PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of clinevidLink to Publisher's site
 
Clin Evid. 2004; 2004: 1208.
Published online 2004 May 1.
PMCID: PMC2907553

Migraine headache in adults

Luis E E Morillo, Associate Professor

Abstract

Introduction

Migraine affects 5-25% of women and 2-10% of men, and, although self limiting, recurrent attacks can affect daily functioning and quality of life.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical question: What are the effects of drug treatments for acute migraine? We searched: Medline, Embase, The Cochrane Library and other important databases up to August 2003 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found 60 systematic reviews, RCTs or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review we present information relating to the effectiveness and safety of the following interventions: diclofenac, eletriptan, ergotamine, ibuprofen, naproxen, naratriptan, rizatriptan, salicylates, sumatriptan, tolfenamic acid, and zolmitriptan.

Key Points

Migraine affects 5-25% of women and 2-10% of men, and, although self limiting, recurrent attacks can affect daily functioning and quality of life.

Oral or intravenous salicylates, alone or with metoclopramide, paracetamol or caffeine, increase headache relief compared with placebo, but can cause gastrointestinal adverse effects.

  • Aspirin plus metoclopramide may be as effective at relieving headache as sumatriptan or zolmitriptan.
  • Oral or intramuscular diclofenac, ibuprofen, naproxen and tolfenamic acid improve headache compared with placebo.
  • Naproxen may be more effective at improving headache compared with ergotamine, but studies have given conflicting results.
  • Ergotamine may improve headache relief compared with placebo but is less effective compared with sumatriptan or naproxen and can cause nausea and vomiting.

Triptans increase headache relief compared with placebo or ergotamine plus caffeine, but we don't know which is the most effective triptan as studies have given conflicting results.

  • Eletriptan may be more effective at relieving headache compared with sumatriptan.
  • Sumatriptan, rizatriptan and zolmitriptan seem to have similar efficacy at relieving headache, while naratriptan may be less effective.
  • Triptans have not been shown to be more effective at relieving headache compared with aspirin plus metoclopramide.
  • There is consensus that sumatriptan should not be used in people with ischaemic heart disease or with ergotamine treatment.

About this condition

Definition

Migraine is a primary headache disorder manifesting as recurring attacks usually lasting for 4-72 hours and involving pain of moderate to severe intensity, often with nausea, sometimes vomiting, and/or sensitivity to light, sound, and other sensory stimuli. The 1988 International Headache Society criteria include separate criteria for migraine with and migraine without associated aura. Unless stated otherwise, RCTs used International Headache Society criteria for migraine with or without aura.

Incidence/ Prevalence

Migraine is common worldwide. Prevalence has been reported to be 5-25% in women and 2-10% in men. Overall, the highest incidence for migraine without aura has been reported between the ages of 10 and 11 years (10/1000 person years). The peak incidence of migraine without aura in males is between ages 10 and 11 years (10/1000 person years) and in females between ages 14 and 17 years (19/1000 person years). The incidence of migraine with aura peaks in males at age 5 years (7/1000 person years) and in females at age 12-13 years (14/1000 person years). Female prevalence of migraine with or without aura has a declining trend after age 45-50 years.

Aetiology/ Risk factors

Data from independent representative samples from Canada, the USA, several countries in Latin America, and several countries in Europe, Hong Kong, and Japan show a female to male predominance and a peak in middle aged women. Migraine has been reported to be 50% more likely in people with a family history of migraine.

Prognosis

Acute migraine is self limiting and only rarely results in permanent neurological complications. Chronic recurrent migraine may cause disability through pain, and may affect daily functioning and quality of life.

Aims of intervention

To reduce frequency of migraine, intensity of accompanying symptoms, and duration of headache, with minimal adverse effects.

Outcomes

Headache relief or being pain free at different times after medication. Pain relief at specific post-dose times. In this review, headache relief is reported at 2 hours unless otherwise stated. Some RCTs include the need for rescue medication and headache recurrence as outcome measures.

Methods

Clinical Evidence search and appraisal August 2003. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ).

Table
GRADE evaluation of interventions for migraine headache

Glossary

Central nervous system (CNS) adverse events
Events associated with triptans, including asthenia, abnormal dreams, agitation, aphasia, ataxia, confusion, dizziness, somnolence, speech disorders, abnormal thinking, tremor, vertigo, and other focal neurological symptoms.
Chest related adverse events
Events associated with triptans, including chest pressure, chest pain, radiating pain to the arms, other chest discomfort, heavy arms, shortness of breath, palpitations, and anxiety.
Headache intensity
Mild: normal activity allowed. Moderate: disturbing, but not prohibiting normal activity; bed rest not necessary. Severe: normal activity discontinued; bed rest may be necessary.
Headache recurrence
In responders, change in headache intensity (see above) from mild/none to moderate/severe within 24 hours of study medication initial dose.
Headache relief
Change in headache intensity (see above) score from severe/moderate to mild/none.
High-quality evidence
Further research is very unlikely to change our confidence in the estimate of effect.
International Headache Society criteria (1988)
Migraine without aura (common migraine) is defined as five or more headache attacks lasting for 4–72 hours with accompanying symptoms of either nausea/vomiting and/or phonophobia and photophobia. Pain should comply with at least two of the following four characteristics: unilateral, throbbing, moderate to severe intensity, and increase with physical activity. For migraine with aura (classic migraine), two or more headache attacks are required that comply with three of the following four characteristics: one or more fully reversible aura symptom indicating focal cerebral cortical and/or brainstem dysfunction; at least one aura symptom developing gradually over more than 4 minutes or two or more symptoms occurring in succession; no aura symptom should last more than 1 hour; and headache follows aura with a pain free (see below) interval of less than 60 minutes. In both migraine with and without aura, secondary causes of headache should be excluded; if any structural damage is found, then it should not explain headache characteristics. Less stringent criteria for migraine without aura can be used. In clinical practice, the so called borderline migraine can be diagnosed when one of the above criteria is not met. International Headache Society criteria were not developed with the intention of identifying potential responders to different medications.
Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Migraine index
Pain scale for migraine resulting from duration times intensity of migraine where intensity is classified as 0 = none, 1 = mild, 2 = moderate, and 3 = severe.
Moderate-quality evidence
Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Pain free
Change in headache intensity (see above) score from severe/moderate to none.
Rescue medication
Additional medications different to study medication permitted in non-responders, usually limited to the habitual medications a person uses to treat their migraine headache.
Very low-quality evidence
Any estimate of effect is very uncertain.

Notes

Disclaimer

The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients.To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

