Migraine Treatment: What’s Old, What’s New
Migraine headaches are a common cause of disability in the United States, affecting approximately 27 million American adults, or 17.1% of women and 5.6% of men. 1 To help better define migraines, the term classical migraine has been replaced with migraine with aura, and non-classical migraine is now referred to as migraine without aura. Chronic migraine, which affects 3.2 million Americans (2%), is defined as having migraine symptoms for at least 15 days per month, lasting at least 4 hours, and for longer than 3 months in duration. This is in contrast to episodic migraine, which causes symptoms on fewer than 15 days per month. 2 Current treatment for chronic migraine is divided into acute, abortive agents (analgesics, triptans, ergots, etc.), and medications that will prevent migraine onset.
This review will highlight the current definitions of migraines as well as treatment options.
A recurring headache that is of moderate or severe intensity, and is triggered by migraine-precipitating factors, usually is considered to be migraine. Precipitating factors can include stress, certain foods, weather changes, smoke, hunger, fatigue, hormones, and so on. Migraine without aura is a chronic idiopathic headache disorder with attacks lasting 4 to 72 hours. Status migrainosus applies to migraine headaches that exceed 72 hours. Migraine features often include a unilateral location and a throbbing or pulsating nature to the pain. There may be associated nausea, photophobia, phonophobia, or dizziness (Table 1). Further characteristics include a positive relationship with menses, decreased frequency during pregnancy, increased pain with physical activity, and history of migraine in first-degree relatives. It has been reported by 70% to 75% of migraine patients that they have a first-degree relative with a history of migraines. 3
Patients who suffer from migraines often have colder hands and feet compared with controls, and the prevalence of motion sickness is much higher in migraine patients. Although most patients will not have all of these characteristics, there are certain diagnostic criteria that have been established by the International Headache Society for the definite diagnosis of migraine. 2 Distinguishing a milder migraine without aura from a moderate or severe tension headache may be difficult, and it is not surprising when “pure” migraine medications are effective for severe tension-type headaches.
Recurrent, repeated attacks of throbbing or severely aching headache are generally regarded as migraine, whether or not the patient has nausea, dizziness, photophobia, or phonophobia. The patient’s history is used to make the diagnosis of migraine. Physical examination and magnetic resonance imaging (MRI) or computed tomography (CT) scans are helpful only in ruling out organic pathology. Recent-onset headaches need to be investigated with an MRI to rule out other organic disorders, particularly brain tumors. In addition to physical exam and imaging, a check of intraocular pressure (IOP) may be warranted. With new-onset headaches, an eye exam is always warranted.
Although the pain is unilateral in 50% of migraine patients, the entire head often becomes involved. The pain may be in the facial or the cervical (neck) areas, and often will shift sides from one occurrence to another. Most patients, however, suffer the severe pain on one favored side from attack to attack.
The typical migraine patient suffers 1 to 5 attacks in a month, but many patients average l<1 (episodic) or >10 per month (chronic). The attack frequency varies with the seasons, and many patients can identify a time of year when their headaches increase significantly. Patients with chronic migraine may have 15 days a month of headache, and many even have 30 days/month, 24/7.
The pain of a migraine often follows a bell-shaped curve, with a gradual ascent, a peak for a number of hours, and then a slow decline (Table 2). Occasionally, the pain may be at its peak within minutes of onset. Many patients with migraine suffer some degree of nausea during the attack, and some experience vomiting as well. The nausea often is mild, and some patients are not bothered by it. Many patients state that the headache is lessened after they vomit. Diarrhea may occur and is usually mild to moderate. The presence of diarrhea renders the use of rectal suppositories impossible.
Lightheadedness often accompanies the migraine, and syncope may occur. Most patients become sensitive to bright lights, sounds, and/or odors. Between migraine attacks, many patients retain the photophobia, and it is common for migraine patients to wear sunglasses most of the time. Sensitivity to bright lights is a distinctive migraine characteristic.
Pallor of the face is common during a migraine; flushing may occur as well but is seen less often. Patients do complain of feeling excessively hot or cold during an attack, and the skin temperature may increase or decrease on the side with pain. Patients with migraines often experience tenderness of the scalp that may linger for hours or days after the migraine pain has ceased. This tenderness may actually occur during the prodrome of the migraine. Both vascular and muscular factors contribute to the scalp tenderness. Autonomic disturbances are relatively common, such as pupillary miosis or dilation, rhinorrhea, eye tearing, and nasal stuffiness. These also are symptoms of cluster headache, including the sharp pain around one eye or temple.
Alterations of mood are seen with many patients before, during, and after migraine attacks. Patients are usually anxious, tired, or depressed. They often feel “washed out” after an attack, but a calm or even euphoric state occasionally is seen as a postdrome to the migraine. Rarely, euphoria or exhilaration may precede a migraine.
Weight gain due to fluid retention may occur, and begins prior to the onset of a migraine. At some point during the migraine, patients may experience polyuria. The weight gain is usually less than 4 lb, and is transient.
Approximately 20% of patients experience visual neurologic disturbances preceding or during the migraine; these auras may be as disturbing to the patient as the migraine pain itself. The visual symptoms usually last 15 to 20 minutes, and most often will be followed by the migraine. Most migraine sufferers experience the same aura with each migraine, but occasionally one person may have several types of auras. “The light of a flashbulb going off” is the description many patients give to describe their aura. The visual hallucinations reported most often consist of spots, stars, lines (often wavy), color splashes, and waves resembling heat waves. The images may seem to shimmer, sparkle, or flicker. These visual occurrences are referred to as photopsia.
Fortification spectra are seen much less often than photopsia. They usually begin with a decrease in vision and visual hallucinations that are unformed. Within minutes, a paracentral scotoma becomes evident and assumes a crescent shape, usually with zigzags. There often is associated shimmering, sparkling, or flickering at the edges of the scotoma.
Patients may experience a “graying out” of their vision, or a “white out” may occur. Some patients suffer complete visual loss, usually for some minutes. Photopsia may be experienced at the same time as the gray-out, white- out, or visual loss.
Miscellaneous Neurologic Symptoms
Numbness or tingling (paresthesias) commonly are experienced by patients as part of the migraine. These are experienced most often in one hand and forearm, but may be felt in the face, peri-orally, or in both arms and legs. Like the visual disturbances, they often last only minutes preceding the pain, but the numbness may continue for hours, and at times the paresthesias are severe. The sensory disturbances usually increase slowly over 15 to 25 minutes, differentiating them from the more rapid pace seen in epilepsy.
Paralysis of the limbs may occur, but this is rare. This is occasionally seen as a familial autosomal dominant trait, and the term familial hemiplegic migraine is applied to this form. With the weakness, aphasia or slurred speech may also occur, and sensory disturbances are seen ipsilateral to the weakness.
Vertigo and/or dizziness are often experienced during migraine, and may be disabling. “Migraine associated vertigo” has become a common diagnosis. At times, the dizziness is more disabling to patients than the other symptoms. Ataxia may occur, but is not common. Rarely, multiple symptoms of brain stem dysfunction occur, with the term basilar migraine being applied to this type of syndrome. The attack usually begins with visual disturbances (most often photopsia), followed by ataxia, vertigo, paresthesias, and other brain stem symptoms. These severe neurologic symptoms usually abate after 15 to 30 minutes, and are followed by a headache. This type of migraine often stops over months or years, and the patient is simply left with migraine headaches without neurologic dysfunction.
Workup for Migraine
As noted, when patients present with a long history of typical migraine attacks, and the headaches are essentially unchanged, scans of the head usually are not absolutely necessary. Whether to do any testing at all depends on the physician’s clinical suspicion of organic pathology (see box). Sound clinical judgment, based on patient history and a physical exam, is crucial in deciding who needs which exam.
