Analgesic Use:
A Predictor of Chronic Pain
and Medication Overuse Headache

This section is compiled by Frank M. Painter, D.C.
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FROM:   Neurology 2003 (Jul 22); 61 (2): 160–164 ~ FULL TEXT

J.A. Zwart, MD, PhD; G. Dyb, MD; K. Hagen, MD, PhD;
S. Svebak, PhD; and J. Holmen, MD, PhD

Department of Clinical Neuroscience,
Faculty of Medicine,
Norwegian University of Science and Technology,

OBJECTIVE:   To examine the relation between analgesic use at baseline and the subsequent risk of chronic pain (> or =15 days/month) and the risk of analgesic overuse.

METHODS:   In total, 32, 067 adults reported the use of analgesics in 1984 to 1986 and at follow-up 11 years later (1995 to 1997). The risk ratios (RR) of chronic pain and RR of analgesic overuse in the different diagnostic groups (i.e., migraine, nonmigrainous headache, neck pain, and low-back pain) were estimated in relation to analgesic consumption at baseline.

RESULTS:   Individuals who reported use of analgesics daily or weekly at baseline showed significant increased risk for having chronic pain at follow-up. The risk was most evident for chronic migraine (RR = 13.3, 95% CI: 9.3 to 19.1), intermediate for chronic nonmigrainous headaches (RR = 6.2, 95% CI: 5.0 to 7.7), and lowest for chronic neck (RR = 2.4, 95% CI: 2.0 to 2.8) or chronic low-back (RR = 2.3, 95% CI: 2.0 to 2.8) pain. Among subjects with chronic pain associated with analgesic overuse, the RR was 37.6 (95% CI: 21.3 to 66.4) for chronic migraine, 14.4 (95% CI: 10.4 to 19.9) for chronic nonmigrainous headaches, 7.1 for chronic neck pain (95% CI: 5.5 to 9.2), and 6.4 for chronic low-back pain (95% CI: 4.9 to 8.4). The RR for chronic headache (migraine and nonmigrainous headache combined) associated with analgesic overuse was 19.6 (95% CI: 14.8 to 25.9) compared with 3.1 (95% CI: 2.4 to 4.2) for those without overuse.

CONCLUSION:   Overuse of analgesics strongly predicts chronic pain and chronic pain associated with analgesic overuse 11 years later, especially among those with chronic migraine.

From the FULL TEXT Article:


Chronic headache (headache 15 days/month) associated with medication overuse is commonly seen in clinic-based populations, [1] and the majority of the patients presenting with primary chronic daily headache use analgesics on a daily or near-daily basis. [2–4] Potentially all analgesic drugs, including specific migraine drugs, may lead to medication overuse headache (MOH). [5] A survey among family doctors in the USA reported MOH as the third most common cause of headache. [6] In cross-sectional population-based studies, the prevalence of MOH is estimated at 1 to 2%. [7–10]

Although cross-sectional epidemiologic data provide prevalence estimates and associations, factors that might influence headache prognosis must be evaluated in longitudinal prospective study designs. To our knowledge, only two population-based follow-up studies have evaluated headache risk among chronic headache sufferers, indicating that continuation of analgesic overuse might be a significant predictor of persistent chronic daily headache. [8, 12] Large prospective population-based studies assessing the association between analgesic overuse and the subsequent risk of chronic pain and MOH have not yet been published.

The main purpose of the current prospective population-based study was to examine the relationship between analgesic overuse reported in 1984 to 1986 and the risk for having chronic headache (migraine and nonmigrainous headache) and chronic headache associated with analgesic overuse at follow-up 11 years later (1995 to 1997). In addition, for comparison, this relationship was also examined for other common chronic pain conditions like chronic neck and chronic low-back pain.


