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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.
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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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