Introduction
Worldwide, migraine is the second most disabling disorder [
1]. Additionally, in the age group 15–49 years, migraine is the top cause of years lived with disability [
1], magnifying its impact on the working population [
1]. On average eighteen days per year per migraine patient are missed from work or household activities. Mean annual costs per-person are €1222 for migraine, which leads to high costs for society [
2].
The use of a prophylactic treatment is recommended if headache is present more than 8 days per month, disability is present despite acute medication, headache is present more than three days per month when acute medication is not effective [
3‐
6]. These prophylactic drugs, however, might not be tolerated that well by patients or patients might request non-pharmacological alternatives [
4,
7,
8]. In migraine, other non-drug related prophylactic treatments like self-management strategies, manual therapy and aerobic exercise are also being employed [
9‐
14]. In aerobic exercise, a moderate intensity training is performed over a longer period of time, e.g. 30 min.
The rationale for using aerobic exercise in migraine is based on the fact that exercise can play a substantial role in the modulation of pain processing [
15‐
18]. Moreover, the analgesic effects of both short-term [
16] and long-term [
15,
18] aerobic exercise have been observed at both a central and peripheral level [
15,
16,
18].
In 2008, the first narrative review on the effect of aerobic exercise in the treatment of migraine showed promising, though inconclusive results [
19]. During the past decade, new studies on the use of exercise as a prophylactic treatment in migraine have been published. The updated version of the International Classification of Headache Disorders (ICHD-III) [
20] specifically indicates there is a need for a thorough and systematic overview regarding the effects of aerobic exercise in migraine.
Therefore, the aim of the present study is to summarize the literature published after 2004 on the effectiveness of aerobic exercise in migraine. The research question of this systematic review is: what is the effect of aerobic exercise on the number of migraine days, duration and pain intensity in patients with migraine?
Discussion
The aim of this systematic review was to explore the effect of aerobic exercise in patients with migraine on the number of migraine days, attack duration and pain intensity. Moderate quality evidence indicates that in patients with migraine aerobic exercise therapy decreases the number of migraine days. Low quality evidence indicates that aerobic exercise can decrease pain intensity or duration of migraine attacks. To our knowledge, the only other existing review on this topic was published in 2008 [
19]. However, Busch et al. [
19] acknowledged themselves that none of the included studies in this narrative review met valid criteria of good clinical practice. Therefore, a systematic review was conducted to explore the effects of aerobic exercise using higher quality studies.
Five RCTs [
24,
26‐
29] and one CCT [
25] published after 2004, reporting on the effect of aerobic exercise in patients with migraine, were included in this review. The risk of bias of the included trials was low to moderate with a high risk of performance and detection bias due to a lack of blinding of participants, personnel and outcome assessors.
Based on our meta-analysis, there is moderate evidence that aerobic exercise can lead to a decrease of 0.6 migraine days per month. The clinical relevance of this finding is low. However, it may be of interest if it is added to the value of current usual care. Furthermore, higher training intensities might provide interesting results as the training intensity in the included studies was low. This finding is in line with the findings of Busch et al. [
19], who found a decrease of 3.7 migraine days per month. However, this result is based on a single report. In their review two RCTs [
32,
33] and six single cohort studies [
34‐
38] were included. However, as mentioned above none of those studies met valid criteria of good clinical practice [
19]. In 2015, Luedtke et al. [
39] evaluated interventions used by physiotherapists for patients with headache, such as aerobic exercise. Based on six studies, of which the data of one study was not estimable, their meta-analysis indicated a reduction of 2.99 days with migraine, although not significant (
p = 0.23). In contrast, pooling of data from one CCT [
25] and three RCTs [
26,
28,
29] in this review shows a significant reduction of migraine days per month. We obtained the mean reduction by using the difference between pre- and post-intervention data. Additionally, all studies provided a long-term exercise protocol for at least ten weeks. This can explain the difference between our results and those in the systematic review of Luedtke et al. [
39].
Interestingly, we found that topiramate and tricyclic antidepressants show similar results compared to aerobic exercise in decreasing the number of migraine days per month [
28]. Aerobic exercise appears to be a valuable alternative, taking into account that side effects are common with a pharmacological treatment, such as weight changes, memory loss and fatigue [
3,
40,
41].
