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Chronic Daily Headache: Is Analgesic
Overuse a Cause Or a Consequence?
Lipton RB, Bigal MD.
Posted: May 2004  
Neurology 2003;61:154-155

In the current issue of Neurology, Zwart et al. present data on the role of medication overuse in the subsequent development of chronic daily headache (CDH) and other pain disorders. CDH is defined as a primary headache disorder with attacks 15 or more days per month (or 180 or more days per year) with an average duration of 4 or more hours per day. Up to 80% of the patients seen in headache centers have CDH. In population-based surveys, the prevalence of CDH is a staggering 4%. Chronic migraine (CM) is the most common subtype of CDH in specialty care and an important disorder from the perspectives of societal costs and individual suffering. Subjects with CM usually undergo a process of transformation over months or years, characterized by increasing headache frequency.

Candidate risk factors for the development of CM include female sex, high frequency of headaches before transformation, obesity, stressful life events, hypertension, alcohol overuse, hypothyroidism, viral infections, snoring, and sleep disturbances. Overuse of acute medications is commonly identified as the most important risk factor for CM; it is present in more than 80% of patients with CM in subspecialty clinics.

The importance of medication overuse as a risk factor for the development of CDH is supported by several lines of evidence. Clinical observation suggests that medication overuse is associated with CDH and that it can make headaches refractory to preventive medication. Discontinuation of overused medications results in significant improvement in headache. In clinical practice, causal attribution is difficult because, in addition to withdrawal, medication overuse is usually simultaneously treated with other pharmacologic and behavioral interventions. Medication withdrawal has been demonstrated to cause headache in a well-controlled trial of caffeine. Finally, medication overuse is associated with CDH in the population after adjusting for confounders.

Whereas overuse of acute medication is common in patients with CDH, the causal sequence is unclear. It is possible that medication overuse precedes and is a risk factor for CDH. Alternatively, people with frequent headache may take medication in response to pain. It is also possible that in patients with frequent headache, medication overuse is an exacerbating factor.

The controversy about analgesic overuse as a cause or a consequence of CDH is far from over. These viewpoints may not be mutually exclusive. The current population study adds important information by showing that frequent analgesic use is associated with CDH more than 10 years later. Although it is a risk factor, analgesic overuse is neither necessary nor sufficient to induce CDH. In the United States, 20 to 30% of persons with CDH in the population do not overuse medication and in other countries the proportions are similar. Some people who overuse medication do not develop CDH. In an arthritis clinic, of 103 regular users of analgesics, only 8 had CDH, and all of those individuals had a history of migraine. Thus 92% of people taking frequent analgesics did not develop CDH, supporting the concept that at least in a vulnerable subgroup medication overuse is associated with the development of CDH.

While awaiting additional data, neurologists should endeavor not only to treat CDH but also to prevent its development, particularly because medication overuse is, at least in part, an iatrogenic risk factor. Potential strategies include limiting the use of acute medications to no more than 10 days per month, reducing headache frequency with preventive medications when appropriate, and endeavoring to modify risk factors for CDH. The benefits of these strategies to prevent headache exacerbation or progression await testing in well-designed studies.