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9 Articles in Volume 14, Issue #6
Migraine Treatment From A to Z
Alternative Medicine in Chronic Migraine 2014: What Clinicians Need to Know
Hormone Abnormalities in Uncontrolled Chronic Pain Patients: Use of Hormone Profiles
Interpreting Negative Urine Drug Test Results
Case Challenge: Chronic Opioid Use Causing Adrenal Insufficiency
Editor's Memo: Toxic Insurance Plans
Guest Editor's Memo: The Forgotten Patients: Those Who Benefit From Opioid Treatment
Ask the Expert: Multiple Benzo Prescriptions
Ask the Expert: Burning Foot Syndrome

Migraine Treatment From A to Z

Migraine is a very common and disabling illness. Choosing a therapeutic agent that is best for each individual patient requires consideration of the patient's history, lifestyle, comorbid conditions, and individual preferences.

Migraine headaches are a common cause of disability in the United States, affecting approximately 60 million American adults, or 17.1% of women and 5.6% of men.1 To help define migraines better, the term classical migraine has been replaced with migraine with aura, and nonclassical migraine now is 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 to prevent migraine onset.

This review will highlight the current definitions of migraines as well as treatment options.

Migraine Characteristics

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 migrainosis 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. Between 70% and 75% of migraine patients report 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 definitive 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.

Taking a History

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 scan 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 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 less than 1 (episodic) or more than 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 per month, with pain described as 24/7.

The pain of the 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 many patients experience vomiting as well. The nausea is often mild, and some patients are not bothered by it. Many patients state that the headache is lessened after they vomit. Diarrhea may occur and usually is 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 very sensitive to bright lights (photophobia), sounds (phonophobia), 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 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 actually may occur during the prodrome of the migraine. Both vascular and muscular factors contribute to the scalp tenderness. Autonomic disturbances, such as pupillary miosis or dilation, runny nose, eye tearing, and nasal stuffiness, are relatively common. These also are symptoms of cluster headache, including the sharp pain about one eye or temple.

Alterations of mood are seen in 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 an 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 prior to the onset of the migraine. The weight gain is usually less than 6 pounds, and is transient. At some point during the migraine, patients often experience polyuria.

Visual Disturbances

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 headache. 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 seen 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 a migraine. These are experienced most often in one hand and forearm, but may be felt in the face, periorally, 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 those with a more rapid pace that are seen in epilepsy.

Paralysis of the limbs may occur, but this is rare. This occasionally is seen as a familial autosomal dominant trait, which is termed familial hemiplegic migraine. With the weakness, aphasia or slurred speech may also occur, and sensory disturbances are seen ipsilateral to the weakness.

Vertigo occasionally is experienced during migraine, and may be disabling. “Migraine-associated vertigo” has become a common diagnosis. Ataxia may occur, but it is not common. Rarely, multiple symptoms of brain stem dysfunction occur, with the term migraine with brainstem aura (previous called 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 may not be 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 which exams a given patient needs.

In addition to the MRI and CT scan, tests that are generally 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, idiopathic intracranial hypertension, hydrocephalus, pheochromocytoma, stroke or transient ischemic attack, internal carotid artery dissection, and systemic illness.

Headache Triggers

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 3 or more meals per day, and going to bed and awaking 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 rather 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. If a person 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, and Pilates, 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 per day. Relaxation techniques such as biofeedback, deep breathing, and imaging also can be helpful for daily headache patients, particularly when stress is a factor.

Many migraine patients have accompanying neck pain. Physical therapy may help, and acupuncture or chiropractic treatments occasionally help as well. Certain physical therapists “specialize” in head and neck pain. Massage may be effective, but the relief often is short-lived. Temporomandibular disorder (TMD), with clenching and/or bruxing, may exacerbate migraine. For patients with TMD, physical therapy, a bite splint, and/or onobotulinum toxin A (Botox) injections may help. It often “takes a village” to help a person with pain, and we recruit other “villagers,” such as physical therapists and psychotherapists.

Caffeine Use

Although caffeine can help headaches, overuse may increase headaches. Patients must limit total caffeine intake from all sources (eg, coffee, caffeine pills, or combination analgesics). 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 per day (Table 3).

Foods to Avoid

As noted, multiple food sensitivities are not common. Patients tend to focus on food, because it is a tangible trigger that one can control (as opposed to weather, for example). However, most people are sensitive to only 2 or 3 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 that food. Table 4 provides a list of foods to avoid.

Medications: Abortives

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 has become the gold standard in abortive headache treatment. The usual dose is 1 tablet every 3 hours, as needed; maximum dose, 2 tablets per day. However, clinicians do need to limit triptan use (ideally, 3 days per week) to avoid rebound headaches or medication overuse headaches (MOH).

Triptans are helpful for moderate as well as more severe migraines. Certain patients may tolerate one triptan better than others, and it is worthwhile for patients to try several. 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.

As noted, if patients do not do well with one triptan (lack of efficacy or side effects), it is usually worthwhile for them to try at least 1 or 2 other triptans. While they are all very similar, the minor chemical differences between them mean that some patients do well with one, and not another.

