Main Medications Most Frequently Associated With Headache

Several medications on the list were less likely to be associated with headaches.

The results cast doubt on the review mechanism for the headache warning on drugs. Photo: Shutterstock.

During the annual conference of the American Society of Headachea group of researchers presented the medicines that are most related to headache after consumption.


These are monoclonal antibodies, antivirals, immunomodulators, and pulmonary arterial vasodilators, which top the list of drugs most often linked as causes of headaches in a federal database of side effects to which anyone can contribute.

“Surprising findings included the significant amount of immunosuppressants and immunomodulators present in the data,” study senior author Brett Musialowicz, a medical student at Robert Wood Johnson School of Medicine, New Brunswick, New Jersey, said in an interview. “Furthermore, our data provide evidence suggesting that several drugs belonging to these drug classes were less likely to be associated with drug-induced headaches,” raising questions about the mechanism.

Drugs most often associated with headaches

The researchers launched their study to better understand headache as a side effect of medication use, Musialowicz said. They analyzed the Food and Drug Administration Adverse Event Reporting System entries for the period July 2018 to March 2020 and listed the 30 most commonly reported medications related to headaches and their likelihood ratio (ROR). informed.

According to a website dedicated to pharmacovigilance training, ROR refers to “the odds of a given event occurring with your drug, compared to the odds of the same event occurring with all other drugs in the database” .

After consolidating generic and brand-name data, the drug most commonly associated with headaches was apremilast with 8,672 reports, followed by adalimumab (5,357), tofacitinib (4,276), fingolimod (4,123), and etanercept (4,111). These drugs treat autoimmune disorders such as psoriasis, multiple sclerosis, and Crohn’s disease.

The other drugs in the top 15 ranked by frequency are treatments for hepatitis C (4 drugs), pulmonary arterial hypertension (4 drugs), arthritis (1 drug), and asthma (1 drug).

Of the top 30 drugs most often associated with headaches, epoprostenol, a drug for pulmonary hypertension, ranked 23rd, had the highest ROR at 12.8. Next highest were the hepatitis C drugs glecaprevir and pibrentasvir, tied for 10th in the frequency analysis and both with an ROR of 9.4.

“Pulmonary arterial dilators and vasodilators are thought to cause headaches by sensitizing extracranial arteries. Clinical evidence suggests that there is a vascular component to some types of headache,” Musialowicz said.

“Monoclonal antibodies are suggested to cause headache via an immune response. Several monoclonal antibodies are in receptor-directed trials [del péptido relacionado con el gen de la calcitonina], which is believed to be involved in migraine. These trials will help further elucidate headache mechanisms and potential medications to treat these conditions.”

Is the data useful?

Stewart Tepper, a neurologist at Geisel School of Medicine in Dartmouth, Hanover, New Hampshire, who is familiar with the study’s findings, dismissed the new research in an interview. He pointed out that any member of the public can contribute to the federal database of adverse events (drug manufacturers are required to contribute), and the data says nothing about denominators.

“It’s not a reasonable way to assess adverse effects, for everyone and their uncles to say, ‘This particular drug did this to me. It’s not helpful in any way,'” he said. However, he added that the database sometimes ” It gives you a little sign so you can go back and try to get scientifically collected data.”

When asked to respond, study co-author and neurologist Pengfei (Phil) Zhang, MD, of the Robert Wood Johnson School of Medicine, noted that the FDA created the database “for a reason.” He also pointed out that the researchers used a statistical analysis technique, ROR, that was invented to adjust for weaknesses in databases.

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