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Research · Medication

Triptans

For a migraine attack, oral sumatriptan 50 mg left 28% pain free at 2 hours against 11% on placebo, and a 6 mg injection 59% against 15%. Network analyses rank eletriptan and rizatriptan highest. Tingling and chest or neck tightness are the frequent side effects. Labels contraindicate triptans in coronary disease and after a stroke.

Add to Bio HackChecked 2026-11-13
Status
Prescription drugs in the US. Sumatriptan tablets are FDA-approved for the acute treatment of migraine with or without aura in adults, and the label states they are not for preventing migraine. The label lists coronary artery disease, prior stroke and uncontrolled high blood pressure among contraindications. It carries no boxed warning.
Also called
sumatriptan, Imitrex, Tosymra, Zembrace, Onzetra, rizatriptan, Maxalt, zolmitriptan, Zomig, eletriptan, Relpax, naratriptan, Amerge, almotriptan, Axert, frovatriptan, Frova, sumatriptan with naproxen, Treximet, 5-HT1B/1D agonists, migraine abortives
Taken for
migraine attacks, migraine with aura, cluster headache, menstrual migraine, migraine in teenagers, headache

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help8

Reported risks6

What people take it for, and what was found

Shown to help8

StrongVery common

Stopping a migraine attack

Shown to stop a migraine attack, with 28% pain free 2 hours after oral sumatriptan 50 mg against 11% on placebo.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Across Cochrane reviews of sumatriptan, the oral 50 mg dose left 28% pain free at 2 hours against 11% on placebo, a number needed to treat of 6.1 (95% CI 5.5 to 6.9) in 6,447 participants. For headache relief at 2 hours the number needed to treat was 3.5 (3.2 to 3.7) at oral 100 mg. Treating early, while pain was mild, gave better results than waiting [1][2]. In a meta-analysis of 53 trials, sumatriptan 100 mg gave a headache response at 2 hours in 59%, pain freedom at 2 hours in 29% and sustained pain freedom in 20% [3]. A network meta-analysis of 137 trials found every triptan superior to placebo for pain freedom at 2 hours, with odds ratios from 1.73 (95% CI 1.27 to 2.34) for naratriptan to 5.19 (4.25 to 6.33) for eletriptan [4].
Population
52,236 participants across Cochrane reviews of sumatriptan by all routes [1]; 37,250 participants in 61 studies of oral sumatriptan [2]; 24,089 patients in 53 trials of oral triptans [3]; 89,445 participants in 137 trials of 17 drugs [4].
Sources
[1], [2], [3], [4]
Caveats
Trials treat a single attack or a few. Twelve of the 53 trials in the earlier meta-analysis were unpublished [3].
ModerateVery common

Injected sumatriptan for migraine

Shown to leave 59% pain free 2 hours after a 6 mg sumatriptan injection against 15% on placebo, a larger effect than by mouth.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
A 6 mg injection under the skin left 59% pain free at 2 hours against 15% on placebo, a number needed to treat of 2.3 (95% CI 2.1 to 2.4) in 2,522 participants, and acted faster than other routes [1]. Numbers needed to treat were 2.9 for pain freedom at 1 hour, 2.1 for headache relief at 2 hours and 6.1 for sustained pain freedom at 24 hours. A second injection after a poor response to the first gave no added relief [5].
Population
9,365 participants in 35 studies of injected sumatriptan [5].
Sources
[1], [5]
Caveats
Adverse events were more frequent with the injection than with other routes [1].
Strong

Differences between triptans

Shown to differ within the class, with eletriptan and rizatriptan ranking above sumatriptan for pain freedom at 2 hours and naratriptan lowest.

The numbers and sources
Effect
In head-to-head comparisons within a network of 137 trials, eletriptan had the highest odds of pain freedom at 2 hours, followed by rizatriptan, sumatriptan and zolmitriptan, and naratriptan had the lowest odds against placebo (OR 1.73) [4]. Against sumatriptan 100 mg, an earlier meta-analysis found better pain relief with rizatriptan 10 mg, better pain relief and lower tolerability with eletriptan 80 mg, and lower pain relief with better tolerability for naratriptan 2.5 mg [3]. A third network analysis found the most favorable results for injected sumatriptan, orally dissolving rizatriptan and zolmitriptan, and eletriptan tablets [6].
Population
89,445 participants in 137 trials [4]; 24,089 patients in 53 trials, 22 of them comparing triptans directly [3]; 133 randomized trials [6].
Sources
[4], [3], [6]
Caveats
Many rankings rest on indirect comparison through placebo. Confidence in the network estimates ranged from high to very low [4].
Moderate

Compared with NSAIDs, acetaminophen and newer migraine drugs

Shown to match or exceed NSAIDs, aspirin and acetaminophen for headache relief at 2 hours, and to outperform lasmiditan, rimegepant and ubrogepant in a network analysis.

