The role of personality, disability and physical activity in the development of medication-overuse headache: a prospective observational study

DOI: https://doi.org/10.1186/s10194- 018- 0863- 1

Abstract-Summary Factors associated with development of medication-overuse headache (MOH) in migraine patients are not fully understood, but with respect to prevention, the ability to predict the onset of MOH is clinically important.

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The aims were to examine if personality characteristics, disability and physical activity level are associated with the onset of MOH in a group of migraine patients and explore to which extend these factors combined can predict the onset of MOH. Migraine disability score (OR=1.02, 95 % CI: 1.00 to 1.04), intensity of head- ache (OR=1.49, 95 % CI: 1.03 to 2.15) and headache frequency (OR=1.02, 95 % CI: 1.00 to 1.04) were associated with the onset of MOH adjusting for age and gender.

To identify which of the variables predict onset MOH, we used a LASSO regres- sion model, and evaluating the predictive performance of the LASSO-mode (con- taining the predictors MIDAS score, MIDAS-intensity and –frequency, neuroticism score, time with moderate physical activity, educational level, hours of sleep daily and number of contacts to the headache clinic) in terms of area under the curve (AUC) was weak (apparent AUC=0.62, 95% CI: 0.41-0.82).

Disability, headache intensity and frequency were associated with the onset of

MOH whereas personality and the level of physical activity were not.

The multivariable LASSO model based on personality, disability and physical activity is applicable despite moderate study size, however it can be considered as a weak classifier for discriminating between absence and presence of MOH.

Background Migraine is the primary headache for many MOH patients, however, not all migraine patients develop MOH.

The psychological profile of migraine patients developing MOH is not fully understood, but the association between migraine and personality has been a topic of interest for many years [540, 541].

A population-based study investigating risk factors for a new onset of MOH in chronic headache patients found that physical inactivity and smoking were risk fac- tors for developing MOH [512].

The aims of this study were firstly to investigate if personality, disability and physical activity level of migraine patients are associated with the development of MOH in a group of migraine patients who are in active treatment and secondly, to analyze to which extend these factors together can predict the onset of MOH.

We hypothesized that personality, disability and level of physical activity varied

between migraine patients (+MOH) and migraine patients (−MOH). Methods The design was a single-center prospective observational study of patients in active treatment recruited from the multidisciplinary Danish Headache Clinic, Hospital of Southwest Jutland in Denmark, between October 2015 and June 2017.

All patients received standard treatment at the Headache Clinic, which included

consultations with a neurologists or headache nurse every three months.

As standard, patients were informed about the risk and criteria for MOH at the

initial consultation.

Patients were informed about the study by the neurologists at the consultations

in the Headache Clinic.

3.5 Medication Overuse and Addiction

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Number of consultations in the clinic and years diagnosed with migraine varied,

however all included patients were seen regularly in the clinic.

Throughout the study period, patients’ were followed regularly in the Headache clinic and during these consultations patients’ self-reported headache diaries together with the physician’s examination and assessment formed the basis of a confirmed diagnosis.

Measurements To quantify the extent of disability, the MIDAS questionnaire was used, which is one of the most frequently used measures to assess disability in migraine patients [91, 542, 543].

MIDAS consists of two additional questions on number of days with headache during the previous three months and intensity of headache measured on a numeric rating scale ranging from 0-10 where 0 is “no pain” and 10 is “worst imagin- able pain”.

To measure physical activity level, the questionnaire Physical Activity Scale 2.1

(PAS 2.1) was used [544].

In PAS 2.1, the patients were asked to specify number of hours and minutes in an average 24-hour day spent on physical activity categorized as i) sleeping, ii) work related sitting/standing/walking and heavy physical work, iii) transportation to or from work (walking/cycling to work), and iv) sedentary leisure time activities (e.g. TV-viewing).

Statistical Analyses Each of the following variables were tested in a separate regression model: Unemployment, neuroticism, extraversion, openness, agreeableness, conscientious- ness, MIDAS score, MIDAS-intensity and MIDAS-frequency, and physical activity level divided into hours weekly on light, moderate or vigorous activity.

The following predictors were included: age, gender, civil status, educational level, primary diagnosis, contacts to the headache clinic, the five NEO-FFI-3 domains as separate variables, disability using MIDAS score, intensity and fre- quency, measurements from PAS 2.1 on times spent for sleeping, sedentary leisure time activities and times for light activities, moderate activities or vigorous activi- ties and a binary variable indicating if patients were unemployed.

We used the statistics software R (version 3.3.2) together with the packages glm- net version 2.0-10 [545], ROCR version 1.0-7 [546], pROC version 1.10.0 [547] and caret version 6.0-76 [548] to carry out the LASSO logistic regression model, calculate the AUC and its confidence intervals and to plot the ROC curve.

Results The migraine (+MOH) group had a significantly higher numbers of contacts to the Headache Clinic during the study period; median (IQR) contacts 8.5 (4 to 10) as compared to the migraine (-MOH) group with median (IQR) contacts 6 (3 to 7) (p= 0.028).

Migraine (+MOH) had significantly higher headache intensity median (IQR) 7(6.5-8) as compared to the migraine (-MOH) group with median (IQR) of 6 (5-7), (p=0.041).

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Given the fact that the corrected AUC is 0.62 (95% CI: 0.41-0.82), our model (containing the predictors MIDAS score, MIDAS-intensity and –frequency, neu- roticism score, time with moderate physical activity, educational level, hours of sleep daily and number of contacts to the headache clinic)) the model can be con- sidered as an weak classifier for discriminating between absence and pres- ence of MOH.

Discussion The main findings of the present study were that the logistic regressions indicated that the headache intensity and headache frequency were associated with onset of MOH and therefore could be factors to take into account to prevent the develop- ment of MOH.

Both patients with migraine (-MOH) and migraine (+MOH) spent very few hours on physical activities per week, which probably could be caused by head- ache burden.

It is challenging, but clinically relevant, to identify patients at risk of developing MOH and therefore studies developing predictive models of headache chronifica- tion are important [549].

Our findings substantiates that multiple factors potentially contributes to the onset of MOH, which is in line with another similar predictive study [550] were they found an AUC of 0.76 when including factors of personality, gene polymor- phisms, headache characteristics and lifestyle.

This study indicates how many migraine patients developed MOH during treat-

ment at a headache clinic.

Conclusion Our findings support that focus on headache frequency and intensity is essential for targeting a subgroup of migraine patients at risk of developing MOH.

Acknowledgement A machine generated summary based on the work of Mose, Louise S.; Pedersen, Susanne S.; Debrabant, Birgit; Jensen, Rigmor H.; Gram, Bibi. 2018 in The Journal of Headache and Pain.

Chronic Migraine with Medication Overuse: Clinical Pattern and Evolution from a Retrospective Cohort in Seville, Spain