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Headache is the medical problem most commonly observed by neurologists, causes substantial pain and disability, and is associated with a high burden and considerable cost. Headache is listed among the World Health Organization’s major causes of disability, with a global prevalence of 47% (symptoms occurring at least once in the past year) (30). Women are disproportionately affected (3:1) and its higher prevalence among those of working age adds to the socioeconomic burden with loss of productivity.
• Headache is the most common medical problem observed by neurologists and a major cause of disability in young people.
• Diagnosis of headache is based on well-defined clinical criteria according to the International Headache Society.
• Approach to headache patient includes pharmacological treatment and recommendations about lifestyle adjustments.
• Headache assessment includes not only headache-related parameters but also patients’ quality of life assessment (through patient-related outcomes).
• CGRP-targeted monoclonal antibodies are the first preventive treatment that is migraine specific.
Approach to headache patient includes an accurate clinical assessment in order to make a correct diagnosis and consequently to start the most appropriate treatment, to establish an acute and preventive medical treatment according to the individual’s characteristics, and to provide headache education in order to empower patients and to perform precision medicine.
In neurologic practice, headache accounts for 25% of new referrals and yet a large proportion of these patients feel dissatisfied (APPGPHD 2014). Therefore, it is mandatory that healthcare professionals are aware of headache and can handle it looking for an improvement in a patient’s quality of life. Performing an adequate clinical history and physical examination is essential in order to get a reliable diagnosis and in consequence to establish the most appropriate medical treatment.
Clinical history. Diagnosis in headache disorders is based on well-defined and established criteria by the International Headache Society (17). Therefore, it is essential to know about the most common sections, mainly migraine as the most common primary headache. It is important to watch out for red flags in order to discard secondary headaches.
Physical examination. The physical examination must be systematic, including neurologic examination and the cranial area (14). The general examination tends to detect signs of a secondary headache.
Craniofacial examination includes fundoscopy in order to assess papilledema, hemorrhage, or exudates; an inspection assessing autonomic symptoms, tropism, and color changes; and palpation in order to assess allodynia and tenderness or triggering of headache in the cranial nerve trajectory. Neck movements may help to diagnose cervicogenic headache.
Comorbidities. It is essential to assess comorbidities because they have an important impact on the treatment. Suffering from concurrent disorders such as other neurologic and psychiatric disorders, chronic pain, cardiovascular diseases, gastrointestinal complaints, allergy or asthma, and obesity would also make the treatment more complicated. Regarding migraine, ie, these comorbidities may additionally be involved in the transformation from episodic to chronic migraine (26; 23; 05).
Questionnaires and headache diaries. Questionnaires can help to determine the degree of disability at baseline and to evaluate the response to treatment such as the Headache Impact Test (HIT 6) and the Migraine Disability Assessment Test (MIDAS). The Hospital Anxiety and Depression Scale (HADS) can also help to assess the emotional and psychiatric comorbidity. This is particularly important in these patients and may influence the decision on preventative therapy because many of these can exacerbate depression and anxiety.
Using a headache diary help us to quantify the headache and to provide a contemporary record of pain, as otherwise this can suffer from recall bias. Moreover, it improves the doctor-patient relationship and it facilitates decision making. The diaries also assist when monitoring the treatment response, identifying triggers, the relationship to menses, and the frequency of analgesic use.
Clinical and scientific evidence supports that proper management of patients with headache should be multimodal including appropriate use of pharmacological and nonpharmacological interventions. Regarding migraine, its treatment is increasingly focusing in a personalized approach: the right drug to the right patient.
Nonpharmacological treatment. It is important to have knowledge of nonpharmacological treatment because these therapies are frequently requested by individuals with headache. It is also important to know that nowadays there is a wide range of alternative therapies with variable and scarce scientific evidence.
Several physical therapies including spinal joint manipulation and/or mobilization, soft tissue interventions, therapeutic exercises, and needling therapies are proposed to be effective for the management of headaches. However, current evidence has shown that the effectiveness of these interventions will depend on proper clinical reasoning because not all interventions are equally effective for all headache pain conditions (13).
With regard to stress management strategies in headache patients, relaxation techniques, biofeedback, behavioral interventions, and cognitive-behavioral therapy have been shown to be effective. The choice of one or the other technique will depend on the type of stressor or its consequences.
