Amitriptyline May Help Reduce Migraine Frequency

Last updated: December 2009

If you're among the one in 10 Americans who regularly suffers from migraines, you'll know that pain relief sometimes isn't enough. In fact, overuse of pain relievers can make symptoms worse. Migraines are more than just bad headaches; symptoms can include nausea, vomiting, sensitivity to light, and changes in vision that can last hours or even days if not treated, which can be debilitating. To help reduce symptoms, many people are often prescribed drugs to prevent a migraine from occurring.

The Food and Drug Administration has approved four drugs to prevent migraine headaches: two beta-blockers, propranolol (Inderal and generic) and timolol; and two anticonvulsant drugs, topiramate (Topamax and generic) and valproic acid (Depakote and generic). Another group of drugs, called tricyclic antidepressants, are also prescribed for migraines even though they're not approved by the FDA for this purpose. They include amitriptyline, doxepin, imipramine, nortriptyline, and protriptyline. (Doctors can legally prescribe almost any medication "off-label," that is, for a use they deem appropriate.)

Of these tricyclic antidepressants, one drug, amitriptyline, has been studied more frequently than the others, and is the only one in this class that has consistently been found in clinical studies to reduce the frequency of migraine attacks.

Should you consider taking a drug to prevent migraine?

Guidelines from the U.S. Headache Consortium, a coalition of medical groups led by the American Academy of Neurology, suggest that preventive treatment may be appropriate if migraines are frequent or disruptive. Prevention measures may also be called for if overuse of acute treatments is causing "rebound" headaches.

Before taking a drug for migraine prevention, you should know that none of them are totally effective. Treatment is typically considered successful when the number of migraines is reduced by half. Only about 10 percent of the people who take any type of prevention therapy are completely headache-free.

For those reasons, it's worth considering environmental factors that may cause your migraines. It helps to keep track of them to determine what may trigger them, such as certain activities, drinks, or foods.

Other treatments, including acupuncture, biofeedback, using sensors to track blood flow or muscle activity, cognitive-behavioral therapy, and relaxation training, have also been effective in preventing migraines in clinical trials, either alone or in combination with drug treatments. Finding an optimal treatment can vary from person to person, so it may take some trial and error to determine the right combination of lifestyle modification and medication.

Who should consider amitriptyline?

If you and your doctor decide to try amitriptyline, the U.S. Headache Consortium considers it to be a Group 1 preventive therapy, meaning it has medium to high efficacy, good strength of evidence, and mild-to-moderate side effects. In head-to-head comparisons, amitriptyline sometimes performed better than—although sometimes not as well as—propranolol. In terms of patient satisfaction, 70 percent of the patients in a study reported that they found acceptable relief from amitriptyline.

Indeed, amitriptyline may work better than other drugs for people with mixed migraine and tension-type headaches rather migraines alone.

People who have trouble falling asleep or staying asleep may also find amitriptyline particularly helpful. It has not been adequately studied to make a recommendation about its use by children or adolescents.

Amitriptyline has been found to cause frequent side effects. Two commonly used drugs, propranolol and timolol, seem to have less-frequent side effects. Other drugs in this class, called beta-blockers (also used to treat high blood pressure), such as metoprolol (Lopressor and generic), nadolol (Corgard and others) and atenolol (Tenormin and generic) , are also commonly used. Two other drugs, topiramate (Topamax and generic) and valproic acid, which are used to treat epileptic seizures, can be effective at preventing migraines.

Another class of drugs, calcium-channel blockers, is sometimes used to prevent migraines, but the evidence for how well they work is not very strong. The only exception is verapamil, which has shown to be somewhat more effective than a placebo, but the studies were fairly small.

If you try amitriptyline, or any other preventive treatment for migraines, it is recommended that you start with a lower dose and keep a log of your migraines over several months to gauge its effect. It could take several months before you see a reduction in migraines, though CU medical advisers say it may take just a few weeks. During that time, if you have a migraine, try to avoid overusing drug treatments so that they don't induce a "rebound" migraine.

