Sumatriptan Drug Interactions: What to Avoid and What to Tell Your Doctor

Sumatriptan is generally safe when used correctly, but it has several important drug interactions that every patient needs to know about. Some of these interactions are contraindicated (meaning you should never use the two drugs together), while others require monitoring. Here's what to watch for.

Contraindicated Combinations: Never Use Together

MAOIs (Monoamine Oxidase Inhibitors)

Do not take sumatriptan if you've used an MAOI within the past 14 days. MAOIs inhibit the enzyme monoamine oxidase, which breaks down sumatriptan in the body. When sumatriptan can't be metabolized properly, blood levels rise dramatically, increasing the risk of serotonin syndrome and other serious effects.

Common MAOIs include: phenelzine (Nardil), tranylcypromine (Parnate), isocarboxazid (Marplan), selegiline (Emsam), rasagiline (Azilect), and linezolid (the antibiotic). Methylene blue (a dye sometimes used in surgery) also has MAOI-like activity.

Ergotamines and Ergot Derivatives

Do not take sumatriptan within 24 hours of taking ergotamine or dihydroergotamine (DHE). Both sumatriptan and ergotamines cause vasoconstriction. Combining them can cause additive vasospasm — dangerous narrowing of blood vessels that can cut off blood supply.

Ergotamine products include: Ergomar (ergotamine tartrate), Migranal nasal spray (DHE), Trudhesa (DHE nasal spray), and D.H.E. 45 (IV/IM dihydroergotamine).

Other Triptans

Do not take sumatriptan within 24 hours of another triptan. All triptans cause vasoconstriction through the same mechanism, and combining them risks additive vasospasm. This includes: rizatriptan (Maxalt), zolmitriptan (Zomig), eletriptan (Relpax), naratriptan (Amerge), frovatriptan (Frova), and almotriptan (Axert).

Major Interactions: Use With Caution (Monitor Closely)

SSRIs and SNRIs (Antidepressants)

SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin-norepinephrine reuptake inhibitors) both increase serotonin levels in the brain. Combined with sumatriptan's serotonin-receptor-activating effects, this raises the risk of serotonin syndrome.

Common SSRIs: fluoxetine (Prozac), sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), paroxetine (Paxil), fluvoxamine (Luvox). Common SNRIs: venlafaxine (Effexor), duloxetine (Cymbalta), desvenlafaxine (Pristiq).

Note: The combination of sumatriptan and antidepressants is extremely common in migraine patients, who have higher rates of depression and anxiety. Most patients use this combination without incident. However, you should know the warning signs of serotonin syndrome (see below) and report them immediately if they occur.

Tricyclic Antidepressants (TCAs)

TCAs like amitriptyline (Elavil), nortriptyline (Pamelor), and protriptyline also affect serotonin and can increase serotonin syndrome risk when combined with sumatriptan. TCAs are also sometimes used as migraine preventives, so this interaction is clinically relevant.

Lithium

Lithium (used for bipolar disorder) increases serotonin levels and can add to serotonin syndrome risk when combined with sumatriptan. Tell your doctor if you take lithium.

Medications That Raise Blood Pressure

Sumatriptan can temporarily raise blood pressure due to vasoconstriction. Stimulants (amphetamines, ADHD medications), decongestants containing pseudoephedrine or phenylephrine, and sympathomimetic drugs can amplify this effect. Use with caution if you take these medications.

Ozanimod (Zeposia) and Other MAO-Inhibiting Drugs

Ozanimod (used for multiple sclerosis and ulcerative colitis) produces a metabolite that inhibits MAO-B, which can increase serotonin levels. Coadministration with sumatriptan is not recommended. Similarly, metaxalone (a muscle relaxant) may increase serotonin levels.

Serotonin Syndrome: Know These Warning Signs

Serotonin syndrome is a potentially life-threatening condition caused by too much serotonin activity in the nervous system. Symptoms include:

Agitation, restlessness, or confusion

Rapid heart rate (tachycardia)

High body temperature (hyperthermia)

Muscle twitching or rigidity

Diarrhea, nausea, vomiting

Hyperreflexia (exaggerated reflexes) or loss of coordination

If you experience these symptoms after taking sumatriptan — especially if you also take an antidepressant — seek medical attention immediately.

What to Tell Your Doctor Before Taking Sumatriptan

Always disclose these to your prescriber:

All antidepressants (SSRIs, SNRIs, TCAs, MAOIs)

Blood pressure medications and blood pressure readings

Any other migraine medications, especially ergotamines or other triptans

Lithium or mood stabilizers

Stimulants or ADHD medications

Any heart or blood vessel conditions

For more on sumatriptan's side effects, see sumatriptan side effects: what to expect. For a full overview of the drug, see what is sumatriptan.