References

1. Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and face pain. Cephalalgia 1988;8:12–96. [PubMed]
2. Stewart W, Linet M, Celentano D, et al. Age and sex specific incidence rates of migraine with and without visual aura. Am J Epidemiol 1991;134:1111–1120. [PubMed]
3. O'Brien B, Goerre R, Streiner D. Prevalence of migraine headache in Canada: a population based survey. Int J Epidemiol 1994;23:1020–1026. [PubMed]
4. Pryse-Phillips W, Findlay H, Tugwell P, et al. A Canadian population survey on the clinical, epidemiological and societal impact of migraine and tension type headache. Can J Neurol Sci 1992;19:333–339. [PubMed]
5. Stewart W, Lipton R, Celentano D, et al. Prevalence of migraine headache in the United States. JAMA 1992;267:64–69. [PubMed]
6. Kryst S, Scherl E. A population based survey of social and personal impact of headache. Headache 1994;34:344–350. [PubMed]
7. Morillo L, Sanin L, Takeuchi Y, et al. Headache in Latin America: a multination population-based survey. Neurology 2001;56(suppl 3):A454.
8. Bank J, Marton S. Hungarian migraine epidemiology. Headache 2000;40:164–169. [PubMed]
9. Henry P, Michel P, Brochet B, et al. A nationwide survey of migraine in France: prevalence and clinical features. Cephalalgia 1992;12:229–237. [PubMed]
10. Rasmussen B, Jensen R, Schroll, et al. Epidemiology of headache in a general population: a prevalence study. J Clin Epidemiol 1991;44:1147–1157. [PubMed]
11. Steiner T, Stewart W, Kolodner K, et al. Epidemiology of migraine in England. Cephalalgia 1999;19:305.
12. Cheung RTF. Prevalence of migraine, tension type headache and other headaches in Hong Kong. Headache 2000;40:473–479. [PubMed]
13. Sakai F, Igarashi H. Prevalence of migraine in Japan: a nationwide survey. Cephalalgia 1997;17:15–22. [PubMed]
14. Stewart W, Staffa J, Lipton R, et al. Familial risk of migraine: a population based study. Ann Neurol 1997;41:166–172. [PubMed]
15. Chabriat H, Joire J, Danchot J, et al. Combined oral lysine acetylsalicylate and metoclopramide in the acute treatment of migraine: a multicentre double-blind placebo-controlled study. Cephalalgia 2001;14:297–300. [PubMed]
16. Tfelt-Hansen P, Henry P, Mulder L, et al. The effectiveness of combined oral lysine acetylsalicylate and metoclopramide compared with oral sumatriptan for migraine. Lancet 1995;346:923–926. [PubMed]
17. Deiner H. Efficacy and safety of intravenous acetylsalicylic acid lysinate compared to subcutaneous sumatriptan and parenteral placebo in the acute treatment of migraine: a double-blind, double-dummy, randomized, multicenter, parallel group study. The ASASUMAMIG Study Group. Cephalalgia 1999;19:581–588. [PubMed]
18. Limmroth V, May A, Diener H. Lysine-acetylsalicylic acid in acute migraine attacks. Eur Neurol 1999;41:88–93. [PubMed]
19. Tfelt-Hansen P, Olesen J. Effervescent metoclopramide and aspirin (Migravess) versus effervescent aspirin or placebo for migraine attacks: a double-blind study. Cephalalgia 1984;4:107–111. [PubMed]
20. Lange R, Schwarz JA, Hohn M. Acetylsalicylic acid effervescent 1000 mg (aspirin) in acute migraine attacks; a multicentre, randomized, double-blind, single dose, placebo-controlled parallel group study. Cephalalgia 2000;20:663–667. [PubMed]
21. MacGregor EA, Dowson A, Davies PTG. Mouth-dispersible aspirin in the treatment of migraine: a placebo-controlled study. Headache 2002;42:249–259. [PubMed]
22. Lipton R, Stewart W, Ryan RJ, et al. Efficacy and safety of paracetamol, aspirin, and caffeine in alleviating migraine headache pain: three double-blind, randomized, placebo-controlled trials. Arch Neurol 1998;55:210–217. [PubMed]
23. Boureau F, Joubert JM, Lasserre V, et al. Double-blind comparison of an acetaminophen 400 mg-codeine 25 mg combination versus aspirin 1000 mg and placebo in acute migraine attack. Cephalalgia 1994;14:156–161. [PubMed]
24. The Oral Sumatriptan and Aspirin plus Metoclopramide Comparative Study Group. A study to compare oral sumatriptan with oral aspirin plus metoclopramide in the acute treatment of migraine. Eur Neurol 1992;32:177–184. [PubMed]
25. Titus F, Escamilla C, da Costa Palmeira MM, ET AL. A double-blind comparison of lysine acetylsalicylate plus metoclopramide vs ergotamine plus caffeine in migraine effects on nausea, vomiting and headache symptoms. Clin Drug Invest 2001;21:87–94.
26. Geraud G, Compagnon A, Rossi A. Zolmitriptan versus a combination of acetylsalicylic acid and metoclopramide in the acute oral treatment of migraine: a double-blind, randomised, three-attack study. Eur Neurol 2002;47:88–98. [PubMed]
27. Massiou H, Serrurier D, Lasserre O, et al. Effectiveness of oral diclofenac in the acute treatment of common migraine attacks: a double-blind study versus placebo. Cephalalgia 1991;11:59–63. [PubMed]
28. Dahlof C, Bjorkman R. Diclofenac-K (50 and 100 mg) and placebo in the acute treatment of migraine. Cephalalgia 1993;13:117–123. [PubMed]
29. The Diclofenac-K/Sumatriptan Migraine Study Group. Acute treatment of migraine attacks: efficacy and safety of nonsteroidal anti-inflammatory drug, diclofenac-potassium in comparison to oral sumatriptan and placebo. Cephalalgia 1999;19:232–240. [PubMed]
30. Bigal ME, Bordini CA, Speciali JG. Intramuscular diclofenac in the acute treatment of migraine: a double-blind placebo controlled study. Arq Neuropsiquiatr 2002;60:410–415. [In Portuguese] [PubMed]
31. Karachalios G, Fotiadou A, Chrisikos N, et al. Treatment of acute migraine attack with diclofenac sodium: a double blind study. Headache 1992;32:98–100. [PubMed]
32. Kellstein D, Lipton R, Geetha R, et al. Evaluation of a novel solubilized formulation of ibuprofen in the treatment of migraine headache: a randomized, double-blind, placebo-controlled, dose-ranging study. Cephalalgia 2000;20:233–243. [PubMed]
33. Kloster R, Nestvold K, Vilming S. A double-blind study of ibuprofen versus placebo in the treatment of acute migraine attacks. Cephalalgia 1992;12:169–171. [PubMed]
34. Havanka-Kanniainen H. Treatment of acute migraine attack: ibuprofen and placebo compared. Headache 1989;29:507–509. [PubMed]
35. Codispoti JR, Prior MJ, Fu M, et al. Efficacy of non-prescription doses of ibuprofen in treating migraine headache. A randomized clinical trial. Headache 2001;41:665–679. [PubMed]
36. Sandrini G, Franchini S, Lanfranchi S, et al. Effectiveness of ibuprofen-arginine in the treatment of acute migraine attacks. Int J Clin Pharmacol Res 1998;18:145–150. [PubMed]
37. Andersson P, Hinge H, Johansen O, et al. Double-blind study of naproxen v placebo in the treatment of acute migraine attacks. Cephalalgia 1989;9:29–32. [PubMed]
38. Nestvold K, Kloster R, Partinen M, et al. Treatment of acute migraine attack: naproxen and placebo compared. Cephalalgia 1985;5:115–119. [PubMed]
39. Pradalier A, Rancurel G, Dordain G, et al. Acute migraine attack therapy: comparison of naproxen sodium and an ergotamine tartrate compound. Cephalalgia 1985;5:107–112. [PubMed]
40. Treves T, Streiffler M, Korczyn A. Naproxen sodium versus ergotamine tartrate in the treatment of acute migraine attacks. Headache 1992;32:280–282. [PubMed]
41. Sargent J, Baumel B, Peters K, et al. Aborting a migraine attack: naproxen sodium v ergotamine plus caffeine. Headache 1988;28:263–266. [PubMed]
42. Sandrini G, Farkkila M, Gurgess G, et al. Eletriptan versus sumatriptan: a double-blind, multiple migraine attack study. Neurology 2002;59:1210–1217. [PubMed]
43. Myllyla V, Havanka H, Herrala L, et al. Tolfenamic acid rapid release versus sumatriptan in the acute treatment of migraine: comparable effect in a double-blind, randomized, controlled, parallel-group study. Headache 1998;38:201–207. [PubMed]
44. Hakkarainen H, Vapaatalo H, Gothoni G, et al. Tolfenamic acid is as effective as ergotamine during migraine attacks. Lancet 1979;2:326–328. [PubMed]
45. Norrelund N, Christiansen L, Plantener S. Tolfenamic acid versus paracetamol in migraine attacks. A double-blind study in general practice. Ugeskr Laeger 1989;151:2436–2438. [PubMed]
46. Tokola R, Kangasniemi P, Neuvonen P, et al. Tolfenamic acid, metoclopramide, caffeine and their combinations in the treatment of migraine attacks. Cephalalgia 1984;4:253–263. [PubMed]
47. Dahlof C. Placebo-controlled clinical trials with ergotamine in the acute treatment of migraine. Cephalalgia 1993;13:166–171. Search date 1991; primary sources Medline, Embase, and hand searches of reference lists. [PubMed]
48. Multinational Oral Sumatriptan Cafergot Comparative Study Group. A randomized, double-blind comparison of sumatriptan and Cafergot in the acute treatment of migraine. Eur Neurol 1991;31:314–322. [PubMed]
49. Bourea F, Kappos L, Schoenen J, et al. A clinical comparison of sumatriptan nasal spray and dihydroergotamine nasal spray in the acute treatment of migraine. Int J Clin Pract 2000;54:281–286. [PubMed]
50. Hakkarainen H. Ergotamine vs. metoclopramide vs. their combination in acute migraine attacks. Headache 1982;22:10–12. [PubMed]
51. Lipton R. Ergotamine tartrate and dihydroergotamine mesylate: safety profiles. Headache 1997;37:S33–S41. [PubMed]
52. Ferrari MD, Goadsby PJ, Roon KI, et al. Triptans (serotonin, 5-HT1B/1D agonists) in migraine: detailed results and methods of a meta-analysis of 53 trials. Cephalalgia 2002;22:633–658. Search date: 2000; primary sources five pharmaceutical companies and systematic review of literature (no details). [Erratum in: Cephalalgia 2003;23:71] [PubMed]
53. Stark R, Dahlos C, Haughie S, et al. Efficacy, safety and tolerability of oral eletriptan in the acute treatment of migraine: results of a phase III, multicentre, placebo controlled study across three attacks. Cephalalgia 2002;22:23–32. [PubMed]
54. Mathew NT, Schoenen J, Winner P, et al. Comparative efficacy of eletriptan 40 mg versus sumatriptan 100 mg. Headache 2003;43:214–222. [PubMed]
55. Eletriptan Steering Committee in Japan. Efficacy and safety of eletriptan 20 mg, 40 mg and 80 mg in Japanese migraineurs. Cephalalgia 2002;22:416–423. [PubMed]
56. Färkkilä M, Olesen J, Dahlöf C, et al. Eletriptan for the treatment of migraine in patients with previous poor response or tolerance to oral sumatriptan. Cephalalgia 2003;23:463–471. [PubMed]
57. Sheftell F, Ryan R, Pitman V. Efficacy, safety, and tolerability of oral eletriptan for treatment of acute migraine: a multicenter, double-blind, placebo-controlled study conducted in the United States. Headache 2003;43:202–213. [PubMed]
58. Havanka H, Dahlof C, Pop P, et al. Efficacy of naratriptan tablets in the acute treatment of migraine: a dose-ranging study. Clin Ther 2000;22:970–980. [PubMed]
59. Stark S, Spierings E, McNeal S, et al. Naratriptan efficacy in migraineurs who respond poorly to oral sumatriptan. Headache 2000;40:513–520. [PubMed]
60. Gobel H, Winter P, Boswell D, et al. Comparison of naratriptan and sumatriptan in recurrence-prone migraine patients. Clin Ther 2000;22:981–989. [PubMed]
61. Pascual J, Vega P, Deiner H-C, et al. Comparison of rizatriptan 10 mg vs. zolmitriptan 2.5 mg in the acute treatment of migraine. Cephalalgia 2000;20:455–461. [PubMed]
62. Christie S, Gobel H, Mateos V, et al. Crossover comparison of efficacy and preference for rizatriptan 10 mg versus ergotamine/caffeine in migraine. Eur Neurol 2003;49:20–29. [PubMed]
63. Tfelt-Hansen P. Efficacy and harms of subcutaneous, oral, and intranasal sumatriptan used for migraine treatment: a systematic review based on number needed to treat. Cephalalgia 2001;18:532–538. Search date 1997; primary sources Medline and hand searches of Arch Neurol, Neurology, Headache, and Cephalalgia from 1990. [PubMed]
64. Boureau F, Chazot G, Emile J, et al. Comparison of subcutaneous sumatriptan with usual acute treatments for migraine. French Sumatriptan Study Group. Eur Neurol 1995;35:264–269. [PubMed]
65. Burke-Ramirez P, Asgharnejad M, Webster C, et al. Efficacy and tolerability of subcutaneous sumatriptan for acute migraine: a comparison between ethnic groups. Headache 2001;41:873–882. [PubMed]
66. Savani N, Brautaset NJ, Reunanen M, et al. A double-blind placebo-controlled study assessing the efficacy and tolerability of 50 mg sumatriptan tablets in the acute treatment of migraine. Sumatriptan Tablets S2CM07 Study Group. Int J Clin Pract Suppl 1999;105:7–15. [PubMed]
67. Peikert A, Becker WJ, Ashford EA, et al. Sumatriptan nasal spray: a dose-ranging study in the acute treatment of migraine. Eur J Neurol 1999;6:43–49. [PubMed]
68. Diamond S, Elkind A, Jackson RT, et al. Multiple-attack efficacy and tolerability of sumatriptan nasal spray in the treatment of migraine. Arch Fam Med 1998;7:234–240. [PubMed]
69. Ryan R, Elkind A, Baker CC, et al. Sumatriptan nasal spray for the acute treatment of migraine. Results of two clinical studies. Neurology 1997;49:1225–1230. [PubMed]
70. Sakai F, Iwata M, Tashiro K, et al. Zolmitriptan is effective and well tolerated in Japanese patients with migraine: a dose–response study. Cephalalgia 2002;22:376–383. [PubMed]
71. Dowson AJ, MacGregor EA, Purdy RA, et al. Zolmitriptan orally disintegrating tablet is effective in the acute treatment of migraine. Cephalalgia 2002;22:101–106. [PubMed]
72. Gruffyd-Jones K, Kies B, Middleton A, et al. Zolmitriptan versus sumatriptan for the acute oral treatment of migraine: a randomized, double-blind, international study. Eur J Neurol 2001;8:237–245. [PubMed]
73. Gallagher R, Dennidh G, Spierings E, et al. A comparative trial of zolmitriptan and sumatriptan for the acute oral treatment of migraine. Headache 2000;40:119–128. [PubMed]
74. Lipton RB, Stewart WF, Stone AM, et al. Stratified care vs step care strategies for migraine: the Disability in Strategies of Care (DISC) study: a randomized trial. JAMA 2000;284:2599–2605. [PubMed]
2004; 2004: 1208.
Published online 2004 May 1.

