Antidepressants
Reviewed by: HU Medical Review Board | Last reviewed: October 2025 | Last updated: January 2026
Antidepressants are drugs that are mainly used for treating mental health conditions like depression. However, there is evidence that antidepressants can help treat migraine. Some healthcare providers may prescribe antidepressants for someone who has migraine, even if they do not have mental health issues.1
How do antidepressants help treat migraine?
Antidepressants may be used to prevent migraine disease or lower its severity. In fact, certain types of antidepressants were some of the first drugs used to treat migraine. It is now less common to use antidepressants for treating migraine attacks. This is because antidepressants may cause noticeable and unpleasant side effects.1,2
Antidepressants work by targeting certain chemicals in the brain. They may target serotonin, norepinephrine, or both. Serotonin and norepinephrine play a role in mood. They also have a role in pain and migraine. This may be the reason that antidepressants can reduce the frequency or severity of migraine attacks.1,2
Some medicines work better than antidepressants for migraine prevention. However, antidepressants could be a good option if you have migraine and depression, anxiety, or trouble sleeping.1,2
Examples of antidepressants for migraine
Different classes of antidepressants may be used to treat migraine. The most common is a type of drug called tricyclic antidepressants (TCA). TCAs used to treat migraine include:2
- Amitriptyline
- Nortriptyline
Another type of antidepressant that may be used to treat migraines is called a serotonin and norepinephrine reuptake inhibitor (SNRI). Examples of SNRIs used to treat migraine may include:2
- Venlafaxine
- Duloxetine
Lastly, a type of drug called a selective serotonin reuptake inhibitor (SSRI) may treat migraines. Fluoxetine is an SSRI that may help treat migraine in some people.2
What are the possible side effects of antidepressants?
Side effects can vary depending on the specific drug you are taking.
TCA side effects
Side effects of TCAs may include:2
- Tiredness
- Weight gain
- Dry mouth
- Constipation
SNRI side effects
Side effects of SNRIs may include:2
- Nausea
- Hot sweats
- Constipation
- Dry mouth
- Trouble sleeping
- Tiredness
- High blood pressure
- Sexual dysfunction/decreased libido
SSRI side effects
Side effects of SSRIs may include:2
- Nausea
- Diarrhea
- Tiredness
- Trouble sleeping
- Sexual dysfunction/decreased libido
All antidepressants may cause an increased risk of suicidal thoughts. Contact your provider if you notice changes in your thoughts or mood while taking antidepressants.3
It is important not to stop taking any antidepressants suddenly. This can cause negative side effects and increase the risk of depressive thoughts. If you need to stop taking an antidepressant, your provider will work with you to slowly cut your dose back.1
These are not all the possible side effects of antidepressants. Talk to your provider about what to expect when taking antidepressants. You also should call your provider if you have any changes that concern you when taking antidepressants.
Other things to know
Amitriptyline is the best-studied and most common antidepressant used for migraine prevention. It has a long history of use for migraine. For some people, amitriptyline may work well but cause intolerable side effects. In this case, nortriptyline may be an alternative. It is a TCA-like amitriptyline but causes fewer side effects.2
SSRIs or SNRIs may be another option for treating migraine. Of these drugs, venlafaxine is most commonly used for migraine. If the side effects of venlafaxine are not bearable, your provider may recommend duloxetine. Duloxetine is also an SNRI, but it causes less intense side effects.2
Before beginning treatment for migraine, tell your provider about all your health conditions and any other drugs, vitamins, or supplements you are taking. This includes over-the-counter drugs.