Treating Migraine with Antidepressants

Studies show that certain types of antidepressants can help prevent migraine. Although this is a popular off-label alternative, more research is needed to understand the effects fully.

Migraine and depression show a bidirectional link. This means that people with a migraine diagnosis are more likely to also experience depression, and the reverse, that people with a diagnosis of depression are more likely to also experience migraine.

While this can feel like a double whammy of diagnoses, it can also open some considerations when looking at treatment options. In fact, certain antidepressants have been used to prevent migraine episodes with some success, and the research indicates that more options are possible.

Whether you live with both migraine and depression or you’re just curious about your treatment options, keep reading for more information.

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What are antidepressants?

Antidepressants are medications that help 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 migraine. Read on to learn more.

Types of antidepressants

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. These include:

• citalopram
• escitalopram
• fluoxetine
• sertraline

Serotonin-norepinephrine reuptake inhibitors (SNRIs)

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

• desvenlafaxine
• duloxetine
• levomilnacipran
• venlafaxine

Tricyclic antidepressants

These medications, also known as cyclic antidepressants, increase the amounts of serotonin and norepinephrine. They also have anticholinergic and antihistamine effects. These include:

• amitriptyline
• doxepin
• imipramine
• nortriptyline

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.

Doctors now rarely prescribe MAOIs for depression because they can cause more serious side effects.

How well do antidepressants prevent migraine?

Experts aren’t exactly sure what causes migraine, which makes it difficult to pinpoint why antidepressants may help with prevention. People with depression have lower levels of serotonin in their brains, and migraine is also associated with a drop in serotonin levels. This might partially explain why antidepressants seem to help in prevention.

While tricyclic antidepressants like amitriptyline are commonly prescribed for migraine prevention, the evidence for other antidepressants is somewhat limited. However, a 2025 review found SSRIs and SNRIs worked similarly and caused fewer side effects than tricyclic antidepressants.

Another 2019 review pointed out that while tricyclic antidepressants might work best for those with insomnia, thanks to the sedating effects, an SNRI may be the most effective option for those living with both migraine and depression.

More recent research from 2022 looked at an SNRI, venlafaxine, for the prevention of migraine. While this was a small study of only 80 participants, results suggested that it was comparable to amitriptyline in prevention, but with fewer side effects.

Finally, newer research from 2025 examined the use of fremanezumab, a calcitonin gene-related peptide (CGRP) antagonist, to treat migraine and depression. While this class of medications is used to treat migraine, it’s not well understood how it affects depression, and it’s not classed as an antidepressant. However, the results of this study showed a reduction in both monthly migraine days and depressive symptoms.

While these studies give us some insights, many more large-scale, controlled studies are needed to fully understand how antidepressants affect migraine.

Also, keep in mind that antidepressants are used to prevent migraine episodes, 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.

Are antidepressants safe?

Antidepressants are generally safe. However, taking antidepressants to treat migraine 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 migraine. 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 migraine.

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 a 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 can happen when you take antidepressants, especially MAOIs, with other medications, supplements, or illegal drugs that increase your serotonin levels.

Consult with your healthcare professional before starting an antidepressant if you already take any triptan therapies for migraine, such as:

• 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 medications
• herbal supplements, including ginseng and St. John’s wort
• other antidepressants
• illegal drugs, including ecstasy, cocaine, and amphetamines

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

• confusion
• muscle spasms and tremors
• muscle rigidity
• shivering
• rapid heart rate
• overactive reflexes
• dilated pupils
• seizures
• unresponsiveness

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 migraine episodes that don’t respond to other treatments, talk with your doctor about trying antidepressants.