Salicylates

Summary

SYMPTOM RELIEF Oral lysine acetylsalicylate plus metoclopramide compared with placebo or sumatriptan: Oral lysine acetylsalicylate plus metoclopramide is more effective than placebo but equally effective as sumatriptan at increasing headache relief ( moderate-quality evidence ). Intravenous lysine acetylsalicylate compared with placebo or sumatriptan: Intravenous lysine acetylsalicylate is more effective than placebo, but less effective than subcutaneous sumatriptan at increasing headache relief (moderate-quality evidence). Intravenous lysine acetylsalicylate compared with ergotamine: We don't know whether intravenous lysine acetyl salicylate is more effective than subcutaneous ergotamine at increasing headache relief ( low-quality evidence ). Effervescent aspirin compared with placebo: Effervescent aspirin with or without metoclopramide is more effective at increasing headache relief (moderate-quality evidence). Dispersible aspirin compared with placebo: Dispersible aspirin may be more effective at increasing headache relief at 2 hours and at reducing the need for rescue medication (low-quality evidence). Other combinations compared with placebo: We don't know whether aspirin and paracetamol based combinations are more effective at improving headache relief ( very low-quality evidence ). Aspirin compared with sumatriptan: Aspirin plus metoclopramide, and sumatriptan are equally effective at relieving headache at 2 hours (moderate-quality evidence). Aspirin compared with tolfenamic acid or ergotamine: We don't know whether aspirin is more effective at increasing headache relief but it may be less effective at reducing the duration of an attack in women with common or classic migraine (low-quality evidence). Compared with zolmitriptan: Aspirin plus metoclopramide, and zolmitriptan seem to be equally effective at increasing headache relief at 2 hours over 3 migraine attacks but aspirin plus metoclopramide is less effective at increasing the proportion of people who are pain free at 2 hours (moderate-quality evidence). Oral lysine acetylsalicylate compared with ergotamine plus caffeine: Lysine acetylsalicylate is more effective at increasing headache relief or nausea and vomiting at 2 hours (moderate-quality evidence).

Benefits

We found no systematic review but found 12 RCTs.

Oral lysine acetylsalicylate (L-ASA) versus placebo:

One RCT (266 people, 475 migraine attacks) found that oral L-ASA 1620 mg plus metoclopramide 10 mg significantly increased headache relief compared with placebo (AR 56% with L-ASA v 28% with placebo; RR 2.0, 95% CI 1.6 to 2.5). A second RCT compared three treatments: oral L-ASA 1620 mg plus metoclopramide 10 mg, oral sumatriptan 100 mg, and placebo. It found that L-ASA plus metoclopramide significantly increased headache relief compared with placebo (AR 57% with L-ASA v 24% with placebo; RR 2.4, 95% CI 1.7 to 3.3). The difference between active treatment groups was not significant (AR 57% with L-ASA v 54% with sumatriptan; P = 0.50).

Intravenous L-ASA versus sumatriptan or placebo:

One RCT (278 people) compared three treatments: L-ASA 1800 mg intravenously, sumatriptan 6 mg subcutaneously, and placebo. It found that both L-ASA and sumatriptan significantly increased headache relief compared with placebo, and that sumatriptan significantly increased headache relief compared with L-ASA (AR 74% with L-ASA v 91% with sumatriptan v 24% with placebo; RR for L-ASA v placebo 3.1, 95% CI 1.8 to 5.4; RR for L-ASA v sumatriptan 0.8, 95% CI 0.7 to 0.9). A second, smaller, crossover RCT (112 attacks in 56 people) compared L-ASA 1000 mg intravenously versus ergotamine 0.5 mg subcutaneously. It found no significant difference between groups in pain intensity score on a visual analogue scale.

Effervescent aspirin versus placebo:

One crossover RCT (120 people) compared effervescent aspirin 650 mg with and without metoclopramide 10 mg versus placebo. At 2 hours aspirin with or without metoclopramide reduced headache significantly more than placebo (P < 0.001). A second RCT (374 people) compared effervescent aspirin 1000 mg versus placebo. It found that aspirin significantly increased headache relief compared with placebo (AR 55% with aspirin v 37% with placebo; RR 1.5, 95% CI 1.2 to 1.9).

Dispersible aspirin versus placebo:

One crossover RCT (101 people with migraine, 73 of whom received both treatments) compared mouth dispersible aspirin 900 mg versus placebo in two consecutive attacks. When assessing results after crossover in 73 participants that had received both treatments, the RCT found that aspirin significantly increased headache relief at 2 hours compared with placebo, and significantly reduced need for rescue medication (AR for headache relief 48% with aspirin v 19% with placebo; P = 0.0005; difference in need for rescue medication: P < 0.01).

Other combinations versus placebo:

One large RCT (1357 people with non-disabling migraine) compared oral paracetamol 250 mg plus aspirin 250 mg plus caffeine 65 mg versus placebo. Combination treatment improved headache relief compared with placebo (AR 59% with combination v 33% with placebo; RR 1.8, 95% CI 1.6 to 2.1). A second, crossover RCT (198 people treated for 3 consecutive migraine attacks) found no significant difference in headache relief between aspirin 1000 mg orally and paracetamol 400 mg plus codeine 25 mg. However, both improved headache relief compared with placebo (P = 0.0003 with aspirin and P = 0.0002 with paracetamol plus codeine).

Aspirin versus sumatriptan:

One RCT (358 people) found no significant difference between oral aspirin 900 mg plus metoclopramide 10 mg and oral sumatriptan 100 mg in headache relief at 2 hours (AR 45% with aspirin plus metoclopramide v 56% with sumatriptan; P = 0.078).

Aspirin versus tolfenamic acid:

See benefits of tolfenamic acid.

Aspirin versus zolmitriptan:

See benefits of zolmitriptan.

Aspirin versus ergotamine:

See benefits of ergotamine.

Harms

One RCT reported adverse effects related to L-ASA in 2%, to sumatriptan in 15%, and to placebo in 2% of people treated. In this trial, severe harms were related to L-ASA in 3%, to sumatriptan in 5%, and to placebo in 2% of people treated. Another trial reported premature withdrawal of treatment in 1% with L-ASA, 3% with sumatriptan, and 2% with placebo. The most frequently reported harms for L-ASA were somnolence, abdominal pain, nausea or vomiting, fatigue, and headache. The RCT comparing the combination of paracetamol, aspirin, and caffeine versus placebo reported no serious adverse effects.

Aspirin versus zolmitriptan:

See harms of zolmitriptan.

Aspirin versus ergotamine:

See harms of ergotamine.

Comment

None.

Substantive changes

No new evidence

2004; 2004: 1208.
Published online 2004 May 1.

Diclofenac

Summary

SYMPTOM RELIEF Compared with placebo: Diclofenac, oral or intramuscular is more effective at increasing headache relief and the need for rescue medication ( moderate-quality evidence ). Compared with paracetamol: Intramuscular diclofenac is more effective than intramuscular paracetamol at increasing the proportion of people with partial relief of migraine symptoms within 35 minutes (moderate-quality evidence).

Benefits

We found no systematic review.

Diclofenac versus placebo:

We found three RCTs of oral diclofenac and one RCT of intramuscular diclofenac. The first RCT (170 people) found that diclofenac improved treatment success compared with placebo (success defined at 2 hours as a visual analogue scale score < 10 mm or headache duration of < 2 hours without need for rescue medication within this period: AR 27% with diclofenac v 19% with placebo; RR 1.5, 95% CI 1.0 to 2.2). The second RCT (72 people) found that diclofenac 50 or 100 mg significantly increased headache relief compared with placebo (AR 39% with 50 mg v 44% with 100 mg v 22% with placebo; RR diclofenac 50 mg v placebo 1.8, 95% CI 1.0 to 3.1; RR diclofenac 100 mg v placebo 1.9, 95% CI 1.1 to 3.3). The RCT found no significant difference between 50 mg and 100 mg doses of diclofenac. However, it found that diclofenac 100 mg significantly reduced need for rescue medication compared with placebo (AR 37% with diclofenac v 58% with placebo; RR 0.64, 95% CI 0.44 to 0.93). The third RCT (120 people with migraine with or without aura) compared intramuscular diclofenac 75 mg versus placebo. At 1 hour, it found that diclofenac improved headache relief and reduced need for rescue medication compared with placebo in people with and without aura (headache relief in people without aura: AR 43.3% with diclofenac v 16.7% with placebo; P < 0.01; headache relief in people with aura: AR 50% with diclofenac v 13.3% with placebo; P < 0.01; rescue medication in people without aura: 20% with diclofenac v 50% with placebo; P < 0.05; rescue medication in people with aura: 11% with diclofenac v 42% with placebo; P < 0.05). The fourth RCT (156 people meeting International Headache Society criteria for migraine with or without aura) compared three treatments: diclofenac potassium 50 or 100 mg, oral sumatriptan 100 mg, and placebo. The trial found that diclofenac significantly reduced headache pain (measured on a visual analogue scale) at 2 hours compared with placebo (P < 0.001).

