Can Tricyclic Antidepressants Like Nortriptyline Treat Migraine Attacks?

Curated by Claudia Shannon / Research Scientist / ishonest

How nortriptyline and other tricyclic antidepressants treat migraines

Nortriptyline is a tricyclic antidepressant. This class of medications works on the central nervous system by increasing the level of serotonin in your brain. Serotonin drops when a migraine attack strikes.

Tricyclic antidepressants like nortriptyline are usually used to treat depression, but there’s some evidence that they can also be beneficial in treating migraine.

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There are many theories as to what causes migraine. One of these involves an imbalance in neurotransmitters like serotonin. There are several types of medications that can help balance these neurotransmitters, and nortriptyline is one of them.

While other medications may be used to treat the many symptoms of migraine, antidepressants like nortriptyline may be useful in preventing them.

Side effects of using nortriptyline for migraines

There are a number of side effects of tricyclic antidepressants. While they may be useful in reducing migraine attacks, there are serious risks to consider, too.

The Food and Drug Administration (FDA) has issued a Black Box warning — the agency’s strongest warning — for nortriptyline. The warning notes that taking this medication can actually increase depression in children, teens, and young adults, resulting in episodes of major depressive disorder (MDD) and even a risk for suicide.

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More common side effects of this medication include:

  • nausea
  • drowsiness
  • weakness
  • tiredness
  • anxiety
  • nightmares or trouble sleeping
  • dry mouth
  • changes in appetite or weight
  • constipation
  • changes in urination
  • changes in sex drive
  • excessive sweating

More serious side effects have been observed in people taking this medication, too. Seek immediate medical care if you experience:

  • jaw, neck, or back muscle spasms
  • speech changes
  • a shuffling walk
  • shakiness
  • fever
  • difficulty breathing or swallowing
  • rash
  • yellowing of the skin or eyes
  • irregular heart rate or palpitations
  • increased depression
  • suicidal thoughts

Can nortriptyline and other TCAs prevent migraines?

In clinical studies, nortriptyline and other TCAs significantly reduced the frequency of migraine attacks. Other classes of antidepressants, like selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs), worked well, too.

Your doctor will consider your specific health history and tolerance of these medications when choosing the right therapy for you.

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These medications are effective in reducing the frequency of migraine attacks because they help to balance neurotransmitter levels that may play a role in migraine development. Other medications may be used to manage symptoms when migraines occur.

What’s the proper dosage of nortriptyline and other TCAs to treat migraines?

Like many other antidepressant treatments, nortriptyline treatment starts with a small dose that can be increased in stages until you’ve reached a therapeutic level. The drug is available in 10 milligrams (mg), 25 mg, 50 mg, and 75 mg formulations.

Dosing usually begins at 25 mg taken at bedtime. You and your doctor will discuss a plan to increase this dosage as needed until your migraine attacks are significantly reduced.

Doses are increased in increments of 25 mg, with a week between each dose increase. The maximum dose is 150 mg per day for adults.

Where to get nortriptyline

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Nortriptyline is available only with a prescription from a doctor. It comes in pill or liquid form. It’s available as a brand-name medication (Pamelor) or as a generic medication.

If you routinely get migraine attacks, make an appointment with your doctor. If you don’t have one, you can use the ishonest FindCare tool to find one in your area.

Alternative migraine treatments

There are a number of ways to treat migraine, and no one treatment works for everyone. Below are some of the ways migraine can be treated.

Over-the-counter medications

Over-the-counter medications may work for some people. Examples of these medications include acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) like:

  • aspirin
  • ibuprofen
  • naproxen
Prescription medications
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A number of prescription medications can be used to treat migraine pain and the numerous other symptoms that can accompany them.

Medications aimed at stopping migraine attacks or treating migraine pain include:

  • ketorolac (Toradol)
  • dihydroergotamine (DHE-45, Migranal)
  • ergotamine (Ergomar)
  • ergotamine and caffeine (Cafatine, Cafergot, Cafetrate, Ercaf, Migergot, Wigraine)
  • methysergide (Sansert)
  • methylergonovine (Methergine)
  • almotriptan (Axert)
  • eletriptan (Relpax)
  • frovatriptan (Frova)
  • naratriptan (Amerge)
  • rizatriptan (Maxalt, Maxalt-MLT)
  • sumatriptan (Imitrex)
  • sumatriptan and naproxen (Treximet)
  • zolmitriptan (Zomig)
  • codeine
  • meperidine (Demerol)
  • morphine
  • oxycodone (OxyContin)

For nausea that can sometimes accompany migraine attacks, your doctor may prescribe medications like:

  • dimenhydrinate (Gravol)
  • metoclopramide (Reglan)
  • prochlorperazine (Compazine)
  • promethazine (Phenergan)
  • trimethobenzamide (Tigan)

Nortriptyline isn’t the only medication used in migraine prevention. A number of treatments are available and include:

  • erenumab (Aimovig)
  • fremanezumab (Ajovy)
  • atenolol (Tenormin)
  • metoprolol (Toprol XL)
  • nadolol (Corgard)
  • propranolol (Inderal)
  • timolol (Blocadren)
  • diltiazem (Cardizem, Cartia XT, Dilacor, Tiazac)
  • nimodipine (Nimotop)
  • verapamil (Calan, Covera, Isoptin, Verelan)
  • amitriptyline (Elavil, Endep)
  • fluoxetine (Prozac, Sarafem)
  • imipramine (Tofranil)
  • paroxetine (Paxil, Pexeva)
  • sertraline (Zoloft)
  • venlafaxine (Effexor)
  • divalproex-sodium (Depakote, Depakote ER)
  • gabapentin (Neurontin)
  • levetiracetam (Keppra)
  • pregabalin (Lyrica)
  • tiagabine (Gabitril)
  • topiramate (Topamax)
  • valproate (Depakene)
  • zonisamide (Zonegran)
  • Botulinum toxin type A (Botox injections)
Lifestyle changes
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One way to manage migraine is with lifestyle changes. There are many triggers for migraine in the foods we eat, stress, and other factors.

Below are some diet, situational, and complementary changes you can make to your lifestyle to help manage migraine:

  • Avoid eating food high in nitrates, like processed meats.
  • Keep a journal of foods or activities that trigger migraine attacks.
  • Use herbs like lavender, feverfew, peppermint oil, and ginger in home remedies.
  • Add magnesium to your diet with supplements and foods like legumes and whole grains.
  • Try to manage daily stress.


Migraine is a complex neurological condition that can cause many painful symptoms. There’s no one treatment that works for migraine, and most people use several therapies to manage their migraine pain.

Antidepressants like nortriptyline are one class of medication that can help reduce the frequency of migraine attacks, but they may have serious side effects. Speak with a doctor if you need help managing migraine.

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