Off-Label Meds: Caveat Prescriptor

March 13, 2011

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.


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