Polypharmacy in Primary Headache Risks Chronicization and Further Complications

array of colorful pills
array of colorful pills
Polypharmacy in individuals with primary headache may arise out of a prescribing cascade.

Polypharmacy in individuals with primary headache may arise out of a prescribing cascade, in which concomitant medications create a cycle of side-effects and treating side-effects that eventually evolves into possible chronicization and medication overuse, according to a study published in CNS Drugs.

This cross-sectional, observational study included 300 individuals with primary headache as defined in the International Classification of Headache Disorders. Researchers divided the study population into 2 groups: episodic headache and chronic headache. The study notably included almost all adult women (95%) who were mostly married and working. Information on each study participant’s specific headache diagnosis, demographic characteristics, number and type of comorbidities, and the presence of polypharmacy (type and dosage of all medications from the past 3 months) was collected and assessed.

Results found that 40.7% of the study population used 5 or more medications, mainly to treat headache. For the whole cohort, an average 4.37 medications were taken over 3 months. Polypharmacy in patients with chronic headache was double what subjects with episodic headache reported (58.8% vs 28.7%). This may be explained by the presence of comorbidities, which were significantly higher in subjects with chronic headache than in subjects with episodic headache. The most common classes of medication used to treat disorders other than headache were consistent with the most frequently reported comorbidities (gastrointestinal, thyroid, rheumatological, and psychiatric disorders).

The authors of the study suggested that part of the subjects’ polypharmacy stems from a prescribing cascade beginning with medications taken for headache management, then drugs treating comorbidities (for example, medications to treate gastropathy, a side-effect from frequent NSAID use, were prevalent in the study), and finally, drugs to treat the side-effect of the concomitant medication. Limitations of the study include a high prevalence of women in the sample population and data derived through cross-sectional or secondary analysis.

Related Articles

This study reveals that polypharmacy is a significant issue in individuals with primary headache, and a more precise approach would benefit the treatment of primary headache. The recent role of calcitonin gene-related peptide in the pathophysiology of migraine may offer a future of migraine management without polypharmacy and medication overuse.


Ferrari A, Baraldi C, Licata M, Rustichelli C. Polypharmacy among headache patients: a cross-sectional study [published online May 11, 2018]. CNS Drugs. doi: 10.1007/s40263-018-0522-8