Abstract
Objectives: To examine the prevalence of chronic headache (≥15 days/month) associated with analgesic overuse in relation to age and gender and the association between analgesic overuse and chronic pain (i.e., migraine, nonmigrainous headache, neck and low-back pain).
Methods: In the Nord–Trøndelag Health Study 1995 to 1997 (HUNT-2), a total of 51,383 subjects responded to headache questions (Head-HUNT), of which 51,050 completed questions related to musculoskeletal symptoms and 49,064 questions regarding the use of analgesics.
Results: The prevalence of chronic headache associated with analgesic use daily or almost daily for ≥1 month was 1% (1.3% for women and 0.7% for men) and for analgesic overuse duration of ≥3 months 0.9% (1.2% for women and 0.6% for men). Chronic headache was more than seven times more likely among those with analgesic overuse (≥1 month) than those without (odds ratio [OR] = 7.5, 95% CI: 6.6 to 8.5). Upon analysis of the different chronic pain subgroups separately, the association with analgesic overuse was strongest for chronic migraine (OR = 10.3, 95% CI: 8.1 to 13.0), intermediate for chronic nonmigrainous headache (OR = 6.2, 95% CI: 5.3 to 7.2), and weakest for chronic neck (OR = 2.6, 95% CI: 2.3 to 2.9) and chronic low-back (OR = 3.0, 95% CI: 2.7 to 3.3) pain. The association became stronger with increasing duration of analgesic use for all groups and was most evident among those with headache, especially those with migraine.
Conclusions: Chronic headache associated with analgesic overuse is prevalent and especially chronic migraine is more strongly associated with frequent intake of analgesics than other common pain conditions like chronic neck and chronic low-back pain.
In the 1988 International Headache Society (IHS) classification, drug-induced headache is defined as 1) headache appearing at least 15 days/month, 2) regular intake of analgesics or ergot alkaloids, and 3) headache disappearing after withdrawal of substance.1 Revisions of these criteria have been proposed,2-4⇓⇓ and the term “drug-induced headache” has been replaced by the term “medication overuse headache” (MOH) in the new IHS classification.5 The revised IHS criteria are more specific with regard to headache features and type of medication overuse and require that the headache worsened or increased in frequency during symptomatic medication overuse. These criteria may be useful in clinical practice but are difficult to apply in large epidemiologic studies.
Cross-sectional population-based epidemiologic studies, using the previously proposed criteria for chronic daily headache,4 indicate that chronic headache is common, with prevalence rates between 2 and 5%6-11⇓⇓⇓⇓⇓ and a prevalence of chronic headache associated with medication overuse of about 1%.6,9,11⇓⇓ There are several factors that may contribute to the development of chronic headache,9,11-14⇓⇓⇓⇓ including analgesics and specific migraine drugs.15-20⇓⇓⇓⇓⇓ There are, however, arguments both for and against such a casual relationship.21,22⇓ In a recently published prospective population-based study from Norway, we endeavored to examine the relationship between analgesic overuse reported in 1984 and 1986 and the subsequent risk at follow-up 11 years later (1995 to 1997) for having chronic headache (migraine and nonmigrainous headache) with or without analgesic overuse.23 For comparison, similar analyses were performed for other common chronic pain conditions like chronic neck and chronic low-back pain. The results showed that overuse of analgesics strongly predicted chronic pain and chronic pain associated with analgesic overuse 11 years later. The association was much stronger for headache, particularly among those with chronic migraine.23 Chronic headache associated with symptomatic medication overuse is a major health problem in many countries, but the age and gender distribution in the general population is unknown. Thus, the main purpose of the current cross-sectional population-based study (HUNT 1995 to 1997) was to examine the prevalence of chronic headache associated with analgesic overuse in relation to age and gender and also the relation between analgesic overuse duration and chronic headache (both migraine and nonmigrainous headache). In addition, for comparison, this relationship was also examined for other common chronic pain conditions like neck and low-back pain.
Methods and patients.
Study population.
In HUNT-2, all residents aged 20 years and older in Nord–Trøndelag County, Norway, were invited to participate in the health survey between 1995 and 1997. The study population, including both participants and nonparticipants, has been described in detail previously.7 In brief, of 92,566 eligible individuals, 64,560 (70%) participated. Two questionnaires including >200 health-related questions were administered to the participants. The first questionnaire (Q1) was enclosed with the invitation letter and delivered during attendance at the health examination. The second questionnaire (Q2) was filled in after the examination and returned by mail.
