Migraine cure: a patients' perspective

Objective To conduct a web-based survey concerning patient’s perspective in the migraine cure. Material and Methods A total of 1,102 patients fitting the International Classification of Headache Disorders (ICHD3) migraine criteria, seeking medical care at the Brain Research Institute at Albert Einstein Hospital in Sao Paulo, Brazil, from January to December 2015, participated in the survey. The online-based survey was accessed via the institute’s website and consisted of demographic data, a description of migraine symptoms, diagnosis and treatment, and the patient’s opinion of migraine cure and which treatment they would consider taking. Results Migraine intensity was significantly higher in female participants than male participants. Chronic migraine tended to affect female participants more than male participants. There was a significant difference in the rate of migraine cure belief between patients with episodic and chronic migraine. Conclusion Some points that were important to migraineurs have been identified in this study. Ultimately, the findings of this study may facilitate the migraine treatment decision process, by providing a better understanding of patients’ perspectives and beliefs, thus creating a more friendly communication between migraineurs and care providers and hopefully, improving the quality of life of patients. Mario F. P. Peres, MD, PhD E-mail: mario.peres@hc.fm.usp.br Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil Edited by: Marcelo Moraes Valença


Introduction
M igraine is a common primary, but not exclusively, headache disorder characterised by recurrent episodes of headache, often associated with nausea, vomiting, photophobia, and phonophobia. Although headache is the primary requirement for the diagnosis in many classifications, the manifestations of migraine may not include headache. 1 Global migraine prevalence is reported to be around 11.5% with variation between countries, sexes and socio-economic status. 2 A recently published report provided updates on the prevalence of migraine and severe headache in the United States. It has been reported that prevalence estimates have remained remarkably stable for many years, but migraine continues to be a common, disabling medical condition that affects almost one in six Americans. 3 Alone, migraine is the sixth leading cause of disability of any condition, and is the leading cause of neurological disability globally. In Brazil, the 1-year prevalence of migraine is 15.2% and migraine is a leading cause of disability in terms of days lost from work, school or domestic activities. 4 The management of migraine includes both acute medications and prophylactic treatment. 5 Because migraine can be observed as a progressive or pervasive disorder, the prophylactic treatment may slow or prevent such progression 6,7 . Prophylactic treatments may include medications such as topiramate 8 , gabapentin 9 , tizanidine 10 , fluoxetine 11 , amitriptyline 6 , and valproate 12 or local injections of botulinum neurotoxin 13 .
For acute treatment, options included analgesics such as acetylsalicylic acid and acetaminophen (paracetamol), the combination of analgesics with caffeine, non-steroidal antiinflammatory drugs (NSAIDs) such as ibuprofen, naproxen, ketoprofen or diclofenac 14,15 , and other medications with less clear mechanisms of action, such as metamizole 16 . Ergotamine preparations have also been used. 17 Depending on the measure used, many patients are nonresponsive to the aforementioned treatments; therefore, new drugs 18 have been proposed. Successful new approaches for the treatment of acute migraine target calcitonin generelated peptide (CGRP) and serotonin (5-hydroxytryptamine, 5-HT1F) receptors. In migraine prevention, the most promising new approaches are humanised antibodies against CGRP or the CGRP receptor. 18 Alternative approaches 19,20 include food or dietary supplements that provide medicinal or health benefits (i.e. riboflavin, coenzyme Q10, magnesium, butterbur root extract, and feverfew) 21 , behavioral interventions (i.e. relaxation, thermal, electromyographic biofeedback, stress management and cognitive-behavioural therapy) which have been used in migraine therapy to help patients to better cope with symptoms and identify potential triggers for headache 22,23 , invasive or non-invasive neuromodulation 20 , acupuncture 13 , 24 , meditation 25,26 , and others. Although the efficacy of behavioral interventions for migraine is well established, other emerging behavioral therapies show considerable promise for improving outcomes of migraine patients, particularly in reducing headache-related disability and affective distress, but efficacy to date is limited. 23 Despite the numerous treatments available, many people suffer prolonged and frequent attacks which have a major impact on their quality of life. The majority of studies focused solely on efficacy, tolerability or discontinuation rates of treatments; however, some migraineurs may never achieve the goal of becoming permanently pain free and treatments may prioritise the outcome of improved functioning above symptom reduction.
Nevertheless, the patient's perception of an improvement of symptoms and a cure of migraine is still unknown. Therefore, we conducted a qualitative study to understand the patient's perspective concerning migraine cure and which treatment outcomes are most important for those patients.

Experimental Design
This study enrolled 1,102 patients fitting the International Classification of Headache Disorders (ICHD-3) migraine criteria 1 seeking medical care, from January to December 2015, at the Brain Research Institute at Albert Einstein Hospital, located in Sao Paulo, Brazil.
All patients answered questions concerning their medical care, preference for treatment, and opinions on migraine cure via a web-based survey.
Written informed consent was obtained, in which patients agreed to share their responses for research purposes, and the study was approved by the local institutional review board.

Questionnaire
The online-based survey was accessed via the institute's website and consisted of three main sessions. The first session contained questions concerning demographic data such as age and sex and description of migraine symptoms; the second session included migraine diagnosis and treatment; and the third session investigated the patient's opinion about migraine cure and which treatment they would consider taking (Table1).

