Issue #156 - May/June 2007
Richard Wenzel, PharmD
Diamond Headache Clinic Inpatient Unit
St. Joseph’s Hospital, Chicago, IL
Off-Label Prescribing: Why Drugs Ranging From Antidepressants to Anti-Seizure Medications are Used for Headache Management
When educating headache patients, I commonly encounter questions regarding the use of medications designed for an illness other than headache. “Why did my doctor give me a blood pressure pill if my blood pressure is fine?” I’m asked. Or, “Why am I being prescribed an antidepressant? Does my doctor think my migraines are just depression?” These questions arise primarily because patients are unaware of the varied uses of drugs for multiple illnesses.
The U.S. Food and Drug Administration (FDA) is the government agency responsible for determining the effectiveness and safety of prescription and non-prescription medications. The FDA requires drugs to successfully complete an approval process, in which research is conducted among individuals suffering from a particular disease. Upon successful approval, a drug is assigned an “indication,” which signifies that the FDA officially recognizes that the medication is safe and effective for that particular illness.
Yet once FDA approved, drugs can be legally prescribed for illnesses other than the original indication, a practice known as “off-label” use. Off-label prescribing has been practiced for decades with many medications and for countless diseases. Off-label prescribing is widespread for rare or poorly researched illnesses as a practical reality. Since healthcare providers have few FDA-approved drug choices for these illnesses, they may attempt off-label treatment with a medication they reasonably expect to be of benefit. Historically, headache has been inadequately researched. Thus a large portion of therapy has been, and still remains, off-label. One Medication, Two Diseases
Off-label prescribing has been practiced for decades with many medications and diseases, especially for diseases that share a similar problem. For example, blood vessel changes occur during migraine attacks. Therefore, it is not surprising that drugs that affect blood vessels, such as certain blood pressure medications, can also be successfully used for migraine. Seizures and migraine are both partially caused by inappropriate activity of chemicals in the brain. Thus, medications that affect chemicals in the brain can be used for either illness.
For example, topiramate (Topamax®) was originally FDA-approved a decade ago for treatment of seizures. Over time, patients with migraine as well as seizures reported that their headaches improved when they were prescribed topiramate. These reports prompted researchers to study the drug in migraineurs who did not have seizures, which ultimately led to topiramate receiving an FDA indication for migraine prevention.
This situation highlights an important patient role—if you are taking a drug for an illness other than headache, but notice an improvement in your headaches, please inform your healthcare provider or pharmacist. They will forward this information to the pharmaceutical company, which will evaluate if further studies are warranted.
Patients should also be aware that the dose of a medication when used to treat headache may differ from the FDA-approved dose for its original indication. Topiramate’s seizure dose usually exceeds 200 mg per day, but the migraine dose is typically less that 200 mg daily. As an added benefit, lower doses generally cause fewer side effects.
Topiramate is one of the few examples of successful off-label usage resulting in an FDA migraine indication. Depakote® (divalproex sodium) followed a similar path to its FDA approval for migraine prevention. Older medications that have been found to be effective for headache—for example, the antidepressant amitriptyline and the blood-pressure medication propranolol—are unlikely to ever obtain an FDA headache indication. The FDA approval process requires many years of research and costs tens of millions of dollars. Older drugs tend to be only available as generics and few, if any, generic pharmaceutical companies are willing to incur large expenses. Furthermore, these medications are already widely prescribed for migraine, diminishing any economic incentive to seek an FDA indication.
So, the next time your healthcare provider prescribes an off-label drug, for example a blood pressure, antiseizure or other non-headache drug, ask why. The provider’s rationale may range from something simple, such as other headache patients reporting benefits from the drug, to stronger evidence, such as findings from a large study published in a medical journal. Or the drug may now be FDA-approved for headache. And remember, if you are taking the drug for your headache, then it is in fact a headache drug, regardless of the medication’s FDA indication.