Experiencing headaches after taking medicine is common—and a concern for people living with migraine. A new study outlines medications consistently linked with headaches and creates a foundation for future research.

While medications may offer relief from pain or other symptoms or treat a specific disease, they often come with side effects. For people living with migraine, trying to piece together the specific cause of a headache already feels like trying to find a light switch in the dark. Medications that are consistently linked with headache—a common medication side effect—can complicate your migraine management plan even further.

We spoke with Dr. Pengfei Zhang, Assistant Professor of Neurology, Rutgers Robert Wood Johnson Medical School, about a recent study he helped author to identify medications most commonly linked with headache. During our conversation, Dr. Zhang broke down the results of the study and how the findings will allow patients to better advocate for their treatment.

It’s important to note the study does not claim that any of the medications it identifies cause headache. There are many reasons someone might get a headache, so patients and doctors are encouraged to use the study’s results as a starting point for discussing whether or not a specific medication may be causing a headache.

Evaluating Medications Most Often Linked With Headache

Our conversation with Dr. Zhang started with a simple question: What are some drugs that can be linked to headache?

“I had an idea of the categories of medication that can sometimes cause headaches,” Dr. Zhang says. “But the thing I was most curious about was, if we were to gather all the data we have, could we find out what the top [medications linked to headaches] are?”

Dr. Zhang and his team turned to the FDA Adverse Event Reporting System (FAERS), a database that gathers patient feedback to many different medications. They looked through FAERS entries from July 2018 through March 2020 to find which medications were most commonly linked with reports of headache.

“We calculated this value called a reporting odds ratio (ROR),” says Dr. Zhang. “It gave us a sense of how likely a drug was to be causing a specific kind of side effect.” In this case, that side effect was headache. The 30 most frequently appearing medications were then ranked by their ROR values.

The Most Common Types of Medications Linked With Headache

Dr. Zhang and his team sorted the medications most often linked with headache by their drug type. “The most commonly reported medications tended to be monoclonal antibody drugs associated with immunosuppression, vasodilators and antiretrovirals,” he says.

Certain monoclonal antibody drugs are commonly used for cancer treatment and autoimmune diseases, vasodilators generally treat heart or blood vessel conditions, and antiretrovirals mainly function as part of an HIV/AIDS management plan but are also used for hepatitis C treatment.

Top Thirty Medications Linked with Headache From FAERS (Sorted by ROR)
Medication (Brand Name) Condition(s) commonly prescribed for:
1 selexipag (Uptravi) Heart and blood vessel disease
2 epoprostenol (Flolan and Veletri) Heart and blood vessel disease
3 glecaprevir (Mavyret) Hepatitis C
4 pibrentasvir  (Mavyret) Hepatitis C
5 velpatasvir (Epclusa, Sofosvel, Velpanat) Hepatitis C
6 alemtuzumab (Campath and Lemtrada) Cancer
7 sofosbuvir (Epclusa, Sofosvel, Velpanat) Hepatitis C
8 macitentan (Opsumit) Heart and blood vessel disease
9 treprostinil (Tyvaso, Remodulin, Orenitram) Heart and blood vessel disease
10 abaloparatide (Tymlos) Osteoporosis
11 apremilast (Otezla) Arthritis
12 omalizumab (Xolair) Asthma
13 ambrisentan (Letairis) Heart and blood vessel disease
14 fingolimod (Gilenya) Multiple sclerosis (MS)
15 levothyroxine (Synthroid, Levoxyl, Unithyroid, Tirosint) Hypothyroidism
16 tocilizumab (Actemra) Arthritis and autoimmune diseases
17 leflunomide (Arava) Arthritis and autoimmune diseases
18 abatacept (Orencia) Arthritis and autoimmune diseases
19 tofacitinib (Xeljanz) Arthritis and autoimmune diseases
20 hydroxychloroquine (Plaquenil) Arthritis and autoimmune diseases
21 erenumab (Aimovig) Migraine
22 infliximab (Remicade, Inflectra, Renflexis) Arthritis and autoimmune diseases
23 rituximab (Rituxan, MabThera) Arthritis and autoimmune diseases
24 certolizumab (Cimzia) Arthritis and autoimmune diseases
25 pregabalin (Lyrica) Nerve pain, fibromyalgia and epilepsy
26 adalimumab (Humira, ‎Amjevita‎, ‎Hyrimoz‎) Arthritis and autoimmune diseases
27 etanercept (Enbrel) Arthritis and autoimmune diseases
28 secukinumab (Cosentyx) Arthritis and autoimmune diseases
29 evolocumab (Repatha) Heart and blood vessel disease
30 valsartan (Diovan) Heart and blood vessel disease

The study provides some possible answers to the question of which drugs are more likely to be linked to headaches—however, Dr. Zhang notes that people with migraine and headache disorders should not automatically assume they need to avoid these medications.

“I would be cautious in thinking, if you’re a patient and see your drug on this list, that you should [drop] this drug without thinking through the whole clinical scenario,” says Dr. Zhang. “The point of the study is not to tell people to stop these meds.”

Rather, the researchers hope people will be able to use these insights to have more informed discussions with their doctors about their headache symptoms and medication management.

Primary and Secondary Headache Disorders

Dr. Zhang also notes that just because a headache occurs alongside a medication does not mean the medication is causing it. In some cases, it could even be the underlying condition the medication has been prescribed for that is actually causing headaches. For example, the researchers found that erenumab—an anti-CGRP treatment commonly used for migraine—came up in their list of the 30 drugs most commonly linked to headache.

“This study is not there to implicate specific drugs,” Dr. Zhang says. “[It’s there to] help specific patients who are actually on these drugs think to themselves: ‘Do I have a primary or secondary headache?’”

A primary headache disorder is one that directly causes headaches, like tension, migraine or cluster headache. A secondary headache is caused by another condition altogether, and headache is a symptom of that condition. For people living with migraine, it can be difficult but important to distinguish between head pain caused by a migraine attack and head pain caused by another factor (such as a side effect to a medication).

If you have migraine and start experiencing headaches while on medication, speak with your doctor about whether or not this may be a side effect of the medication or simply a symptom of migraine.

A Bright Future for Medication and Headache Research

While Dr. Zhang and his team’s research stopped short of identifying medications that cause headaches, he hopes this study will set the stage for future research to clarify these connections. Specifically, he hopes doctors and researchers will be able to use this information to answer some lingering questions about what causes headaches, both for people with migraine and those experiencing secondary headaches.

“The term ‘exploratory’ is applicable to this study. We probably should take [our findings] with a grain of salt,” he says. “But this likely does tell us something about the pathophysiology of headaches… Maybe with this data, we can inspire people to investigate specific pathways that we haven’t thought of before in headache.”

Life with migraine often includes a revolving door of treatment plans and medications as you try to find what works best for you. But research like this gets us one step closer to a world where migraine can be better managed. For the latest research and developments in migraine, keep an eye on our Resource Library.

Click here to read the full study.

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.