The usual triptan side effects may include pressure (or tightness) in the chest/neck (or other muscle areas), tingling, and fatigue. These are usually transient, lasting 10 to 30 minutes. If a patient experiences moderate to severe chest/throat/neck pressure (or pain), we usually discontinue the triptan or substitute a milder one (naratriptan/frovatriptan). The chest symptoms are rarely cardiac in nature, which is the primary concern with chest symptoms.

There are a number of triptan choices. Sumatriptan, zolmitriptan, rizatriptan, and naratriptan are available in generic fomulations. Eletripton (Relpax) is a very effective triptan and almotriptan (Axert) is useful for many patients. Treximet is a combination of sumatriptan and naproxen. Frovatriptan (Frova) is a “slow onset,” milder triptan, which has a longer half-life. Zolmitriptan (Zomig) nasal spray is not generic, but it is very effective, with a quick onset of action. The sumatriptan injections (available in various forms) remain the most effective migraine abortives.

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, ibuprofen, and Prodrin (similar to Midrin, but without the sedative). We often combine 2 first-line approaches—for example, a triptan and a non-steroidal anti-inflammatory drug (NSAID).

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. Intravenous DHE primarily is a “venoconstrictor” with few arterial effects. This renders it very unlikely to cause cardiac problems. Indeed, since its introduction in 1945, DHE has been remarkably safe. Intravenous DHE can be administered in the office or emergency room. Nasal (Migranal Nasal Spray) and inhaled forms of DHE (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, they 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 use 3 to 6 abortives: a triptan, NSAID, Excedrin, an antinausea medication, and a painkiller (opioid/butalbital). Patients will use each medication in different situations, for different types and degrees of headache. Tables 5 to 7 review all the first- and second-line migraine-abortive medications.

Miscellaneous Approaches

Muscle relaxants (carisoprodol, diazepam) or tranquilizers (clonazepam, alprazolam) occasionally are useful, primarily to aid in sleeping. Intravenous valproate sodium (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 (Table 8). Certain preventive medications, such as valproic acid, or divalproex sodium (Depakote), topiramate (Topamax), and amitriptyline­–in low doses every 4 to 6 hours–may be useful on an as-needed basis. The antihistamine diphenhydramine occasionally is useful when administered intramuscularly. At times, patients may have injections for home use (ketorolac, orphenadrine, sumatriptan, diphenhydramine, promethazine, etc).

Medication Overuse Headache

Much is written about MOH, with many patients diagnosed with this condition. Often a patient will be overusing abortive agents but will not be suffering “rebound/withdrawal” headaches (medication overuse, but not MOH). Up until recently, all NSAIDS were lumped under “medications that cause MOH,” and this simply is not correct. For some patients, opioids, butalbital, and medications containing a lot of caffeine cause MOH. Triptans are implicated occasionally as well. However, preventives may not be effective for most patients with chronic migraine (daily or near-daily headaches), and they use abortives to help themselves get through the day.

There are more questions in the area of MOH than answers. The pathophysiology of MOH is unclear. Some patients will have MOH from taking 2 Excedrin daily, while others do not suffer from MOH consuming 8 Excedrin per day. When patients are using abortives frequently, we often withdraw them from that abortive, encourage the use of preventives, and attempt to minimize analgesics. However, for many chronic migraine sufferers, preventives are not very effective. For those sufferers, abortives allow them to live with a reasonable quality of life.

Preventive Medications

There are no treatment algorithms to determine which migraine patient should be prescribed preventive headache medication. The choice of who qualifies for medication depends on the patient’s age, medical and psychiatric comorbidities, and frequency and severity of the patient’s migraine, as well as the patient’s preference. Patients have to be willing to take daily medication (many are not). There is no absolute rule that applies to headache treatment. For a patient with 2 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 5 headaches a month but can obtain relief from Excedrin or a triptan, preventive medicine may not be optimal.

Comorbidities often determine which preventive medications are used. If a patient has hypertension, a medication for blood pressure will be used. When patients concurrently suffer with anxiety or depression, various antidepressants are utilized to manage the headache and mood disorder. We want to minimize medications and treating 2 conditions with 1 medication is ideal.

In using medication, a realistic goal is to decrease the severity of headaches by 40% to 70%, not to completely eliminate the headaches. “Clinical meaningful pain relief” usually is around a 30% improvement. It is wonderful when the headaches are 90% improved, but the idea is to minimize medication. 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 remainding patients try various abortives.

As noted, patients should play an active role in medication choice. Preventive medications should be selected based on the patient’s comorbidities, GI system, medication sensitivities, and the like. Fatigue and/or weight gain are major reasons why patients abandon a preventive medication. Headache patients commonly complain of fatigue, and they 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 to achieve results. 

First-line Preventive Medications for Migraine

Table 9 provides a summary of first-line preventive medications. Onobotulinum toxin A has been studied extensively in patients with migraines. Nearly 4 million people have had onobotulinum toxin A injections for headache. Onobotulinum toxin A has been found to significantly improve quality of life and reduce headache impact.4 Botox is the only onobotulinum 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 can decrease headaches for 1 to 3 months. There also is a cumulative benefit, in which 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.

