Introduction

Migraine is a debilitating and costly chronic illness, the etiology of which is not yet fully known; however, it is understood that it is partly attributable to genetically determined factors that play a relevant role. It is estimated that migraines affect 18% of women and 6% of men¹.

Treatment is based on the control of acute attacks and the prophylactic management of chronic forms. This includes the use of different categories of medication, although it has been demonstrated that not all subjects have the same clinical response to these forms of medication. The general picture is further exacerbated by the need for the frequent use of polytherapy to treat comorbidities, which may interfere with the pharmacologic action of migraine medications, including both symptomatic and preventative treatments. The main objective of personalized medicine is to set optimal therapies in the light of the functional biochemical active substance and of the comorbidities of each individual patient, to obtain the best clinical response. There are now novel therapeutic perspectives that have provided options for managing this pathology; nonetheless, the pharmacologic interactions and their metabolic destiny must always be studied by the application of pharmacogenomics².

In the last decade, migraine research has identified novel pharmacologic targets and therapies that represent great progress3. However, preventive treatments continue to be underused, and this is due to significant factors, including adherence to treatment and patient preferences. Adherence to therapy, though a key factor for successful treatment, is low among patients with chronic conditions such as migraines. Dose frequency plays a major role in adherence, as is having flexible dosing options which allow for greater and better acceptance and adherence to treatment among adults with migraine⁴.

The objective of this study is to find out whether preventive treatments are used by patients with migraine in different countries in Europe, as well as observing the differences according to their social and demographic conditions, as by doing so it will be possible to contemplate more effective and targeted actions based on the results obtained.

Methods

A cross-sectional observational study performed by means of an anonymous web-based multiple-choice questionnaire with 32 questions, not validated, located on the European Migraine and Headache Alliance (EMHA)'s website, and scientifically backed by the Spanish Association of Specialists in Occupational Medicine (AEEMT). 3352 patients participated from Spain, Italy, France, Portugal, Ireland, United Kingdom, Germany, and other European Union (EU) countries which were not included in the initial study design and who responded to it. The inclusion criteria were that the patients must have been previously diagnosed with migraines, be working at the time of the questionnaire, or have been working in the previous year, and the patients had to participate voluntarily. The data were collected from September 2018 to January 2019.

Based on the initial description, the responses corresponding to the management of the migraines were analyzed according to sociodemographic variables: age up to 20 years, between 21 and 40, between 41 and 60, more than 61; gender: man, and woman; place of residence: Spain, Italy, France, Portugal, Ireland, United Kingdom, Germany, and other country in the EU; type of town/city where they live: up to 500 inhabitants, 501-10,000 inhabitants, 10,001-250,000 inhabitants, 250,001-1 million inhabitants, and more than a million inhabitants; level of studies completed: elementary, intermediate, and higher; and environment in which they live: rural (town) and urban (capital).

The options for preventive treatment were defined by question 12 of the survey: i always take preventive treatment, I take seasonal preventive treatment, I always take several preventive treatments, I take several seasonal preventive treatments, I do not take preventive treatments, I do not know what a preventive treatment is.

Bivariate analysis was performed for each of the proposed options, as well as in relation to the different sociodemographic parameters.

Contingency tables were presented, which showed the absolute frequency (n) and the percentage (%) for each cross tab. Depending on the nature of the variables in the survey (categorical variables), the Chi-squared test or Fisher's exact test was used to analyze the possible relationship between the characteristics of the migraine and the sociodemographic variables.

The data for each of the possible answers were analyzed separately.

Results

The sociodemographic characteristics of the population who responded to the survey are shown in table 1 and indicate a heterogeneous distribution by country, and the highest percentage of responses was received from Spain and Germany. About 85.13% of the individuals who filled out the survey were in the middle age block and were predominantly women (90%). The majority of the participants responded that they lived in an urban environment (68.63%), in medium-large sized cities (35% in towns/cities with more than 250,000 inhabitants and 72.5% in towns/cities with more than 10,000 inhabitants), that they were qualified workers (69% with higher studies and 27% with intermediate studies), and that they received moderate support from their environment during the migraine attacks (44.06%).

The overall results for the use of the different preventive treatment options for migraines and their percentual relationship with the different sociodemographic variables that have been studied are shown in table 2.

By differentiating between each of the preventive options in relation with the studied variables and by only taking the statistically significant results into account, we see that.