In addition to the MRI and CT scan, tests that are sometimes useful for diagnosis of headache, include lumbar puncture, IOP testing, CT scan of the sinuses, and blood tests. A magnetic resonance angiogram (MRA) allows the detection of most intracranial aneurysms.
The problems that need to be excluded in a patient with new-onset migraine include sinus disease, meningitis, glaucoma, brain tumor, arteritis, subarachnoid hemorrhage, low pressure headache, idiopathic intracranial hypertension, hydrocephalus, pheochromocytoma, stroke or transient ischemic attack, internal carotid artery dissection, and systemic illness.
With migraine and chronic daily headache sufferers, avoidance of triggers should be emphasized. The most common triggers are stress (both during and after stress), weather changes, perimenstruation, missing meals, bright lights or sunlight, under- and oversleeping, food sensitivity, perfume, cigarette smoke, exercise, and sexual activity. Some foods can be headache triggers, but foods tend to be overemphasized. In general, headache patients do better with regular schedules, eating three or more meals per day and going to bed and waking at the same time every day. Many patients state that “I can tell the weather with my head.” Barometric changes and storms are typical weather culprits, but some patients do poorly on bright “sun-glare” days.
Regarding stress as a trigger, it is not so much extreme stress, but daily hassles that increase headaches. When patients are faced with overwhelming daily stress, particularly when they are not sleeping well at night, headaches can be much worse the next day.
Psychotherapy is extremely useful for many headache patients with regard to stress management, coping, life issues, family-of-origin issues, and so on. Although psychotherapy may be recommended, it is crucial to legitimize the headaches as a physical condition; headaches are not a “psychological” problem, but rather a physical one that stress may exacerbate. Once one inherits the brain chemistry for headache, these triggers come into play; without the inherited genetics, most people may have stress/weather changes/hormonal changes, but not experience a headache.
Managing stress with exercise, yoga/Pilates/meditation, etc., often will reduce the frequency of headaches. The ideal would be for the patient to take a class weekly, then do the stretches and breathing for 10 minutes a day. Patients may experience some relief from associated neck or back pain. Relaxation techniques such as biofeedback, deep breathing, and imaging also may be helpful for daily headache patients, particularly when stress is a factor.
Many migraine patients have accompanying neck pain and physical therapy may help; acupuncture or chiropractic treatments occasionally help. Certain physical therapists “specialize” in head and neck pain. Massage may be effective, but the relief is often short-lived. Temporomandibular disorder (TMD), with clenching and/or bruxing, may exacerbate migraine; with TMD, physical therapy, a bite splint, and/or Botox may help. It often “takes a village” to help a person with pain, and we recruit other “villagers”, such as physical therapists or psychotherapists.
Although caffeine can help headaches, overuse may increase headaches. Whether in coffee, caffeine pills, or combination analgesics, patients must limit total caffeine intake. The maximum amount of caffeine taken each day varies from person to person, depending on sleep patterns, presence of anxiety, and sensitivity to possible rebound headaches. In general, caffeine should be limited to no more than 150 or 200 mg a day (Table 3).
Foods to Avoid
As noted, food sensitivities are not that common. Patients tend to focus on the foods, as they are a tangible trigger that one can control (as opposed to weather, for example). However, most people are sensitive to only two or three types of food in the diet. If a particular food is going to cause a headache, it usually will occur within 3 hours of eating. Table 4 provides a list of foods to avoid.
Tables 5 to 7 review all the first- and second-line migraine-abortive medications. Keys to treatment management are outlined in the Figure.
The most common first-line treatment for migraines includes triptans. More than 200 million patients worldwide have used triptans. The most effective way to use triptans is to take them early in the headache—the earlier a patient takes these agents, the better the effect. Sumatriptan is an extremely effective migraine-abortive medication with minimal side effects. It is effective for approximately 70% of patients and is the gold standard in abortive headache treatment. The usual dose is one tablet every 3 hours, as needed; maximum dose, two tablets per day. However, clinicians do need to limit triptan use (ideally, 3 days per week) to avoid rebound headaches or medication overuse headache (MOH). See section on rebound/MOH.
Triptans are helpful for moderate as well as more severe migraines. Certain patients tolerate one of the triptans better than another, and it is worthwhile to try several in an individual patient. Triptans are an excellent choice for migraine patients who are not at risk for coronary artery disease (CAD). Patients in their 50s or 60s can use these drugs, but they should be prescribed cautiously, and only in those patients who have been screened for CAD. Over the 23 years that triptans have been available, serious side effects have been few; they appear to be much safer than was previously thought in 1993. Most of the triptans are now available as generics.
For patients who cannot tolerate triptans, there are a number of other effective non-triptan first-line approaches, including diclofenac potassium powder (Cambia), Excedrin Migraine, naproxen, ketorolac (po/IM/nasal: Sprix nasal spray), ibuprofen, and Prodrin (similar to Midrin, but without the sedative). We often combine 2 first-line approaches (a triptan and a non-steroidal anti-inflammatory drug [NSAID] combination, for instance).
In general, drugs containing ergotamine (also called ergots) are effective second-line therapy for migraines. They were the first anti-migraine drugs available, but they have many side effects, and at most, should be used only 2 days per week. Dihydroergotamine (DHE) is the safest ergot derivative. DHE is primarily a “venoconstrictor,” with little arterial effects. This renders it very unlikely to cause cardiac problems. Indeed, since its introduction in 1945, DHE has been remarkably safe. Intravenous DHE is a very effective migraine-abortive agent administered in the office or emergency room. Nasal (Migranal Nasal Spray) and inhaled forms of DHE (hopefully soon to be released) have been found to be safe and effective as well. Barbiturates and opioids have been studied and are effective, but because of the risk for addiction, should be used sparingly. For severe prolonged migraines, corticosteroids (oral, IV, or intramuscular) often are effective. It is important to use low doses of steroids.
Many patients have 3 to 6 abortives: triptan, NSAIDs, Excedrin, an anti-nausea medication, and a painkiller (opioid/butalbital). They use each in different situations, for different types and degrees of headache.
Muscle relaxants (carisoprodol, diazepam) or tranquilizers (clonazepam, alprazolam) occasionally are useful, primarily to aid in sleeping. Intravenous sodium valproate (Depacon) is safe and can be effective. The atypical antipsychotics, such as olanzapine (Zyprexa) or quetiapine (Seroquel), occasionally may be useful on an as-needed basis. In the emergency room, IV administration of antiemetic agents such as prochlorperazine (Compazine, others) or metoclopramide (Reglan) may be useful.
Certain preventive medications, such as valproic acid (Depakote), topiramate (Topamax), and amitriptyline, may be useful on an as-needed basis, utilizing low doses every 4 to 6 hours. The antihistamine diphenhydramine is occasionally useful when administered intramuscularly. At times, patients may have injections for home use: ketorolac, orphenadrine, sumatriptan, diphenhydramine, promethazine, etc.
Table 8 outlines commonly prescribed antiemetic agents for the management of nausea and other gastrointestinal (GI) symptoms.
Medication Overuse Headache (MOH)
Much is written about MOH, with many patients diagnosed with this condition. Often a patient will be overusing abortive medications (medication overuse), but not be suffering “rebound/withdrawal” headaches (medication overuse, but NOT medication overuse headache). Up until recently, all NSAIDS were lumped under “meds that cause MOH,” and this simply is not true. For some patients, opioids, butalbital, and high-caffeine containing meds cause MOH. Triptans are occasionally implicated as well. However, for most patients with chronic migraine, they have daily (or near-daily) headaches, the preventives may not be effective, and they use abortives in an attempt to get through the day.
