Medications Used for Prevention

Many drugs are being used or investigated for preventing migraines. To date, most standard drugs provide only modest protection.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) for Prevention

Standard NSAIDs. Nonsteroidal anti-inflammatory drugs (common pain relievers that are available over-the-counter or in prescription form). NSAIDs may be used for prevention of migraine under the following circumstances:

  • Nonprescription NSAIDs. Regular, preventive use of low-dose aspirin (so-called baby aspirin), ibuprofen (Advil), and naproxen (Aleve) may reduce the occurrence of migraine headaches by about 20%. (Even with nonprescription NSAIDs, no one should take them regularly without consulting a doctor.)
  • Prescription-strength NSAIDs. Prescription-strength NSAIDs can reduce the frequency of attacks in over half of migraine sufferers. There are many prescription brands available. Mefenamic acid (Ponstel) and naproxen (Anaprox) are particularly useful for preventing migraines associated with menstruation.

Long-term use of these drugs can lead to stomach ulcers and gastrointestinal bleeding.

Beta-Blockers

Beta-blockers are usually prescribed to reduce high blood pressure. Some, however, are also useful in reducing the frequency of migraine attacks and their severity when they occur. Propranolol (Inderal) and timolol (Blocadren) have been approved specifically for prevention of migraine. Others that may be effective include metoprolol (Lopressor, Toprol XL), and nadolol (Corgard).

Side Effects. Side effects may include:

  • Fatigue and lethargy are common.
  • Some people experience vivid dreams and nightmares, depression, and memory loss.
  • Dizziness and lightheadedness may occur upon standing.
  • Exercise capacity may be reduced.
  • Other side effects may include cold extremities, asthma, decreased heart function, gastrointestinal problems, and sexual dysfunction.

If side effects occur, the patient should call a doctor, but it is extremely important not to stop the drug abruptly. There is some evidence that people with migraines who have had a stroke should avoid beta-blockers.

Anti-Seizure Drugs

Anti-seizure drugs, also called anti-epileptics or anticonvulsants, affect the neurotransmitter gamma aminobutyric acid (GABA), which helps prevent nerve cells from over-firing. GABA may also have a role in migraines. These drugs are commonly used for epilepsy and bipolar disease. Anti-seizure drugs are more expensive than other drugs. They also have significant side effects. Some experts, then, recommend them only as second-line prevention after older drugs have failed.

Valproate and Divalproex Sodium. Valproate (Depakene) and a similar drug, divalproex sodium (Depakote), are the only drugs approved for preventing migraines. Studies report that valproate reduces migraine frequencies by 30 - 50% or greater by the end of 1 year, after which the benefits remain stable.

Gabapentin (Neurontin). A 2001 multicenter study found that 2,400 mg/day of gabapentin may be an effective preventive drug for patients with migraine headaches. Side effects are similar to those of valproate and may include sleepiness, dizziness, fatigue, and weight gain.

Topiramate (Topamax). In 2004, the FDA approved topiramate for prevention of migraines in adults. Studies from 2006 indicated that the drug works well when used on a long-term basis. Patients in these studies experienced significantly fewer migraines for up to 14 months. Another 2006 study, presented at the American Headache Society meeting, reported that topiramate may help reduce the frequency and severity of migraine attacks in people who experience chronic daily headache. Topiramate’s most common side effect is a tingling sensation in the arms and legs. Weight loss is also a side effect. In clinical trials, patients lost an average of 3.8% of their body weight.

Levetiracetam (Keppra). Levetiracetam significantly reduces the frequency and impact of headaches in patients with transformed migraine, according to a study presented at the 2004 meeting of the American Academy of Neurology. Earlier studies suggested that levetiracetam, when used alone and in combination with other treatments, can help provide migraine pain relief.

Other Anti-Seizure Drugs Under Investigation. These include Felbamate (Felbatol), Tiagabine (Gabitril), oxcarbazepine (Trileptal) and Zonisamide (Zonegran). Patients taking oxcarbazepine 300 mg/day for other medical conditions have reported a decrease in migraine frequency. Zonisamide has reduced migraine frequency in some clinical trials.

