When a migraine attack hits, the main thing on your mind is likely how to make it stop—but the search for effective treatments is rarely easy. A new study examines common over the counter pain medications and discovers factors that may influence how an individual responds to different medication types.

What medications actually work to relieve pain and symptoms during a migraine attack? This is the most pressing question for many people living with migraine, and yet there is no easy answer. There are many factors that can impact response to pain medication, and the treatment strategy that works for one person may not work for the next.

We spoke with Dr. Ali Ezzati, Associate Professor, Department of Neurology, University of California, Irvine, about a study he authored reporting on participants’ recall of the effectiveness of four types of commonly used acute migraine medications. Below, Dr. Ezzati breaks down the results of the study and how his findings make the case for a more individualized approach to migraine management.

Finding a Personalized Approach to Migraine Management

Doctors and patients share a common problem when it comes to finding the right medications to manage migraine: Not all medications work the same for each individual. This means that for many people living with migraine, the journey to find relief often starts with a trial-and-error process involving a mix of over-the-counter medications, home remedies and lifestyle changes.

“[By the time] patients end up going to the doctor, they still have the same problem—they want to receive the best medication,” Dr. Ezzati says. “There is a pool of medications that each doctor prescribes … based on either their patient’s insurance or their previous experience, but these are not necessarily based on evidence and data from previous clinical studies.”

There is no one-size-fits-all treatment strategy for migraine, but this study helps doctors and patients understand that not every patient responds in the same way to certain over the counter medications. Dr. Ezzati hopes the study will give doctors the ability to adjust treatment plans to patients based on more individualized factors.

Examining the Most Common Migraine Medications

Dr. Ezzati and his research team started by looking at the most commonly used medications for migraine. “We focused on the four most common acute migraine medication categories,” Dr. Ezzati says. “This was based on what patients are actually using in the real world.”

These four categories included:

These categories represent approximately 98-99% of OTC medication usage among people in the United States who are managing migraine.

The research team looked at data from 2,224 participants of the American Migraine Prevalence and Prevention (AMPP) study who completed self-reported questionnaires about medication effectiveness and their health issues. While they didn’t find many differences in pain response, the researchers were able to find several factors associated with  differences in treatment-response within each OTC class.

Factors That Impact Response to Acute Migraine Treatment

There are many different personal and medical factors that can influence an individual’s response to pain medications. However, Dr. Ezzati and his team were able to identify certain factors that may impact response to medication. “These individual differences between people can define which medication is more appropriate for them,” Dr. Ezzati says.


There are strong links between migraine and mental health, with many people living with migraine also experiencing anxiety and depression. Dr. Ezzati’s team found that in some cases these conditions may not only influence migraine symptoms, but actually impact how a person responds to specific types of treatments.

“People who report more depressive symptoms are less likely to respond to NSAIDs or acetaminophen,” Dr. Ezzati says. “So for those who have migraine and depressive symptoms … other classes of OTC medicine, like caffeine combination products, [may be more effective]—or maybe we should just skip OTC medication as a whole for them and go to prescription medication.”

Pain Intensity

The intensity level of headache pain seems to play a role in medication response as well. “Those who report a higher level of pain intensity are, on average, more responsive to caffeine combination products,” Dr. Ezzati says. This may help guide acute treatment plans for people who consistently report severe head pain as a primary symptom during a migraine attack.


Arguably the most surprising finding to come out of the study is that certain pain medications may work differently based on gender. “We saw that men have a higher chance of responding to caffeine combination products than women,” Dr. Ezzati says. “This gives us a hint that caffeine combination products might work better for men than women.”

Dr. Ezzati notes that we need more research to better understand how the above factors may influence someone’s response to different types of medication. “The caveat here is that we didn’t evaluate other factors that might affect this relationship,” he says. “[For example] the reason we are seeing this might be that women also have higher levels of depression, and that might be why they end up not being very responsive to caffeine combination products.”

For both patients and doctors, this information can be used to create more effective treatment plans and direct someone toward the acute OTC medications that have the highest chance of working for them. “A medication isn’t going to necessarily work 100% of the time,” he says. “But the odds of a positive response will be higher when evidence is used to guide treatment.”

Embracing Personalized Medicine

This study is an important first step toward more personalized diagnosis and treatment for migraine. “We can actually use patients’ characteristics prospectively, meaning that we can enter [their information] in models that give us the probability of response to a specific type of medication,” Dr. Ezzati says. “And these models are more accurate than just arbitrarily going and selecting something from off the shelf.”

Dr. Ezzati also hopes to follow up with more studies that follow larger groups of people who can log their experiences with migraine symptoms and OTC pain management in real time. “This is actually possible thanks to smartphone and web apps,” he says. “We are hopeful that we can gather long-term data from people on an almost daily basis.” This kind of long-term research would help doctors create better treatment plans for people living with migraine.

Whether you have found a medication that helps relieve migraine symptoms or not, Dr. Ezzati urges you not to lose hope. “Some people need to try five to eight different medications until they find the one that is actually optimal for them,” he says. “We are on a path to building these personalized treatments tools that, instead of prescribing eight medications to find [one that works], we can select one medication and say, ‘There is a 90% chance of success with this medication.’ We are not there yet, but that doesn’t mean we won’t get there.”

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Click here to read the full study.

Disclaimer: This study only examined over-the-counter (OTC) pain medications. These options may not be helpful for people with severe pain or whose attacks are associated with other symptoms like nausea and vomiting, as these symptoms may require prescription medications. Like prescription medications, OTC pain medications can cause side effects, including medication overuse headache.

The American Migraine Foundation is committed to improving the lives of those living with this debilitating disease. To learn more about all of your migraine treatment options, visit the AMF Resource Library. For help finding a healthcare provider, check out our Find a Doctor tool. Together, we are as relentless as migraine.