There are more questions in the area of MOH than we have answers. The pathophysiology of MOH is unclear. Some patients will have MOH from 2 Excedrin daily, while others do not suffer from MOH consuming 8 per day. When patients are using frequent abortives, we often withdraw them from that abortive, push preventives, and attempt to minimize analgesics. However, for many chronic migraine sufferers, the preventives are not very effective. For those sufferers, abortives allow them to live with a reasonable quality of life.
There is no algorithm to determine who is to go on preventive headache medication. The number of monthly headaches is one factor, along with comorbidities. Patients have to be willing to take daily medication (many do not want any daily meds). There is no absolute rule that applies to headache treatment. For a patient with two headaches a month that are severe, prolonged, and not relieved by drugs, preventive medicine might be used. On the other hand, for the person who has five headaches a month, but can obtain relief from Excedrin or a triptan, preventive medicine may not be optimal. The choice of who qualifies for medication depends on the patient’s age, medical and psychiatric comorbidities, and frequency and severity of the migraine, as well as the patient’s preference. Comorbidities often determine which preventive meds are used. If a patient has HTN, a med for blood pressure will be used. When patients concurrently suffer with anxiety or depression, various antidepressants are utilized for the headache and mood disorder. We want to minimize meds, and treating 2 conditions with one medication is ideal.
In using medication, a realistic goal is to decrease the headache severity by 40% to 70%, not to completely eliminate the headaches. It is wonderful when the headaches are 90% improved, but the idea is also to minimize medication. “Clinical meaningful pain relief” is usually around a 30% improvement. Most patients need to be willing to settle for moderate improvement. Preventives may take 3 to 6 weeks to work, and “educated guesswork” often is used to find the best approach for each patient. In the long run, preventive medications are effective for approximately 50% of patients. The other 50% scramble with various abortives.
As noted, patients should play an active role in medication choice. Preventive medications should be selected depending on the patient’s medical and psychological comorbidities, GI system, medication sensitivities, weight, sleep, family history of reaction to medications, finances, willingness to take daily meds, and many other factors. Fatigue and/or weight gain are major reasons why patients abandon a preventive medication. Headache patients commonly complain of fatigue, and tend to give up on medications that increase tiredness. A patient’s occupation also may guide the caregiver away from certain medications; for example, an accountant may not be able to tolerate the memory problems associated with topiramate.
Side effects are possible with any medication; the patient must be prepared to endure mild side effects in order to achieve results.
First-line Preventive Medications for Migraine
Botulinum Toxin A
Botulinum toxin A (Botox) has been studied extensively in patients with migraines. Nearly 8 million people have had botulinum toxin A injections for headache. 4 Botulinum toxin A has been found to significantly improve quality of life and reduce headache impact. Botox is the only botulinum toxin A that is FDA-approved for treatment of chronic migraine. It is relatively safe and only takes a few minutes to inject. One set of injections may decrease headaches for 1 to 3 months. There also is a cumulative benefit, where the headaches continue to improve over 1 year of injections. Botox may be safer than many of the medications that are used for headache. Botox does not cause the “annoying” side effects that are commonly encountered with preventives. Except for the cost, the experience with Botox has been very positive.
Natural Supplements and Herbs
Feverfew, Petadolex (butterbur), and magnesium oxide have all proven effective in double-blind studies as migraine preventives. Of these, Petadolex has been the most effective.
Petadolex is a purified form of the herb butterbur and is made of extracted plant certified by the German Health Authority. The herb preparation is commonly used in Europe, and has been found to be successful in preventing migraines in several well-designed blind studies. The usual dose is 100 mg per day, and many increase this to 150 mg daily (all at once, or in 2 divided doses). Earlier concerns about carcinogenesis with this family of herbs have decreased with the use of Petadolex. However, there are lingering concerns as to hepatotoxicity. Patients have occasionally experienced GI upset or a bad taste in the mouth, but Petadolex is usually well tolerated. It is prudent to stop it every six months or so.
Magnesium helps many systems in the body to function, especially the muscles and nerves. It has been shown that magnesium levels in the brains of migraine patients tend to be lower than normal. Magnesium oxide is used as a supplement to maintain adequate magnesium in the body. A dose of 400 or 500 mg per day can be used as a preventive; tablets are found in most pharmacies. However, mild GI side effects may limit use. There are also drug interactions that may occur; as always, consult your physician. There are tablets, as well as powdered versions available.
Feverfew has been demonstrated to be mildly effective in some patients for prevention of migraine headache. Feverfew can cause a mild increased tendency toward bleeding, and should be discontinued two weeks prior to any surgery. The problem with many herbal supplements is quality control. The amount of parthenolide (the active ingredient in feverfew) varies widely from farm to farm; certain farms consistently have better quality than others. The usual dose is 2 capsules each morning; there is a liquid form available. Patients occasionally will be allergic to feverfew, and it should not be used during pregnancy.
Miscellaneous herbs/supplements have been used, particularly vitamin B2. CoQ10 and fish oil have also been studied. These occasionally help, but are less effective than Petadolex. MigreLief has been a reliable combination of magnesium, riboflavin, and feverfew. The usual dose is 2 capsules per day, as a preventive. Most people order from MigreLief
Topiramate is an effective migraine preventive, without the weight gain commonly encountered with the other meds. While usually fairly well tolerated, common side effects include memory difficulties (“spaciness”), and tingling. In higher doses, topiramate increases the risk for kidney stones. Topiramate does decrease appetite, leading to weight loss for some patients. This anorexic effect tends to disappear after several months. The usual dose is 50 mg to 100 mg daily, but some do well on as little as 25 mg. The dose may be pushed to 300 or 400 mg per day, in the absence of significant side effects. Topiramate is primarily used for migraine prevention, but has also been utilized for cluster and tension headache as well. Topiramate may cause a metabolic acidosis, with lower bicarbonate levels (and increased chloride). The acidosis may lead to the tingling, which sometimes is alleviated by increasing potassium-containing fruits/vegetables (or adding potassium). Trokendi XR is an excellent long-acting form of topiramate, approved for migraine prophylaxis. The FDA also approved Qudexy XR (topiramate) for once-daily dosing.
Valproate, or divalproex sodium (Depakote), is a longtime staple, popular for migraine prevention. It is usually well tolerated in the lower doses used for headaches; however, the generic may not be as effective. Liver functions need to be monitored in the beginning of treatment. Valproate also is one of the primary mood stabilizers for bipolar disorder. Oral Depakote ER (500 mg) is an excellent once-daily, long-acting agent. As with most preventives, valproate needs 4 to 6 weeks to become effective.
The β-blocker propranolol also is FDA approved as a preventive agent for migraines. Long-acting oral propranolol (Inderal), for example, is very useful in combination with the tricyclic antidepressant amitriptyline. Dosage begins with the long-acting agent given at 60 mg per day, and is usually kept between 60 and 120 mg per day. Lower doses are sometimes effective, such as 20 mg twice a day of propranolol. Other β-blockers also are effective, such as metoprolol (Toprol XL) and atenolol. Some of these are easier to work with than propranolol because they are scored tablets, and metoprolol and atenolol have fewer respiratory effects. Depression may occur. β-blockers are useful for those migraine patients with concurrent hypertension, tachycardia, mitral valve prolapse, and panic/anxiety disorders. Bystolic (nebivolol) is another β-blocker that may be helpful for the prevention of headaches, and has fewer respiratory side effects than other agents. Bystolic probably has the fewest side effects among the β-blockers.
As noted, amitriptyline is an effective, inexpensive agent that is useful for the prevention of daily headaches and insomnia. As a preventive agent, amitriptyline is prescribed at low doses and taken at night. Sedation, weight gain, dry mouth, and constipation are common side effects. Other tricyclic antidepressants such as doxepin and protriptyline can be effective for migraine. Nortriptyline is similar to amitriptyline, with somewhat fewer side effects. These also are used for daily tension-type headaches. Protriptyline is one of the few older antidepressants that does not cause weight gain. However, anticholinergic side effects are increased with protriptyline; protriptyline is more effective for tension headache than for migraine. Although selective serotonin reuptake inhibitors (SSRIs) are used, they are more effective for anxiety and depression than for migraine.