The headache questions (Q2) were designed mainly to determine whether or not the person had headache, determine frequency of headache, and diagnose migraine according to a modified version of the migraine criteria of the Headache Classification Committee of the IHS.1 Subjects who answered “yes” to the question “Have you had headache during the last 12 months?” were classified as headache sufferers.24 Those that reported headache ≥15 days/month during the last year, irrespective of analgesic overuse, were defined as chronic headache sufferers. Based on data from the subsequent 12 headache questions, they were also classified into two groups: either migraine or nonmigrainous headache. The diagnoses were mutually exclusive. Persons were classified as having migraine if they reported having migraine or fulfilled the following three criteria: 1) headache attacks lasting 4 to 72 hours (<4 hours was accepted for those who reported often visual disturbances before headache); 2) headache with at least one of the following three characteristics: pulsating quality, unilateral location, or aggravation by physical activity; 3) during headache, at least one of the following: nausea or photo-phonophobia. Persons who did not fulfill the criteria for migraine were classified as having nonmigrainous headache. Subjects fulfilling the criteria for migraine or nonmigrainous headache and reporting headache ≥15 days/month during the last year, irrespective of analgesic overuse, were defined as chronic migraine or chronic nonmigrainous headache sufferers. The classification of the subjects in the current study has been described in detail previously, and the questionnaire-based diagnoses have been validated by interview diagnoses.24 In short, for migraine, the positive predictive value (PPV) was 84% and the negative predictive value (NPV) was 78%; for nonmigrainous headache, the PPV was 68% and the NPV was 76%; and for chronic headache ≥15 days/month, the PPV was 71% and the NPV was 90%.24
The Q1 and Q2 included questions about musculoskeletal symptoms assessed by the Nordic Questionnaire,25 the validity and reliability of which have been evaluated previously.26,27⇓ Participants who answered “yes” to the question “Have you during the last year continuously for at least three months had pain and/or stiffness in muscles and joints?” were then asked to indicate on a drawing one or more of the following locations: 1) neck, 2) shoulders, 3) elbows, 4) wrists/hands, 5) chest/abdomen, 6) upper back, 7) low back, 8) hips, 9) knees, and/or 10) ankles/feet. They were also asked to indicate the number of months and years with complaints and number of days with complaints during the last month. Those who reported that they had complaints in the neck or low back for at least 3 months during the last 12 months and ≥15 days with pain during the last month were defined as chronic pain sufferers.
In Q2, the participants were asked whether they during the last 12 months had used analgesics (“painkillers”) daily or almost daily with two answer options: yes or no. Those who answered “yes” were asked to indicate for how many months they had taken analgesics: either prescription or over-the-counter (OTC) drugs. The types of analgesics used were not specified in the questionnaire, but the most commonly used OTC analgesic in Norway is paracetamol.28 The use of analgesics daily or almost daily for ≥1 month during the last 12 months was defined as analgesic overuse. The subjects with chronic pain (migraine, nonmigrainous headache, neck or low-back pain) also reporting daily or almost daily use of analgesics for ≥1 month during the last 12 months were defined as chronic pain sufferers with analgesic overuse.
A total of 51,383 subjects completed the headache questionnaire in Q2 and constituted the Head-HUNT population, of which 51,050 responded to the questions related to musculoskeletal symptoms and 49,064 responded to the question regarding the use of analgesics.
The study was approved by the Regional Committee for Ethics in Medical Research and by the Norwegian Data Inspectorate.
Statistical analysis.
Multivariate analyses, using multiple logistic regression, were corrected for sex, age, and educational level. The reported use of analgesics was used as the explanatory variable, and the odds ratio (OR) was calculated for each diagnostic group. Separate analyses were also performed with regard to the duration of analgesic use during the last 12 months (i.e.,1 to <3, 3 to 6, and >6 months). All analyses were adjusted for coexisting pain (headache, neck or low-back pain). The precision of the OR was assessed with 95% CI. Statistical analyses were performed using the Statistical Package for the Social Sciences (version 8.0; SPSS Inc., Chicago, IL).
Results.
The demographic data for each of the chronic pain groups with or without analgesic overuse are displayed in table 1. The female preponderance was most marked among those with headache, especially among those with migraine, compared with the other groups. Also, there were some differences between the groups regarding mean age and educational level. The statistical analyses were, however, adjusted for these potential confounding factors.
Table 1 Demographic data for the different chronic pain groups (total n = 49,064)
The overall prevalence of chronic headache (chronic migraine and chronic nonmigrainous headache) associated with analgesic overuse was 1% (1.3% for women and 0.7% for men). The prevalence rates for the different age groups are displayed in the figure. The prevalence of chronic headache associated with analgesic overuse duration of ≥3 months was 0.9% (1.2% for women and 0.6% for men), with the same age distribution as for overuse duration of ≥1 month (data not shown).
Figure. The prevalence of chronic headache (i.e., chronic migraine and chronic nonmigrainous headache) associated with daily or almost daily use of analgesics for ≥1 month during the last 12 months in different age groups.