What are the warnings and side effects of amitriptyline?

The most common side effects of amitriptyline include drowsiness, weight gain, dry mouth, constipation, sedation, and blurred vision. In one study, about 60 percent of the patients reported gaining weight, with an average gain of almost 12 pounds. Alcohol may increase the sedative effects of this drug.

Amitriptyline should not be taken by people who are recovering from a recent heart attack. If you have heart disease, you should be extremely cautious because this type of drug is associated with an increased risk of irregular heart rhythms, heart attacks, and strokes. Tricyclic antidepressants are considered a last resort preventative treatment for migraines in pregnant women because of concerns about potential harm to the fetus, and there are some serious risks using drugs of this type for children and young adults.

Amitriptyline, along with all antidepressants, has a black-box warning from the FDA, the strongest kind of warning, urging parents to be aware that children and young adults under the age of 24 have become suicidal while taking antidepressants during clinical trials for treatment of major depressive disorder (MDD) and other psychiatric disorders.

Older adults should also use caution when taking amitriptyline because they may be more sensitive to the sedation that the drug causes. It may also trigger other side effects, including confusion, constipation, visual changes, or urinary retention. And older adults may have problems with kidney or liver function, which are important in metabolizing the drug, which could increase the likelihood or severity of the side effects.

People who take amitriptyline could also experience mental changes. If you, a family member, or a caregiver notice the following changes in your behavior, notify a doctor right away:

  • new or worsening depression
  • suicidal ideas
  • extreme worry, agitation, panic attacks
  • difficulty falling asleep or staying asleep
  • aggressive behavior
  • irritability
  • severe restlessness or abnormal excitement

Amitriptyline may cause other side effects. Tell your doctor if any of these symptoms occur:

  • nausea
  • vomiting
  • drowsiness
  • weakness or tiredness
  • nightmares
  • headaches
  • dry mouth
  • constipation
  • difficulty urinating
  • blurred vision
  • pain, burning, or tingling in the hands or feet
  • changes in sex drive or ability
  • excessive sweating
  • changes in appetite or weight
  • confusion
  • unsteadiness

Some side effects can be serious. If you experience any of the following, call 911 and go to an emergency room:

  • slow or difficult speech
  • dizziness or faintness
  • weakness or numbness of an arm or a leg
  • crushing chest pain
  • rapid, pounding, or irregular heartbeat
  • severe skin rash or hives
  • swelling of the face and tongue
  • yellowing of the skin or eyes
  • jaw, neck, and back muscle spasms
  • uncontrollable shaking of a part of the body
  • fainting
  • unusual bleeding or bruising
  • seizures
  • hallucinating (seeing things or hearing voices that do not exist)

Bottom line. If you suffer from frequent migraines, consider lifestyle and other nondrug approaches first. Also consider keeping a headache diary to help you determine what may trigger the condition. If you and your doctor are discussing a drug for prevention, amitriptyline may be an option to consider, particularly if you suffer from migraines with tension headache symptoms and you don't have heart disease or already take an antidepressant.

This off-label drug use report is made possible through a collaboration between Consumer Reports Best Buy Drugs and the American Society of Health-System Pharmacists. This is the ninth in a series based on professional reports prepared by ASHP.

These materials were made possible by a grant from the state Attorney General Consumer and Prescriber Education Grant Program, which is funded by a multistate settlement of consumer fraud claims regarding the marketing of the prescription drug Neurontin (gabapentin).

E-mail Newsletters

FREE e-mail Newsletters!
Choose from cars, safety, health, and more!
Already signed-up?
Manage your newsletters here too.

Health News


Cars Build & Buy Car Buying Service
Save thousands off MSRP with upfront dealer pricing information and a transparent car buying experience.

See your savings


Mobile Get Ratings on the go and compare
while you shop

Learn more