Diclofenac versus sumatriptan:

The RCT comparing diclofenac, sumatriptan, and placebo found no significant difference between either dose of diclofenac and sumatriptan.

Diclofenac versus paracetamol:

One RCT (86 people) compared intramuscular diclofenac 75 mg versus intramuscular paracetamol in people with paroxysmal headaches accompanied by at least two of the following features: unilateral pain, nausea, visual and limb symptoms, and positive family history. The trial found that diclofenac increased the proportion of people with partial relief of overall migraine symptoms (intensity and duration) within 35 minutes compared with paracetamol (AR 89% with diclofenac v 17% with paracetamol; RR 4.9, 95% CI 2.5 to 9.8).

Harms

In one RCT (72 people), 33% of people reported one or more adverse effects during one or more attacks. Most adverse effects were rated as mild or moderate (gastrointestinal complaints were the most common, followed by tiredness and fatigue), but 12% of people rated adverse experiences as severe. In another RCT (170 people), 14% of people reported at least one adverse effect, with gastrointestinal effects being the most common (50%). Only three people withdrew because of gastrointestinal symptoms. See non-steroidal anti-inflammatory drugs.

Comment

None.

Substantive changes

No new evidence

2004; 2004: 1208.
Published online 2004 May 1.

Ibuprofen

Summary

SYMPTOM RELIEF Compared with placebo: Ibuprofen is more effective at relieving migraine symptoms ( moderate-quality evidence ).

Benefits

Versus placebo:

We found no systematic review but found five RCTs comparing ibuprofen versus placebo. The first RCT (729 people) found that oral ibuprofen (400 and 600 mg in liquigel formulation) significantly improved headache relief compared with placebo (AR 72% with 400 mg v 72% with 600 mg v 50% with placebo; ibuprofen 400 mg v placebo RR 1.4, 95% CI 1.2 to 1.7; ibuprofen 600 mg v placebo RR 1.4, 95% CI 1.2 to 1.7). It found no significant difference in the need for rescue medication. The second RCT (25 people, 146 migraines) found that ibuprofen significantly improved migraine index (25 with ibuprofen v 46 with placebo; P = 0.0014) and reduced the need for rescue medication 4 hours after treatment (26% with ibuprofen v 56% with placebo; P = 0.007) compared with placebo. The third RCT (40 people with common and classic migraine, 345 migraines) compared ibuprofen 800–1200 mg orally versus placebo. The trial found that significantly more attacks were rated as mild with ibuprofen compared with placebo (P < 0.001) and significantly fewer attacks were rated as moderate (P < 0.05) or severe (P < 0.05). It also found that ibuprofen reduced the need for rescue medication compared with placebo (AR 22% with ibuprofen v 81% with placebo; RR 0.27, 95% CI 0.20 to 0.36). One RCT (660 people with headache intensity not requiring bed rest or inhibiting daily activities in more than 50% of attacks) compared ibuprofen 200 or 400 mg versus placebo with a follow up of 6 hours. It found that ibuprofen significantly increased headache relief at 2 hours compared with placebo (AR 41.7% with ibuprofen 400 mg v 40.8% with ibuprofen 200 mg v 28.1% with placebo; P = 0.006 for both doses v placebo). The fifth RCT (40 people) compared an ibuprofen arginine preparation (400 mg orally) versus placebo. It found that more people taking ibuprofen arginine versus placebo achieved “considerable” or “complete” relief within 2 hours (51% with ibuprofen v 7% with placebo; P < 0.01). Fewer people taking ibuprofen arginine received rescue medication (31% with ibuprofen v 48% with placebo) but no statistical analysis was performed.

Harms

One RCT did not report adverse effects. Another RCT reported pain and stomach discomfort in 12% of people on treatment, which was not considered serious. Another reported no significant difference in adverse events among treatment groups, and no serious adverse events. See non-steroidal anti-inflammatory drugs.

Comment

None.

Substantive changes

No new evidence

2004; 2004: 1208.
Published online 2004 May 1.

Naproxen

Summary

SYMPTOM RELIEF Compared with placebo: Naproxen may be more effective at reducing symptoms in people with classic or common migraine ( very low-quality evidence ). Compared with ergotamine alone or ergotamine plus caffeine plus cyclizine: We don't know whether naproxen is more effective at reducing symptoms of migraine or at reducing the need for rescue medication (very low-quality evidence).

Benefits

We found no systematic review.

Naproxen versus placebo:

We found one crossover RCT (38 people with classic or common migraine) comparing oral naproxen 750–1250 mg versus placebo. It found that naproxen significantly reduced headache intensity (P = 0.047). However, it found no significant difference in need for rescue medication (absolute numbers not reported; P = 0.13). A second crossover RCT (40 people with common or classic migraine) comparing naproxen 750–1000 mg versus placebo found that naproxen reduced overall pain intensity (rated as mild, moderate, or severe; P = 0.011; time of evaluation not reported). The need for rescue medication after 2 hours was also significantly lower for naproxen (AR 47% with naproxen v 72% with placebo; P = 0.002; insufficient data for calculation of RR).

Naproxen versus ergotamine:

We found three RCTs, which compared oral naproxen 750–1750 mg versus ergotamine 2–4 mg alone or with caffeine 91.5 mg plus cyclizine chlorhydrate 50 mg. The first RCT (114 people) compared three treatments: naproxen, ergotamine (plus caffeine plus cyclizine), and placebo. It found that naproxen significantly reduced migraine intensity (rated as mild, moderate, severe, or incapacitating) compared with ergotamine plus caffeine plus cyclizine (P = 0.014). However, it found no significant difference in need for rescue medication. The second RCT (37 people with classic or common migraine) compared naproxen versus ergotamine. In this trial, 47% of people were reported to have terminated the study prematurely. The trial found that naproxen significantly reduced migraine intensity (rated as none, mild, moderate, or severe) compared with ergotamine (P = 0.04). However, it found no significant difference in need for rescue medication (23% with naproxen v 29% with ergotamine). The third RCT (41 people) compared three treatments: naproxen, ergotamine, and placebo. It found no significant difference in pain relief at 1 hour after the first dose between naproxen and ergotamine (P = 0.65).

Harms

In one RCT, adverse effects were reported in 5/32 (16%) people taking naproxen; four had stomach pain and dyspepsia, and one withdrew from the trial because of severe stomach pain. One RCT comparing naproxen versus ergotamine found that vomiting was more frequent with ergotamine (10% with naproxen v 34% with ergotamine; P = 0.0083), and more people taking ergotamine withdrew because of severe symptoms (diarrhoea, vomiting, dizziness, nausea, shivering, and sweating) compared with those taking naproxen (2% with naproxen v 8% with ergotamine). In another RCT, more people taking naproxen versus ergotamine discontinued medication (6/19 [32%] with naproxen v 2/17 [12%] with ergotamine). One RCT found that more people taking ergotamine versus naproxen had severe adverse effects (1/48 [2%] with naproxen v 8/48 [17%] with ergotamine), and two people taking ergotamine withdrew from the study. See non-steroidal anti-inflammatory drugs.

Comment

None of the RCTs used the International Headache Society criteria to identify cases.

Substantive changes

No new evidence

2004; 2004: 1208.
Published online 2004 May 1.

Tolfenamic acid

Summary

SYMPTOM RELIEF Compared with placebo or sumatriptan: Tolfenamic acid is more effective than placebo, but equally effective as sumatriptan at increasing headache relief ( moderate-quality evidence ). Compared with aspirin or ergotamine: Tolfenamic acid may be more effective at increasing headache relief and at reducing the duration of an attack in women with common or classic migraine ( low-quality evidence ). Compared with paracetamol: We don't know whether tolfenamic acid is more effective at increasing headache relief (low-quality evidence). Combination preparations compared with placebo: Tolfenamic acid combined with either caffeine or metoclopramide may be more effective at reducing headache intensity and at reducing the need for rescue medication (low-quality evidence).

Benefits

We found no systematic review.

Tolfenamic acid versus placebo or sumatriptan:

One RCT (141 people, 289 migraine attacks) compared three treatments: tolfenamic acid 200 mg, sumatriptan 100 mg, and placebo. The trial found that tolfenamic acid significantly increased headache relief compared with placebo (AR 77% with tolfenamic acid v 29% with placebo; RR 2.6, 95% CI 1.5 to 4.2). However, it found no significant difference between tolfenamic acid and sumatriptan. The use of rescue medication was not significantly different between any of the three arms.

Tolfenamic acid versus placebo or aspirin or ergotamine:

One crossover RCT (20 women with common or classic migraine, 160 migraines) compared tolfenamic acid 200 mg, aspirin 500 mg, and ergotamine 1 mg versus placebo. The RCT found that tolfenamic acid significantly reduced the duration of attacks compared with placebo (P < 0.001; time of evaluation not reported). The mean duration of attack was shortest with tolfenamic acid compared with the other treatments, but this was not significantly shorter than the mean duration of attack with the other drugs combined (P values not reported). The need for rescue medication after 2 hours was not significantly different.

Tolfenamic acid versus paracetamol:

One RCT (149 people with common or classic migraine) compared tolfenamic acid 400 mg versus paracetamol 1000 mg. It found no significant difference between treatments in headache intensity, adverse effects, strength, effect duration, or need for additional medication after 3 hours.

Combination preparations:

One crossover RCT (49 people with common or classic migraine, 482 migraines) compared tolfenamic acid alone or in combination with either caffeine or metoclopramide versus placebo. The trial found that tolfenamic acid, either alone or in combination, significantly reduced headache intensity (measured on a scale of no, slight, moderate, or severe symptoms) compared with placebo. All combinations of tolfenamic acid significantly reduced the need for rescue medication compared with placebo (P < 0.01).

Harms

In one RCT comparing tolfenamic acid versus sumatriptan, the frequency of adverse effects was similar (30% v 41%). See non-steroidal anti-inflammatory drugs.

Comment

None.

Substantive changes

No new evidence

2004; 2004: 1208.
Published online 2004 May 1.

