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Some drugs that treat depression, called antidepressants, have been found to be effective in preventing migraine, even in people who do not experience depression.1

There are different types of antidepressants, including tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs) as well as selective serotonin reuptake inhibitors (SSRIs) and serotonin/norepinephrine reuptake inhibitors (SNRIs). These medicines work by affecting different chemical pathways in the brain.

People with migraine are five times more likely to also suffer from depression and anxiety, so they may benefit especially from using antidepressants as a way to prevent frequent migraine attacks.2 Some antidepressants can also help people who have trouble sleeping, as well.3

How do antidepressants work?

The way antidepressants work to prevent migraine isn’t fully understood. They affect neurotransmitters in the brain, and these may be associated with migraine. They are also effective at blocking pain for a number of conditions, including headache, at lower doses than are needed to prevent depression.2

The evidence of the efficacy of antidepressants for preventing migraine changes over time, as more studies look into prevention. So far, two antidepressant medications have been classified as “probably effective” at preventing migraine. These are amitriptyline (a generic tricyclic antidepressant) and venlafaxine (a generic SNRI).4 Other tricyclics are also sometimes prescribed because they have fewer side effects, but they haven’t been studied as much.1

SSRIs, which are some of the most commonly prescribed medicines for depression, are not effective for migraine prevention.3

What are some common antidepressants that prevent migraine?

Most antidepressants that are used to prevent migraine are available as generics. They can be found in tablets, capsules, and liquid forms.

Common tricyclic antidepressants include:

  • amitriptyline (Elavil® and Vanatrip®)
  • nortriptyline (Aventyl® and Pamelor®)
  • Common serotonin/norepinephrine reuptake inhibitors (SNRIs) include:

  • duloxetine (Cymbalta® and Irenka®)
  • venlafaxine (Effexor®)
  • What are some side effects of antidepressants?

    Side effects are common for people taking antidepressants. However these medicines can be used at lower doses for migraine prevention than for stabilizing mood, and this might reduce the number and severity of side effects for patients. The following is a partial list of side effects associated with antidepressants4:

    • Disturbances in heart rhythm
    • Drowsiness
    • Confusion
    • Dry mouth
    • Painful urination
    • Sexual dysfunction
    • Weight gain
    • Dizziness
    • Blurred vision
    • Lightheadedness
    • Headaches
    • Constipation
    • Insomnia and nervousness

    Some of these symptoms can be more serious in older people, so it’s important to check with your doctor and monitor your health carefully if you are taking antidepressants.4

    Many antidepressants, most notably SSRIs and SNRIs, come with the U.S. Food and Drug Administration’s strongest warning that they are associated with increased risk of suicidal thoughts and behaviors in children, adolescents and young adults taking them for mood disorders.5 Tricyclic antidepressants can be fatal in overdose. If you are taking these medications, you should monitor your mental health and if you experience any changes, notify your doctor immediately.

    What else should I know about antidepressants for migraine?

    Antidepressants can have serious interactions with other drugs. It is important to let your doctor know all other medications you take including oral contraceptives, barbiturates, MAO inhibitors, sleep medicines, antihistamines, painkillers, blood pressure medicines and others.

    Tell your doctor if you have ever had seizures, urinary retention, glaucoma or other chronic eye conditions, a heart or circulatory system disorder, liver problems, or are taking thyroid medication. You should also tell your doctor if you are planning surgery or are pregnant, breastfeeding or may become pregnant before taking an antidepressant.

    Antidepressants can make you drowsy or confused, so you shouldn’t drive, operate heavy machinery, or perform dangerous activities until you know how the medicine will affect you.

    Antidepressants should never be stopped abruptly. First consult your doctor who will advise you on how to gradually cut down your dose.

    Written by: Sara Finkelstein | Last reviewed: August 2019
    1. Migraine. Mayo Clinic. Accessed May 11, 2018.
    2. The Link Between Migraine, Depression, and Anxiety. American Migraine Foundation. Published May 2, 2018. Accessed May 11, 2018.
    3. Prevention of Migraine. American Migraine Foundation. Published September 3, 2014. Accessed May 11, 2018.
    4. Stephen D. Silberstein. Preventive Migraine Treatment. Continuum (Minneap Minn). 2015 Aug; 21(4 Headache): 973–989. doi: 10.1212/CON.0000000000000199 Available at Accessed May 11, 2018.
    5. Prescribing Information: Cymbalta. Eli Lilly and Company. Published 2009. Accessed May 11, 2018.