Pharmacological treatment. Due to its high prevalence and socioeconomic burden, the following sections will refer to migraine disease.
Acute treatment. It is recommended to start with combination therapy with nonsteroidal antiinflammatory drugs (NSAIDs) and triptans. We advise patients to use a triptan at the start of the headache phase of a migraine attack because there is no evidence of efficacy if taken during preceding aura. An antiemetic could be used, even if nausea is not pronounced, to counter gastric stasis and so facilitating tablet absorption and pain relief.
There are 7 triptans and choice depends on the characteristics of acute attacks. The route of administration is therefore best tailored to the individual’s migraine attack. The most effective use of a triptan depends on its route of administration. Thus, subcutaneous sumatriptan is the fastest one followed by nasal preparations.
In general, triptans are well tolerated. There are cardiovascular safety concerns associated with triptan use due to the presence of 5HT1B receptors on vascular smooth muscle. We avoid triptans in people with uncontrolled hypertension and cardiovascular and/or cerebrovascular disease. Triptan sensations such as burning or tingling in the chest or limbs are relatively common (7%) but clinicians can reassure patients that this is not associated with cardiac ischemia (29).
It is important to explain that the acute treatment should be used, on average, on no more than 2 days per week (10 days per month) for triptans and on no more than 15 days/month for NSAIDs, to reduce the risk of medication overuse.
Another treatment option is nerve blocks. Occipital nerve block, consisting of a local anesthetic and/or corticosteroid, has shown to be an effective treatment for the management of migraines. Occipital nerve block has been reported to reduce migraine pain scores, frequency, and duration (12).
Management on medication-overuse headache. Medication-overuse headache is a secondary headache occurring on 15 or more days per month, developing as a consequence of regular overuse of acute or symptomatic headache medication (simple analgesics and NSAIDs on 15 days or more; or triptans, opioids, and combination analgesics on 10 days or more days per month) for over 3 months.
Treatment of medication-overuse headache has 3 components. First, patients need education and counseling to reduce the intake of medication for acute headache attacks. Second, some patients benefit from drug withdrawal (discontinuation of the overused medication). The overused abortive medication should ideally be stopped for at least 1 month. Finally, preventive drug therapy and nonmedical prevention might be necessary in patients at onset of treatment or in patients who do not respond to the first 2 steps. The optimal therapeutic approach requires validation in controlled trials (10). Nowadays there is a lot of controversy as to whether migraine preventatives should be started while there is still ongoing medication overuse.
Preventative treatment. Migraine preventative treatments aim to reduce the frequency and severity of attacks and may help reduce the frequency of analgesic use. It is important to manage patient’s expectations before starting treatment. Prophylactic treatment is typically considered if there are more than 4 migraine days per month. However, it may also be given for less frequent but very disabling attacks (22; 10).
In addition, the choice of a certain preventative treatment is influenced by the guideline’s recommendations for each country, considering type of migraine, patient’s characteristics, and comorbidities.
Oral prophylactics. The agents used can be classified into antiepileptic drugs, beta blockers, antidepressants, serotonergic antagonists (methysergide is no longer manufactured), calcium channel antagonists, and angiotensin modulators (ACE inhibitors and angiotensin-receptor inhibitors). The general rules of thumb are to start treatment at a low dose, gradually increasing to an initial target dose. If there is no effect and no significant side effects, the dose can be further increased for some drugs. We continue the medication for at least 3 months to evaluate efficacy. If effective (about a 50% improvement) the drug may be continued for 6 months, although there is some evidence of fewer rebound headaches if continued for 12 months.
OnabotulinumtoxinA. In 2010, OnabotulinumtoxinA was reported effective for the treatment of chronic migraine in the Phase 3 Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) trials (02; 09) and was approved both by the European Medicines Agency and by the U.S. Food and Drug Administration for the prophylaxis of chronic migraine. OnabotulinumtoxinA has not been found effective in episodic migraine or in tension-type headache. There are European and American guidelines on the use of onabotulinumtoxinA in chronic migraine (28; 03).