The numbers and sources
Effect
Standard-dose triptans relieved headache within 2 hours in 42% to 76% of patients, against 46% to 52% for NSAIDs, aspirin and acetaminophen and 38% for ergots [6]. In a network of 137 trials, eletriptan, rizatriptan, sumatriptan and zolmitriptan were each more likely to give pain freedom at 2 hours than lasmiditan, rimegepant or ubrogepant. For sustained pain freedom to 24 hours, eletriptan and ibuprofen ranked highest [4]. Paracetamol 1,000 mg plus metoclopramide 10 mg did not differ significantly from oral sumatriptan 100 mg for headache relief at 2 hours [7].
Population
133 randomized trials [6]; 89,445 participants in 137 trials [4]; 2,942 participants in 11 studies of paracetamol [7].
Sources
[6], [4], [7]
Caveats
Mostly indirect comparisons across trials with different patients and placebo rates.
ModerateVery common

Sumatriptan taken with naproxen

Shown to leave 28% pain free at 2 hours on sumatriptan plus naproxen against 8% on placebo, more than either drug alone.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
When starting pain was moderate or severe, sumatriptan 85 mg or 50 mg plus naproxen 500 mg left 28% pain free at 2 hours against 8% on placebo (number needed to treat 4.9, 95% CI 4.3 to 5.7). When starting pain was mild the figures were 50% and 18% (3.1, 95% CI 2.9 to 3.5). Where trials compared directly, the combination did better than sumatriptan alone or naproxen alone, and adverse events were less frequent on naproxen than on sumatriptan [8].
Population
13 studies, with 3,663 participants given the combination, 3,682 placebo, 964 sumatriptan and 982 naproxen [8].
Sources
[8]
Caveats
Adverse events were more frequent on the combination than on placebo and rarely led to withdrawal [8].
ModerateVery common

Cluster headache attacks

Shown to leave 48% pain free 15 minutes after a 6 mg sumatriptan injection for a cluster headache attack, against 17% on placebo.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Fifteen minutes after sumatriptan 6 mg under the skin, 48% were pain free and 75% had no or mild pain, against 17% and 32% on placebo (numbers needed to treat 3.3 and 2.4). Zolmitriptan 10 mg by nasal spray left 12% pain free and 28% with no or mild pain, against 3% and 7% on placebo (11 and 4.9) [9].
Population
6 studies of single attacks, with 219 participants given injected sumatriptan, 454 given zolmitriptan and 326 given placebo [9].
Sources
[9]
Caveats
Six small studies, each treating one attack.
ModerateStudied in children

Migraine in children and adolescents

Shown to raise pain freedom in adolescents with migraine, with 6 treated for one extra pain free, and 13 in younger children.

The numbers and sources
Effect
Triptans as a class raised pain freedom against placebo in adolescents (RR 1.32, 95% CI 1.19 to 1.47, number needed to treat 6) across 21 studies, and in children (RR 1.67, 95% CI 1.06 to 2.62, number needed to treat 13) across 3 studies. Minor adverse events were more frequent in adolescents on triptans (risk difference 0.13, 95% CI 0.08 to 0.18) [10].
Population
7,026 adolescents in 21 studies and 273 children in 3 studies, from 27 trials with mean ages of 8.2 to 14.7 years [10].
Sources
[10]
Caveats
The reviewers rated the evidence moderate quality. The sumatriptan tablet label covers adults only [11].
ModerateStudied in women

Preventing menstrual migraine

Shown to raise the share of women free of menstrual migraine when frovatriptan was taken around the period, with about 4 to 7 treated for one extra.

