What is off label prescribing?

By Alan Koenigsberg M.D.

Patients have asked me to explain what is “off label prescribing.” Is it legal, is it safe, why do we do it and so on.Here is a detailed explanation:

In order for a medication to be available for prescription, the Food and Drug Administration (FDA) oversees the application and approval process. Pharmaceutical companies generally provide the lowest dose of a medication that will likely be distinguishable from a placebo in the registration studies.

Volunteers take these medications and report all effects they experience, especially side effects and complications. In order for a study to be valid, one aspect is that a certain percentage of the volunteers fully complete the study.

Being volunteers, if they experience unpleasant side effects, they tend to drop out of the study. In order to minimize dropouts, the drugs given tend to be low doses, just enough to separate from a placebo.

This explains why, for many medications, there is the impression that medications are barely better than a placebo. The trials are double blinded, placebo controlled, crossover studies. That means the drugs are coded, and neither the administrators of the study nor the patients know who is getting the placebo or the active medication, thus minimizing any unwanted bias toward the active medication. Placebo controlled means the drugs are compared to an identical placebo pill, not just to no treatment. We know that for many illnesses, placebo effects may account for as much as 30% improvement. Thus, the medication must show better improvement than a placebo.

Lastly, crossover means that at some point, the placebo and active medications are switched, and everyone will receive the active medication at some point.

Now we come to the FDA approval process. When the FDA approves a new prescription medication, it limits the pharmaceutical company to promoting the medication for the approved indications, and only those indications, and at the doses in the study.

In actual practice, we tend to use higher doses, as those tend to be more effective for the majority of our patients. This accounts for the much better results in actual practice than in the studies. Thus, this is considered “off label.”

Secondly, over time, we may find that a particular medication is effective in other conditions that have not been formally evaluated by the FDA. It can be entirely appropriate to prescribe these medicines for those indications if it has been shown in published medical literature that the medication is effective, or if, in our experience, it makes sense that it would work.

Amitriptyline, one of the original antidepressants, is sometimes used to prevent migraines. Propranolol, a medicine for high blood pressure, may be used to treat tremors and stage fright. Antidepressants may be used at higher doses to treat anxiety disorders. The antipsychotic medication Seroquel is often prescribed at low dose to treat insomnia. There are countless examples of off label prescribing, and for certain medications, they may be the treatment of choice.

The bottom line is that off label prescribing accounts for about one in five prescriptions written. In my practice, when I prescribe off label, it is most often for the original indicated condition, but at a higher dose. I explain why I’m doing so, and have the patient ask all the questions they can think of. I strongly suggest everyone do so with their physicians. When properly done, off label prescribing may be entirely appropriate and helpful.

Alan Koenigsberg, M.D., is a practicing psychiatrist and clinical professor of psychiatry at UTSW Medical School in Dallas.

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