Can Tricyclic Antidepressants Like Nortriptyline Treat Migraine Attacks?

Key takeaways

• Nortriptyline and other tricyclic antidepressants (TCAs) may help prevent migraine by boosting serotonin in the brain, which often falls during an attack.
• Although nortriptyline can lower how often migraines occur, it carries potential adverse effects, including a higher risk of depression and suicidal thinking, particularly in younger people. The FDA has placed a Black Box warning on this drug.
• Beyond nortriptyline, there are many other options to treat migraine, including OTC and prescription drugs, lifestyle adjustments, and complementary therapies.

Migraine is more than a simple headache. Over 4 million adults experience this neurological disorder on a daily basis, which brings ongoing pain, nausea, and other troubling symptoms.

Migraines can be hard to identify and even harder to control, so many people end up seeking emergency help when relief is elusive. In the U.S., more than 1 million emergency department visits each year are due to migraine.

During a migraine episode, serotonin levels decline. Researchers exploring new ways to manage migraine have found that certain antidepressants that stabilize serotonin might help prevent migraine attacks before they begin.

Continue reading to understand how tricyclic antidepressants (TCAs) fit into migraine care and what to consider before using them.

FDA warning: Suicide risk

• This medicine carries a black box warning, the FDA’s most serious alert, which flags potentially dangerous drug effects.
• Nortriptyline may raise the chance of suicidal thoughts and behaviors in people under 24. A history of depression or other psychiatric conditions increases this risk. Your prescriber will monitor you for changes in mood, unusual behaviors, or self-harm thoughts.

How nortriptyline and other tricyclic antidepressants treat migraines

Nortriptyline is part of the tricyclic antidepressant family. These drugs act on the central nervous system by raising brain serotonin levels, which typically drop during a migraine.

While TCAs are commonly prescribed for depression, evidence suggests they can also be effective in preventing migraine.

There are multiple theories about migraine causes; one centers on imbalances in neurotransmitters such as serotonin. Several drug classes aim to correct these imbalances, and nortriptyline is among them.

Though other medications address acute migraine symptoms, antidepressants like nortriptyline may be helpful for reducing how often attacks occur.

Side effects of using nortriptyline for migraines

Tricyclic antidepressants come with a range of potential side effects. While they can lower the frequency of migraine episodes, they also present important risks to weigh.

The Food and Drug Administration (FDA) has issued a Black Box warning — the agency’s strongest caution — for nortriptyline. It states that the drug can increase depressive symptoms in children, adolescents, and young adults, potentially leading to major depressive episodes and an elevated suicide risk.

More common side effects include:

• nausea
• drowsiness
• weakness
• fatigue
• anxiety
• nightmares or insomnia
• dry mouth
• changes in appetite or weight
• constipation
• urinary changes
• altered libido
• excessive sweating

Medical emergency More severe reactions have been linked to this medication. Get urgent medical attention if you experience: jaw, neck, or back muscle spasms; speech difficulties; a shuffling gait; tremors; fever; trouble breathing or swallowing; rash; yellowing of the skin or eyes; irregular heartbeat or palpitations; worsening depression; or suicidal thoughts.

Can nortriptyline and other TCAs prevent migraines?

In clinical trials, nortriptyline and other TCAs have been shown to notably lower the number of migraine attacks. Other antidepressant categories, such as SSRIs and SNRIs, have also demonstrated benefit.

Your clinician will evaluate your medical history and how well you tolerate these medications when selecting the most suitable prevention strategy.

These drugs reduce migraine frequency by helping normalize neurotransmitter activity that may contribute to migraine onset. Other medications remain available to control symptoms during acute attacks.

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

As with many antidepressants, nortriptyline treatment begins at a low dose that may be gradually increased until a therapeutic effect is reached. The medication comes in 10 mg, 25 mg, 50 mg, and 75 mg strengths.

Typical starting dosing is 25 mg at bedtime. You and your provider will plan stepwise dose increases if needed until migraine frequency is meaningfully reduced.

Doses are usually raised by 25 mg increments, spaced about a week apart. The maximum recommended daily dose for adults is 150 mg.

Where to get nortriptyline

Nortriptyline is prescription-only and is available as tablets or liquid. It’s marketed under a brand name (Pamelor) and as a generic formulation.

If you suffer recurrent migraines, schedule an appointment with your healthcare provider. If you don’t have one, consider using the Anthem FindCare tool to locate a clinician in your area.

Alternative migraine treatments

There are many approaches to managing migraine, and no single treatment fits everyone. Below are common strategies used to treat migraine.

Over-the-counter medications

For some people, OTC medicines provide relief. Examples include acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) such as:

• aspirin
• ibuprofen
• naproxen

Prescription medications

A variety of prescription drugs can be used to treat migraine pain and related symptoms.

Medications that target stopping attacks or relieving pain include:

• ketorolac (Toradol)
• dihydroergotamine (DHE-45, Migranal)
• ergotamine (Ergomar)
• ergotamine with 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 with naproxen (Treximet)
• zolmitriptan (Zomig)
• codeine
• meperidine (Demerol)
• morphine
• oxycodone (OxyContin)

For migraine-related nausea, clinicians may prescribe:

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

Nortriptyline is only one preventive option. Other preventive therapies 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

Adjusting daily habits is another way to control migraine. Many triggers stem from diet, stress, and other environmental factors.

Consider these dietary, situational, and complementary strategies to help reduce migraine:

• Limit foods high in nitrates, such as processed meats.
• Keep a diary of foods or activities that seem to trigger attacks.
• Use herbs and oils like lavender, feverfew, peppermint oil, and ginger in home remedies.
• Increase magnesium intake through supplements and magnesium-rich foods like legumes and whole grains.
• Work on daily stress management techniques.

Takeaway

Migraine is a multifaceted neurological disorder that causes debilitating symptoms for many people. No single treatment is universally effective, and most patients use a combination of approaches to manage their pain.

Tricyclic antidepressants such as nortriptyline can help decrease the frequency of migraine attacks, but they can also produce serious side effects. Talk with a healthcare provider if you need assistance controlling migraine.