Abstract
The authors followed 532 consecutive patients with episodic migraine (<15 days/month) for 1 year. Sixty-four patients (14%) developed chronic headache (≥15 days/month). The odds ratios for developing CH were 20.1 (95% CI 5.7 to 71.5) comparing patients with a “critical” (10 to 14 days/month) vs “low” (0 to 4 days/month) and 6.2 (95% CI 1.7 to 26.6) in patients with an “intermediate” (6 to 9 days/month) vs “low” headache frequency and 19.4 (95% CI 8.7 to 43.2) comparing patients with and without medication overuse.
Chronic daily headache (CDH) is defined as headache occurring ≥15 days/month.1 Transformed migraine is the most frequent and important part of CDH. Population-based studies suggest that up to 2.4% of the general population experience transformed migraine and that 30 to 50% of those overuse headache medication.2,3⇓ Prospective investigations on factors leading to headache chronicity are lacking.
We sought to assess the incidence and to identify risk factors of headache chronicity in patients with episodic migraine.
Methods.
The study was approved by the Ethics Committee of the University of Essen, Germany. Written informed consent was obtained from all patients.
Five hundred thirty-two consecutive patients with episodic migraine (<15 days/month)4 were studied. Symptomatic headaches were excluded by clinical examination, Doppler/duplex sonography, and cranial CT/MRI.
Baseline.
We collected information on age, gender, and headache type. Data on headache frequency, type, and frequency of acute headache drug use were collected from headache diaries. Patients without clear documentation were asked to complete the headache diaries for at least 1 month. Patients with a current headache frequency of ≥15 days/month, history of chronic headache, or major depression were excluded.
According to previous results,5 we defined overuse of headache medication as intake of any kind of acute headache medication on >10 days/month.
Follow-up.
A headache specialist performed a standard telephone follow-up interview 1 year after the initial patient assessment. Data on headache frequency (days/month) and intake of acute or preventive headache medication in the last 3 months were collected. Primary study endpoint was headache chronicity defined as headache frequency of ≥15 days/month for at least 3 months.
Statistical analysis.
We compared responders and nonresponders with the follow-up using the Student t-test for continuous and χ-quadrate test for categorical variables. We used logistic regression to assess the impact of potential risk factors of headache chronicity. We considered baseline characteristics including age (quartiles: <34, 34 to 41, 42 to 51, >51 years), gender, headache type (migraine vs combination of migraine and tension-type headache), headache frequency (“low” 0 to 4, “intermediate” 5 to 9, and “critical” 10 to 14 days/month), duration of primary headache (tertiles: <14, 14 to 22, >22 years), type of acute headache drug (none, analgesics, ergots, triptans, opioids), intake of one vs two or more different acute headache drugs, overuse of acute headache medication, and regular intake (vs no intake) of preventive medication as potential risk factors for chronicity of headache. We calculated crude and multivariable-adjusted odds ratios and their corresponding 95% CI. We used a stepwise selection procedure to identify the most important multivariable adjusted risk factors for chronicity of headache using a p value of ≤0.02 as inclusion or exclusion criteria. We tested the fit of the final model using the Hosmer-Lemeshow goodness-of-fit test.6 We evaluated the predictive ability of the model by determining the area under the receiver operating characteristic (ROC) curve.6 All analyses were performed using SAS (version 8.2; SAS Institute, Cary, NC).
Results.
Follow-up was successfully performed in 450 patients. Seventy-one patients (13%) were lost to follow-up, and 11 patients (2%) refused the follow-up interview. Baseline demographics and clinical characteristics of patients with follow-up did not differ from those without follow-up (table 1).
Table 1 Demographics and clinical features of patients with and without follow-up
Baseline data.