The anticonvulsant agents topiramate (Topamax) and valproate acid (Depakote) are FDA-approved as migraine preventives. Topiramate is used to manage migraine, chronic daily headaches, and cluster headache; however, sedation and cognitive side effects, such as confusion or memory problems, may limit its use. Topiramate often decreases appetite, which leads to weight loss; this is unusual among headache preventives. The use of topiramate increases the risk for kidney stones. Bicarbonate levels should be monitored because this agent may cause dose-related metabolic acidosis. This acidosis may lead to “tingling,” which sometimes may be counteracted by potassium (in foods or supplements).

Natural Supplements and Herbs

Feverfew, Petadolex (butterbur), and magnesium oxide have all proven effective as migraine preventives in double-blind studies. Of these, Petadolex has been the most effective. Petadolex, a purified form of the herb butterbur, is made of extracted plant certified by the German Health Authority. This herb preparation is used commonly 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; many patients require an increase to 150 mg per day (all at once, or in 2 divided doses). Earlier concerns about carcinogenesis with this family of herbs have decreased with the use of Petadolex. 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 3 months or so. Petadolex is available by calling 1-888-301-1084 or through www.petadolex.com or Amazon.com.

Magnesium is a naturally occurring mineral that helps many systems in the body to function, especially the muscles and nerves. It has been shown that magnesium levels in the brain 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 and powder versions are found in most pharmacies. However, mild GI side effects may limit use. There also are drug interactions that may occur; as always, advise your patients to consult with a physician before taking any supplements.

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 2 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 herbs than others. It is available in both capsule and liquid forms. The usual dose is 2 capsules each morning. Patients occasionally will be allergic to feverfew, and it should not be used during pregnancy.

Miscellaneous hers/supplements have been used, particularly vitamin B2. CoQ10 and fish oid have also been studied. These occationally help, but they are less effective than Petadolex (Table 10).

Medications: First Line

As noted, topiramate is an effective migraine preventive. While usually fairly well tolerated, topiramate commonly causes side effects including memory difficulties (“spaciness”) and tingling. 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 to 100 mg daily, but some patients do well on as little as 25 mg per day. The dose may be increased to 300 or 400 mg per day in the absence of significant side effects.

Valproate, or divalproex sodium, (Depakote) is a long-time staple, popular for migraine prevention. It is usu-ally 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 beta-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 usually is kept between 60 and 120 mg per day. Lower doses, such as 20 mg twice per day of propranolol, sometimes are effective. Other b-blockers, such as metoprolol (Toprol XL) and atenolol, also are effective. 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. Beta-blockers are useful for migraine patients with concurrent hypertension, tachycardia, mitral valve prolapse, and panic/anxiety disorders. Bystolic (Nebivolol) is another beta-blocker that may be helpful for the prevention of headaches, with the least amount of side effects.

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 it frequently causes GI upset that increases as a person ages. Effective as an abortive, it may be combined with other first-line preventive medications. Other NSAIDs similarly can be used for migraine prevention. As with all anti-inflammatories, GI side effects increase as people age, and, therefore, NSAIDs are used much more frequently in the younger population. Blood tests are needed to monitor liver and kidney function.

Second-line Migraine Preventive Therapy

There are a number of second-line migraine treatments (Table 11). The antiseizure medication gabapentin has been demonstrated to be 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. Pregabalin is fairly safe, but sedation and weight gain often occur.

A safe, nonaddicting 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 it helps some patients with migraine and chronic daily headache.

There have been a number of studies on using angiotensin receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEIs) for the prevention of migraine. ARBs are preferred because of minimal side effects. Examples include losartan (Cozaar), olmesartan (Benicar), 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.

Venlafaxine (Effexor XR) is an excellent antidepressant that is occasionally helpful for the prevention of migraine. At lower doses, venlafaxine functions primarily as an SSRI, but at higher doses (100-150 mg), it also increases norepinephrine. In fact, antidepressants with such dual mechanisms (serotonin and norepinephrine) are more effective for pain and headache. Another similar medication is duloxetine (Cymbalta, others), with typical doses being 30 mg to 60 mg daily. Duloxetine has several pain indications, but it is probably more effective for moods than for headache.


Polypharmacy is common in migraine prevention. Polypharmacy commonly is employed when significant comorbidities (anxiety, depression, hypertension, etc) are present. Two first-line medications often are used together and the combination of 2 preventives can be more effective than a single drug alone.6 For example, valproic acid often is combined with an antidepressant. Amitriptyline may be combined with propranolol (or other b-blockers), particularly if the tachycardia of the amitriptyline needs to be offset by a b-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. Unfortunately, polypharmacy brings the risk of increased side effects.


Migraine is a very common and disabling illness. Outside of medications, 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 one algorithm for determining which medication is best for which patient. Each patient is unique, and comorbidities drive where we go with treatment. The goal is to decrease head pain while minimizing medications.

Last updated on: January 24, 2018

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