CGRP-targeted monoclonal antibodies (CGRP-mABs). The CGRP mAbs are the first class of preventive medication to specifically target the pathophysiology of migraine. Their efficacy, tolerability, and lack of drug-drug interactions make them ideal for many patients who have been unsuccessfully treated with other preventives (08).
Nowadays there are 3 CGRP-mABs placed on the market. Financing conditions are different for each country. One of the approved drugs targets the CGRP receptor (erenumab) whereas 2 target the CGRP ligand (fremanezumab and glacanezumab). All of these drugs are given by subcutaneous injection monthly although 1 of them can be given quarterly (fremanezumab). They have been found effective in episodic and chronic migraine.
Outcomes. Although measuring disability is a key step toward managing it, stratified care-based treatment guidelines, which match the severity of disability to the intensity of therapeutic interventions, may be needed to close the loop between process measures and functional outcomes.
By improving the recognition of secondary headaches, by developing novel acute and preventive treatment approaches using drugs and devices, and by assessing and implementing quality improvement programs, we should be able to improve the lives of our patients with headache disorders (21).
Education in headache
Lifestyle adjustments. Irrespective of treatment modalities applied, trigger control and lifestyle modification are indispensable to the successful management of migraine (24). This is especially important in children, adolescents, or pregnant women where drug treatments must be especially limited.
Although there is no robust evidence for most of the recommendations, most are general health measures that, given the lack of adverse effects and the benefit for general well-being, we consider should be recommended in all patients.
Avoid triggers. Many patients attribute the onset or worsening of pain to specific triggers such as stress, sleep changes, food, or atmospheric changes, among others. It is even possible that the relationship occurs inversely, so that premonitory symptoms such as sleep disturbances and appetite 48 to 72 hours before the onset of pain can be misinterpreted by the patient as the trigger of migraine attacks. The therapeutic implications of this relationship are also unclear. There are possible triggers such as sleep deprivation, fasting, or certain foods that can be easily avoidable. But avoiding other triggers can lead to very restrictive lifestyles with a reduction in quality of life that does not outweigh the potential beneficial (18).
Sleep. Another complex relationship is headache and sleep. An excess or lack of sleep can trigger migraine attacks and at the same time rest is one of the most used treatments to improve the symptoms of the migraine attack. Additionally, migraine and other headaches occur comorbidly with sleep disorders. Patients with chronic migraine have a higher prevalence of sleep disorders, specifically poor sleep habits and nonrestorative rest (31).
Regarding general sleep measures for patients with headache, it is recommended to define regular sleep schedules that allow 8 hours of rest per day, insisting that they remain constant also during the weekend; have dinner 4 hours before bedtime and avoid liquids in the last 2 hours; and eliminate naps and avoid using screens, television, reading, or listening to music in bed. A nonpharmacological intervention to improve sleep habits can improve headache frequency and even reverse chronic to episodic migraine (06).
Diet. In the scientific literature, but especially in the informative websites and magazines, multiple and varied diets are proposed that aim to reduce the frequency of headaches. There are 2 main approaches: elimination diets, which consist of suppressing potentially triggering foods such as chocolate, alcohol, cheese, nuts, or citrus fruits and diets that provide high or low amounts of certain components, ie, rich in vitamin B12, B6, or D or low in histamine, lactose, or fatty acids. The studies are not very rigorous and most do not have a control group (25). In addition, it must be considered that food triggers were only associated with onset of headache in less than 10% of the participants (27).
Dietary recommendations for patients with migraine should be the same as for the general population with special emphasis on the prevention of obesity, which is a factor related to headache chronification. It is recommendable to have a varied diet, eating 5 meals a day to avoid periods of prolonged fasting and incorporating water intake to reach around 2.5 liters per day, which should be increased in case of physical activity or increase in temperature or humidity. Specific diets should be recommended solely based on whether there are other comorbidities in the patient (27).
Caffeine at moderate doses (< 400mg / day: equivalent to 2 cups of coffee) does not seem to have a negative effect on headache frequency although it should be taken regularly to avoid withdrawal headaches (25).
Although patients with migraine headaches and cluster headaches may be more susceptible to alcohol as a precipitant, there is no evidence to recommend abstinence from alcohol in all patients. Individual predisposition and cultural factors must be considered (11).