The numbers and sources
Effect
Taken for 5 to 6 days starting 2 to 3 days before the expected headache, frovatriptan 2.5 mg once a day raised the chance of a period free of menstrual migraine against placebo (RR 1.48, 95% CI 1.27 to 1.72, number needed to treat 7.22), and twice a day more so (RR 1.82, 95% CI 1.58 to 2.09, number needed to treat 3.90). Numbers needed to treat for zolmitriptan 2.5 mg were 4.98 twice a day and 2.52 three times a day [12].
Population
Women with menstrual migraine in 6 randomized trials: 1,217 given frovatriptan, 462 naratriptan, 163 zolmitriptan and 1,104 placebo [12].
Sources
[12]
Caveats
All participants were women, with mean ages of 36 to 38. No trial compared one triptan with another [12]. The sumatriptan label states it is not indicated for preventing migraine [11].

Doses studied

The oral sumatriptan trials used 25, 50 and 100 mg, and the injection trials mostly 6 mg [2][5]. The combination trials used sumatriptan 85 mg or 50 mg with naproxen 500 mg [8]. The comparisons between triptans used rizatriptan 10 mg, eletriptan 20 to 80 mg, naratriptan 2.5 mg, zolmitriptan 2.5 and 5 mg and almotriptan 12.5 mg [3]. The menstrual migraine trials used frovatriptan 2.5 mg once or twice a day around the period [12].

The sumatriptan tablet label describes single doses of 25, 50 or 100 mg, a second dose at least 2 hours after the first, and no more than 200 mg in 24 hours [11].

Risks

Reported risks3

ModerateCommon

Tingling, warmth and chest, neck or jaw tightness

Shown to raise tingling, warm or cold sensations and pressure or tightness, with chest symptoms in 2% on sumatriptan 50 or 100 mg against 1% on placebo.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In the label's placebo-controlled trials, tingling was reported by 3% to 5% on sumatriptan tablets and 2% on placebo, pain and pressure sensations by 6% to 8% against 4%, chest pain, tightness or pressure by 1% to 2% against 1%, neck, throat or jaw tightness by up to 3% against under 1%, and tiredness by 2% to 3% against under 1%. The label states that these sensations are usually not from the heart [11]. Across 53 trials, sumatriptan 100 mg added 13 percentage points to the share with any adverse event over placebo, 6 points for nervous system events and 1.9 points for chest events [3]. In adolescents, minor adverse events were 13 percentage points more frequent than on placebo [10].
Population
1,625 people on sumatriptan tablets and 309 on placebo [11]; 24,089 patients in 53 trials [3]; 7,026 adolescents [10].
Sources
[11], [3], [10]
Caveats
The band here is taken from the 2% with chest symptoms named in the Finding. Any adverse event was more frequent than that.
LimitedRare

Serotonin syndrome with antidepressants

The label warns of serotonin syndrome with SSRI or SNRI antidepressants. One study found 2 definite cases among 19,017 people prescribed both.

The numbers and sources
How common
Rare: fewer than 1 in 1,000 people.
Effect
The label states that serotonin syndrome may occur with sumatriptan, particularly with SSRIs, SNRIs, tricyclic antidepressants and MAO inhibitors [11]. Among 19,017 people prescribed a triptan together with an SSRI or SNRI over 14 years, serotonin syndrome was suspected in 17 and classified as definite in 2, a rate of 0.6 per 10,000 person-years of exposure (95% CI 0.0 to 1.5), or 2.3 per 10,000 with 5 possible cases added [16].
Population
47,968 people prescribed triptans in one Boston-area health system, 19,017 of them also prescribed an SSRI or SNRI, with 30,928 person-years of exposure [16].
Sources
[11], [16]
Caveats
One records-based study from one health system, which counts prescriptions and not doses taken together.
LimitedHow often is not known

With MAO inhibitors, ergot drugs and other triptans

The label contraindicates sumatriptan with MAO-A inhibitors, which raise its blood levels 7-fold, and within 24 hours of an ergot drug or another triptan.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label states that MAO-A inhibitors increase exposure to sumatriptan 7-fold and contraindicates use with one or within 2 weeks of one. It contraindicates use within 24 hours of ergotamine-type drugs or another triptan because their effects on blood vessels may add together [11].
Population
People taking these drugs together, as described in the label [11].
Sources
[11]
Caveats
The label gives no rate.

Mixed results3

ModerateRare

Heart attack and stroke

Mixed results: cohort studies found no rise in heart attack or stroke with triptans overall, and one found a rise just after a first prescription in under 0.01% of users.