Statistical analysis
Data are expressed as the mean ± standard deviation for continuous variables, while percentages are used for categorical variables. Generalised linear models (GzLM) were used to investigate the following relationships: -Participants' sex and migraine intensity (from one to ten), using gamma with log link distribution; -Chronic migraine and migraine cure belief, using binary logistic regression; -Participants' sex and age and (i) chronic migraine, and (ii) migraine cure belief, using binary logistic regression.
The results are expressed as unstandardised regression coefficient (B), or odds ratio (OR), with 95% confidence intervals (CI) and p-values. The α error rate adopted was 5%. The analysis was performed using SPSS Statistics 21 (IBM, New York, New York, USA).

Discussion
Despite the major advances in defining migraine pathophysiology and the subsequent discovery of novel medicines for the acute treatment and prevention of migraine headaches, the process of conducting research and analysing evidence reveals gaps in our understanding of which and how treatments should be conducted and for which kind of patient. There is also a general lack of understanding concerning patient beliefs and treatment decision processes related to the use of migraine medications.
The present study investigated the patient's perspective of migraine cure and which treatment outcomes are most important for migraine patients. When asked about the cure for migraine, the majority of patients reported not believing in the cure and less than one-third of participants consider migraine cure as to "never experience a headache again" or to "never experience a strong headache again", while most patients consider "stopping a migraine attack faster" or a "90% improvement in migraine attacks" to indicate a migraine cure. In addition, there was a significant difference in the rate of migraine cure belief between patients with acute and chronic migraine, with the belief in the cure of a migraine being decreased by more than 70% among chronic migraineurs.
As reported by Smitherman et al. 19 , many chronic pain patients will never achieve the often unrealistic goal of becoming permanently pain free. Cognitive distortions as catastrophizing can negatively impact the patient´s perception of results, and adherence to treatment. Therefore, the clinician-patient conversation about preventive therapies must set realistic expectations regarding the likely magnitude of benefit, considering that a reduction but not elimination of migraine burden is expected. Providing a rationale education is critical for engaging patients with migraine in treatment. 27 Patients with chronic migraine represent the more severe end of the spectrum. To meet diagnostic criteria for chronic migraine, patients must have a history of migraine, and have had a headache for more than 14 days a month for at least 3 months. 1 Our evidence suggests that this group of patients have less hope of a cure. Future studies could investigate the consequences of these belief, as nonadherence to treatment.
It has been described that feelings of pain and aspects of emotional, physical, and social functioning impacted by pain may influence treatment outcomes. 28 Also, the pain behaviour is influenced by private events, including thoughts and beliefs and one's response to those cognitive processes. 28 In light of this, psychological approaches to treat chronic pain may be valuable.
Alternative treatments including acceptance and commitment therapy 28 , mindfulness-based interventions 27,29 , and others have been investigated and proved to be efficient for the treatment of migraine. When asked which treatment to consider, most patients opted for more conventional approaches, such as taking "daily prescription medicines" or to "exercising three times a week"; however, other less conventional strategies have also been considered, such as acupuncture and, by fewer participants, even religious and spiritual treatments.
The treatments suggested here and other aforementioned alternatives are preventive approaches. However, "to have the migraine attacks blocked faster" was considered to indicate a cure for migraine by most of the participants. In a previously reported analysis of the needs and expectations of patients who present to the emergency department for the management of migraine, it was also observed that migraine patients express an appreciation for medications that afforded the rapid and durable relief of headache; however, complaints about medication-induced side effects, particularly drowsiness and dizziness, are also common. 30 There are many options for acute migraine attack treatment, but none are ideal for all patients. It was recognised over a century ago that patient response to medications for migraine attacks is idiosyncratic and that treatment must be tailored to the individual. 31 Medication choice for the acute treatment of migraine attacks is difficult, given the multiple medications available and the fact that one cannot predict which medication will work best for any given patient. 32 Acute migraine treatment in chronic migraine is particularly important. The acute medications used in these cases are the same as those used in episodic migraine and acute migraine; in chronic migraine, however, presents a difficult challenge because of the high headache frequency and the importance of avoiding medication overuse. 31 Corroborating previous reports, it was observed in the present study that women are more likely to have migraine than men. Burch et al. 3 reported that one in five women between the ages of 15 and 64 years old have experienced migraine or severe headache in the previous three months. The female preponderance of migraine seems to be related to hormonal milestones 33, 34 . Considerable evidence has linked ovarian steroid hormones oestrogen and progesterone to migraine. [35][36][37] Fluctuations in oestrogen levels influence migraine attacks, with oestrogen withdrawal before menses probably being a notable trigger 38 . This highlights the importance of expanding knowledge of reproductive endocrinology in the management of migraine in the largest population of migraineurs, in women.
This study has limitations. Given the self-reported nature of this survey, the possibility of misreporting cannot be excluded. In addition, the survey enrolled patients seeking medical care at a Brain Research Institute, where severe migraineurs are likely over-represented compared with the general population. More than 45% of our population were chronic migraineurs, which is not representative of the general population. Nevertheless, data acquired from this population could help to understand the perspective concerning migraine treatment and cure of a large crosssection of the most disabled migraineurs.
In conclusion, some points that were important to migraineurs have been identified in this study. Despite the majority of our patients showing disbelief in the existence of a migraine cure, most of those that reported believing in a cure considered "cure" a rapid relief of headache. In addition, chronic migraineurs' belief in the existence of a migraine cure was dramatically affected. Ultimately, the findings of this study may facilitate the migraine treatment decision process by providing a better understanding of patients' perspectives and beliefs, thus creating a more friendly communication between migraineurs and care providers and hopefully, improving patients' quality of life.