Ergotamine

Summary

SYMPTOM RELIEF Compared with placebo: Ergotamine (with or without caffeine) may be more effective at improving some symptoms of migraine but may increase the risk of nausea or vomiting ( very low-quality evidence ). Ergotamine preparations compared with sumatriptan: Ergotamine plus caffeine, and dihydroergotamine nasal spray are less effective at increasing headache relief and reducing the need for rescue medication ( moderate-quality evidence ). Ergotamine plus cafffeine compared with eletriptan: Ergotamine plus caffeine is less effective than eletriptan (40 mg and 80 mg) at increasing headache relief and nausea at 2 hours ( high-quality evidence ). Ergotamine plus cafffeine compared with rizatriptan: Ergotamine plus caffeine is less effective at increasing headache relief and at reducing nausea and vomiting at 2 hours (moderate-quality evidence). Ergotamine plus metoclopramide compared with ergotamine alone: Ergotamine plus metoclopramide may be no more effective at reducing headache intensity or the need for rescue medication in women with common or classic migraine ( low-quality evidence ). Ergotamine alone or ergotamine plus caffeine plus cyclizine compared with naproxen: We don't know whether ergotamine is more effective at reducing symptoms of migraine but ergotamine and naproxen may be equally effective at reducing the need for rescue medication (very low-quality evidence). Ergotamine plus caffeine compared with salicylates: Ergotamine plus caffeine is less effective than lysine acetylsalicylate at increasing headache relief or nausea and vomiting at 2 hours (moderate-quality evidence).

Benefits

Ergotamine versus placebo:

We found one systematic review (search date 1991, 7 RCTs, 588 people). Ergotamine was given orally at doses between 1 and 6 mg. Ergotamine was given alone in three RCTs, combined with caffeine in three RCTs, and combined with alkaloids and barbiturates in one RCT. The RCT of ergotamine plus alkaloids plus barbiturates was not evaluable. None of the trials used International Headache Society criteria for participant inclusion, and defined responders according to a variety of 3 point to 10 point scales. Two RCTs identified by the review found that ergotamine alone significantly increased headache relief compared with placebo (P < 0.01 in 1 RCT; reported as “significant” in the other RCT; P value not reported) and one RCT found that ergotamine alone significantly reduced the duration of attacks compared with placebo (P < 0.001). Two RCTs identified by the review found a similar use of rescue medication with ergotamine alone and with placebo (P value not reported; no further data reported). Two RCTs identified by the review measuring nausea or vomiting associated with migraine found similar results with ergotamine alone and placebo (P value not reported). One RCT identified by the review found that ergotamine plus caffeine significantly increased headache relief (reported as “significant”; P value not reported) compared with placebo, but another RCT found no significant difference (P value not reported). The RCTs comparing ergotamine plus caffeine versus placebo did not assess duration of attack. Two RCTs identified by the review found that ergotamine plus caffeine significantly reduced need for rescue medication (P < 0.05 in 1 RCT; reported as “significant” in the other, P value not reported). Two RCTs identified by the review measuring nausea or vomiting found that placebo reduced these symptoms compared with ergotamine plus caffeine (no statistical analysis reported).

Ergotamine versus sumatriptan:

One RCT (580 people) compared oral ergotamine 2 mg plus oral caffeine 100 mg with oral sumatriptan 100 mg. The trial found that ergotamine plus caffeine significantly reduced headache relief compared with sumatriptan (AR 48% with ergotamine plus caffeine v 66% with sumatriptan; RR 0.73, 95% CI 0.62 to 0.85; P < 0.001). Significantly more people required rescue medication with ergotamine plus caffeine than with sumatriptan (AR 44% with ergotamine plus caffeine v 24% with sumatriptan; RR 1.82, 95% CI 1.38 to 2.39). A second RCT (crossover design; 368 people treating 2 attacks) compared dihydroergotamine nasal spray (1 or 2 mg) with sumatriptan nasal spray (20 mg). It found that sumatriptan significantly increased headache relief at 1 and 2 hours, and significantly reduced nausea at 1 hour compared with dihydroergotamine (headache relief at 1 hour: 53% with sumatriptan v 41% with dihydroergotamine; P < 0.001; headache relief at 2 hours: P = 0.003; relief of nausea at 1 hour: 64% with sumatriptan v 40% with dihydroergotamine; P = 0.006). However, the RCT found no significant differences between treatments with respect to relief from vomiting, photophobia, or phonophobia.

Ergotamine versus eletriptan:

See benefits of eletriptan.

Ergotamine versus rizatriptan:

See benefits of rizatriptan.

Ergotamine plus metoclopramide:

One RCT (24 women with common or classic migraine, 176 migraines) found no significant difference between ergotamine alone and ergotamine plus metoclopramide in headache intensity (measured on a 3 point scale as more than usual, usual, or less than usual) or need for rescue medication.

Ergotamine versus naproxen:

See benefits of naproxen.

Ergotamine plus caffeine versus salicylates:

One RCT (250 people randomised, 227 in efficacy analysis) found that lysine acetylsalicylate (L-ASA) 1620 mg plus metoclopramide 10 mg significantly increased headache relief compared with ergotamine 2 mg plus caffeine 200 mg (86/112 [77%] with L-ASA plus metoclopramide v 70/115 [61%] with ergotamine plus caffeine; P = 0.01). It found that L-ASA plus metoclopramide significantly reduced nausea and vomiting compared with ergotamine plus caffeine after 2 hours (people free from nausea or vomiting: 73/112 [65%] with L-ASA plus metoclopramide v 46/115 [40%] with ergotamine plus caffeine; P = 0.001).

Harms

Ergotamine versus placebo:

In the systematic review comparing ergotamine versus placebo, two RCTs measuring nausea and vomiting found that ergotamine alone increased nausea and vomiting compared with placebo (no statistical analysis reported), and two RCTs found that ergotamine plus caffeine increased nausea and vomiting compared with placebo (no statistical analysis conducted). We found one overview of the safety of dihydroergotamine mesylate (DHE) and ergotamine tartrate. This overview identified two trials (24 and 311 people), which found that adverse effects with intramuscular DHE occurred in fewer than 10% of people (with leg cramps and pain at the injection site being most common) and that harms resolved within 1 hour. Three RCTs in the overview found that nausea and vomiting were the most common adverse effects, which subsided within 15 minutes. In another open trial (300 people), 32% of people taking DHE complained of nausea. Post-marketing surveillance studies have reported ischaemic complications, nausea, vomiting, seizures, cardiac and non-cardiac vascular disorders such as vasospasm and infarction, liver abnormalities, leg pain, chest pain, hypertensive crisis, injection site reactions, head and shoulder pain, and paraesthesia. Treatment related phenomena were reported in fewer than 4% of people receiving intranasal DHE. A bitter or unpleasant taste was reported by 2%. Dizziness and muscle pain were reported by less than 1%. Discontinuation of treatment occurred in 1% of people included in the RCTs. Worsening of baseline nausea or vomiting was suggested in 5/7 RCTs comparing acute administration of ergotamine tartrate versus placebo. Single case reports of less common adverse effects include abdominal discomfort, numbness or tingling of fingers or toes, ischaemic complications, swollen fingers, and leg cramps. With chronic use in excessive doses, ischaemic neuropathy, anorectal ulcers following suppository use, habituation, and overuse headaches have been reported.

Ergotamine versus sumatriptan:

In the RCT comparing sumatriptan versus dihydroergotamine nasal sprays, the incidence of adverse events was similar (about 10%) in both treatment groups after the first dose. The most common were disturbance of taste after sumatriptan, and nasal or sinus symptoms such as congestion, irritation, and rhinitis after dihydroergotamine. These were reported as being mild and self limiting.

Ergotamine plus caffeine versus salicylates:

One RCT found no significant difference in the proportion of people reporting at least one adverse event between L-ASA 1620 mg plus metoclopramide 10 mg and ergotamine 2 mg plus caffeine 200 mg (17% with L-ASA plus metoclopramide v 23% with ergotamine plus caffeine). It found that the most common adverse events with the L-ASA regimen were somnolence (3.2%), dizziness (1.6%), and dry mouth (1.6%) and that abdominal pain (6.65), malaise (3.3%), anxiety (2.5%), and nervousness (1.7%) were the most common adverse events with the ergotamine regimen.

Comment

None.

Substantive changes

No new evidence

2004; 2004: 1208.
Published online 2004 May 1.

Eletriptan

Summary

SYMPTOM RELIEF Compared with placebo: Eletriptan is more effective at increasing headache relief at 2 hours ( high-quality evidence ). Compared with sumatriptan: Eletriptan at doses of 40 mg and 80 mg is more effective at increasing headache relief at 2 hours ( moderate-quality evidence ). Compared with ergotamine plus caffeine: Eletriptan (40 mg and 80 mg) is more effective at increasing headache relief and nausea at 2 hours (high-quality evidence).

Benefits

Eletriptan versus placebo:

We found one systematic review (search date 2000, 8 RCTs, 5370 people) and six subsequent RCTs. The review found that all doses of eletriptan significantly increased headache relief compared with placebo at 2 hours (eletriptan 20 mg, 499 people; eletriptan 40 mg, 1870 people; eletriptan 80 mg, 1393 people; total placebo groups 1113 people; AR for 20 mg: 48.9%; for 40 mg: 60.2%; for 80 mg: 65.8%; AR for placebo about 25%; ARR for 80 mg v placebo 42%, 95% CI 36% to 48%; for 40 mg v placebo 35.2%, 95% CI 29.8% to 40.7%). All six subsequent RCTs found that eletriptan significantly improved headache relief compared with placebo (See table 1 ).

