipolar disorder, maybe on particular symptoms or in a certain subgroup of patients. Or, I might find some completely unrelated condition in which it might be effective. If so, I should be able to go ahead and use it—assuming I’ve exhausted the established, accepted, and less costly treatments already. Convincing my patient’s insurance company to pay for it would be another story… but I digress.

I don’t mean to imply that marketing has no place in medicine and that all decisions should be made by the physician with the “purity” of data alone. In fact, for a new drug like Latuda, sales reps and advertising materials are effective vehicles for disseminating information to physicians, and most of the time it is done responsibly. I just think doctors need to evaluate the messages more critically (isn’t that something we all learned to do in med school?). Fortunately, most sales reps are willing to engage doctors in that dialogue and help us to obtain hard data if we request it.

The bottom line is this: psychiatric disorders are complicated entities, and medications may have potential far beyond their “approved” indications. While I agree that pharmaceutical marketing should stick to proven data and not anecdotal evidence or hearsay, doctors should be permitted to use drugs in the ways they see fit, regardless of marketing. But—and this is critical—doctors have a responsibility to evaluate the data for both unapproved and approved indications, and should be able to defend their treatment decisions. Pleading ignorance, or crying “the rep told me so,” is just thoughtless medicine.

7 Responses to Off-Label Meds: Caveat Prescriptor

  1. moviedoc says:

    I agree, but you don’t go far enough. The cost of bringing a drug to market, especially of getting approval, has risen so high that it discourages innovation, and encourages deceit. Instead of requiring the drug company to decide whether to invest millions in a new drug, could we require FDA to look at all the data and decide for which illnesses or symptoms the drug may be useful, the same way we physicians do now. The problem I foresee is getting funding for good, unbiased research. I hate to propose a tax, but as a starting point for discussion, might we consider funding such research with a tax on all pharmaceutical sales, maybe even generics. More questions: How to decide which new chemical entities would be funded for trials, who would conduct the trials, how to decide which populations to treat? Would it be ethical to test the drug on a group of mixed patients and look for which ones get better? What safeguards would be needed?

    • SteveBMD says:

      moviedoc, we’re thinking along the same lines:

      How nice it would be to be told what a drug does, or how it works, instead of what it’s approved for. After all, the FDA approval process requires studies that are, almost by definition, devoid of any real-world applicability. Just give the drug to 100 people, tell me how their mood/anxiety/impulsivity/psychosis/EPS/etc scores change, and let me decide to which patients I’ll prescribe it.

      It’ll never happen, but one can dream, right?

  2. Carolyn Thomas says:

    “…for a new drug like Latuda, sales reps and advertising materials are effective vehicles for disseminating information to physicians, and most of the time it is done responsibly….”

    But how does a busy physician know how often “most of the time” actually is? While most studies indicate that physicians adamantly deny they are influenced at all by Big Pharma marketing strategies, they also observe that the reality appears to be quite different.

    Big Pharma spends over $12 billion a year on drug detailing visits from your sales reps. They do this for only one reason: Reps work to boost sales. Period. And they do a singularly brilliant job of it. For more on this remarkably successful sales model, see:

    And promoting off-label usage of drugs approved for other purposes is an especially effective way to boost sales. Companies can’t do this legally – so instead they hire doctors to give speeches or lead courses or speak at conferences for them.

    Small personal example: A local doctor who spoke to 200 of my fellow heart attack survivors’ group recently held up a ziploc baggie of his ‘heart attack prevention kit’ – a mega dose of Plavix (600 mg – about
    nine times the standard therapeutic dose) plus Crestor. He added that “we used to recommend aspirin at the first sign of heart attack, but this Plavix/Crestor combo is better!”

    “Better?” Really? Interested in finding the study that had trashed the conventional aspirin advice at the first sign of a heart attack, I contacted him later for study sources of this new therapy. He replied that there actually were no RCTs for this practice, but he’d been at a big medical conference in Montreal and some “speaker” there had told the audience to recommend this from now on. Bingo. This unpublished advice is now being disseminated free of charge. Great news for Bristol Myers Squibb and AstraZeneca.

    When it comes to medical advice, it’s now a good idea to “follow the money”….

  3. Jill says:

    “Fortunately, most sales reps are willing to engage doctors in that dialogue and help us to obtain hard data if we request it.”

    Sure, data that supports their claims. I highly doubt they’ll be bringing you anything from the literature that questions their claims any time soon – and having both sides and evaluating them together is the definition of critical analysis. I mean… they literally *bury* data that shows their drugs are ineffective (think Seroquel Trial 0015) and are only now starting to suffer the consequences of this longstanding practice. Reliance on detailers is a bad move – a lazy move.

    • stevebMD says:

      Jill, to your point: It’s critical that doctors know what to ask for, and how to interpret it once they get it. Doctors should also be able to differentiate a good study from a piece of trash (or a thinly veiled sales pitch). Frequently, these skills are lacking. I’ve been to talks like the one Carolyn described in which the entire audience fell for a thoroughly unsubstantiated statement about a drug.

      It’s sort of like an arms race. Pharma companies have their own weapons (and “armies” of reps); doctors, in turn, need to understand their opponents’ strengths and weaknesses, and retaliate by analyzing and critiquing what they’re given, and make decisions that ultimately benefit the patient and no one else. I guess it’s unfortunate that medicine has to be practiced this way, but it’s the price we pay for progress.

  4. […] I’ve written before, I have no philosophical—or practical—opposition to pharmaceutical companies, commercial […]

  5. dressers says:

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