Among them are how often you have migraine attacks, the severity of your headache pain, and any other symptoms you have in addition to headache. Your health history, including any drugs you already take and any other chronic conditions you may have, such as high blood pressure or depression, will also be taken into account before your doctor prescribes medication for migraine. But no matter how carefully you choose your regimen, sometimes a migraine therapy — or multiple migraine therapies — don’t effectively shorten your migraine attacks, lead to pain relief, or reduce your number of headache days. This frustrating situation is referred to as a drug failure or treatment failure.

What Constitutes Drug Failure?

Drug failures in migraine treatment can be placed into one of two categories: lack of efficacy or lack of tolerability, says Simona Sacco, MD, a full professor of neurology at the University of L’Aquila, in Italy, and the director of the clinical unit of neurology and the stroke unit at Avezzano Hospital. Dr. Sacco was one of 32 migraine experts featured at the sixth annual Migraine World Summit, held in March 2021. “There’s a portion of patients who don’t get relief from their migraine from available remedies,” Sacco says. Because many medications take months to titrate — to adjust the dose for maximum benefit with fewest side effects — it might take a person several years to try all possible medications currently prescribed for migraine, according to Sacco. But there are instances when drug failures — both of abortive medications, which are taken at the first sign of an attack to stop it, and preventive medications, which are taken every day to prevent migraine attacks from occurring — could potentially be avoided with different medication management, she says. Here are seven expert strategies that may help.

1. Talk With Your Doctor About What to Expect When Starting a New Drug

Many patients don’t tolerate preventive migraine therapies because of side effects, which can lead them to stop taking those meds, says Sacco. But in some cases, these side effects can be tolerated if the person is warned about them before they happen, she says. Topamax (topiramate) is a good example of that, says Sacco. A common side effect of the drug is a “pins and needles,” or a numb feeling, on the ends of fingers. If people are warned ahead of time and told that this a normal side effect that’s harmless, it’s more likely that they won’t discontinue the drug, she says. Kiran Rajneesh, MBBS, a neurologist and pain medicine specialist at the Ohio State University Wexner Medical Center in Columbus, Ohio, agrees, saying that people can manage specific side effects more effectively when they are told to expect them. “For example, there are certain medications that we use for headache that are mild diuretics, where you lose more water through urine. Knowing that, and making a plan to increase your hydration, can help compensate for that,” says Dr. Rajneesh.

2. Give Your Preventive Migraine Medication Time to Work

“There are two concepts that are helpful in understanding how long you need to take a medication to find out whether it will work for you, which is time of onset and peak duration,” says Rajneesh. Time of onset is when you first start noticing the beneficial effects of a drug, and peak action is when it reaches its peak efficacy, he explains. One way to understand this concept is to imagine you are walking toward a hill in the distance, says Rajneesh. “When you start your walk, that is like starting your medication. Once you reach the base of the hill, that’s the time of onset, and when you reach the very top of the hill, that is the peak of onset, when the drug will be most beneficial,” he says. The time of onset and the peak of onset varies for different migraine medications, says Rajneesh. “Preventive migraine medications such as beta-blockers and antidepressants may take at least 15 to 20 days to start working and then peak around three months,” he says. “What we tell patients is ideally we’d want to try any medication for at least three months to determine if it’s working, but there can be exceptions, and so you should always discuss this with your doctor. If there are adverse events [unexpected or unwanted medical developments associated with the drug] we may stop or switch medications earlier,” says Rajneesh.

Sometimes drug failure can be a result of a person taking less than the recommended dose, says Sacco. “There are some patients who tend to take lower than recommended doses,” she says. “This is not good.” It’s better to take a full dose and have complete pain relief than to take a half dose at first, and then have to take the second half later on because the half dose didn’t work well enough, says Sacco. There is a desired concentration of medication in the body, where there is enough medication circulating in your blood and eventually reaching the brain and other organs to get the beneficial effects, says Rajneesh. “By taking too little of the drug, you may not be getting enough of the drug in your blood in terms of concentration,” he says. “Each medication lasts a certain time in the body, which is what we call half-life, and that’s different for each medication,” says Rajneesh. The recommended dose is planned around how long the drug will last, and if you don’t take that amount, there may be long durations of time where there is no medication in your body, he explains.

