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Treating Migraines with Antidepressants

Managing Migraine

June 26, 2018

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by Noreen Iftikhar, MD


Medically Reviewed by:

Seunggu Han, M.D.


by Noreen Iftikhar, MD


Medically Reviewed by:

Seunggu Han, M.D.


A recent medical review suggests that certain types of antidepressants can help prevent migraine. Although this is a popular off-label alternative, more research is needed to understand their affects fully.

What are antidepressants?

Antidepressants are medications that help to treat symptoms of depression. Most of them alter a type of chemical called a neurotransmitter. These carry messages between the cells in your brain.

Despite their name, antidepressants may treat a variety of conditions besides depression, including:

  • anxiety and panic disorders
  • eating disorders
  • insomnia
  • chronic pain
  • hot flashes

Antidepressants may also effectively prevent migraines. Read on to learn more.

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What are the different types?

There are four main types of antidepressants:

Selective serotonin reuptake inhibitors (SSRIs)

SSRIs increase the amount of the neurotransmitter serotonin in your brain. Doctors often prescribe these first because they cause the fewest side effects.

Serotonin-norepinephrine reuptake inhibitors (SNRIs)

SNRIs increase the amount of serotonin and norepinephrine in your brain.

Tricyclic antidepressants

These medications, also known as cyclic antidepressants, increase amounts of serotonin and norepinephrine.

Monoamine oxidase inhibitors (MAOIs)

Serotonin, norepinephrine, and dopamine are all monoamines. Your body naturally creates an enzyme called monoamine oxidase that destroys them. MAOIs work by blocking this enzyme from acting on the monoamines in your brain.

MAOIs are rarely prescribed anymore because they cause more serious side effects.

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How do antidepressants prevent migraines?

Experts aren’t sure what causes migraines. According to the Mayo Clinic, an imbalance in neurotransmitters might play a role. Serotonin levels also drop during a migraine. This might explain why antidepressants seem to help in prevention.

Tricyclic antidepressants are one of the most commonly prescribed medications for migraine prevention. However, a 2017 review of existing studies found SSRIs and SNRIs worked similarly. This finding is significant because SSRIs and SNRIs tend to cause fewer side effects than tricyclic antidepressants.

While the studies mentioned in this review are promising, the authors note that many more large-scale, controlled studies are needed to fully understand how antidepressants affect migraines.

If you get regular migraines that haven’t responded to other treatments, ask your doctor about trying antidepressants. Keep in mind that antidepressants are used to prevent migraines, not treat active ones.

What are the side effects of antidepressants?

Antidepressants can cause a range of side effects. SSRIs generally cause the fewest side effects, so your doctor might suggest trying this type first.

Common side effects across different types of antidepressants include:

  • dry mouth
  • nausea
  • nervousness
  • restlessness
  • insomnia
  • sexual problems, such as erectile dysfunction or delayed ejaculation

Tricyclic antidepressants, including amitriptyline, can cause additional side effects, such as:

  • blurred vision
  • constipation
  • drops in blood pressure when standing
  • urinary retention
  • drowsiness

Side effects also vary between medications, even within the same type of antidepressant. Work with your doctor to choose an antidepressant that provides the most benefit with the fewest side effects. You might have to try a few before you find one that works.

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Are antidepressants safe?

Antidepressants are generally safe. However, taking antidepressants to treat migraines is considered off-label use. This means that antidepressant manufacturers haven’t conducted the same rigorous trials to ensure safety and effectiveness when it comes to treating migraines. Most doctors don’t prescribe medication for off-label use unless other treatments have failed.

Your doctor can help you weigh the benefits and risks of using antidepressants for migraines.

Antidepressants can also interact with other medications, so tell your doctor about all over-the-counter (OTC) and prescription medications you take. This includes vitamins and supplements.

You should also tell your doctor if you have:

  • high cholesterol
  • a history of heart disease
  • an increased risk for heart attack or stroke
  • glaucoma
  • an enlarged prostate

Serotonin syndrome

Serotonin syndrome is a rare but serious condition that happens when your serotonin levels are too high. It tends to happen when you take antidepressants, especially MAOIs, with other medications, supplements, or illicit drugs that increase your serotonin levels.

Don’t take antidepressants if you already take any of the following medications for migraines:

  • almotriptan (Axert)
  • naratriptan (Amerge)
  • sumatriptan (Imitrex)

Other things that can interact with antidepressants and cause serotonin syndrome include:

  • dextromethorphan, a common ingredient in OTC cold and cough medicines
  • herbal supplements, including ginseng and St. John’s wort
  • other antidepressants
  • illicit drugs, including ecstasy, cocaine, and amphetamines

Seek emergency medical treatment if you experience any of these side effects while taking antidepressants:

The bottom line

Migraine treatment is one of the more popular off-label uses of antidepressants. While more large-scale, high-quality studies are needed, existing research suggests that antidepressants may be effective for prevention if someone doesn’t respond well to other treatments. If you regularly get migraines that don’t respond to other treatments, talk with your doctor about trying antidepressants.

Medically reviewed on June 26, 2018

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About the author

Noreen Iftikhar, MD

Noreen Iftikhar, MD, is a physician, nutrition expert and health writer. She wrote a column called “Eat to Beat Illness” for seven years that focused on how diet impacts well-being, including mental health. Noreen has also been published in several other online and print magazines including Livestrong, Women’s Health, Alive, and KidsHealth.

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