Naproxen is a very useful agent for the treatment of daily headaches, as well as for younger women suffering from menstrual migraine. Naproxen is nonsedating, but frequently causes GI upset or pain. Effective as an abortive, it may be combined with other first-line preventive medications. Other NSAIDs can similarly be used for migraine prevention. It is crucial to use low doses. As with all anti-inflammatories, GI side effects increase as people age, and therefore NSAIDs are used more often in the younger population. Blood tests are needed to monitor liver and kidney function.
Table 9 reviews first-line migraine preventive therapy.
Second-line Migraine Preventive Therapy
There are a number of second-line migraine treatments. The anti-seizure medication gabapentin has been demonstrated to be mildly useful in migraine and tension headache prophylaxis. In a large study on migraine, doses averaged approximately 2,400 mg per day, but lower doses are usually prescribed. 5 Some patients do well with very low doses (200 or 300 mg per day). Sedation and dizziness may be a problem; however, gabapentin does not appear to cause end-organ damage, and weight gain is relatively minimal. Gabapentin can be used as an adjunct to other first-line preventive medications. Pregabalin (Lyrica) has a similar mechanism of action to gabapentin. Lyrica is fairly safe, but sedation and weight gain often occur.
A safe, non-addicting muscle relaxant, tizanidine is useful for migraine and chronic daily headache. Tizanidine may be used on an as-needed basis for milder headaches, or for neck or back pain. Cyclobenzaprine (10 mg) is helpful for sleeping, and helps some with migraine and chronic daily headache.
There have been a number of studies on the efficacy of using angiotensin receptor blockers (ARBs) and the angiotensin-converting enzyme inhibitors (ACEs) for the prevention of migraine. ARBs are preferred because of minimal side effects. Examples include losartan (Cozaar) and candesartan (Atacand). These may be useful for the patient with hypertension and migraine. Side effects include dizziness, among others, but they are usually well tolerated, with no sedation or weight gain.
Similar to the ARBs, the calcium channel antagonists have been utilized for migraine prevention. Verapamil ER (extended release) is the most commonly used form, with doses ranging from 120 mg daily up to 360 mg per day. Verapamil is probably more effective as a cluster headache preventive.
Polypharmacy is common in migraine prevention. Two first-line medications often are used together, and the combination of 2 preventives can be more effective than a single drug alone. For example, valproate often is combined with an antidepressant. Amitriptyline may be combined with propranolol (or other β-blockers), particularly if the tachycardia of the amitriptyline needs to be offset by a β-blocker; this combination is commonly used for “mixed” headaches (migraine plus chronic daily headache.) NSAIDs may be combined with most of the other first-line preventive medications. Thus, naproxen often is given with amitriptyline, propranolol, or verapamil. Naproxen is employed simultaneously as preventive and abortive medication. Polypharmacy commonly is employed when significant comorbidities (anxiety, depression, hypertension, etc.) are present. Unfortunately, polypharmacy brings the risk of increased side effects.
Venlafaxine (Effexor XR) is an excellent antidepressant, occasionally helpful for the prevention of migraine. It is used primarily as an SSRI at lower doses; at higher doses (100-150 mg) norepinephrine also is increased. In fact, antidepressants with dual mechanisms (serotonin and norepinephrine) are more effective for pain and headache. Another similar medication is duloxetine (Cymbalta), with typical doses being 30 mg to 60 mg daily. Cymbalta has several pain indications, but is probably more effective for moods than for headache.
A review of second-line treatment can be found in Table 10. 6
What’s New in Headache
Transcranial magnetic stimulation (TMS) has been the primary new therapy to emerge. In addition to TMS, ketamine is (occasionally) being utilized for refractory headaches. Calcitonin gene-related peptide (CGRP) inhibitors are in the late stages of development for the prevention of migraine; however, if they are approved, CGRP inhibitors will not be available until mid-2018 (at the earliest).
Transcranial Magnetic Stimulation (TMS)
TMS has primarily been utilized for depression. The repetitive TMS units give thousands of pulses in an hour. The SpringTMS (from eNeura) hand-held system imparts only a single pulse. There have been a number of well-done studies on TMS for headache and depression. The patient uses a hand-held TMS device, 4 pulses twice daily (as a preventive). This takes about 5 to 10 minutes for the 4 pulses. TMS may be used abortively as well. Long-term efficacy is not well established. However, early results are promising, at least for a subset of refractory chronic migraineurs. TMS has been safe, although some patients do not like the “thump” that each pulse imparts. The cost is $450 for the first 3 months (the company rents the machine to the user).
Ketamine has been used to treat refractory pain or depression for the past several years. Ketamine is an NMDA receptor glutamate antagonist. In addition, ketamine affects several other receptors as well. Ketamine has been used for treatment-resistant depression, primarily as the IV formulation. Ketamine has been a drug of abuse, and has major addiction potential. There have been a number of successful trials utilizing ketamine, either intravenously or as a nasal spray. A nasal spray form of Ketamine may be marketed for severe depression in 2019.
The intravenous treatment may be more effective than using ketamine as a nasal spray. However, this author has found that the nasal spray is exceedingly well tolerated, with few side effects. The usual side effects include feeling euphoric, sleepy, dizzy, and (with the IV form) hallucinations.
This author has utilized ketamine for 42 refractory headache patients, some of whom also suffered from severe depression. Our results indicated that ketamine is more helpful for the depression than the pain. The decrease in headache tends to be short-lived. However, certain patients do well with both depression and headache. We have used only the nasal spray. It is formulated as a liquid, 10 mg ketamine per 0.1 mL. The patient does the treatment in our office once per week. The usual dose is 10 mg (one spray) every 10 to 15 minutes. Usually the total dose for the treatment ranges from 50 mg to 100 mg. We check vitals after every 2 sprays (occasionally blood pressure will rise with ketamine).
Several newer formulations of older migraine medications have emerged. Onzetra nasal powder is a new form of sumatriptan nasal spray. Onzetra uses a unique “breath powered” delivery system. Onzetra delivers 11 mg of sumatriptan powder per breath; the usual dose is 22 mg at one time. This places the sumatriptan powder posteriorly, where there is respiratory epithelium. This epithelium is more conducive for absorption of medication than is the anterior squamous epithelium. Onzetra has excellent efficacy, and is well tolerated.
Trokendi XR is a long-acting formulation of topiramate. Trokendi has the indication for migraine prophylaxis. In our (anecdotal) experience, approximately 70% of patients prefer the Trokendi XR, versus the generic topiramate.
Medical cannabis has been used for about 5,000 years. Cannabis has multiple active ingredients—tetrahydrocannabinol (THC) is the main cannabinoid for analgesia and also produces the euphoric effect. Cannabidiol (CBD), the other important compound, is an anti-inflammatory. CBD also may enhance analgesia. One advantage of medical marijuana is that the dispensary is able to manipulate the percentage of THC vs. CBD. It often takes weeks to months in order to achieve optimum results. Vaporized inhalation is the most commonly employed route. Marijuana may help with anxiety as well as the pain.
Vagal Nerve Stimulation
Non-invasive vagal nerve stimulation (VNS)—the gammaCore VNS system from the company electroCore— was approved in April 2017 for use in episodic cluster headache (not yet approved for migraine) in adults. VNS may suppress glutamate levels in the trigeminal nucleus caudalis, resulting in decreased head pain. The portable gammaCore VNS has demonstrated efficacy for cluster headache. The long-term results in migraineurs has yet to be established. This form of VNS has minimal side effects or dose limitations. The device is not indicated for patients with an active implantable medical device, such as a pacemaker or hearing aid; those with carotid atherosclerosis, or who have had a cervical vagotomy. Also patients with hyper- or hypotension, bradycardia, or tachycardia are not candidates for the device.