The use of preventive treatments increases with age in all cases (Table 3), and these treatments are most commonly used in patients over the age of 40 years. Preventive treatments are most commonly used in Spain, Germany, the United Kingdom, Italy, and the rest of the EU countries (p < 0.0001). Out of all of the countries, Spain is the country with the highest use of seasonal preventive medication (Table 4) (p < 0.0001). The use of preventive treatments is lowest in patients under the age of 40 years (p = 0.002) and in female patients (p = 0.028). Spain, Germany, and the rest of the countries in the EU have the highest percentage of patients who do not take preventive treatments (p < 0.0001) (Table 5). Patients under the age of 40 years (p < 0.0001) in Spain, Germany, and the rest of the countries in the EU that were not included in the initial design but who responded to the survey (p < 0.0001) (Table 6) have the greatest lack of knowledge regarding preventive treatment.

Discussion

To be able to evaluate the rates and predictive factors of adequate care for patients with migraines, three essential steps are required: medical consultation, accurate diagnosis, and the minimal necessary pharmacologic treatment (with acute and preventive treatments). Socioeconomic, demographic, and headache-specific variables have a joint influence.

The Chronic Migraine Epidemiology and Outcomes study showed that more than 5% of people with chronic migraines have to traverse these barriers (consultation, diagnosis, and treatment), which represents an unmet need for improving care in this population group. The predictive factors in this professional consultation and in the adequate diagnosis and treatment indicate that the consultation increases with age, more in women, and likewise the need for public health efforts to improve the results obtained in patients with migraine through interventions and educational efforts aimed at improving the consultation rates, diagnostic accuracy, and adherence to minimal symptomatic and/or preventive pharmacologic treatment were indicated⁵.

The results from our survey demonstrated that age does not significantly modify the use of preventive treatments in migraine; nonetheless, statistically significant results were observed in terms of the lack of knowledge about or the non-use of these treatments; likewise, it was observed that younger patients know less about these preventive treatments (especially those patients aged under 20 years) and that it is patients of adult age (between 41 and 60 years) who make the greatest use of said treatments.

Studies show that primary headaches, especially migraines, and tension-type headaches are some of the most frequent conditions at a young age. In the case of these young patients, even before pharmacological treatment, an appropriate lifestyle must be adopted, avoiding triggers, given that the specific and effective pharmacologic treatments for migraines and tension-type headaches are never lacking in side effects, nonetheless, in specific cases their recommended use is scientifically backed, both for specific medications for treating the crisis and the prophylactic pharmacologic therapies when the situation so requires⁶.

Most headaches in young patients can be classified according to the International Classification of Headache Disorders criteria. Migraine is the most frequent diagnosis, and it is commonly associated with a negative impact on the quality of life; however, the majority of young patients receive little preventive treatment before being referred to specialized clinics⁷.

The approach to headaches in young patients is complex; nonetheless, it is one of the most common conditions affecting children, adolescents, and young people in industrialized countries. Although effective pharmacologic treatments without secondary effects are still lacking, over the last few years, several options (Ginkgolide B) have proven to be an effective and well-tolerated preventive treatment for reducing migraine attack frequency and in attenuating the use of symptomatic medication for primary headaches in this group of young patients⁸.

In our survey, no significant results were observed among men and women in the use of preventive therapy, although there seems to be a greater lack of awareness among men. In contrast, the Migraine in America Symptoms and Treatment study carried out in 2016 in the United States evaluated gender differences in sociodemographics and headache features, consultation and diagnosis patterns, and patterns of acute and preventive treatment for migraine. The results showed that men (14.5%) were more likely than women (10.4%) to take daily oral preventive medication (p < 0.001), but that in both, acute prescription and preventive migraine treatments are underused⁹.

In our survey, significant differences in the use of preventive treatments were observed depending on the country. Patients in Spain and Germany demonstrated the greatest lack of knowledge with regard to preventive treatment, and these treatments are least commonly used in Spain and Portugal. Italy, the United Kingdom, and other countries in the EU which were not included in the initial design but who responded to the questionnaire make the greatest use of one or several preventive treatments always. There was no relationship between the size of town/city in terms of the number of inhabitants and the use of preventive treatments. Studies carried out in Spain among neurologists are in line with the majority of the internationally established guidelines where first choice preventive drugs are concerned. This is recorded in the survey which was recently carried out by the Spanish Society of Neurology¹⁰; however, the My Migraine Voice survey published in 2018 demonstrated that in a large proportion of patients with more than four migraine attacks per month, and for whom at least one preventive migraine treatment had failed which had led to resistance to use, future treatments could address existing unmet needs, allowing these individuals with migraine to be able to maximize their contribution to society¹¹.