The numbers and sources
How common
Rare: fewer than 1 in 1,000 people.
Effect
The label states that there have been rare reports of serious cardiac reactions, including heart attack, within hours of sumatriptan, that it may cause coronary artery spasm, and that stroke, brain hemorrhage and marked rises in blood pressure have been reported with this drug class. It contraindicates use in coronary artery disease, prior stroke or transient ischemic attack, peripheral vascular disease and uncontrolled hypertension [11]. Among people with migraine in the General Practice Research Database, triptan prescription was not associated with stroke (HR 1.13, 95% CI 0.78 to 1.65) or heart attack (HR 0.93, 95% CI 0.60 to 1.43) [13]. A review of 4 observational studies pooled an odds ratio of 0.86 (95% CI 0.52 to 1.43) for serious ischemic events with intense triptan use, and called the stroke evidence conflicting [14]. Among 429,612 people filling a first triptan prescription in Denmark, 11 (0.003%) had a heart attack and 18 (0.004%) an ischemic stroke in the time windows studied, with odds ratios of 3.3 (95% CI 1.0 to 10.9) and 3.2 (95% CI 1.3 to 8.1) for the period just after the prescription [15].
Population
63,575 people with migraine, 13,664 of them prescribed a triptan [13]; 4 observational studies [14]; 429,612 first-time triptan users, median age 38 [15].
Sources
[11], [13], [14], [15]
Caveats
Observational. People with heart disease are steered away from triptans, which lowers event rates among users. The people with events after a first prescription had a median age of about 60 and a high-risk cardiovascular profile [15].
LimitedHow often is not known

Headaches from frequent use

The label warns that using triptans on 10 or more days a month may worsen headaches. One cohort found triptan use did not predict chronic migraine a year later.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label states that overuse of acute migraine drugs, naming ergotamine, triptans and opioids taken on 10 or more days a month, may lead to medication overuse headache, with daily migraine-like headaches or more frequent attacks [11]. Of 8,219 people with episodic migraine, 2.5% had chronic migraine a year later. Against acetaminophen users, triptan use at baseline was not associated with that change (OR 1.25, 95% CI 0.9 to 1.7), and use of barbiturates (OR 2.06) or opiates (OR 1.98) was [17].
Population
8,219 adults with episodic migraine in 2005, followed to 2006 [17].
Sources
[11], [17]
Caveats
Observational, and the cohort measured any use at baseline, not use on 10 or more days a month.
ModerateStudied in pregnancyHow often is not known

Use in pregnancy

Mixed results: pooled studies found no more birth defects or prematurity, and more miscarriage than in healthy women but not than in women with untreated migraine.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Against women with migraine who took no triptan, exposure was not associated with major congenital malformations (OR 0.84, 95% CI 0.61 to 1.16), prematurity (OR 0.90, 95% CI 0.35 to 2.30) or spontaneous abortion (OR 1.27, 95% CI 0.58 to 2.79). Against healthy controls, malformations (OR 1.18, 95% CI 0.97 to 1.44) and prematurity did not differ and spontaneous abortion was more frequent (OR 3.54, 95% CI 2.24 to 5.59). Women with migraine who took no triptan had more malformations than healthy controls (OR 1.41, 95% CI 1.11 to 1.80) [18]. In the manufacturer's pregnancy registry cited on the label, major birth defects followed 4.2% of first-trimester exposures to sumatriptan (20 of 478), and the label states that the data have not detected an increased frequency of birth defects [11].
Population
4,208 infants of women who used triptans in pregnancy and 1,466,994 children of women who did not, in 6 studies [18]; 626 infants and fetuses in the registry [11].
Sources
[18], [11]
Caveats
Observational. Migraine itself was associated with adverse outcomes, which makes the choice of comparison group decisive [18].

Claims tested and not found

  1. That newer migraine drugs outperform triptans. In a network of 137 trials with 89,445 participants, eletriptan, rizatriptan, sumatriptan and zolmitriptan were each more likely to give pain freedom at 2 hours than lasmiditan, rimegepant or ubrogepant [4].
  2. That a second sumatriptan injection helps when the first did not. A Cochrane review found no added migraine relief from a second 6 mg dose after an inadequate response to the first [5].
  3. That triptan use leads to chronic migraine. In 8,219 people with episodic migraine, triptan use was not associated with chronic migraine a year later (OR 1.25, 95% CI 0.9 to 1.7) [17].