Migraine is a common and disabling illness. Outside of meds, it is important for migraineurs to watch their headache triggers, and exercise regularly. Physical therapy and/or psychotherapy may be of help (“it takes a village”). There is no good algorithm for determining which medication is best. Each patient is unique, and comorbidities drive where we go with treatment. The goal is to decrease head pain, while minimizing medications.
How To Prevent Menstrual Migraine
Unfortunately, many women have resigned to menstrual migraine (also known as hormonal migraine) because they believe if there’s little you can do about your cycle then there is not much you can do about your migraine attacks. Right?
There a number of options to treat and prevent, yes, prevent menstrual migraine attacks. To understand how and why these treatments can help, it is important to understand what happens and how things change during the month.
How The Menstrual Cycle Can Cause Migraine
Women who experience menstrual migraine may be sensitive to hormonal fluctuations experienced just prior to the onset of menstruation. Just before menstruation there is a natural drop in progesterone levels.
The two important females hormones involved are progesterone and estrogen.
Progesterone is a natural steroid hormone involved in the female menstrual cycle that stimulates the uterus to prepare for pregnancy. It is a naturally occurring hormone in the female body that helps a healthy female function normally.
Estrogens or oestrogens (American and British English spelling respectively), are a group of compounds that are important in the menstrual and reproductive cycles. They are also naturally occurring steroid hormones in women that promote the development and maintenance of female features of the body.
It is important to note that estrogens are used as part of some oral contraceptives and in estrogen replacement therapy for some postmenopausal women.
Throughout the natural menstrual cycle the levels of these hormones fluctuate. During the cycle, the levels of progesterone and estrogens also change in relation to each other. See the image below for how these levels change throughout the cycle.
These fluctuations are normal and part of being a healthy and fertile woman.
Several research studies confirm that migraine is significantly more likely to occur in association with falling estrogen in the late luteal/early follicular phase of the menstrual cycle. 
Researchers failed to find an absolute level of estrogen associated with migraine in this phase which supports the theory that falling levels of estrogen are more important than an absolute level. [8,9]
The withdrawal of estrogen is independent of several important factors :
- It is independent of ovulation as it can trigger migraine during the hormone-free interval of combined hormonal contraceptives.
- It is independent of menstruation and progestin as migraine can be triggered in those who have had hysterectomies.
Interestingly, no clear relationship between progesterone and migraine was found. 
Is estrogen withdrawal the sole trigger for menstrual migraine?
Researchers suggest no. Menstrual migraine is associated is menstrual cramps and painful periods, both of which respond to nonsteroidal anti-inflammatory drugs. This suggests the involvement of prostaglandins. Prostaglandins are hormones created at the site of injury or illness. They help control inflammation, blood flow, and the formation of blood clots.
Prostaglandins levels have been shown to increase threefold during the luteal phase of the menstrual cycle with a further increase during the first 48 hours of menstruation. This mirrors the timing of an increased risk of a migraine attack. 
Timing Is Important
Across the menstrual cycle menses typically occurs from day 1 to day 5. This is where up to 40% of women reported a migraine attack. In the three days prior to day one, the incidence of migraine in women rises by approximately 10% to 25%. 
The timing of a menstrual migraine attack provides clues on how best to treat each case. Below are different hormonal states that may be causing regular menstrual migraine.
- If it occurs just prior to the onset of menstruation then it may be due to the natural drop in progesterone levels.
- Headaches or migraine can also occur at ovulation when estrogen and other hormones peak.
- Or it may occur during menstruation itself when estrogen and progesterone are at their lowest.
Knowing when your menstrual migraine occurs will determine the best prevention strategy.
A good way to determine when your migraine attacks are occurring is by keeping a record of at least 3 cycles to track exactly when your migraine attacks occurred. Remember to note the precise day(s) of your cycle as closely as possible.
Once you have a clear understanding of which days in your menstrual cycle the migraine is occurring, then you are in a better position to begin treating it. A simple diary can be very helpful.
Menstruation increases the likelihood of migraine without aura, but not for migraine with aura. 
Most women with migraine associated with menstruation also have additional attacks with or without aura at other times of the cycle.  The diagnosis for this type of migraine is referred to as Menstrually-Related Migraine.
Fewer than 10% of women report migraine exclusively with menstruation and at no other time in the month. The formal diagnosis for this minority of female patients is Pure Menstrual Migraine. 
In those who have Menstrually-Related Migraine, attacks that occur during menses are likely to be more severe, disabling, last longer, and be less responsive to medications compared to attacks at other times of the cycle. 
Interestingly, migraine with aura appears to be unaffected by menopause whilst migraine without aura can be exacerbated by menopause. 
To diagnose menstrual migraine a history, examination, and diary analysis is required by your healthcare professional. There should only be investigations or further tests required to rule out any other primary causes of migraine.
Relying solely on memory is considered insufficient and a diary over at least two to three consecutive menstrual cycles is considered best practice. 
International Classification of Headache Disorders (ICHD) III
A1.1.1 Pure menstrual migraine without aura
A. Attacks, in a menstruating woman, fulfilling criteria for 1.1 Migraine without aura and criterion B below
B. Occurring exclusively on day 1 ± 2 (i.e. days −2 to + 3) of menstruation in at least two out of three menstrual cycles and at no other times of the cycle
A1.1.2 Menstrually related migraine without aura
A. Attacks, in a menstruating woman, fulfilling criteria for 1.1 Migraine without aura and criterion B below
B. Occurring on day 1 ± 2 (i.e. days −2 to + 3) of menstruation in at least two out of three menstrual cycles, and additionally at other times of the cycle
A188.8.131.52 Pure menstrual migraine with aura
A. Attacks, in a menstruating woman, fulfilling criteria for 1.2 Migraine with aura and criterion B below
B. Occurring exclusively on day 1 ± 2 (i.e. days −2 to + 3) of menstruation in at least two out of three menstrual cycles and at no other times of the cycle
A184.108.40.206 Menstrually related migraine with aura
A. Attacks, in a menstruating woman, fulfilling criteria for 1.2 Migraine with aura and criterion B below
B. Occurring on day 1 ± 2 (i.e. days −2 to + 3) of menstruation in at least two out of three menstrual cycles, and additionally at other times of the cycle
Menstrual Migraine Management
The most effective strategy to manage menstrual migraine depends on several factors :
- How well acute treatments work for the patient
- Predictability and regularity of the menstrual cycle
- Use of or need for contraception
- The presence of menstural disorders or perimenopausal symptoms
Treatments indicated for acute migraine can be used to treat menstrual migraine.  Most treatments have not been tested specifically for menstrual migraine attacks so the true efficacy of some of these treatments in menstrual attacks is unclear.
Table: Acute Treatment of Menstrual Attacks of Migraine 
If used only around the time of menses then the risk of developing medication overuse headaches is low. Due to the long duration of menstrual attacks, repeated relapse can be an issue and a need for prevention is may be required.
Those who have frequent migraine throughout their cycle regardless of the relationship to menstruation are likely to benefit from prevention strategies.
If preventive treatment reduces the frequency and severity of nonmenstrual attacks but not menstrual attacks, then a “mini” perimenstrual preventive strategy is indicated.
The prefix “peri” refers to prevention around menstruation. These are short term treatments which target the time of increased risk during the cycle. This differs from standard preventive strategies which continue on an ongoing basis across the full cycle.
Important: For perimenstrual prevention the use of the treatment is different from the label so the drug will likely need to be prescribed off-label. Always seek medical advice and supervision if considering perimenstrual prevention.
