Jun. 26, 2023
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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 costs. 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) (40). 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-reported outcomes).
• New specific treatments for the acute and preventive treatment are now available including CGRP-targeted monoclonal antibodies, gepants, and ditans.
Approach to a 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 promote healthcare patient-based.
With the aim of supporting care and clinical decision-making, primary care practitioners, neurologists, and headache specialists published a consensus statement in 2021 (17). The authors thoroughly state 10 practical steps divided in three parts: diagnosis, acute and preventive treatment, and clinical management and follow-up.
In neurologic practice, headache accounts for 25% of new referrals and yet a large proportion of these patients feel dissatisfied (02). 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 (23). 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. Physicians have to suspect migraine if patient has recurrent headache of moderate to severe intensity, visual aura, family history of migraine, or onset of symptoms around puberty (17).
Physical examination. The physical examination must be systematic, including neurologic examination and the cranial area (18). 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 (35; 32; 07).
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.
In this part, it is important to emphasize patient centricity and education. Physicians must provide appropriate reassurance, agree on realistic objectives, identify predisposing and/or trigger factors, and follow a strategy to individualize therapy according to symptoms and needs (17).
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 acknowledge of nonpharmacological treatment because these therapies are frequently requested by individuals with headache, and in particular in specific situations such as childhood, pregnancy, and breastfeeding. Nowadays, it is also important to know that there is a wide range of alternative therapies, but they have variable and scarce scientific evidence.
Some evidence supports the use of noninvasive neuromodulatory devices (37), biobehavioral therapy (41), and acupuncture (21), although a study of acupuncture indicated that it is not superior to sham acupuncture (14). Contrary to popular belief, little to no evidence exists for physical therapy, spinal manipulation, and dietary approaches (31). Other therapeutic options, such as melatonin, magnesium, and riboflavin, have limited evidence for their efficacy, and their use in clinical practice is limited (25).
Pharmacological treatment. Due to its high prevalence and socioeconomic burden, the following sections will refer to migraine disease.
Individualized approaches using a combination of new substances with oral prophylactic drugs or botulinum toxin A, switching between new drugs, and adjusting treatment duration could enhance excellence in practice.
Acute treatment. It is recommended to start with combination therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) and triptans. Triptans are the gold standard for the migraine attack treatment. We advise patients to use a triptan at the start of the headache phase because there is no efficacy evidence if taken during preceding aura. An antiemetic could be used, even if nausea is not pronounced, to counter gastric stasis and facilitate tablet absorption and pain relief.
There are seven 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 (39).
It is important to explain that the acute treatment should be used, on average, on no more than two 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.
If all available triptans fail after an adequate trial period (no or insufficient therapeutic response in at least three consecutive attacks) or their use is contraindicated, ditans or gepants could be used. Lasmiditan (a selective serotonin receptor (5-HT1B/1D) is the only ditan approved; ubrogepant and rimegepant are the only gepants approved for the acute treatment of migraine (19; 30; 29). The gepants and ditans will likely offer a comparable alternative to triptans for patients with cardiovascular risk factors (19), and it seems that they do not lead to medication overuse headache. Furthermore, post-hoc analyses reported no differences in efficacy of gepants/ditans between responders and nonresponders to triptans (11).
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 (16). Nerve blocks with lidocaine is a suitable option for migraine treatment during pregnancy if it is needed.
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 three months.
Treatment of medication-overuse headache has three 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 one 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 two steps. The optimal therapeutic approach requires validation in controlled trials (13). 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 recommended for patients adversely affected on greater than or equal to two days per month despite optimized acute therapy (17).
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 three months to evaluate efficacy. If effective (about a 50% improvement) the drug may be continued for six 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 (04; 12) 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 (38; 05).
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 (10).
Currently, there are four CGRP-mABs placed on the market. Financing conditions are different for each country. One of the approved drugs targets the CGRP receptor (erenumab), whereas three target the CGRP ligand (fremanezumab, galcanezumab, and eptinezumab). Erenumab, galcanezumab and fremanezumab are given by subcutaneous injection monthly, although fremanezumab can also be given quarterly. Eptinezumab is given by intravenous infusion quarterly. They have been found to be effective in episodic and chronic migraine (01).
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 (28).
Lifestyle adjustments. Irrespective of treatment modalities applied, trigger control and lifestyle modification are indispensable to the successful management of migraine (33). 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 (24).
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 (42).
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 two 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 (08).
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 two 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 (34). In addition, it must be considered that food triggers were only associated with onset of headache in less than 10% of the participants (36).
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 five 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 (36).
Caffeine at moderate doses (< 400mg/day: equivalent to two cups of coffee) does not seem to have a negative effect on headache frequency although it should be taken regularly to avoid withdrawal headaches (34).
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 (15).
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 (26). The clinical benefit of yoga as an add-on therapy in patients with episodic migraine has been demonstrated (27).
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 (09).
Gepants. Clinical trials are currently ongoing, which are studying the efficacy and safety of atogepant as a preventive treatment of 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 two 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 (03).
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. Despite relatively poor efficacy, paracetamol should be used as the first-line medication for acute treatment; NSAIDs can be used only during the second trimester, and triptans should be used only under the strict supervision of a specialist, as the safety data available are limited and originate from post-marketing surveillance; most data relate to the use of sumatriptan. If preventive therapy is considered clinically indicated because of frequent and disabling migraine attacks, the best available safety data support the use of propranolol or, if propranolol is contraindicated, amitriptyline. 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 (06).
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 (22).
All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.
Patricia Pozo-Rosich MD PhD
Dr. Patricia Pozo-Rosich of Vall d’Hebron University Hospital & Institute of Research received honorariums as speaker and consultant from Teva Pharmaceuticals.See Profile
Alicia Alpuente MD
Dr. Alicia Alpuente of Vall d’Hebron University Hospital has received honorariums as a speaker for Allergan, Eli Lilly, and Novartis and as a 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, has no relevant financial relationships to disclose.See Profile
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