Does chronic daily headache arise de novo in association with regular use of analgesics?

The prevalence of chronic daily headache in association with regular use of analgesics is about 2%. Whether regular use of analgesics has a causal or consequential relationship to daily headache has not been established. A causal relationship has been suggested consequent to the observation of improvement or resolution of headache following analgesic withdrawal in patients attending headache clinics, but this observation has not been validated by controlled trials.

The aim of our investigation was to determine whether regular use of analgesics is associated with the development of chronic daily headache de novo and to characterize the clinical phenotype of those headaches by carefully studying chronic daily headache in patients with regular use of analgesics for a nonheadache indication.

Patients attending a rheumatology-monitoring clinic of second-line agents were interviewed by a training neurologist with regard to their analgesic and headache history. Headache classification was according to the criteria of the International Headache Society. Daily headache characteristics were surveyed via a standardized questionnaire, and headache features were further explored by a trained medical interviewer.

Of 110 patients presenting to a rheumatology-monitoring clinic, 73% had a diagnosis of rheumatoid arthritis, 23% had seronegative arthritis, and 4% comprised a miscellaneous group. One hundred three were using one or more analgesics regularly for their arthritis. Of this group, 8 (7.6%) reported a history of chronic daily headache, each of whom reported a history of migraine. The onset of migraine occurred before the onset of chronic daily headache in 7 patients and at about the same time as the chronic daily headache in 1 patient. In those with onset of migraine prior to chronic daily headache, the mean interval before the onset of headache was 30 years (range, 10 to 50 years). Regular use of analgesics preceded the onset of daily headache in 5 patients by a mean of 5.4 years (range, 2 to 10 years). In 1 patient, analgesic use and the development of daily headache occurred at about the same time. In 1 patient, the onset of daily headache preceded regular use of analgesics by almost 30 years. Five of those with regular use of analgesics had been taking an opiate-based preparation in combination with a nonsteroidal anti-inflammatory agent in 4. Two had been on a combination of acetaminophen (paracetamol) and a nonsteroidal anti-inflammatory drug. The minimum number of tablets per week was 7, and the mean was 48 (range, 7 to 87). Of those patients who did not have daily headache, 41% had a history of migraine and 27% reported a history of tension-type headache.

These findings suggest that individuals with primary headache, specifically migraine, are predisposed to developing chronic daily headache in association with regular use of analgesics.