Related

NSAIDs

Sources

  1. Derry CJ, Derry S, Moore RA. Sumatriptan (all routes of administration) for acute migraine attacks in adults - overview of Cochrane reviews. Cochrane Database of Systematic Reviews. 2014. https://doi.org/10.1002/14651858.CD009108.pub2
  2. Derry CJ, Derry S, Moore RA. Sumatriptan (oral route of administration) for acute migraine attacks in adults. Cochrane Database of Systematic Reviews. 2012. https://doi.org/10.1002/14651858.CD008615.pub2
  3. Ferrari MD, Roon KI, Lipton RB, Goadsby PJ. Oral triptans (serotonin 5-HT1B/1D agonists) in acute migraine treatment: a meta-analysis of 53 trials. The Lancet. 2001. https://doi.org/10.1016/S0140-6736(01)06711-3
  4. Karlsson WK, Ostinelli EG, Zhuang ZA, et al. Comparative effects of drug interventions for the acute management of migraine episodes in adults: systematic review and network meta-analysis. BMJ. 2024. https://doi.org/10.1136/bmj-2024-080107
  5. Derry CJ, Derry S, Moore RA. Sumatriptan (subcutaneous route of administration) for acute migraine attacks in adults. Cochrane Database of Systematic Reviews. 2012. https://doi.org/10.1002/14651858.CD009665
  6. Cameron C, Kelly S, Hsieh SC, et al. Triptans in the Acute Treatment of Migraine: A Systematic Review and Network Meta-Analysis. Headache. 2015. https://doi.org/10.1111/head.12601
  7. Derry S, Moore RA. Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults. Cochrane Database of Systematic Reviews. 2013. https://doi.org/10.1002/14651858.CD008040.pub3
  8. Law S, Derry S, Moore RA. Sumatriptan plus naproxen for the treatment of acute migraine attacks in adults. Cochrane Database of Systematic Reviews. 2016. https://doi.org/10.1002/14651858.CD008541.pub3
  9. Law S, Derry S, Moore RA. Triptans for acute cluster headache. Cochrane Database of Systematic Reviews. 2013. https://doi.org/10.1002/14651858.CD008042.pub3
  10. Richer L, Billinghurst L, Linsdell MA, et al. Drugs for the acute treatment of migraine in children and adolescents. Cochrane Database of Systematic Reviews. 2016. https://doi.org/10.1002/14651858.CD005220.pub2
  11. Sumatriptan tablets, prescribing information. DailyMed, US National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1d2cd01c-05e7-44cf-a71d-0f474e826b7e
  12. Hu Y, Guan X, Fan L, Jin L. Triptans in prevention of menstrual migraine: a systematic review with meta-analysis. The Journal of Headache and Pain. 2013. https://doi.org/10.1186/1129-2377-14-7
  13. Hall GC, Brown MM, Mo J, MacRae KD. Triptans in migraine: the risks of stroke, cardiovascular disease, and death in practice. Neurology. 2004. https://doi.org/10.1212/01.WNL.0000110312.36809.7F
  14. Roberto G, Raschi E, Piccinni C, et al. Adverse cardiovascular events associated with triptans and ergotamines for treatment of migraine: systematic review of observational studies. Cephalalgia. 2015. https://doi.org/10.1177/0333102414550416
  15. Petersen CL, Hougaard A, Gaist D, Hallas J. Risk of Stroke and Myocardial Infarction Among Initiators of Triptans. JAMA Neurology. 2024. https://doi.org/10.1001/jamaneurol.2023.5549
  16. Orlova Y, Rizzoli P, Loder E. Association of Coprescription of Triptan Antimigraine Drugs and Selective Serotonin Reuptake Inhibitor or Selective Norepinephrine Reuptake Inhibitor Antidepressants With Serotonin Syndrome. JAMA Neurology. 2018. https://doi.org/10.1001/jamaneurol.2017.5144
  17. Bigal ME, Serrano D, Buse D, Scher A, Stewart WF, Lipton RB. Acute migraine medications and evolution from episodic to chronic migraine: a longitudinal population-based study. Headache. 2008. https://doi.org/10.1111/j.1526-4610.2008.01217.x
  18. Marchenko A, Etwel F, Olutunfese O, Nickel C, Koren G, Nulman I. Pregnancy outcome following prenatal exposure to triptan medications: a meta-analysis. Headache. 2015. https://doi.org/10.1111/head.12500

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