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
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
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
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.