The best evidence supports the use of Frovatriptan. This is given the highest level rating as “A” for its efficacy evidence. Frovatripan can be taken at 5 mg twice daily starting two days before day 1 of the cycle, then 2.5 mg for five days from day one of the cycle (total of six days). [7,9]
Naproxen has a “B” level rating but it still the next best option to try if Frovatriptan has negative side effects or is contraindicated for any reason. 500 mg of naproxen is taken daily for 14 to seven days over the high-risk window during the cycle. This treatment can commence one week prior and continue until one week after day one of the cycle. 
Level B evidence also supports the consideration of naratriptan and zolmitriptan. Naratriptan 1 mg, two times a day is taken for six days, starting three days before the expected onset of menstrual migraine. Zolmitriptan 2.5 mg is taken two-three times a day for seven days starting two days before the expected onset. 
Estradiol gel, an estrogen supplement, has a “C” level rating but is also another option. 1.5 mg daily is used for seven days. This treatment regime commences five days before the onset of menstruation and continues until day two. This strategy prevents the late luteal phase drop in estrogen that can trigger estrogen withdrawal migraine. Important note: women using should be menstruating regularly with natural progesterone following ovulation providing endometrial protection. 
Continuous hormonal options aim to suppress ovarian activity and maintain hormonal levels.
For women who also need contraception, there are several contraceptive strategies that may also benefit migraine. For migraine with aura, combined hormonal contraceptives have additional benefits including a reduced risk of endometrial and ovarian cancer. 
Estrogen withdrawal during the hormone-free interval can trigger migraine attacks but can prevented using estrogen supplements. Estrogen supplements that may be considered include :
- 10 mcg of oral ethinyl estradiol
- 0.9 mg oral conjugated equine estrogens
- 100 mcg estradiol patches
- 2 g estradiol gel
A simpler way to reduce the number of withdrawal bleeds and number of attacks may be to use an extended cycle of 84/7 regimes or to none through continuous combined hormonal contraceptive use. 
Continuous combined hormonal contraceptive use are well tolerated. Unscheduled bleeding is common in the early cycles of treatment but usually resolves over time. Typically by 10-12 months 80-100% of women experience no bleeding.
Some evidence suggests that if menses is avoided consistently then that can benefit the migraine condition. 
Combined hormonal contraceptives are associated with an increase in stroke by twofold. This risk should not be a significant concern for patients with no other cardiovascular risk factors. Patients should be screened for these risk factors before prescription.
Common cardiovascular risk factors:
- High blood pressure
- High Cholesterol
- Family history of cardiovascular event
- Migraine with aura
- Poor diet
- Lack of physical activity
The presence of migraine with aura is associated with a twofold increase in stroke. Therefore patients with migraine with aura are not advised to add further risk by taking combined hormonal contraceptives. 
Gonadotrophin-releasing hormone analogues
This treatment has been found useful in resistant menstrual migraine conditions for some patients. It causes a reversible ‘medical’ menopause resulting in the cessation of ovarian activity. Add-back hormone replacement therapy is usually required to treat any unwanted side effects and preserve bone density. 
A hysterectomy with or without the removal of one or both ovaries increases the risk of migraine.  Therefore surgery is not recommended for menstrual migraine.
If a hysterectomy is indicated for other gynecologic factors then the effect on migraine can be managed with the immediate use of continuous transdermal estrogen replacement therapy. 
Therefore to answer the question: Should you get a hysterectomy for menstrual migraine? The answer is a definitive no.
A hysterectomy purely for menstrual migraine is permanent, invasive and an expensive surgical operation that has been shown to make migraine worse. 
Why is it ineffective for menstrual migraine?
Menstrual migraine attacks are caused by a fall in hormones which are triggered by the ovaries. Whilst menstruation stops with a hysterectomy, it does not stop the ovaries from continuing to produce monthly hormonal fluctuations which can trigger migraine.
There are other ways to non-surgically address the hormonal fluctuations caused by the ovaries. See hormonal treatments listed above.
Complementary Menstrual Migraine Treatments
There are many different approaches to help manage menstrual migraine some involve medicinal treatments and others do not. Often it may involve a combination.
Rest assure that it is possible to reduce and in some cases eliminate menstrual migraine. But it may involve working with a specialist and some trial and error.
Complementary approaches for those with menstrual migraine include:
- Dietary changes
- Lifestyle factors
- Hormonal balancing
- Other natural therapies
Most women with menstrual migraine have a healthy hormonal balance. However, if there is an imbalance of estrogen in relation to progesterone then a healthy diet is the first step (in fact it should be one of the first steps for migraine patients). What we eat plays a huge role in our overall health and wellbeing.
“Nothing else affects our health more than what we eat.”
If you experience migraine attacks then your diet can be important.
We hear all the time from the health community something like ‘eat a varied and well-balanced diet to help prevent disease’. It’s been said so many times we can become numb to this important advice.
To complicate things, some healthy foods may also act as triggers. Finding out which foods trigger attacks is not always easy.
Why Might Diet Important For Menstrual Migraine?
Estrogen levels require stricter regulation compared to other hormones in your body to ensure the natural rhythm runs smoothly (2). If this balance is slightly off for what your body requires, then you may experience discomfort with symptoms such as PMS, breast tenderness, headaches and, in susceptible women, migraine attacks.
Small variances above or below the normal regulated levels can have significant impacts on your health.
The liver metabolizes estrogen. A healthy liver will rapidly metabolize estrogen but if it is overloaded with medications, artificial substances, chemicals or harmful substances from food or drinks can affect the metabolization of estrogen.
Our diet is thought to be the biggest factor affecting our hormones through the exposure to certain chemicals in food products. Research suggests that diet can attribute up to 90% of all factors affecting your hormones (3).
“Compared to other hormones such as progesterone, estrogen levels need to be tightly regulated for the ‘choreography’ to run as smoothly as Mother Nature intended — even small excesses or deficiencies of estrogen can have huge effects on your well-being. A healthy liver metabolizes estrogen rapidly into the more benign of its metabolites. But when it’s bogged down with detoxing medications, environmental chemicals, and harmful substances from food or drink, it can over-metabolize estrogen into its less desirable forms, which can pose a real threat to your health if allowed to accumulate.”
Certain food ingredients act like toxins which can disrupt your hormonal balance, so reducing or eliminating these help keep your hormones in balance. Examples of toxins you may commonly come across include:
- MSG (monosodium glutamate) – found as a flavor enhancer in many processed foods.
- Hydrolysed Vegetable Protein
Avoid or, if possible, eliminate
- simple carbohydrates
- refined sugars
- processed foods
- avoid well-known migraine trigger foods.
If in doubt about what food triggers your attacks, it may be worth considering some of the following:
- keep a food diary
- food allergy test
- consult a certified dietitian or nutritionist
Keeping a food diary is highly recommended. Be careful to include in your diary not just what you eat, but also record other factors which may affect your migraine attacks to minimize misattribution of a migraine attack to a particular food or trigger. Uncovering what exactly caused the attack takes a some time and patience but the process gives you more control and confidence over your condition. The results are often surprising.
Food allergy tests unfortunately do not test for specific migraine triggers. But they can be effective at showing what foods your body is reacting abnormally too. Eliminating foods which cause stress or overreactions in the body may improve your migraine frequency or severity.
A detoxification may help cleanse your system of the offending substances but there is little scientific evidence supporting the efficacy of a detoxification. It may simply be a psychological way to push the ‘restart’ button when beginning a new eating regime.
If you are serious, consulting a certified health care professional like a nutritionist or dietitian to assist you is a good idea. Elimination diets can be tricky and sometimes dangerous to do by yourself. There is a risk of malnutrition if you don’t know exactly what you’re doing.
To ensure your wellbeing seek qualified professional support. That way you will have the best chance of reducing your attacks without malnourishment or starvation.