Table 1
Eletriptan versus placebo

Eletriptan versus sumatriptan:

We found one systematic review and two subsequent RCTs. The review (search date 2000, 2 RCTs) found that eletriptan 40 and 80 mg significantly increased headache relief at 2 hours compared with sumatriptan 100 mg. It found no significant difference between eletriptan 20 mg and sumatriptan 100 mg (ARI for complete headache relief: eletriptan 80 mg: 18%, 95% CI 9% to 26%; eletriptan 40 mg: 11%, 95% CI 2% to 19%; eletriptan 20 mg: –1%, 95% CI –13% to +12%). It found that eletriptan 40 and 80 mg significantly increased headache relief at 2 hours compared with sumatriptan 50 mg (ARI for eletriptan 80 mg: 15%, 95% CI 8% to 23%; eletriptan 40 mg: 10%, 95% CI 3% to 18%). The first subsequent RCT (1008 people) compared two doses of eletriptan (40 and 80 mg), two doses of sumatriptan (50 and 100 mg), and placebo. It found that both doses of eletriptan significantly increased headache relief compared with sumatriptan at 2 hours (AR 108/169 [64%] with eletriptan 40 mg v 107/160 [67%] with eletriptan 80 mg v 88/176 [50%] with sumatriptan 50 mg v 85/160 [53%] with sumatriptan 100 mg; P < 0.01 for either dose eletriptan v sumatriptan 50 mg; P < 0.05 for either dose eletriptan v sumatriptan 100 mg). The second subsequent RCT (2072 people) compared three treatments: eletriptan 40 mg, sumatriptan 100 mg, and placebo. It found that that eletriptan 40 mg significantly increased headache relief compared with sumatriptan 100 mg at 2 hours (67% with eletriptan v 59% with sumatriptan; P < 0.001). It found that eletriptan significantly reduced nausea compared with sumatriptan 100 mg at 2 hours (nausea absent: 74% with eletriptan v 67% with sumatriptan; P < 0.01).

Eletriptan versus ergotamine plus caffeine:

We found one RCT (733 people treated included in the systematic review) that compared two doses of eletriptan (40 and 80 mg), ergotamine plus caffeine, and placebo. It found that both doses of eletriptan significantly increased headache relief and reduced nausea at 2 hours compared with ergotamine plus caffeine (headache relief: 111/206 [54%] with eletriptan 40 mg v 142/209 [68%] with eletriptan 80 mg v 65/197 [33%] with ergotamine plus caffeine; P < 0.05; nausea: results presented graphically; P ≤ 0.0001 for both comparisons).

Harms

Eletriptan versus placebo:

We found one systematic review (search date 2000) and four subsequent RCTs that reported harms. The review found that higher doses of eletriptan 40 and 80 mg significantly increased any adverse event and central nervous system (CNS) adverse events compared with placebo. It found no significant difference in adverse event rates with eletriptan 20 mg (ARI compared with placebo for any adverse event: 20 mg +1.9%, 95% CI –15.5% to +19.3%; 40 mg 7.3%, 95% CI 2.7% to 11.8%; 80 mg 18.9%, 95% CI 11.2% to 26.6%; CNS events: 20 mg +2.6%, 95% CI –6.6% to +11.7%; 40 mg 7.5%, 95% CI 4.5% to 10.6%; 80 mg 14.6%, 95% CI 10.2% to 19.0%). It found that 80 mg eletriptan significantly increased chest symptoms compared with placebo. It found no significant difference with 40 and 20 mg eletriptan (ARR compared with placebo, 20 mg –0.3%, 95% CI –3.1% to +2.6%; 40 mg +0.9%, 95% CI –0.2% to +2.0%; 80 mg 2.6%, 95% CI 0.6% to 4.5%). The first subsequent RCT (2072 people analysed) found similar rates of adverse events between eletriptan 40 and 80 mg and placebo (about 30% in each group, P value not reported). The second subsequent RCT (309 people analysed) found that eletriptan 20, 40, and 80 mg increased adverse events compared with placebo (16.3% with eletriptan 20 mg v 62.5% with eletriptan 40 mg v 45.5% with eletriptan 80 mg v 15.5% with placebo; P value not reported). The most common adverse events were asthenia, nausea, and somnolence (asthenia: 1.3% with eletriptan 20 mg v 2.5% with eletriptan 40 mg v 11.7% with eletriptan 80 mg v 1.2% with placebo; nausea: 3.8% with eletriptan 20 mg v 7.5% with eletriptan 40 mg v 10.4% with eletriptan 80 mg v 2.4% with placebo; somnolence: 6.3% with eletriptan 20 mg v 10.0% with eletriptan 40 mg v 16.9% with eletriptan 80 mg v 3.6% with placebo, P value not reported).The third subsequent RCT found that eletriptan 40 and 80 mg increased nausea, chest symptoms, and asthenia compared with placebo (nausea: 5% with eletriptan 40 mg v 11% with eletriptan 80 mg v 8% with placebo; chest symptoms: 4% with eletriptan 40 mg v 5% with eletriptan 80 mg v 0% with placebo; asthenia: 5% with eletriptan 40 mg v 12% with eletriptan 80 mg v 2% with placebo, P value not reported). The fourth subsequent RCT found that the most common adverse event was somnolence (2.8% with eletriptan 20 mg v 7.1% with eletriptan 40 mg v 8.7% with eletriptan 80 mg v 4.5% with placebo, P value not reported). Other common adverse events with higher doses of eletriptan were asthenia and dizziness (asthenia: 3.1% with eletriptan 20 mg v 3.4% with eletriptan 40 mg v 7.1% with eletriptan 80 mg v 2.7% with placebo; dizziness: 2.8% with eletriptan 20 mg v 5.1% with eletriptan 40 mg v 6.1% with eletriptan 80 mg v 3.1% with placebo, P value not reported).

Eletriptan versus sumatriptan:

The systematic review (search date 2000, 2 RCTs) found no significant difference between eletriptan 40 mg and sumatriptan 100 mg in adverse events or CNS related events (ARI, any event: 0%, 95% CI –11% to +11%; CNS events: –3%, 95% CI –13% to +8%). It found that sumatriptan 50 mg significantly reduced adverse events and CNS related events compared with eletriptan 40 mg (ARR, any event: 8%, 95% CI 1% to 15%; CNS events: 8%, 95% CI 2% to 13%). One subsequent RCT found similar rates of adverse events with eletriptan 40 mg and with sumatriptan 100 mg (31% with eletriptan v 37% with sumatriptan).

Eletriptan versus ergotamine plus caffeine:

One RCT (733 people treated) that compared two doses of eletriptan (40 and 80 mg), ergotamine 1 mg plus caffeine 100 mg, and placebo found that the most common adverse events were nausea and asthenia (nausea: 5% with eletriptan 40 mg v 10% with eletriptan 80 mg v 7% with ergotamine plus caffeine; asthenia: 4% with eletriptan 40 mg v 10% with eletriptan 80 mg v 3% with ergotamine plus caffeine, P value not reported).

Comment

None.

Substantive changes

No new evidence

2004; 2004: 1208.
Published online 2004 May 1.

Naratriptan

Summary

SYMPTOM RELIEF Compared with placebo: Naratriptan is more effective at increasing headache relief at 2 hours ( moderate-quality evidence ). Naratriptan seems to be beneficial in people who have responded poorly to sumatriptan in a first attack. Compared with sumatriptan: Naratriptan is less effective than sumatriptan (100 mg) at increasing headache relief at 4 hours but is equally effective at reducing headache recurrence (moderate-quality evidence). Compared with zolmitriptan: Naratriptan and zolmitriptan are equally effective at increasing headache relief at 4 hours (moderate-quality evidence). Compared with rizatriptan: Naratriptan is less effective at increasing headache relief at 2 hours (moderate-quality evidence).

Benefits

Naratriptan versus placebo:

We found one systematic review (search date 2000, 5 RCTs, 1077 people) and two subsequent RCTs. The review found that naratriptan significantly increased headache relief compared with placebo (ARI 22.2%, 95% CI 16.9% to 27.5%). The first subsequent RCT (643 people) found that naratriptan 2.5 mg or sumatriptan 100 mg significantly increased headache relief at 4 hours compared with placebo (AR 63% with naratriptan v 80% with sumatriptan v 31% with placebo; P < 0.05 for either drug compared with placebo). In the second subsequent RCT a subgroup of 206 people with a poor response to sumatriptan 50 mg in a first attack were randomised 1 week later to either naratriptan 2.5 mg orally or placebo. Naratriptan significantly increased headache relief at 2 hours (AR 25% with naratriptan v 10% with placebo; RR 2.5, 95% CI 1.3 to 4.7) and at 4 hours (AR 41% with naratriptan v 19% with placebo; RR 2.2, 95% CI 1.4 to 3.5) compared with placebo.

Naratriptan versus sumatriptan:

We found one systematic review (search date 2000, 2 RCTs, 480 people) and one subsequent RCT. The review found that sumatriptan 100 mg significantly increased headache relief at 4 hours compared with naratriptan 2.5 mg (AR not reported; ARI: 8%, 95% CI 0% to 16%). The subsequent RCT comparing naratriptan 2.5 mg orally with sumatriptan 100 mg orally found no significant difference in headache recurrence.

Naratriptan versus zolmitriptan:

We found one systematic review (search date 2000, 1 RCT, 179 people). It found no significant difference between naratriptan 2.5 mg and zolmitriptan 2.5 mg in headache relief at 4 hours (difference: +1%, 95% CI –15% to +17%).

Naratriptan versus rizatriptan:

See benefits of rizatriptan.

Harms

Naratriptan versus placebo:

The systematic review found no significant difference in overall adverse events, central nervous system (CNS) adverse events, and chest related adverse events between naratriptan 2.5 mg and placebo (ARI for naratriptan v placebo; any event: +2.4%, 95% CI –2.2% to +7.0%; CNS events: +1.9%, 95% CI –12.2% to +5.0%; chest symptoms: +0.4%, 95% CI –0.8% to +1.6). One subsequent RCT found similar adverse effects with naratriptan 2.5 mg orally and placebo (21% with naratriptan v 23% with placebo; significance not reported).

Naratriptan versus sumatriptan:

The systematic review (search date 2000, 2 RCTs) found that sumatriptan 100 mg significantly increased adverse events compared with naratriptan 2.5 mg (difference: 11.3%, 95% CI 1% to 22.5%).

Naratriptan versus zolmitriptan:

The systematic review (search date 2000, 1 RCT) found that naratriptan 2.5 mg significantly reduced adverse events compared with zolmitriptan 2.5 mg (difference: –23%, 95% CI –37% to –8%).

Naratriptan versus rizatriptan:

See harms of rizatriptan.

Comment

Clinical guide

Naratriptan or a different triptan in a second attack may be beneficial in people responding poorly to sumatriptan in a first attack, but this requires confirmation in further RCTs.

Substantive changes

No new evidence

2004; 2004: 1208.
Published online 2004 May 1.

Rizatriptan

Summary

SYMPTOM RELIEF Compared with placebo: Rizatriptan is more effective at increasing headache relief at 2 hours ( moderate-quality evidence ). Compared with zolmitriptan: Rizatriptan and zolmitriptan are equally effective at increasing headache relief at 2 hours (moderate-quality evidence). Compared with naratriptan: Rizatriptan is more effective at increasing headache relief at 2 hours (moderate-quality evidence). Compared with ergotamine plus caffeine: Rizatriptan is more effective at increasing headache relief and at reducing nausea and vomiting at 2 hours (moderate-quality evidence).

