Migraine Treatments

What to Know About Antidepressants for Migraine Prevention

Trying an antidepressant to treat migraine headaches might seem surprising. After all, aren’t depression and migraines two different conditions?

Yes, they are. However, research shows that certain antidepressants, such as amitriptyline, can be effective in migraine prevention.

So don’t let the word “antidepressant” get in the way of you learning more about this treatment and exploring if it could be the right one for you.

And if it’s not right for you? Well, that’s what Cove’s here for. Our entire mission is to make it easier for migraine sufferers to get the ongoing support and access to the care they need.

So, let’s dive into antidepressant medication for migraines and you can see if it’s a potential treatment option for you.

What are antidepressants?

Antidepressants are FDA-approved prescription drugs used to treat several different conditions that range from major depressive disorder to chronic pain to generalized anxiety disorder to migraines.

There are several different types of antidepressants, including:

  • SSRIs (selective serotonin reuptake inhibitors)
  • MAOIs (monoamine oxidase inhibitors)
  • SNRIs (serotonin–norepinephrine reuptake inhibitors)
  • SMSs (serotonin modulators and stimulators)
  • SARIs (serotonin antagonists and reuptake inhibitors)
  • Tricyclic antidepressants

We know—that’s a whole lot of abbreviations and long words. The good news is that you only have to focus on one right now: tricyclic antidepressants.

How do tricyclic antidepressants help prevent migraines?

During a migraine, doctors believe that your serotonin levels plummet. Tricyclic antidepressants help prevent migraines from happening as frequently by maintaining a healthy serotonin level.

Note the word frequently. Unfortunately, these won’t work 100% of the time. While we’re hopeful that one day there will be a migraine cure, we recommend working with a doctor to find the right migraine treatment plan for you. For some people, that means combining preventative treatment with acute relief—for example, NSAIDs.

How long until they start working to prevent migraine?

Many people start to see results within one month and one study published in the National Institute of Health shows they become more effective the longer you take them—six months to be exact.

If you don’t see results within two months, reach out to your doctor to discuss other treatment options.

How do you take antidepressants?

Antidepressants are a long-term preventative treatment that need to be taken at the same time every day. They’re oral pills, so you’ll want water—however you don’t need to take them with food (although it doesn’t hurt if you do).

Because they can cause drowsiness, many people prefer to take them before bed.

Who should take antidepressants for migraine prevention?

Antidepressants are a good treatment option for migraine sufferers who endure several migraines a month, who can’t use acute treatment at all, or who need additional treatment support beyond acute medication.

Who shouldn’t take tricyclic antidepressants for migraine prevention?

While antidepressants are generally considered safe and effective, there are people who should consider other migraine treatments.


  • people who are breastfeeding
  • people who are pregnant or planning to become pregnant
  • people who have a history of heart disease or have recently had a heart attack
  • people who have liver disease
  • people who have epilepsy
  • people who have bipolar disorder or schizophrenia
  • people who have any kind of drinking problem

That said, every person’s different and we recommend speaking with your doctor about your specific needs and concerns. (We know, you’d like to read this article and know what’s right for you. But we’re committed to providing you with the best migraine care, and in this case, that means not making any claims we can’t stand by.)

What are common tricyclic antidepressant side effects?

While antidepressants are generally considered safe, like many medications, there are possible side effects.

These could include:

  • anxiety, nervousness
  • dry mouth or unpleasant taste
  • constipation, diarrhea, indigestion, nausea
  • excessive sweating
  • headache
  • fatigue, sedation
  • insomnia
  • sensitivity to sunlight or heat
  • weight gain

You should immediately contact your doctor if you experience signs of serious allergic reaction, dizziness, or difficulty breathing while taking these medications.

What’s the best antidepressant for migraine prevention?

Amitriptyline has been used to treat migraines for longer than any other tricyclic antidepressant. Nortriptyline, a commonly prescribed alternative to amitriptyline, also has a strong track record.

But migraines are personal, so the best antidepressant for someone else may not be the best for you. Ask a Cove doctor about your options for a personalized recommendation.

What tricyclic antidepressants does Cove offer?

Cove currently offers amitriptyline (generic Elavil®) and nortriptyline (generic Pamelor®) because they’re two of the best antidepressants for migraine prevention.

We know this can feel like a lot of information to process, and you may still have questions. But don’t worry, you’re not in this alone. Cove works with licensed doctors to help each and every person find a treatment plan that helps them feel more in control of their condition. If you’d like to speak to a Cove physician about your headaches, simply click here.

If you’d like to read about other options, we recommend checking out our migraine treatment resource to read up on: triptans, NSAIDs, beta blockers, and anticonvulsants.

The information provided in this article is not a substitute for professional medical advice, diagnosis, or treatment. You should not rely upon the content provided in this article for specific medical advice. If you have any questions or concerns, please talk to your doctor.

Amitriptyline is used to treat low mood (depression). It may be given to you for other reasons. Do not stop taking this drug all of a sudden without calling your doctor. You may have a greater risk of signs of withdrawal. Drugs like this one have raised the chance of suicidal thoughts or actions in children and young adults. The risk may be greater in people who have had these thoughts or actions in the past. All people who take this drug need to be watched closely. Call the doctor right away if signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur. This drug is not approved for use in children. You can read more about amitriptyline’s side effects, warnings, and precautions here. Full prescribing information for amitriptyline is available here. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch: https://www.fda.gov/Safety/MedWatch/default.htm or call 1-800-FDA-1088.

Nortriptyline is an oral medication indicated that is used to treat depression. Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this drug while you are pregnant. Tell your doctor if you are breast-feeding. Call your doctor right away if you have allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue, fever with increased sweating, hallucination, seizures, signs and symptoms of a dangerous change in heartbeat or heart rhythm like chest pain; dizziness; fast, irregular heartbeat; palpitations; feeling faint or lightheaded; falls; breathing problems; suicidal thoughts or other mood changes; yellowing of the eyes or skin. Call your doctor right away if you have signs and symptoms of a stroke like changes in vision; confusion; trouble speaking or understanding; severe headaches; sudden numbness or weakness of the face, arm or leg; trouble walking; dizziness; loss of balance or coordination. Call your doctor right away if you have signs and symptoms of serotonin syndrome like irritable; confusion; diarrhea; fast or irregular heartbeat; muscle twitching; stiff muscles; trouble walking; sweating; high fever; seizures; chills; vomiting.

You can read more about nortriptyline’s side effects, warnings, and precautions here. Full prescribing information for nortriptyline is available here. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch: https://www.fda.gov/Safety/MedWatch/default.htm or call 1-800-FDA-1088.