brand logo

Am Fam Physician. 2021;104(5):509-512

This clinical content conforms to AAFP criteria for CME.

Author disclosure: No relevant financial affiliations.

Key Clinical Issue

How effective are pharmacologic and nonpharmacologic acute treatments for episodic migraine in adults?

Evidence-Based Answer

Nonsteroidal anti-inflammatory drugs (NSAIDs) and triptans, individually and combined, are superior compared with placebo in resolving episodic migraine pain and are first-line choices for acute treatment. (Strength of Recommendation [SOR]: A, based on consistent, good-quality patient-oriented evidence.) Acetaminophen and dihydroergotamine also relieve migraine pain better than placebo. (SOR: A, based on consistent, good-quality patient-oriented evidence.) Calcitonin gene-related peptide antagonists and lasmiditan improve pain and function in acute migraines compared with placebo. (SOR: A, based on consistent, good-quality patient-oriented evidence.) Opioids do not improve pain or function, and adverse events are greater, compared with established migraine treatment options. (SOR: B, based on inconsistent or limited-quality patient-oriented evidence.) Acupuncture does not relieve migraine pain compared with sham acupuncture, but noninvasive vagus nerve stimulation and remote electrical neuromodulation relieve acute migraine pain compared with sham stimulation.1 (SOR: B, based on inconsistent or limited-quality patient-oriented evidence.)

Treatment (cost for 10 doses)*Findings (95% CI)Number of studies (participants)Strength of evidence
Triptans ($15)More pain relief at all time points; NNT < 10 in every systematic review9 systematic reviews (n = 101,276)●●●
NSAIDs ($3)More pain relief at all time points; NNT < 10 in every systematic review4 systematic reviews (n = 10,272)●●●
Acetaminophen ($2)More pain relief at 2 hours; NNT = 121 systematic review (n = 2,942)●●●
More restored function at 2 hours; RR = 1.80 (1.27 to 2.54)2 RCTs (n = 729)●●○
No difference in total adverse events2 RCTs
Dihydroergotamine ($800)More pain relief at 2 hours; RR = 1.83 (1.58 to 2.13)3 RCTs (n = 1,299)●●●
More pain relief at 1 week; RR = 1.48 (1.22 to 1.80)1 RCTs (n = 903)●●○
No difference in total adverse events4 RCTs
Ergotamine plus caffeine ($90)No difference in function1 RCT (n = 309)●○○
More pain relief at 2 hours; RR = 1.61 (1.05 to 2.49)1 RCT (n = 309)●●○
No difference in total adverse events2 RCTs
Chlorpromazine ($20)No difference in function1 RCT (n = 36)●○○
More pain relief at 2 hours; RR = 5.46 (2.97 to 10.05)2 RCTs (n = 123)●○○
No difference in total adverse events1 RCT
Droperidol ($180)More pain relief at 2 hours; RR = 1.39 (1.11 to 1.74)1 RCT (n = 305)●○○
More total adverse events; RR = 1.61 (1.18 to 2.20)1 RCT
Haloperidol ($9)More pain relief at 2 hours; RR = 5.33 (1.84 to 15.49)1 RCT (n = 40)●○○
More total adverse events; RR = 6 (2.12 to 120.65)1 RCT
Metoclopramide ($3)More pain relief at 2 hours; RR = 1.91 (1.47 to 2.48)3 RCTs (n = 268)●○○
No difference in total adverse events2 RCTs
Prochlorperazine ($6)More pain relief at 2 hours; RR = 1.80 (1.10 to 2.94)2 RCTs (n = 90)●○○
More total adverse events; RR = 6.48 (1.49 to 28.17)1 RCT
Rimegepant ($1,000)More pain relief at 2 hours; RR = 1.36 (1.26 to 1.46)3 RCTs (n = 3,336)●●○
More pain relief at 1 week; RR = 1.64 (1.40 to 1.93)1 RCT (n = 1,466)●●○
More restored function at 2 hours; RR = 1.43 (1.26 to 1.62)2 RCTs (n = 2,652)●●○
More total adverse events; RR = 1.23 (1.00 to 1.50)3 RCTs
Ubrogepant ($900)Improved function at 2 hours; RR = 1.26 (1.12 to 1.42)2 RCTs (n = 3,358)●●●
More pain relief at 2 hours; RR = 1.21 (1.12 to 1.31)3 RCTs (n = 4,192)●●●
No difference in pain relief at 2 weeks1 RCT (n = 833)●○○
No difference in total adverse events3 RCTs
Lasmiditan ($900)More pain relief at 2 hours; RR = 1.38 (1.14 to 1.68)4 RCTs (n = 5,742)●●●
More restored function at 2 hours; RR = 1.42 (1.26 to 1.61)2 RCTs (n = 5,100)●●●
More total adverse events; RR = 2.67 (2.10 to 3.39)4 RCTs
Dexamethasone ($10)No difference in restored function at 2 hours1 RCT (n = 205)●○○
More restored function at 1 week; RR = 1.49 (1.04 to 2.13)1 RCT (n = 115)●○○
No difference in total adverse events2 RCTs
Lidocaine ($10)More pain relief at 2 hours; RR = 2.14 (1.16 to 3.96)2 RCTs (n = 130)●○○
More total adverse events; RR = 3.30 (1.76 to 6.17)2 RCTs
Magnesium sulfate ($100)More pain relief at 2 hours; RR = 3.86 (2.11 to 7.07)1 RCT and 1 crossover RCT (n = 150)●○○
Octreotide ($25)More pain relief at 1 day; RR = 3.06 (1.11 to 8.44)1 RCT (n = 29)●○○
No difference in total adverse events1 RCT
TreatmentFindings (95% CI)Number of studies (participants)Strength of evidence
Acupuncture vs. sham acupunctureLess pain relief at 1 day; RR = 0.74 (0.56 to 0.97)1 RCT (n = 175)●○○
No difference in total adverse events1 RCT
External trigeminal nerve stimulation vs. sham stimulationNo difference in pain relief at 2 hours1 RCT (n = 106)●○○
No difference in total adverse events2 RCTs
Magnetic stimulation vs. sham stimulationNo difference in pain relief at 2 hours1 RCT (n = 201)○○○
No difference in total adverse events1 RCT
Noninvasive vagus nerve stimulation vs. sham stimulationMore pain relief at 2 hours; RR = 1.49 (1.04 to 2.13)1 RCT (n = 248)●●○
No difference in total adverse events1 RCT
Remote electrical neuromodulation vs. sham stimulationMore pain relief at 2 hours; RR = 1.65 (1.22 to 2.24)1 RCT (n = 252)●●○
No difference in total adverse eventsMore pain relief at 1 week; RR = 2.27 (1.30 to 3.95)
1 RCT

