Medication overuse headache: The trouble with prevalence estimates

MOH commentary

Headache occurring on 15 or more days/month in a patient with a pre-existing primary headache and developing as a consequence of regular overuse of acute or symptomatic headache medication (on 10 or more or 15 or more days/month, depending on the medication) for more than 3 months. It usually, but not invariably, resolves after the overuse is stopped (1, p. 122).

Epidemiological evidence from many countries indicates that more than half of people with headache on 15 or more days/month have 8.2 Medication-overuse headache (1, p. 122).

In this issue of Cephalalgia, Westergaard et al. present an epidemiological study of medication overuse headache (MOH) in Denmark. The authors used the results of a 2017 survey of 104,950 Danish adults to update estimates of the prevalence of chronic headache (CH) and MOH in Denmark, and to identify the most commonly overused medications (2). The response rate was modest, at 52.6%, but weighting techniques were used to compensate for the potential effects of differential non-response. Using these methods, the authors found that 3% of respondents reported headache 15 or more days a month, and 2% met the study criteria for overuse of symptom-relieving medications. Paracetamol was the most commonly overused medication.

The case definition for MOH used in this and similar studies requires concurrent frequent headache (≥15 days per month) and intake of pain medication above a certain threshold (e.g. 10 or 15 treatment days per month depending on medication type). The concept of MOH is controversial and its importance or even existence has been debated for years (3–7). We will not restate these arguments but will instead discuss MOH nomenclature and some personal observations. These comments are not intended to single out the Westergaard study in particular, but to foster discussion.

The term “medication overuse headache” assumes causality: It implies that an individual meeting the case definition has chronic headaches at least in part because of overuse of pain medication rather than the reverse. If some individuals who meet current MOH criteria (frequent headache + medication overuse) have true MOH – chronic headaches induced by medication overuse – what is the proportion? In other words, what is the positive predictive value (PPV) of the MOH classification as operationalized in most epidemiologic studies? This is not known. We suspect that not even the strongest proponents of the concept of MOH would suggest that the true proportion is 100%, since that is not a scientifically defensible proposition. The authors of one study (8) (to our knowledge) estimated that 60% (15/25) of individuals in the general population who met screening criteria for MOH have true MOH, based on reversion to episodic headache after detoxification. Some caveats apply, including the assumptions that a) headaches induced by medication use are reversible, and b) headaches did not remit due to natural variability or regression to the mean or non-specific placebo response (9). This estimate of a 60% PPV was used in the Global Burden of Disease Study (10).

The true positive predictive value is enormously important not only when calculating prevalence, but also when extrapolating to the population level in order to calculate aggregate economic or societal burden. Depending on the PPV, MOH is either a leading determinant of disability-adjusted life years (using the 60% PPV) (9), is non-existent, or somewhere in between. Yet it is often claimed, uncritically and without caveats, that the prevalence of medication overuse headache in the general population is 1–2% without acknowledging that these statistics may be based on a faulty premise. To the great credit of Westergaard et al. (2), they recognize the difficulty of studying MOH in epidemiologic studies:

MOH is challenging to study epidemiologically. In surveys such as the current study, the case definition fulfills only two of three diagnostic criteria: Frequent headache and frequent intake of medications for acute relief of pain, but not the criterion regarding exclusion of other headache diagnoses. No gold-standard neurologic assessments or ancillary examinations were done to exclude other diagnoses. This might lead to an overestimation of prevalence.

We suspect that the PPV and consequently the true population prevalence of MOH is, for all practical purposes, unknowable (11). We respectfully suggest that we, as the headache scientific community, (again) revise MOH nomenclature to reflect this uncertainty. First, the term “medication overuse headache” should be reconsidered and replaced with a name and case definition that is neutral, scientifically justifiable, and measurable. As an example, the National Pain Strategy Population Research working group proposed and tested a definition of “high impact chronic pain” based on pain frequency, persistence, and impact (12). Second, we suggest avoiding the stigmatizing and imprecise term “overuse,” particularly given that the current definition is extremely conservative and at the lower margins includes individuals who do not meet any reasonable definition of excessive use of symptom-relieving medications.

Finally, it has been our personal observation that the perceived importance of MOH appears to vary considerably by geography, with stronger adherents in Europe compared to North America. This was borne out by a quick PubMed search that found 70% of the last 100 “medication overuse headache” publications were from European countries compared with 12% from North America. In contrast, 40% of the last 100 migraine papers were from Europe and 37% from North America (Table 1). These geographic differences of opinion and emphasis merit further research and debate.

Table 1.

Source of most recent 100 citations on Pubmed for medication overuse headache and migraine*.

	Europe	North America	Asia	All others**	Total
Medication overuse headache	70	12	16	2	100
Migraine	41	37	14	8	100

*

Line 1: Title contains “medication overuse” AND (headache or migraine); Line 2: Title contains any of: Migraine, migraines, migraineur, migraineurs, excluding medication overuse publications; geographic location based on affiliation of first author; Pubmed search 17 July 2019.

**

Australia, Africa, South America.