For both sexes combined, chronic headache (chronic migraine and chronic nonmigrainous headache) was more than seven times more likely among those with analgesic overuse (≥1 month) than those without (OR = 7.5, 95% CI: 6.6 to 8.5). For the respective chronic pain subgroups analyzed separately, the association with analgesic overuse was strongest for chronic migraine (OR = 10.3, 95% CI: 8.1 to 13.0), intermediate for chronic nonmigrainous headache (OR = 6.2, 95% CI: 5.3 to 7.2), and weakest for chronic neck (OR = 2.6, 95% CI: 2.3 to 2.9) and chronic low-back (OR = 3.0, 95% CI: 2.7 to 3.3) pain. This pattern was found for both men and women (data not shown).
There was a significant association between chronic pain and the duration of analgesic overuse. As can be seen in table 2, the OR increased with increasing duration of reported use of analgesics, most evident among those with headache, especially those with migraine.
Table 2 Prevalence OR with 95% CI* of chronic pain (≥15 days/month) of either migraine, nonmigrainous headache, or neck or low-back pain related to duration of analgesic use daily or almost daily during the last 12 months
Discussion.
This is the first study reporting the age and gender distribution of chronic headache associated with analgesic overuse in a general population. The overall prevalence of chronic headache associated with analgesic overuse was 1%, which is in accordance with recent population-based studies.6,9,11⇓⇓ The prevalence increased until middle age and declined after that, with a peak at 40 to 49 years of age in women and at 50 to 59 years of age in men.
This study demonstrates a significant association between chronic pain and analgesic overuse. The results confirm previous reports that chronic neck and low-back pain are highly prevalent in the general population,29,30⇓ but they indicate that the association between analgesic overuse and chronic headache is stronger than the association between analgesic overuse and chronic neck or chronic low-back pain. This study also showed that the association between analgesic overuse and headache is stronger for migraine than nonmigrainous headache. Approximately 80% of the subjects with nonmigrainous headache in the current study had tension-type headache,24 and although the association between analgesic use and chronic nonmigrainous headache was weaker than for migraine, it was clearly stronger than for chronic neck or low-back pain. Moreover, the association between chronic pain and the duration of analgesic overuse became stronger with increasing duration of reported use of analgesics. This was most evident among those with headache, especially those with migraine, which may indicate that migraine patients are more prone to develop headache associated with medication overuse.
The causal relationship cannot, however, be addressed in cross-sectional studies. Accordingly, one cannot exclude the possibility that higher intake of analgesics among headache sufferers simply reflects a more severe pain in this group than in those with neck or low-back pain. The greater strengths of the associations, however, especially with respect to the duration of analgesic use, do suggest the possibility that analgesics may play a different role in headache than in other pain disorders. The results are in accordance with our recently published prospective population-based study, which showed that analgesic overuse strongly predicted chronic pain associated with analgesic overuse 11 years later, especially among those with chronic migraine.23 Analgesic overuse may induce alterations in nociceptive neural networks,31 and it has been reported that patients without a previous history of headache taking analgesics on a regular basis for other conditions do not develop chronic headache.32,33⇓
The strengths of this study were the large and unselected population and the use of validated diagnoses, but there are limitations that must be taken into account. Questionnaire-based headache diagnoses are not optimal compared with interview-based diagnoses,24 which may introduce bias caused by misclassification. Most likely, possible differences between migraine and nonmigrainous headache sufferers are underestimated owing to the presence of migraine subjects in the nonmigrainous headache group and vice versa, making the two groups more similar than they may actually be. Misclassification may not be a very large problem, however, because the prevalence of migraine in the current population is consistent with data from other population-based studies in the Western countries.7 It is also well known that headache and musculoskeletal symptoms coexist,34 but the statistical analyses were adjusted for these potential confounding factors. The fact that neither headache, neck and low-back pain, nor analgesic use was the primary objective of the study makes selective participation unlikely.
It must also be pointed out that this study does not provide information about the type of analgesics used or the use of other pain-moderating substances. Potentially, all drugs may lead to MOH,20 but it is well documented that OTC medications are the most common drugs used among headache sufferers.35,36⇓ In a Norwegian study, only a minority of the patients with chronic headache used specific migraine drugs, and most patients used more than one compound.35
The high number of individuals with analgesic overuse has important clinical implications, and physicians should be aware of the potential risk of analgesic overuse among those with chronic pain, especially among those with migraine.23 Information about the hazards of frequent intake of symptomatic medication is important, and prophylactic treatment should possibly be considered at an early stage to prevent an “overuse” pattern and subsequent risk for MOH.
Acknowledgments
The Nord–Trøndelag Health Study (HUNT Study) is a collaboration between the HUNT Research Centre, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Verdal, Norwegian Institute of Public Health, and Nord–Trøndelag County Council. This part of the study (Head-HUNT Study) was also supported by an unconditional grant from GlaxoSmithKline, Norway. J.-A.Z. receives a research grant from the Norwegian Research Council.
- Received June 13, 2003.
- Accepted in final form December 23, 2003.
References
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