Practice Pointers

Migraine headaches are one of the most common acute medical problems.2 More than one in six adults in the United States reported having a migraine or severe headache in the past three months, and in one-half of those people, it caused severe impairment such as missing work or school.3 Episodic migraines are defined as headaches with at least two of the following: unilateral location, pulsating quality, moderate to severe pain intensity, and aggravated by or causes avoidance of routine physical activity. Episodic migraines also must be associated with nausea or photophobia and phonophobia and last four to 72 hours when untreated.4

The Agency for Healthcare Research and Quality (AHRQ) review assessed the effectiveness of pharmacologic and nonpharmacologic options for the acute treatment of episodic migraine. The review included 15 existing systematic reviews of NSAIDs and triptans and 141 studies (n = 37,653) of other migraine treatments in the outpatient or emergency department setting.1,5

The AHRQ review concludes that NSAIDs and triptans are first-line treatments of acute migraines. Four systematic reviews (n = 10,272) comparing NSAIDs with various interventions, including placebo and triptans, found that NSAIDs lead to pain relief and resolution at all time points with a number needed to treat (NNT) of less than 10 in all studies for two-hour migraine pain relief and 24-hour sustained pain relief.

Triptans improved pain and function at two and 24 hours compared with placebo in nine systematic reviews (n = 101,276) with an NNT of less than 10 in all studies. Higher doses of triptans were significantly more effective; 100 mg of sumatriptan was significantly more effective at 24-hour pain relief than a 50-mg dose (NNT = 4.5). However, an increase in doses of triptans was also associated with an increase in harms compared with placebo (e.g., sumatriptan, 100 mg [number needed to harm (NNH) = 5.2], 50 mg [NNH = 13], and 25 mg [NNH = not statistically significant]). Adverse events included nausea, dizziness, paresthesias, somnolence, and chest discomfort. Earlier treatment during the mild phase of the migraine appeared to be more effective, although none of the studies were intentionally designed to evaluate timing of administration.6

Two systematic reviews found that combining a triptan and an NSAID is effective and well tolerated, leading to relief of moderate to severe headaches at two hours compared with placebo (NNT = 3.2; NNH = 11). The most commonly reported adverse events were dizziness, nausea, dyspepsia, paresthesia, somnolence, dry mouth, and chest discomfort.1,7

The AHRQ review confirms that opioids should not be used in the acute treatment of migraines. Most of the studies that included opioids found them to be less effective and associated with more adverse events compared with other medications or placebo in the treatment of episodic migraine.1 Physicians should avoid opioids for the acute treatment of migraine in all settings if possible. This is consistent with the Choosing Wisely recommendation from the American Headache Society.8

Already a member/subscriber?  Log In

Subscribe

From $145
  • Immediate, unlimited access to all AFP content
  • More than 130 CME credits/year
  • AAFP app access
  • Print delivery available
Subscribe

Issue Access

$59.95
  • Immediate, unlimited access to this issue's content
  • CME credits
  • AAFP app access
  • Print delivery available

Article Only

$25.95
  • Immediate, unlimited access to just this article
  • CME credits
  • AAFP app access
  • Print delivery available
Purchase Access:  Learn More

The Agency for Healthcare Research and Quality (AHRQ) conducts the Effective Health Care Program as part of its mission to produce evidence to improve health care and to make sure the evidence is understood and used. A key clinical question based on the AHRQ Effective Health Care Program systematic review of the literature is presented, followed by an evidence-based answer based on the review. AHRQ’s summary is accompanied by an interpretation by an AFP author that will help guide clinicians in making treatment decisions.

This series is coordinated by Kenny Lin, MD, MPH, deputy editor. A collection of Implementing AHRQ Effective Health Care Reviews published in AFP is available at https://www.aafp.org/afp/ahrq.

Continue Reading

More in AFP

More in Pubmed

Copyright © 2021 by the American Academy of Family Physicians.

This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP.  See permissions for copyright questions and/or permission requests.