Exercise. Aerobic exercise can prevent or reduce symptoms of multiple chronic diseases, including headache. With some methodological limitations, there are studies that demonstrate benefits of aerobic exercise as a therapeutic intervention to reduce the frequency and intensity of headaches, as well as the quality of life measured by questionnaires. Exercise can have a beneficial effect on headaches directly but also indirectly, improving sleep quality, mood, cardiovascular function, and preventing weight gain. In addition, it can improve the control of other diseases frequently comorbid with headache such as obesity, hypertension, anxiety, depression, or sleep disorders (19). The clinical benefit of yoga as an add-on therapy in patients with episodic migraine has been demonstrated (20).
Obesity. A higher body mass index is associated with greater frequency, intensity, and disability of migraine. Also keep in mind that the migraine preventive treatments (except topiramate) can potentially cause weight gain. Therefore, weight loss could improve the impact of the headache.
In patients with migraine headaches and overweight, education to avoid weight gain including dietary measures and frequent exercise should be added to their nonpharmacological treatment plan (07).
Treatments on the horizon
Ditans and gepants. Two new classes of acute treatments, developed based on insights into migraine pathophysiology, were designed to be free of the vasoconstrictive effects of triptans and ergot alkaloids. Gepants, as exemplified by rimegepant and ubrogepant, are small molecule calcitonin gene related peptide (CGRP) receptor antagonists. Ditans, represented by lasmitidan, are 5HT (serotonin) 1F receptor antagonists. The gepants and ditans will likely offer a comparable alternative to triptans for patients with cardiovascular risk factors (15).
Clinical trials are currently ongoing regarding another CGRP-mAB (Eptinezumab) as well as gepants as a preventive treatment in migraine.
Neuromodulation. There are some approaches available but these treatments are underutilized because of a lack of awareness and poor reimbursement. Three noninvasive approaches approved as acute treatments include single-pulse transcranial magnetic stimulation, external trigeminal nerve stimulation, and noninvasive vagal nerve stimulation. The first 2 approaches are also approved as preventive treatments. These approaches are important for people who do not want or cannot take medication, including pregnant women, and provide a useful adjunct to pharmacologic for and behavioral treatments.
Pregnancy and breastfeeding. It is worth noting that pregnancy is a risk factor for many types of secondary headache. First-line interventions for management of migraine during pregnancy are optimization of lifestyle factors and introduction of nonpharmacologic techniques and therapies. Lifestyle factors include improvement of sleep duration and quality, maintaining regular meals and good hydration, and a good schedule of physical activity. Nonpharmacologic treatments including relaxation training and biofeedback have shown efficacy for prevention of migraine and are most effective when practiced regularly. The effects of most medications on fetal development and pregnancy outcomes are poorly studied and this is generally true of medications used for migraine as well (04).
Children. Children and adolescents with primary headache are at risk of persistent somatic symptoms and reduced quality of life due to pain and pain-related behaviors, such as avoiding school and activities. Acute treatment strategies include use of over-the-counter analgesics and triptan medications that have been approved by the U.S. FDA for use in children and adolescents. Preventative treatment approach includes lifestyle modifications, behavioral strategies, and consideration of preventive medications with the lowest side effect profiles (Greene and Irwin 2019).
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- References especially recommended by the author or editor for general reading.
Patricia Pozo-Rosich MD PhD
Dr. Patricia Pozo-Rosich of Vall d’Hebron University Hospital has received honoraria as a consultant and speaker for Allergan, Almirall, Biohaven, Chiesi, Eli Lilly, Medscape, Neurodiem, Novartis and Teva. Her research group has received research grants from Allergan, AGAUR, la Caixa foundation, Migraine Research Foundation, Instituto Investigación Carlos III, MICINN, PERIS; and has received funding for clinical trials from Alder, Electrocore, Eli Lilly, Novartis and Teva.See Profile
Alicia Alpuente MD
Dr. Alicia Alpuente of Vall d’Hebron University Hospital has received honoraria as speaker for Allergan and as consultant for Novartis.See Profile
Shuu-Jiun Wang MD
Dr. Wang of the Brain Research Center, National Yang-Ming University, and the Neurological Institute, Taipei Veterans General Hospital, received consulting fees from Eli Lilly and Novartis for advisory board membership and honorariums from AbbVie as a speaker.See Profile
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