Side Effects. Anti-seizure medication's side effects vary by drug but may include:

  • Nausea and vomiting
  • Diarrhea
  • Cramps
  • Hair loss
  • Dizziness
  • Sleepiness
  • Blurred vision
  • Weight gain
  • Valproate and divalproex can cause serious side effects of inflammation of the pancreas (pancreatitis) and damage to the liver

Tricyclic and Other Antidepressants

Certain antidepressants are quite effective in preventing all forms of headache, including migraine. The effects of any of these antidepressants on headaches are most likely due to their effects on serotonin, a chemical messenger in the brain that influences depression and migraine.

Tricyclics. Tricyclics are the most effective antidepressants for migraine prevention. They include amitriptyline (Elavil, Endep), nortriptyline (Pamelor, Aventyl), doxepin (Sinequan), and protriptyline (Vivactil). They are beneficial for patients who suffer from both depression and migraine, and may be particularly useful for patients who suffer from both migraines and tension headaches. Low doses may also help prevent cyclic vomiting in childhood migraine. They can have significant side effects, including disturbances in heart rhythms. They can also be fatal in overdose.

Other Antidepressants. Serotonin-reuptake inhibitors (SSRIs) include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), and fluvoxamine (Luvox). SSRIs are sometimes helpful in reducing migraines, although in general their effects are disappointing.

Newer antidepressants target neurotransmitters, such as norepinephrine, alone or in addition to serotonin. Nefazodone (Serzone) and venlafaxine (Effexor) are such drugs that are showing some promise in preventing migraines.

Calcium-Channel Blockers

Calcium-channel blockers have been prescribed for preventing both migraine and cluster headaches. They must be taken for weeks to months before any benefit is noticed. Certain calcium-channel blockers may be particularly beneficial for preventing migraines in patients who have experienced stroke.

Verapamil (Calan) is most commonly used for prevention of migraines. Others used or being investigated for migraines include diltiazem (Cardizem), nimodipine (Nimotop), nifedipine (Procardia), amlodipine (Norvasc), felodipine (Plendil), and nisoldipine (Sular). Novel calcium blockers, such as dotarizine and flunarizine (Sibelium), are being investigated and show promise for migraines. Flunarizine, available overseas but not in the U.S., is reportedly effective and may help prevent migraines in children. (Other calcium-channel blockers are not useful for children.)

Side Effects. Side effects vary depending on the drug. They may include:

  • Fluid accumulation in the feet
  • Drop in blood pressure, with accompanying dizziness
  • In some people, they cause headaches as severe as the migraines they are preventing
  • Constipation
  • Fatigue
  • Impotence
  • Gingivitis
  • Flushing, and allergic symptoms

Note: Grapefruit boosts the effects of calcium-channel blocking drugs.

Other Drugs Investigated for Preventing Migraines

Angiotensin Converting Enzyme (ACE) Inhibitors. Commonly used for treating high blood pressure, ACE inhibitors block the production of the protein angiotensin, which constricts blood vessels and may be involved in migraine. Studies using the ACE inhibitor lisinopril (Prinivil, Zestril) are reporting significant reduction in migraine attacks.

Angiotensin-Receptor Blockers (ARBs). Angiotensin-receptor blockers (ARBs) have actions similar to ACE inhibitors, but may have fewer side effects. In one study, patients who took the ARB candesartan (Atacand) experienced significant reduction in the number of headaches compared to patients who received placebo.

Botulinum. Botulinum toxin A (Botox) injections, a common wrinkle treatment, causes small muscles to relax. This approach is now being used with some success for treating disorders that involve over-excited muscle activity, including myofascial pain syndrome and migraine. One study reported complete migraine relief in more than half of patients being tested and improvement of more than 50% in another 35% of patients. Relief lasted 3 - 4 months with no adverse effects. A study presented at the 2005 meeting of the American Headache Society reported that patients who regularly received Botox injections every 3 months reduced both the frequency of migraine attacks and their reliance on pain medications

Leukotriene-Antagonists. Leukotriene-antagonists are anti-inflammatory drugs that block leukotrienes, powerful immune system factors that are important in causing airway constriction. They include zileuton (Ziflo), zafirlukast (Accolate), montelukast (Singulair), and pranlukast (Ultair, Onon). These drugs are being used in asthma, and some doctors have observed a reduction in migraine frequency in asthmatic patients who also had these headaches. In one study that investigated the use of these drugs for migraine prevention, more than half of patients experienced a reduction in frequency of severe attacks. In a controlled study, however, montelukast had no effect on migraines.

Dopamine Agonists. Alpha-dihydroergocryptine is a drug known as a dopamine agonist, which may help prevent common migraine (without aura).