Regarding duration of migraine attacks small to moderate reductions (20–27%) were reported [
25,
27,
29], such as a reduction of 20 migraine hours post-treatment in one study [
29]. This result is similar to the conclusions of Busch et al. [
19]. Due to the heterogeneity of the units of the outcome measurement, interpreting raw data was difficult.
The results of the present review suggest that aerobic exercise can reduce pain intensity (20–54%) in patients with migraine [
25,
27,
29], confirming the findings of Busch et al. [
19]. The analgesic effects on central and peripheral levels have already been reported [
15,
16,
18] but the heterogeneity of the units of the outcome measurement might have biased the results.
Additionally, there is low quality evidence that patients use less analgesic medication as an effect of aerobic exercise [
28]. These results contradict the findings of Busch et al. [
19], who concluded that analgesic medication intake was not altered by aerobic exercise.
Our review shows low quality evidence for greater treatment effects by combining aerobic exercise with amitriptyline [
27].
While our review focuses on the influence of aerobic exercise on clinical parameters of migraine, its underlying mechanisms were beyond the scope of our review. Other reviews provide some hypotheses regarding these mechanisms [
9,
11,
42,
43].
This review’s patient population consisted of 88% females and 12% males. This is an expected distribution, as a 3:1 female:male ratio is reported in other epidemiologic studies [
44]. In the current review, the inclusion criteria were: patients with migraine with and without aura according to the ICHD-II. A similar diagnosis is a major strength of this review as it ensures a homogeneous group and allows pooling of data. Additionally, in all studies patients with and without aura were included. Therefore, patients can easily be compared between studies. However, the control groups consisted of usual care treatments (topiramate and amitriptyline) [
27,
28], alternative treatments (relaxation, maintain daily physical activity and migraine education) [
24,
26,
28,
29] and no treatment [
25]. This may have influenced the comparability, since there might be differences between control groups that received treatment (active controls) and control groups that received no treatment at all (passive controls). Interestingly, no significant difference is found if active controls are compared to aerobic exercise (topiramate, relaxation, migraine education and maintaining habitual function with standard physical activity recommendations) [
24,
26,
28]. One can state that these active groups are equally effective compared to aerobic exercise. Significant treatment effects are found, when comparing aerobic exercise with no treatment or maintaining habitual function [
25,
29].
Dropout rate in total was high in four of the included studies, respectively 28% [
29], 33% [
24] and 50% [
25,
28]. The most important reason for withdrawal of participants was lack of time to get to and attend three supervised exercise training sessions per week. Since stress is an important trigger for migraine attacks, Varkey et al. [
45] suggested home-based training programs to improve compliance and to reduce stress levels [
46]. On the other hand, home-based training might be less therapy compliant, which could lead to false interpretation. Positive findings have been suggested for supervised home-based programs [
19,
35,
45], although these last two showed a high risk of bias due to the lack of a control group and subjective endpoints.
Our review population is mainly comprised of untrained patients with migraine. This selection of subjects might have biased the results as this does not necessarily represent a typical migraine population [
19]. A moderate intensity level training was chosen to avoid exercise-induced migraine and other negative side effects [
28,
29]. Aerobic training was recommended by the American College of Sport Medicine (ACSM) [
47] as training 3–5 days a week, 20–60 min, with an intensity of 55/65–90% of maximum heart rate. In this review patients exercised according to the ACSM recommendations of aerobic training for a period of 10 weeks or more with moderate intensity [
47]. Positive findings were measured in the intervention group and no negative side effects were registered in any of the trials. Larger exercise volumes, such as high-intensity training or higher exercise duration, seem to be related to larger reductions in the number of migraine days in the intervention group [
25,
26,
29].
Recommendations for further research
Major gaps exist in the current knowledge on the effect of aerobic exercise on patients with migraine. Further research to study the effects reported in this systematic review are mandatory to unravel the mechanisms of physical training on migraine [
11,
42]. We recommend that future studies use uniform outcome measures of headache characteristics as recommended by the International Headache Society [
48], use blinded assessors, provide homogeneous patient samples, design randomized controlled trials comparing aerobic training in patients with migraine with and without supervision to explore the difference between both protocol types, investigate the effect of larger exercise volumes as an intervention protocol and finally investigate the combined effect of pharmacological treatment and aerobic exercise in comparison to a pharmacological treatment alone.