Benefits

Rizatriptan versus placebo:

We found one systematic review (search date 2000, 12 RCTs, 6395 people) and one subsequent RCT. The systematic review found that rizatriptan significantly increased headache relief at 2 hours compared with placebo (AR: 62.4% with rizatriptan 5 mg v 68.6% with rizatriptan 10 mg v about 34% with placebo; ARI compared with placebo presented graphically: about 28% with rizatriptan 5 mg v 35% with rizatriptan 10 mg). The subsequent RCT (727 people) compared three treatments: rizatriptan 10 mg, zolmitriptan 2.5 mg, and placebo. It found that rizatriptan significantly increased headache relief compared with placebo (AR 71% with rizatriptan v 30% with placebo; P < 0.05).

Rizatriptan versus zolmitriptan:

We found one systematic review (search date 2000, 1 RCT, 435 people) and one subsequent RCT. The systematic review found no significant difference between rizatriptan 10 mg and zolmitriptan 2.5 mg in headache relief at 2 hours (difference: +4%, 95% CI –4% to +11%). The subsequent RCT (727 people) comparing rizatriptan 10 mg, zolmitriptan 2.5 mg, and placebo found no significant difference between rizatriptan and zolmitriptan in headache relief (AR 71% with rizatriptan v 67% with zolmitriptan; P = 0.23).

Rizatriptan versus naratriptan:

One systematic review (search date 2000; 1 RCT 522 people) found that rizatriptan 10 mg significantly increased headache relief at 2 hours compared with naratriptan 2.5 mg (ARI 20%, 95% CI 11% to 30%).

Rizatriptan versus ergotamine:

One RCT (439 people) compared oral rizatriptan 10 mg with ergotamine 2 mg plus caffeine 100 mg for the first migraine attack with the other treatment for a second attack. It found that rizatriptan significantly increased headache relief and reduced nausea and vomiting at 2 hours compared with ergotamine plus caffeine (headache relief: 75.9% with rizatriptan v 47.3% with ergotamine plus caffeine; P ≤ 0.001; no nausea: 82.7% with rizatriptan v 56.2% with ergotamine plus caffeine; P ≤ 0.001; no vomiting: 96.2% with rizatriptan v 89.5% with ergotamine plus caffeine; P ≤ 0.001).

Harms

Rizatriptan versus placebo:

We found one meta-analysis (search date 2000, 1963 people given rizatriptan 5 mg, 2783 people given rizatriptan 10 mg, and 1649 given placebo) that used individual patient data from published and unpublished RCTs. It found that rizatriptan (5 and 10 mg) significantly increased overall and chest related adverse events compared with placebo (placebo subtracted events: any event 7.9%, 95% CI 4.7% to 11.1% with rizatriptan 5 mg and 13.5%, 95% CI 10.6% to 16.3% with 10 mg rizatriptan; CNS events: 6.1%, 95% CI 3.2% to 9.0% with rizatriptan 5 mg and 9.4%, 95% CI 7.2% to 11.6% with rizatriptan 10 mg). It found no significant difference in chest related adverse events between rizatriptan 5 mg and placebo but found that rizatriptan 10 mg significantly increased chest related adverse events compared with placebo (placebo subtracted chest symptoms: +0.9%, 95% CI –0.04 to +1.8 with rizatriptan 5 mg and 1.5%, 95% CI 0.8% to 2.3% with rizatriptan 10 mg).

Rizatriptan versus zolmitriptan:

The meta-analysis (search date 2000, 1 RCT) found no significant difference in adverse events between rizatriptan 10 mg and zolmitriptan 2.5 mg (difference: –8%, 95% CI –15% to 0%).

Rizatriptan versus naratriptan:

The meta-analysis (search date 2000, 1 RCT) found that rizatriptan 10 mg significantly increased adverse events compared with naratriptan 2.5 mg (difference: 10%, 95% CI 1% to 19%).

Rizatriptan versus ergotamine:

One RCT comparing rizatriptan 10 mg with ergotamine 2 mg plus caffeine 100 mg found no significant difference in adverse events (35.4% with rizatriptan v 34.5% with ergotamine plus caffeine). The most common adverse events were dizziness, nausea, and somnolence (dizziness: 6.7% with rizatriptan v 5.3% with ergotamine; nausea: 4.2% with rizatriptan v 8.5% with ergotamine; somnolence: 5.5% with rizatriptan v 2.3% with ergotamine, P values not reported).

Comment

None.

Substantive changes

No new evidence

2004; 2004: 1208.
Published online 2004 May 1.

Sumatriptan

Summary

SYMPTOM RELIEF Compared with placebo: Sumatriptan (subcutaneous, oral or intranasal) is more effective at increasing headache relief ( moderate-quality evidence ). Compared with aspirin plus metoclopramide: Sumatriptan, and aspirin plus metoclopramide are equally effective at relieving headache at 2 hours (moderate-quality evidence). Compared with tolfenamic acid: Sumatriptan, and tolfenamic acid are equally effective at increasing headache relief (moderate-quality evidence). Compared with ergotamine preparations: Sumatriptan is more effective than ergotamine plus caffeine and dihydroergotamine nasal spray at increasing headache relief at 2 hours and at reducing the need for rescue medication (moderate-quality evidence). Compared with naratriptan: Sumatriptan (100 mg) is more effective than naratriptan at increasing headache relief at 4 hours and is equally effective at reducing headache recurrence (moderate-quality evidence). Compared with zolmitriptan: Sumatriptran and zolmitriptan are equally effective at increasing headache relief (moderate-quality evidence). Compared with eletriptan: Sumatriptan is less effective than eletriptan (40 mg and 80 mg) at increasing headache relief at 2 hours (moderate-quality evidence).

Benefits

Subcutaneous sumatriptan:

We found one systematic review (search date 1997), one additional RCT, and one subsequent RCT. The review found that subcutaneous sumatriptan 6 mg significantly increased headache relief at 1 hour compared with placebo (12 RCTs, 3127 people; 69% with sumatriptan v 19% with placebo; RR 3.7, 95% CI 3.3 to 4.2). One additional crossover RCT (246 people with up to 12 migraines) comparing subcutaneous sumatriptan 6 mg with usual headache treatment (49% combinations, 24% ergotamine, 19% non-steroidal anti-inflammatory drugs, and 7% dihydroergotamine) found that sumatriptan significantly improved headache relief (78% with sumatriptan v 34% with usual treatment; P < 0.001). The subsequent RCT (200 people consisting of 50 white people and 150 non-white people) compared headache relief across multiple attacks. It analysed results by ethnic group. It found that subcutaneous sumatriptan 6 mg significantly increased headache relief in non-white people and white people (non-white: 87% with sumatriptan v 37% with placebo; white: 87% with sumatriptan v 19% with placebo; sumatriptan v placebo P < 0.001 in either ethnic group).

Oral sumatriptan:

We found one systematic review (search date 2000, 11 RCTs, 3185 people), one additional RCT and two subsequent RCTs. The review found that sumatriptan significantly increased headache relief at 2 hours compared with placebo (AR 56.0% with sumatriptan 25 mg v 62.7% with sumatriptan 50 mg v 59.0% with sumatriptan 100 mg v about 30% with placebo; ARI about 25% with sumatriptan 25 mg [presented graphically] v about 33% with sumatriptan 50 mg [presented graphically] v 29%, 95% CI 26% to 34% with sumatriptan 100 mg). The additional RCT (495 people) found that oral sumatriptan 50 mg significantly increased the proportion of people with headache relief after 4 hours in people with one attack compared with placebo (62% with sumatriptan v 32% with placebo; P < 0.001). The first subsequent RCT (1008 people randomised, 774 people treated) compared two doses of eletriptan (40 and 80 mg), two doses of sumatriptan (50 and 100 mg), and placebo. At 2 hours it found that both doses of sumatriptan significantly increased headache relief compared with placebo (50% with sumatriptan 50 mg v 53% with sumatriptan 100 mg v 31% with placebo; P < 0.01 for either dose of sumatriptan v placebo). The second subsequent RCT (2072 people) compared three treatments: eletriptan 40 mg, sumatriptan 100 mg, and placebo. It found that that sumatriptan 100 mg significantly increased headache relief at 2 hours compared with placebo (59% with sumatriptan 100 mg v 26% with placebo; P < 0.0001). It found that sumatriptan 100 mg significantly reduced nausea at 2 hours compared with placebo (nausea absent: 67% with sumatriptan 100 mg v 57% with placebo; P < 0.001).

Intranasal sumatriptan:

We found one review (search date 1997) and three additional RCTs. The review found that intranasal sumatriptan 20 mg significantly increased headache relief compared with placebo (6 RCTs, 1420 people; 61% with sumatriptan v 30% with placebo; RR 2.1, 95% CI 1.8 to 2.4). The three additional RCTs (2475 people) found that intranasal sumatriptan significantly increased headache relief compared with placebo (60–64% with sumatriptan v 25–35% with placebo).

Sumatriptan versus aspirin plus metoclopramide:

See benefits of salicylates.

Sumatriptan versus tolfenamic acid:

See benefits of tolfenamic acid.

Sumatriptan versus ergotamine:

See benefits of ergotamine.

Sumatriptan versus naratriptan:

See benefits of naratriptan.

Sumatriptan versus zolmitriptan:

See benefits of zolmitriptan.

Sumatriptan versus eletriptan:

See benefits of eletriptan.

Sumatriptan versus ergotamine derivatives:

See benefits of ergotamine.

Harms

Subcutaneous sumatriptan:

In one systematic review (search date 1997), 7/12 RCTs found that adverse effects were more common with subcutaneous sumatriptan 6 mg than with placebo (65% with sumatriptan v 32% with placebo; OR 4, 95% CI 3 to 5). The subsequent RCT found that subcutaneous sumatriptan increased adverse events compared with placebo in both non-white and white people (non-white: 63% with sumatriptan v 30% with placebo; white: 63% with sumatriptan v 23% with placebo; P value not reported). It found nine serious adverse events with sumatriptan compared with none with placebo (no details reported and number exposed was not clear).