Another simple dietary preventive strategy is simply a matter of drinking enough water, especially during menses. Herbal teas are also great option for hydration if you’re getting bored with water. In summer a slice of lemon or lime with mint and water can also be a refreshing way to stay hydrated.
Lifestyle factors like sleep, movement or exercise play a central role in migraine management.
The right levels of sleep and exercise are vital for brain health. What is good for the brain is good for migraine.
Sleep is a restorative function for brain and body. It is not just about getting enough sleep each night. It’s about how regular your sleep/wake cycle is. Are you going to bed and waking up at the same time each night? What about on weekends?
It’s also about the quality of sleep. The hours of sleep before midnight count more. 9 hours total sleep starting from 10pm is much better than 10 hours of sleep starting from 1am.
Are you waking up at the same time each morning?
Nobody is perfect, but the better you can get into a consistent routine of high-quality sleep, the better for your condition.
Exercise promotes a healthy metabolism, hormonal balance, reduces stress, assists in sleep, stabilizes your mood and gives you an overall sense of well-being.
Just in case you needed another reason to exercise, the brain loves movment and exercise. Exercise is a great preventive strategy for many with migraine and the science proves it. One study showed  that exercising using the indoor bike for a 20 minute workout three times per week was as effective as one of the most popular migraine preventatives – topiramate.
For a few people exercise can trigger migraine attacks. If that’s the case, start slowly and build gradually. Give yourself a generous and slow warm-up before jumping into your exercise. Be sensible about it. Don’t start by trying to run 5 miles. Don’t exercise on days when your feeling vulnerable to a migraine attack.
If you exercise outside, wear a hat, keep hydrated, and don’t let yourself get too hungry.
The evidence for daily exercise is still being uncovered. Even starting small with a five-minute walk or a short, easy bike ride can be beneficial. Aim for 30 minutes of some activity or movement each day. You can break it up, for example into three 10 minute sessions.
You will feel better for it. When you take care of your body, your body is more likely to take care of you.
Addressing hormones without addressing underlying diet and lifestyle factors is like trying to clean the house by sweeping all the dirt under the rug. It’s a superficial approach.
Hormones do have a significant influence on bodily functions. 80% of pregnant women experience a remission of migraine during pregnancy according to studies. 
To assess hormone levels, blood, saliva, and urine testing may be performed to establish a baseline and to identify any hormonal imbalances which may be contributing to migraine.
Thyroid testing is also important as hypothyroidism is more common in those with migraine.
In menstrual migraine, often the trigger is the falling levels of estrogen which occurs naturally before menses. Estrogen can be topped up in several ways such as via skin patches or gel which is absorbed into the bloodstream. A patch can be applied for seven days beginning three days prior to the first day of menses. Note: if you are trying to get pregnant you should speak to your physician before you explore hormonal treatments.
Another increasingly popular approach to deal with the drop of estrogen involves stabilizing hormones through the use of the low dose estrogen combination pill which has a constant dose (monophasic).
For others with menstrual migraine, problems may appear to arise due to the estrogen dominance and progesterone deficiency. In these cases, bio-identical progesterone in the second half of the female cycle to balance the hormones has shown some success (4).
It is a good idea to consult with a healthcare professional who has experience with menstrual migraine and who understands female hormones. Look for a headache specialist, certified gynecologist or endocrinologist who has a good track record with menstrual migraine.
Dr. Mauskop from the New York Headache Center has found that magnesium supplementation for those with menstrual migraine may be beneficial. He has also found that low magnesium levels may be attributed to a lower migraine threshold. Lower migraine thresholds make you more vulnerable to attacks and require less stimulation and fewer triggers to lead to an attack.
400 mg of magnesium every day can be used as a migraine preventative. Unfortunately there no simple tests for magnesium deficiency as it’s the intracellular level of magnesium that we need to improve. The best way to see if it works for you is to try it and ensure that you are absorbing it effectively.
If the migraine attacks are severe or also occur frequently outside of menses then a migraine preventative may be prescribed.
When considering preventive medicinal treatments it is best to discuss what options might be best for you with your doctor who has your full medical history.
Other Natural Therapies
There is less clinical evidence behind the efficacy of natural and homeopathic therapies, but they may have fewer side effects, be better tolerated and offer a natural alternative.
That said, if they don’t help, you’ve wasted your money.
Do your research before jumping into these kinds of treatments to decide if it’s appropriate. Discover 6 natural, complementary treatments with evidence for migraine.
If you don’t have a well-balanced diet then you may not be getting your required vitamins and minerals. Supplements in this scenario may be useful. Some that have been reported to help those with migraine include Riboflavin, Feverfew, Butterbur, Vitamin B6, Magnesium, Ginger, Coenzyme Q10 (CoQ10) amongst others.
Ordering the cheapest option from Amazon is not your best option. Vitamins are still considered medication but have far less regulation and quality controls in place. Often it’s worth paying extra for a reputable brand to ensure quality and safety.
Many vitamins are contraindicated for pregnant women or women trying to get pregnant so speak to your pharmacist or doctor before ordering them.
Perimenopause increases the risk of migraine and additional complications around irregular periods which can make perimenstrual prevention difficult. Perimenopausal symptoms may also warrant specific treatment often with hormonal replacement therapy. 
Oral estrogen can make migraine worse so non-oral routes are preferred and administered continuously to stabilize hormone levels. 
Endometrial protection with progestin is needed for many women in perimenopause and continuous delivery again is better tolerated than cyclical administration.  Levonorgestrel intrauterine system currently licenses continuous progestin treatment which is available to perimenopausal women.
If estrogen is not an approved option for any reason then paroxetine 7.5 mg at bedtime is the only non-hormonal therapy approved by the FDA for the treatment of perimenopausal symptoms. Gabapentin has grade “A” evidence to help with symptoms from perimenopause but there is currently inadequate or conflicting data to support or refute this treatment for migraine (Grade “U”).
To summarize, if your migraine attacks occur at the same time each month:
- Keep a diary to inform you and your healthcare professional of exactly when the attacks begin during your cycle.
- Take into account how predictable and regular your cycle is.
- Evaluate the need for contraception
- Is there a presence of menstrual disorder or perimenopausal symptoms?
- Consider daily prevention or perimenstrual prevention
- Review your diet
- Get enough quality sleep, consistently
- Exercise regularly
- Stay adequately hydrated, especially during menses
- Try magnesium supplementation
- Balance your hormones
- Consider other natural alternatives or supplements known to help those with migraine.
Often, it is the things we consume or do unknowingly that exacerbate migraine. Identifying and modifying these factors with an improvement to your lifestyle and diet is where you can have the most dramatic and sustainable results.
Still have a question for relating to menstrual migraine? Ask in the in the comments below.
Prevent hormonal or menstrually related migraine attacks with the help of this simple one-page checklist. For a limited time, we are emailing a copy to every reader.
- MacGregor E.A., Brandes J., Eikermann A., Giammarco R. (2004) Impact of migraine on patients and their families: the migraine and zolmitriptan evaluation (MAZE) survey-phase III. Curr Med Res Opin 20: 1143–1150
- Holmes, M NP, http://www.womenshealthnetwork.com/womenshealth/menstrualmigraines.aspx Accessed Oct 2013.
- Fürst P (October 2006). “Dioxins, polychlorinated biphenyls and other organohalogen compounds in human milk. Levels, correlations, trends and exposure through breastfeeding”. Mol Nutr Food Res 50 (10): 922–33.
- Mostovoy, A. ‘Migraines – Helpful Solutions’ http://www.drmostovoy.com/Migraines.html. Accessed Oct 15, 2013
- Varkey, Emma, et al. “Exercise as migraine prophylaxis: a randomized study using relaxation and topiramate as controls.” Cephalalgia 31.14 (2011): 1428-1438.
- Somerville, Brian W. “The role of estradiol withdrawal in the etiology of menstrual migraine.” Neurology 22.4 (1972): 355-355.