This study demonstrates that there was a significantly increased risk of having chronic pain and especially chronic pain associated with analgesic overuse among those who reported daily or weekly use of analgesics 11 years prior to endpoint registration. The risk for chronic headache associated with medication overuse was more than six times higher than the risk for chronic headache without medication overuse. These results are in accordance with two population-based follow-up studies, reporting that analgesic overuse predicted the persistence of chronic daily headache. [8, 10]

Patients with MOH usually have a history of episodic migraine that has been transformed into chronic headache as a result of medication overuse. [20] Patients with tension-type headache may also overuse medication, but this headache type is a less frequent cause of MOH than migraine. [21] It is not unlikely that other factors may contribute to the development of chronic tension-type headache [22] and that the drug use is associated rather than the cause. Approximately 80% of the subjects with nonmigrainous headache in the current study had tension-type headache, [17] and although the RR for chronic nonmigrainous headache associated with analgesic overuse was significantly less than that for chronic migraine, it was significantly higher than the RR for chronic neck or chronic low-back pain. The co-occurrence of headache and musculoskeletal symptoms may partly explain the increased RR for neck and low-back pain. [23] There was a reduction of the RR for neck pain associated with analgesic overuse from 7.1 to 4.9 (95% CI: 3.8 to 6.3) when the analyses were adjusted for coexisting headache. The RR reduction was not that marked for lowback pain, that is, from 6.4 to 5.1 (95% CI: 3.8 to 6.7), which corresponds with our previous findings that headache is more strongly associated with neck than low-back pain. [23] The increased RR for analgesic overuse at follow-up among subjects with chronic neck and chronic low-back pain may reflect a sustained need for pain-relieving medication due to the degenerative nature of these disorders. Another plausible explanation is that analgesic overuse may induce alterations in nociceptive neural networks, which also would apply for those with chronic headache. [24] There are both supportive arguments and arguments against a causal relationship between analgesic overuse and chronic headache. [25] The substantial increase in RR among those with chronic headache compared with those with chronic neck or chronic low-back pain indicates, however, that headache patients are more prone to develop analgesic overuse, especially those with migraine. It seems that patients without a history of headache taking analgesics on a regular basis for other conditions do not develop chronic daily headache. [26]

The strengths of this study were the large and unselected population, the long follow-up period (11 years), and the use of validated endpoint registrations. When interpreting the results of the current study, several limitations must, however, be taken into account. The questionnaire-based headache diagnoses were not optimal compared with the interview diagnoses. [17] The bias caused by misclassification can either exaggerate or underestimate the true difference between headache groups. Most likely, the difference between migraine and nonmigrainous headache sufferers is underestimated owing to the presence of migraine subjects in the nonmigrainous headache group and vice versa, making the two groups more similar than they really are. The impact of nonparticipants has been discussed in more detail previously, [12] and the fact that neither headache nor analgesic use was the primary objective of the study makes selective participation unlikely. In addition, the prevalence of migraine in the current population is consistent with data from other population-based studies in the Western countries. [12]

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 at baseline. It is well documented, however, that over-the-counter medications are the most commonly used drugs among headache sufferers. [27] This has also been found in a Norwegian study, where only a minority of the patients with chronic headache used specific migraine drugs. [28] The reported drugs leading to MOH vary considerably between different studies, and it is often difficult to identify one single substance because most patients use more than one compound. [28] Furthermore, the mean critical duration until onset of MOH and the duration of withdrawal headache after overuse vary: shortest for triptans, intermediate for ergot alkaloids, and longest for analgesics. [5, 29] Another aspect is the exposure assessment, where, because of statistical considerations, patients in HUNT-1 reporting weekly use of analgesics were combined with daily users. In addition, patients in HUNT-2 that reported not using analgesics daily or almost daily may have been using analgesics occasionally. These factors could have resulted in an underestimation of the RR observed.

In the current study, the headache status at the time of analgesic use registration was unknown, and so was the reason why the subjects used analgesics. It is likely, however, that most people used analgesics owing to headache at baseline. In a population-based study in Tromsø, Norway, in 1986 to 1987, 19,137 individuals were asked about their use of analgesics. On average, 28% of the women and 13% of the men had used analgesics the preceding 14 days. The most significant predictor was headache, which was far more common than other types of physical distress such as neckache, backache, and infections. [30] Finally, it is not known whether these individuals continued their analgesic consumption during the 11–year follow-up period. Most people, however, experience their onset of headaches during early adulthood, and among those with neck or lowback pain in the current study, the mean duration of pain was 11 and 13 years. If individuals reduced or increased their use of analgesics after baseline, this would result in an underestimation rather than an overestimation of the relationship. Thus, it seems reasonable to assume that the results from this study do reflect a true relation between analgesic overuse and subsequent pain.


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