Of the 450 patients, 376 (84%) were women, with average age of 42 ± 12 years. Three hundred ninety-seven (88%) patients had migraine, and 53 (12%) patients had a combination of migraine and tension-type headache. Mean duration of primary headache was 19 ± 11 years. Mean headache frequency was 7 ± 4 days/month. One hundred sixty-one patients (36%) had “low” headache frequency, 166 (37%) “intermediate,” and 123 (27%) “critical” headache frequency. Two hundred forty (53%) patients used analgesics, 154 (34%) triptans, 14 (3%) ergots, 5 (1%) opioids, and 37 patients (8%) did not use any acute headache medication at all. Two hundred eighteen patients (48%) used one headache drug and 232 (52%) two or more drugs. Forty-four patients (10%) overused headache medication.
Follow-up data.
Sixty-four patients (14%) developed chronicity of headache. Fifty of them (78%) had daily migraine, and 14 patients (22%) developed tension-type headache in addition to their initial headache.
Table 2 summarizes the univariate risk factors for the chronicity of headache. The stepwise selection procedures identified three main risk factors for chronicity of headache: “intermediate” and “critical” headache frequencies and medication overuse. All other evaluated variables were not included in the final models (table 3). There was no significant effect modification of medication overuse by headache frequency, which may have been due to small sample size. Use of a backward elimination procedure yielded the same final model. The goodness of fit test (p = 0.56) indicated that the final model statistically fitted reasonably well. The area under the ROC curve was 0.85, which is considered as excellent discrimination of the final model.
Table 2 Univariate risk factors for headache chronicity in patients with episodic migraine
Table 3 Multivariable* risk factors for headache chronicity in patients with episodic migraine
Discussion.
Sixty-four (14%) of 450 patients developed headache chronicity during 1 year. We identified “intermediate” and “critical” headache frequencies and medication overuse as risk factors of headache chronicity.
It has been shown that medication overuse coexists in the majority of patients with chronic headache2,3,7⇓⇓ and that patients improve after withdrawal from the overused headache medication.8 This suggests a causal relationship between the medication overuse and chronicity of headache. Our study is in line with these findings showing that patients who overused their headache medication had a high risk of developing chronicity of headache. One-third of patients, however, developed chronic headache without medication overuse, suggesting that medication overuse is an important but not the only factor determining chronicity of headache.
Recently, we were able to show that patients who overused triptans developed headache chronicity faster and that they used fewer single dosages than patients who overused ergots or analgesics.5 In this study, we could not find any differences with regard to the type of drugs used, suggesting that usage of triptans per se does not necessarily bear a risk for chronicity of headache. This finding is, however, limited because of the relatively small sample size.
Another association was found between the initially high headache frequency and headache chronicity. Patients with an “intermediate” headache frequency had an increased risk for headache chronicity, which was further increased in patients with the “critical” frequency. The high headache frequency, however, should not be considered as a causal risk factor. The chronicity of headache could be a consequence of medication overuse or reflect a natural migraine fluctuation.
The regular intake of preventive medication was a univariate predictor for headache chronicity. One explanation for this unexpected finding might be that patients with high headache frequency received preventive headache medication much more frequently than patients with lower headache frequency. Therefore, the relationship between the regular intake of preventive medication and chronicity of headache might have been confounded by the indication of taking preventive drugs. However, inclusion of “preventive medication” into the final multivariable model did not add to the overall prediction of headache chronicity.
Our study has several strengths, including diagnosis of headache by an experienced headache specialist, standardized data collection, and a good response rate for the follow-up interviews. We used stringent inclusion and exclusion criteria for variable selection of the multivariable models, aiming to reduce model overfitting.
Several limitations must be considered. The follow-up data reflected the last 3 months and did not cover the time period of the first 9 months of follow-up. We studied a patient population from a specialized headache center, and therefore we cannot necessarily extend these results to other populations. This could also explain the relatively high 14% 1-year cumulative incidence of headache chronicity. We could not control for psychological factors, which might play a role in the development of headache chronicity.9,10⇓ Our study was not large enough to use data splitting to validate our model. Future population-based studies must determine whether the three predictors identified in our study can be generalized to other populations and whether additional factors can be identified.
Acknowledgments
Supported by the Federal Ministry of Education and Research (BMBF), Germany.
- Received July 15, 2003.
- Accepted October 6, 2003.
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