4. Tell Your Doctor About Bothersome Side Effects

Some side effects can be managed by adjusting the dose or changing the timing of the medication, says Rajneesh. In some cases, a person can have a paradoxical reaction, which is when a medication has an effect on a person that is the opposite what is expected, he says. “Take the medication Elavil (amitriptyline), which is a tricyclic antidepressant. This medication usually makes people sleepy, and so we typically tell people to take it at bedtime. But for some patients, instead of feeling sleepy after taking the drug, their thoughts can get revved up and they feel more alert,” he says. This is a case where you should tell your doctor what is happening. “We might decide to try taking the drug in the morning if it’s going to make you awake and alert. That way you can get through your day and still get the headache relief,” says Rajneesh.

5. Don’t Wait Too Long to Take Abortive Migraine Medication

Triptans are one of the most commonly used abortive therapies in migraine treatment, unless people have specific health conditions where it might be contraindicated, says Rajneesh. He suggests thinking about the pain this way: “Picture yourself standing at the edge of a lake, and imagine throwing a rock the center. The ripples start right at the center where the stone enters and slowly move toward you on the shore.” By taking the triptan early, you can stop the ripples right where the stone fell in; it can break that headache before the wave propagates, he explains. “If you wait too long, you’re letting those ripples move all the way to the shore. That results in more severe pain, and pain for a longer duration; you may even end up having to take a larger dose of the medication,” he says. “Sometimes those waves may actually build on top of each other and you can get what’s called status migrainosus, where you are not able to break your migraine headaches with the medications you’ve been given at home, and you have to visit an urgent care or emergency room to get IV medication or other treatment,” says Rajneesh.

6. If You Have Nausea, Consider a Non-Oral Medication

How a drug is delivered may impact how effective it is in treating a migraine attack, says Sacco. Some people have early nausea with attacks, which can be an indication that there’s some impairment in how the gut is working, she says. “This may lead to delay or incomplete absorption of an oral drug. If this is suspected it’s better to use nonoral drugs,” says Sacco. Nonoral migraine medications can include nasal powder or spray, suppositories, or intramuscular injections. The triptan Imitrex (sumatriptan), for example, is available as a nasal spray and a subcutaneous injection, as well as a pill.

7. If One Drug Doesn’t Work, Consider Trying Another in the Same Class

When it comes to abortive migraine therapies, it’s also important to note that if a person doesn’t have a positive response to one drug in a class — for example, NSAIDs (nonsteroidal anti-inflammatory drugs) — it’s worth trying another drug in the same class, says Sacco. She suggests trying at least two drugs in each class before considering that type of medication a treatment failure. The same goes for triptans, says Rajneesh. “There are different nuances, such as the half-life of each medication. For example, Frova (frovatriptan), which has a very long half-life, can be used in migraine prevention in certain types of migraine, such as menstrual migraine,” he says.

Successful Migraine Treatment Relies on Good Communication

Sometimes treatment failures are unavoidable, but some can be prevented with good communication, says Rajneesh. “Let your doctor know details about your lifestyle, preferences, health conditions, and goals, and choose a doctor who is willing to listen and understand how migraine impacts your health and will help tailor your treatment plan around those needs,” he says.

What Is Resistant or Refractory Migraine?

If many different types of medications don’t work for you, it could mean you have resistant or refractory migraine. Individuals who don’t get adequate pain relief from existing abortive and preventive treatments can be classified as having resistant or refractory migraine, according to Sacco. She is one of the authors of a recent consensus definition of the two conditions put out by the European Headache Federation. Resistant migraine is determined by the number of preventive migraine treatments that have failed — at least three classes — as well as the number of debilitating headache days a person has — at least eight per month for at least three consecutive months without improvement. Refractory migraine is diagnosed when all the available preventive medications have failed to help, and the person experiences at least eight debilitating headache days per month for at least six consecutive months. The European Federation defines a debilitating headache as a “headache causing serious impairment to conduct activities of daily living despite the use of pain-relief drugs with established efficacy at the recommended dose and taken early during the attack; failure of at least two different triptans is required.” It’s not clear how common these types of migraine are in the general population, says Sacco, and one challenge in estimating the number of people with either condition is that up until now, there hasn’t been a widely accepted definition. According to Sacco, however, “Difficult-to-treat patients are a small percentage of people who have migraine.”