Oral sumatriptan versus placebo:

The systematic review found that sumatriptan 25, 50, and 100 mg) significantly increased overall adverse events compared with placebo (ARI: any event 4.4%, 95% CI 0.1% to 8.8% with sumatriptan 25 mg; 7.8%, 95% CI 2.6% to 13.1% with sumatriptan 50 mg; and 13.2%, 95% CI 8.6% to 17.8% with sumatriptan 100 mg). It found that the two higher doses of sumatriptan (50 and 100 mg) significantly increased central nervous system (CNS) adverse events and chest related adverse events compared with placebo. However, it found no significant difference between low dose sumatriptan 25 mg and placebo (ARI; CNS events: +1.7%, 95% CI –1.2% to +4.7% with sumatriptan 25 mg; 3.7%, 95% CI 1.0% to 6.5% with sumatriptan 50 mg; 6.3%, 95% CI 3.2% to 9.5% with sumatriptan 100 mg; chest related events: +0.8%, 95% CI –1.0% to +2.6% with sumatriptan 25 mg; 1.9%, 95% CI 0.4% to 3.3% with sumatriptan 50 mg; 1.7%, 95% CI 0.8% to 2.5% with sumatriptan 100 mg). One subsequent RCT found similar rates of adverse effects between sumatriptan and placebo (37% with sumatriptan v 34% with placebo, P value not reported).

Comment

There is a consensus that sumatriptan should not be used in people with ischaemic heart disease or concomitantly with ergotamine.

Substantive changes

No new evidence

2004; 2004: 1208.
Published online 2004 May 1.

Zolmitriptan

Summary

SYMPTOM RELIEF Compared with placebo: Zolmitriptan may be more effective at increasing headache relief at 2 hours ( low-quality evidence: ). Compared with sumatriptan: Zolmiptran and sumatriptan are equally effective at increasing headache relief ( moderate-quality evidence ). Compared with salicylates: Zolmitriptan, and aspirin plus metoclopramide seem to be equally effective at increasing headache relief at 2 hours over 3 migraine attacks but zolmitriptan is more effective at increasing the proportion of people who are pain-free at 2 hours (moderate-quality evidence). Stratified care compared with step care or step care within attacks: Stratified care may be more effective at increasing the proportion of people with headache relief (low-quality evidence). Compared with naratriptan: Zolmitriptan and naratriptan are equally effective at increasing headache relief at 4 hours (moderate-quality evidence).

Benefits

Zolmitriptan versus placebo:

We found one systematic review (search date 2000, 9 RCTs , 4641 people) and two subsequent RCTs. The systematic review found that zolmitriptan significantly increased headache relief at 2 hours compared with placebo (AR: 63.5% with zolmitriptan 2.5 mg v 62.8% with zolmitriptan 5 mg v about 30% with placebo; ARI: about 30% with zolmitriptan 2.5 mg v about 33% with zolmitriptan 5 mg; results presented graphically). The first subsequent RCT (289 people, 229 in analysis) compared three doses of zolmitriptan (1, 2.5, and 5 mg) versus placebo. It found that zolmitriptan 2.5 mg significantly increased headache relief at 2 hours compared with placebo (53.3% with zolmitriptan 1 mg; 55.6% with zolmitriptan 2.5 mg; 65.4% with zolmitriptan 5 mg; 37.5% with placebo; P = 0.032 for zolmitriptan 2.5 mg v placebo, other P values not reported; analysis not by intention to treat). The open label second subsequent RCT (470 people) found that orally dispersible zolmitriptan 2.5 mg significantly increased headache relief at 2 hours compared with placebo (63% with zolmitriptan v 22% with placebo; OR 6.1, 95% CI 4.0 to 9.3). It found that zolmitriptan reduced nausea at 2 hours compared with placebo, but the statistical significance was not reported (no nausea: 52% with zolmitriptan v 32% with placebo).

Zolmitriptan versus sumatriptan:

We found one systematic review (search date 2000, 3 RCTs) and two subsequent RCTs. The review found no significant difference between zolmitriptan 2.5 and 5 mg and sumatriptan 25, 50, and 100 mg in headache relief at 2 hours (ARR for sumatriptan 100 mg v zolmitriptan 5 mg: +1%, 95% CI –4% to +6%; sumatriptan 50 mg v zolmitriptan 2.5 mg: +2%, 95% CI –6% to +9%; sumatriptan 50 mg v zolmitriptan 5 mg: +1%, 95% CI –4% to +6%; sumatriptan 25 mg v zolmitriptan 2.5 mg: –8%, 95% CI –16% to 0%; sumatriptan 25 mg v zolmitriptan 5 mg: –7%, 95% CI –15% to 0%). In the first subsequent RCT (1522 people), up to six consecutive attacks were treated with zolmitriptan 2.5 mg (500 people, 2671 attacks), zolmitriptan 5 mg (514 people, 2744 attacks), or sumatriptan 50 mg (508 people, 2693 attacks). The RCT found no significant difference among groups for headache relief at 2 hours (AR 62.9% with zolmitriptan 2.5 mg v 65.7% with zolmitriptan 5 mg zolmitriptan v 66.6% with sumatriptan 50 mg). The second subsequent RCT (1445 people) compared zolmitriptan 2.5–5 mg versus sumatriptan 25–50 mg. The trial found no significant difference in headache relief between treatments at any dose.

Zolmitriptan versus salicylates:

One RCT (666 people) found no significant difference between aspirin 900 mg plus metoclopramide 10 mg and zolmitriptan 2.5 mg in headache relief at 2 hours over three migraine attacks. However, it found that zolmitriptan significantly increased the proportion of people who were pain free at 2 hours (headache relief: 32.9% with salicylates v 33.4% with zolmitriptan; OR 1.06, 95% CI 0.77 to 1.47; pain free: 10.7% with zolmitriptan v 5.3% with salicylates; OR 2.19, 95% CI 1.23 to 4.03). It found that rates of nausea were similar with both treatments but the statistical significance was not reported (about 30% in each group).

Zolmitriptan versus naratriptan:

See benefits of naratriptan.

Stratified care versus step care with zolmitriptan:

One open label RCT (835 people) randomised people into three arms. The first arm, named “stratified care”, randomised people with low disability scores to aspirin 800–1000 mg plus metoclopramide 10 mg, and people with higher disability scores to zolmitriptan 2.5 mg. The second arm, named “step care”, involved treating initial attacks with aspirin plus metoclopramide and then switching to zolmitriptan 2.5 mg for the remaining two to three attacks. The third arm involved “step care within attacks”, whereby all attacks were initially treated with aspirin plus metoclopramide, and non-responders were given zolmitriptan after 2 hours. It found that stratified care significantly increased the proportion of people with headache relief compared with either of the step care groups (AR 53% with stratified care v 40% with step care v 36% with step care within attacks; RR stratified care v step care 1.3, 95% CI 1.1 to 1.7; stratified care v step care within attacks 1.4, 95% CI 1.2 to 1.7).

Harms

Zolmitriptan versus placebo:

The systematic review found that zolmitriptan 2.5 and 5 mg significantly increased overall adverse events, central nervous system (CNS) adverse events, and chest related adverse events compared with placebo (ARI compared with placebo; any adverse event: 15.9%, 95% CI 9.6% to 22.1% with 2.5 mg v 24.5%, 95% CI 15.3% to 33.5% with 5 mg; CNS events: 9.9%, 95% CI 4.3% to 15.5% with 2.5 mg v 11.5%, 95% CI 6.1% to 16.8% with 5 mg; chest related events: 2.0%, 95% CI 0.7% to 3.3% with 2.5 mg v 2.9%, 95% CI 1.2% to 4.6% with 5 mg). The first subsequent RCT (289 Japanese people) found that zolmitriptan 5 mg increased asthenia, hypoaesthesia, and abdominal pain compared with placebo (asthenia: 7.0% with zolmitriptan 5 mg v 1.6% with 2.5 mg v 1.7% with placebo; hypoaesthesia: 7.0% with zolmitriptan 5 mg v 1.6% with 2.5 mg v 0% with placebo; abdominal pain: 7.0% with zolmitriptan 5 mg v 1.6% with 2.5 mg v 1.7% with placebo, P values not reported). The open label second subsequent RCT found that zolmitriptan increased asthenia, throat tightness, and somnolence compared with placebo (asthenia: 3.5% with zolmitriptan v 1.3% with placebo; throat tightness: 2.6% with zolmitriptan v 0% with placebo; somnolence: 3.0% with zolmitriptan v 1.7% with placebo, P values not reported).

Zolmitriptan versus sumatriptan:

The systematic review (search date 2000, 3 RCTs) found no significant difference in adverse events between zolmitriptan 5 mg and sumatriptan 50 or 100 mg (ARI for zolmitriptan 5 mg v sumatriptan 100 mg: –2%, 95% CI –8% to +4%; zolmitriptan 2.5 mg v sumatriptan 50 mg: 4%, 95% CI 0% to 8%; zolmitriptan 5 mg v sumatriptan 50 mg: –2%, 95% CI –6% to +2%). However, it found that sumatriptan 25 mg significantly reduced adverse events compared with zolmitriptan 5 mg (ARR: 12%, 95% CI 6% to 18%). The first subsequent RCT comparing zolmitriptan 2.5 and 5 mg with sumatriptan 50 mg found no significant difference in adverse events.

Zolmitriptan versus salicylates:

One RCT found that zolmitriptan increased adverse events compared with salicylates plus metoclopramide but found no difference between treatments in withdrawals due to adverse events (adverse events: 40.8% with zolmitriptan v 29.1% with salicylates plus metoclopramide, P value not reported; withdrawal due to adverse events: 0.9% with zolmitriptan v 1.5% with salicylates plus metoclopramide, P value not reported). It found that zolmitriptan increased paraesthesia (4.3% with zolmitriptan v 1.5% with salicylates plus metoclopramide), dizziness (2.8% with zolmitriptan v 0.6% with salicylates plus metoclopramide), and tightness (3.7% with zolmitriptan v 0.6% with salicylates plus metoclopramide) and that salicylates plus metoclopramide increased abdominal pain (2.8% with zolmitriptan v 5.0% with salicylates plus metoclopramide) and diarrhoea (1.2% with zolmitriptan v 2.1% with salicylates plus metoclopramide).

Comment

None.

Substantive changes

No new evidence


Articles from Clinical Evidence are provided here courtesy of BMJ Publishing Group