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Sumatriptan

Prescription ·Strong evidence ·Reviewed May 2026

Sumatriptan is the prototypical triptan and the first serotonin 5-HT1B/1D receptor agonist developed specifically for the acute treatment of migraine attacks with or without aura. It is also effective for cluster headache. Available in oral, nasal spray, and subcutaneous injection formulations for flexibility based on attack severity and associated nausea.

Evidence tier
Strong
Indexed sources
10 1994–2021
Interactions
3
Category
Prescription
Read the sources → Compare profiles
What it's good for
  • Rapid relief of migraine headache, nausea, and photophobia1,2
  • Subcutaneous injection provides relief within 10-15 minutes
  • Effective for cluster headache
  • Multiple delivery routes available
What to watch for
  • Tingling, warmth, and flushing (triptan sensations)
  • Chest tightness or pressure (usually non-cardiac)
  • Dizziness
  • Ischemic heart disease, coronary artery vasospasm (Prinzmetal's angina), or uncontrolled hypertension
  • History of stroke or TIA

The bottom line

Evidence rating strong. Most-documented uses: rapid relief of migraine headache, nausea, and photophobia, subcutaneous injection provides relief within 10-15 minutes, effective for cluster headache. 10 sources indexed (1994–2021), with 3 interaction records on file.

The science

How it works, mechanistically.

Core mechanism

Selectively activates serotonin 5-HT1B receptors on intracranial blood vessels, causing vasoconstriction of dilated meningeal and cerebral arteries. Also activates 5-HT1D receptors on trigeminal nerve terminals, inhibiting release of pro-inflammatory neuropeptides (CGRP, substance P) and blocking pain signal transmission through the trigeminovascular system.6

Class
Triptan / Antimigraine
Dosing

Dosing & protocol.

Common range
50-100 mg oral; 6 mg subcutaneous; 5-20 mg intranasal; may repeat after 2 hours if needed, max 200 mg oral/day or 12 mg SC/day (as prescribed by your physician)
Recommended form
Oral tablets for mild-moderate attacks; subcutaneous injection (6 mg) for severe attacks or when nausea prevents oral dosing

Oral bioavailability ~15% due to first-pass metabolism and incomplete absorption; subcutaneous bioavailability 97%. Migraine-related gastroparesis may further delay oral absorption.

Safety

Full safety detail.

Side effects

  • Tingling, warmth, and flushing (triptan sensations)
  • Chest tightness or pressure (usually non-cardiac)
  • Dizziness
  • Injection site reactions (SC formulation)
  • Fatigue and drowsiness
  • Medication overuse headache (with frequent use >10 days/month)
  • Serotonin syndrome (rare; risk increased with concurrent SSRIs, SNRIs, or TCAs)

Contraindications

  • Ischemic heart disease, coronary artery vasospasm (Prinzmetal's angina), or uncontrolled hypertension
  • History of stroke or TIA
  • Peripheral vascular disease
  • Concurrent use with MAO-A inhibitors (within 2 weeks) or ergot-containing medications (within 24 hours)
  • Hemiplegic or basilar migraine1,2
  • Severe hepatic impairment
Interactions

Interaction records.

SeriousCaution

5-HTP

5-HTP is a direct serotonin precursor, and sumatriptan is a serotonin receptor agonist used for migraine attacks. Direct case evidence for this exact pair is limited, but combining a serotonin precursor with a triptan can add serotonergic pressure and may increase the risk of serotonin toxicity. Warning signs include agitation, tremor, sweating, diarrhea, clonus, fever, or confusion.

Recommendation: Avoid 5-HTP supplements while using sumatriptan unless your prescriber specifically approves the combination. If both were taken and you develop tremor, fever, marked restlessness, muscle jerks, or confusion, seek urgent care. Food sources of tryptophan are not the issue; concentrated 5-HTP supplements are.

SeriousCaution

St. John's Wort

St. John's wort has serotonergic antidepressant activity and has been linked to clinically important interactions with antidepressant drugs. Sumatriptan also acts on serotonin receptors, so combining it with St. John's wort may increase the risk of serotonin toxicity, even though direct case evidence for this exact pair is limited. Watch for agitation, tremor, sweating, diarrhea, clonus, fever, or confusion.

Recommendation: Avoid St. John's wort if you use sumatriptan for migraines. If you already take St. John's wort, stop it and discuss safer migraine and mood-support options with your prescriber. Seek urgent care if serotonin-toxicity symptoms appear after overlapping use.

DangerousContraindicated

MDMA

MDMA causes a large serotonin release and can produce severe serotonin toxicity and hyperthermia. Sumatriptan is a serotonin receptor agonist, so using it around MDMA exposure adds avoidable serotonergic pharmacology during a high-risk state. This combination is especially dangerous with dehydration, overheating, stimulants, antidepressants, or repeated triptan dosing.

Recommendation: Do not combine MDMA with sumatriptan. If MDMA was used, avoid taking sumatriptan and seek medical advice for severe headache, chest pain, high fever, confusion, muscle rigidity, or repeated vomiting. Treat fever, agitation, clonus, or confusion after overlap as an emergency.

Search all 3 interaction records for Sumatriptan →

Sources

Sources, by evidence tier.

Numbered references. Citations throughout the page link here.

Meta-analyses & systematic reviews

3

Reviews & position papers

2

Reference material

5
Keep exploring

Deep dives & adjacent profiles.

RizatriptanPrescriptionTopiramatePrescriptionRopinirolePrescriptionPropranololPrescriptionPramipexolePrescriptionPhenytoinPrescription

This page is educational. Do not start, stop, or change a supplement or medication based on it without checking with a qualified healthcare professional.

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NutriStack is an informational and organizational tool, not a medical service, and not a substitute for professional advice. Always consult a qualified healthcare professional before starting, stopping, or changing any supplement or medication.