There are no statistically significant differences in our survey between the cultural level and the use of preventive treatments; however, there are differences in the knowledge of the same, as it is lower in patients with elementary or intermediate levels of studies than in those with higher levels of studies.

With regard to the environment in which they live, our results do not show any relationship between this and the use or knowledge of these preventive treatments; however, prior systematic reviews of the global prevalence of migraine at the community level (302 studies which included 6,216,995 participants) showed that migraine affects one in ten people worldwide, with higher prevalence among women, among young people, and among urban residents in comparison with those living in a rural environments (11.2% among urban residents and 8.4% among rural residents)¹².

The results of our survey confirm the scarce use and knowledge of preventive treatments in migraine as confirmed by prior studies despite the scientific evidence that supports their use adjusted to international criteria. The American Academy of Neurology and the Canadian Headache Society have published evidence-based guidelines for preventive pharmacologic treatments for migraines that provide valuable guidance for clinicians; however, these pharmacologic therapies continue to be underused in clinical practice. The primary objective of these guidelines is to assist the practitioner in choosing an appropriate prophylactic medication for a person with migraine, based on current evidence in the medical literature and expert consensus. These guidelines are focused on patients with episodic migraine (headache on ≤ 14 days a month) and there is good evidence from randomized controlled trials for the use of a number of different prophylactic medications in patients with migraines.

Medication choice for an individual patient requires careful consideration of patient clinical features¹³.

The principles of preventive treatment are important to improve compliance, minimize side effects, and improve patient outcomes. The choice of treatment should be based on the presence of comorbid and coexistent illness, patient preference, reproductive potential, and best available evidence¹⁴. The route of administration and preventive treatment-related adverse events has an impact on patient preference and their adherence to treatment¹⁵,¹⁶. Current treatment options for migraine prophylaxis are associated with poor tolerability and low adhesion and persistence, with an irregular course, frequent gaps, and discontinued prophylaxis by the end of the 1^st year¹⁷. Persistence to oral preventive treatments is poor at 6 months and declines further by 12 months. Switching between treatments is common, but persistence worsens as patients cycle through various preventive treatments¹⁸.

Scientific evidence supports the fact that preventive treatment is an important part of migraine therapy. When prescribing medications, physicians should understand patient's preferences and select drugs that most closely meet their needs. Understanding the factors that influence these preferences increases physicians' ability to select appropriate migraine therapy. The results of patient surveys indicate that patients rated efficacy as the most important aspect of preventive therapy of migraine¹⁹. In addition to the functional impact of migraine, the decision to start prophylaxis is based on a complex of considerations from the patient's perspective (e.g., perceived burden of migraine, expected benefits or disadvantages, interaction with relatives, colleagues, and physician), therefore, when advising migraine patients about prophylaxis, their opinions should be taken into account. Patients need to be open to advice and information and intervention have to be offered at an appropriate moment in the course of migraine²⁰.

The biases of this study include the use of a non-validated survey, the subjectivity of the responses, the greater participation by women, the non-uniform distribution of participants by countries, with greater participation from Spain and Germany, and the inclusion of respondent patients from countries that were not contemplated in the initial design.

The sample size and the comparative study by European countries are considered the strengths of this study, as well as the social and demographic variables that have been incorporated.

Conclusions

The use of preventive treatments increases with age, and the use of these treatments is greater in patients over the age of 40 years. The greatest lack of knowledge was observed among patients under the age of 40 years.

No relationship has been observed between the use of preventive treatments in migraine and the size of their place of residence or whether they live in a rural or urban area.

Knowledge of preventive treatments is lower in individuals with elementary or intermediate studies than in those with higher studies.

The greatest use of regular preventive treatments is in Spain, Germany, the United Kingdom, and Italy.

Spain and Germany have the greatest percentage of patients who do not take treatment or who do not know about preventive treatments.

The use of preventive pharmacologic therapies in migraine remains low despite the fact that it is scientifically backed.

It is important to further develop the training of physicians and reinforce patient information, assessing patient preferences to improve their adherence to treatment.