- MacGregor, A. ‘Hormonal Influences In Migraine’. Presented at ANZHS Masterclass. 18 August 2018.
- MacGregor, E. A., et al. “Incidence of migraine relative to menstrual cycle phases of rising and falling estrogen.” Neurology 67.12 (2006): 2154-2158.
- MacGregor, E. Anne. “Migraine management during menstruation and menopause.” Continuum: Lifelong Learning in Neurology 21.4, Headache (2015): 990-1003.
About The Author
Carl stopped taking his health for granted at an early age due to migraine. He has had migraine for 26 years. Over this time health has become central throughout his life and work. Today, he works with charities, foundations, and organizations to help lift the global burden of migraine including Headache Australia, the Brain Foundation, the Coalition of Headache and Migraine Patients, and the European Migraine and Headache Alliance. He is a member of the International Headache Society, he acts on several advisory boards and he also is the author of MigrainePal and co-host for the Migraine World Summit. Carl is a public and passionate patient advocate for migraine. He has spoken nationally and internationally about migraine and the need to increase research funding, reduce stigma, increase patient support and education. He has been featured in national TV, print and radio stations.
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2) As you mentioned some kind of sleep disorder. It may be worth speaking with a sleep specialist if you think your shallow breathing is an issue. The brain needs oxygen. People with sleep apnea and migraines often improve significantly when the sleep apnea is treated.
3) Sleeping environment. i.e. using a supportive pillow; not sleeping on your stomach (and pitching your neck); less common are things are a mouldy environment, very old pillows which need to be replaced etc.
I hope that gives you a few ideas Jan. Good luck!
I hope that helps Billie.
I hope things improve soon!
I hope you continue to enjoy your success!
I hope your Botox treatment goes well. Good luck!
you might like to read through them to see if anyone mentions treatment for menstrual migraine. There is not any reliable scientific evidence on the daith piercing to date.
on November 26, 2020 at 7:15 am
Not for me personally. I love it. Healthy fats!
on September 6, 2018 at 9:36 pm
Proranolol is a preventive treatment for migraine. Sumatriptan is not. If taken too often sumatriptan can lead to medication overuse headache (MOH) or rebound headaches. See this article for more details.https://migrainepal.com/rebound-headache/
From the guide in that article you should get a better understanding of whether you are at risk of MOH or not. Also, for women around your age perimenopause can be a tumultuous time for migraine attacks.
A preventive treatment may really help but if you don’t like the sound of propranolol, there are others. For example those listed here: https://migrainepal.com/preventative-treatments/ I hope this helps.
on December 24, 2019 at 6:29 am
That is a fantastic result Rachel. Congratulations. I agree with you that the body can heal itself… it does this all the time. Sometimes we do need extra help to heal. I haven’t seen any studies supporting the efficacy of your treatment. But the absence of evidence does not always mean the absence of efficacy.
Great article! Thank you for sharing your experience and research. Reading through all the comments is another proof how each migraineur is a unique individual with the challenge to find what works for them specifically. I also appreciate how caring you responded. I have lived with migraines for 33 years now. My first onset was a traumatic experience with the left side of my body going tingly and numb, then the right side. I thought I stubbed my foot in the cement pool floor at first. By the time I got out of the pool to open the locked door I had to hobble in and up the elevator. When I reached out condo I was frantic and my mom helped calm me, but by the time we were ready to go to the Dr’s, both sides were numb and I could not dress myself although I tried (couldn’t the me shoes, button my blouse, or drink water without dribbling). At the doctor’s office I had episodes of blacking out and saying things that were not true (thankfully only to my mom). I went to the children’s hospital for testing and my dad stayed with me. The excruciating head pain along with nausea and vomiting set in, which continued after my hospital stay. Our doctor stated that this was a migraine with onset due to hormone changes, MSG, and the use of Nintendo games (which was brand new to the market). My migraines are hereditary, my paternal grandmother had them, my dad had one in his life. I have not ever experienced another episode like that but currently have had over a year of chronic migraines. I went into remission during pregnancy, but after my third son had another chronic year, then I had 2 more boys over 5 years (mom of 5 boys and so happy for each) and years of less migraines. A neurologist shared a long list of food triggers that I stick to. My chronic migraines are hormone related with also learning of new food or other triggers. My PA has been very helpful this past year with tests and trying to figure out a treatment plan. With a low estrogen birth control pill (first full year ever on one) I at least know when my hormone triggered migraines will come. Like so many others, it is hard to go through and the past year has been rough, but I have learned a great amount on many levels. I started an all natural supplemental health system and have cut down my 16-18 migraine days per month to 11-12 with this month on track to being less. I have learned the pathophysiology of migraines along with reading several articles over this past year of this migraine journey. From your article I learned some things that I had not before read, the point about the liver’s role concerning our hormones. I also learned that there is a yearly migraine summit, which I did not know. I never quite believed migraines were caused by blood vessel dilation/constriction that was theorized for years. Our migraines have numerous factors, including genetic code differences. We each suffer in different ways and a diary of keeping track of symptoms along with food/liquid intake is a great start. I have learned about pre migraine symptoms and post migraine symptoms by keeping track on a small pocket size notepad and calendar. As an Oncology RN who works nights, I am grateful for my intermittent FMLA that helps keep my job secure. I may have to live with migraines all my life, but I am stronger for it. Each individual has something they go through and our kind compassion to each person whether they suffer from migraines or another ailment helps, especially when we are kind to ourselves. Thank you very much for this article and sharing your knowledge.
on January 24, 2020 at 1:10 pm
Something else that has been on my mind is if cerebral spinal fluid levels fluctuate during migraine episodes and if that has any role in the chemical messaging system involving hormone levels. There is such a delicate balance needed and having the right balance or finding it is like a difficult treasure hunt.
on January 29, 2020 at 8:28 am
Not to my knowledge. But there is such a thing as high and low-pressure headaches which relate to the CSF in the brain.
Hi Sharlin, this is the first time I’ve heard of Nintendo games being a migraine trigger from a doctor. Lol.
Thank you for sharing your experience. You’re right. Everyone is an individual. I am too am stronger and healthier because of migraine. There is solace in that.
on June 22, 2020 at 1:43 am
Hi Ed, migraine evolves over time. It is very common to experience a change in symptoms or a shift from head pain to other symptoms such as the aura you mention. Regarding your family history of stroke that’s something your doctor really needs to evaluate on an individual basis. The dose and type of HRT may also affect the risk so there may be more than one option available to you. I hope that helps.
on August 24, 2020 at 7:03 am
This might sound silly but good sleep is important for exhaustion. Good quality sleep takes into account duration (how long), quality (not lots of broken sleep, not having untreated sleep disorders like sleep apnea etc) and consistency of sleeping patterns.
Hi Catherine, I interviewed Dr. Anne MacGregor, a world leading in migraine and hormones on this topic and this is what she said to me:
“A hysterectomy is probably the most inappropriate management of menstrual migraine. The reason being, it is because what is a hormone? A hormone is a chemical messenger that goes from one organ to another, so in the case of menstrual migraine and approaching the perimenopause, the ovaries that are producing the estrogen are receiving messages from an organ within the brain. So actually, if you have a hysterectomy, you remove the womb, you remove the ovaries, you’ve still got the driving organ of the brain that’s trying to send messages to the ovaries, that are no longer there.
So actually, hysterectomy, from the evidence we’ve seen, will initially make migraine worse, because you’ve still got the driving hormones from the brain that now have no messenger to be sent to. So hysterectomy is not an appropriate management strategy for menstrual migraine.”
I hope this makes it a little clearer – she is more articulate than myself. If not please let me know.
A good Massage therapy is a great way to relieve the chronic headache that you feel. With the help of a pure kind essential oil.