European Journal of Clinical Pharmacology

, Volume 75, Issue 10, pp 1369–1378 | Cite as

Efficacy of triptans for the treatment of acute migraines: a quantitative comparison based on the dose-effect and time-course characteristics

  • Mengyuan Hou
  • Hongxia Liu
  • Yunfei Li
  • Ling Xu
  • Yingchun He
  • Yinghua Lv
  • Qingshan ZhengEmail author
  • Lujin LiEmail author



This study aimed to establish a pharmacodynamic model to quantitatively compare the efficacy characteristics of seven kinds of triptans and their different dosage forms in the treatment of acute migraines.


Clinical studies of triptans in the treatment of acute migraines were comprehensively searched in the public databases. Pharmacodynamic models were established to describe the dose-effect and time-course of each kind of triptan for the proportion of patients who became pain free or had pain relief.


A total of 92 articles involving 47,376 subjects were included in the analysis. After eliminating the placebo effect, oral eletriptan (40 mg) had the highest efficacy among all oral drugs at the maximum approved dose, and the proportion of patients who became pain free and had pain relief were 30.9% and 37.9% at 2 h, respectively. However, oral naratriptan (2.5 mg) had the lowest efficacy, and the proportion of patients who became pain free and had pain relief was 10.3% and 21.6% at 2 h, respectively. The efficacy of subcutaneous administration was significantly higher than that of oral administration, and the efficacy of nasal spray administration was comparable to that of oral administration. Regarding the dose-effect, the efficacy of the sumatriptan nasal spray significantly increased within the FDA (Food and Drug Administration)-approved dose range. When the dose was increased from 5 to 20 mg of sumatriptan nasal spray, the proportion of patients who became pain free and had pain relief increased by 16.8% and 18.3% at 2 h, respectively. Regarding the time-course, the time of onset of subcutaneous sumatriptan (6 mg) was the fastest, and the fraction of patients who were pain free at 2 h accounted for 90.6% of that at 4 h.


This study evaluated the efficacy characteristics of seven kinds of triptans and their different dosage forms. The present findings provide necessary quantitative information for migraine medication guidelines.


Migraine Triptans Dose-effect Time-course Pain-free Pain-relief 



This study was provided by the Drug Innovation Major Project (2018ZX09711001-009, 2018ZX09734005-001-002, 2018ZX09734005-006, 2018ZX09731016, 2017ZX09304003), the project of Shanghai Municipal Health Planning Commission (2018YQ48), and Science and Technology Innovation Action Plan of Shanghai (17401970900).

Authors’ contributions

Mengyuan Hou and Hongxia Liu contributed equally to this work; all the information was independently extracted by two researchers. All authors read and approved the final manuscript.

Funding information

This study was provided by the Drug Innovation Major Project (2018ZX09711001-009, 2018ZX09734005-001-002, 2018ZX09734005-006, 2018ZX09731016, 2017ZX09304003), the project of Shanghai Municipal Health Planning Commission (2018YQ48), and Science and Technology Innovation Action Plan of Shanghai (17401970900).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

228_2019_2748_MOESM1_ESM.docx (732 kb)
ESM 1 (DOCX 732 kb)


  1. 1.
    Schulman EA, Cady RK, Henry D, Batenhorst AS, Putnam DG, Watson CB, O'Quinn SO (2000) Effectiveness of sumatriptan in reducing productivity loss due to migraine: results of a randomized, double-blind, placebo-controlled clinical trial. Mayo Clin Proc 75(8):782–789CrossRefGoogle Scholar
  2. 2.
    Thorlund K, Mills EJ, Wu P, Ramos E, Chatterjee A, Druyts E, Goadsby PJ (2014) Comparative efficacy of triptans for the abortive treatment of migraine: a multiple treatment comparison meta-analysis. Cephalalgia 34(4):258–267CrossRefGoogle Scholar
  3. 3.
    Dowson AJ, Massiou H, Laínez JM, Cabarrocas X (2002) Almotriptan is an effective and well-tolerated treatment for migraine pain: results of a randomized, double-blind, placebo-controlled clinical trial. Cephalalgia 22(6):453–461CrossRefGoogle Scholar
  4. 4.
    Marmura MJ, Silberstein SD, Schwedt TJ (2015) The acute treatment of migraine in adults: the american headache society evidence assessment of migraine pharmacotherapies. Headache 55(1):3–20CrossRefGoogle Scholar
  5. 5.
    Diener HC (1994) A review of current treatments for migraine. Eur Neurol 34(Suppl 2):18–25CrossRefGoogle Scholar
  6. 6.
    Diener HC, Jansen JP, Reches A, Pascual J, Pitei D, Steiner TJ, Eletriptan and Cafergot Comparative Study Group (2002) Efficacy, tolerability and safety of oral eletriptan and ergotamine plus caffeine (Cafergot) in the acute treatment of migraine: a multicentre, randomised, double-blind, placebo-controlled comparison. Eur Neurol 47(2):99–107CrossRefGoogle Scholar
  7. 7.
    Solomon GD, Cady RK, Klapper JA, Earl NL, Saper JR, Ramadan NM, The 042 Clinical Trial Study Group (1997) Clinical efficacy and tolerability of 2.5 mg zolmitriptan for the acute treatment of migraine. The 042 Clinical Trial Study Group. Neurology 49(5):1219–1225CrossRefGoogle Scholar
  8. 8.
    Block GA, Goldstein J, Polis A, Reines SA, Smith ME (1998) Efficacy and safety of rizatriptan versus standard care during long-term treatment for migraine. Rizatriptan Multicenter Study Groups. Headache 38(10):764–771CrossRefGoogle Scholar
  9. 9.
    Krymchantowski AV, Barbosa JS (2002) Rizatriptan combined with rofecoxib vs. rizatriptan for the acute treatment of migraine: an open label pilot study. Cephalalgia 22(4):309–312CrossRefGoogle Scholar
  10. 10.
    Xu H, Han W, Wang J, Li M (2016) Network meta-analysis of migraine disorder treatment by NSAIDs and triptans. J Headache Pain 17(1):113CrossRefGoogle Scholar
  11. 11.
    Mandema JW, Cox E, Alderman J (2005) Therapeutic benefit of eletriptan compared to sumatriptan for the acute relief of migraine pain--results of a model-based meta-analysis that accounts for encapsulation. Cephalalgia 25(9):715–725CrossRefGoogle Scholar
  12. 12.
    Shuster JJ (2011) Review: Cochrane handbook for systematic reviews for interventions, Version 5.1.0, published 3/2011. Julian P.T. Higgins and Sally Green, Editors [J]. Res Synth Methods 2(2):126–130CrossRefGoogle Scholar
  13. 13.
    Moskowitz MA, Cutrer FM (1993) SUMATRIPTAN: a receptor-targeted treatment for migraine. Annu Rev Med 44:145–154CrossRefGoogle Scholar
  14. 14.
    Goadsby PJ, Hargreaves RJ (2000) Mechanisms of action of serotonin 5-HT1B/D agonists: insights into migraine pathophysiology using rizatriptan. Neurology 55(9 Suppl 2):S8–S14Google Scholar
  15. 15.
    Ferrari MD, Goadsby PJ, Roon KI, Lipton RB (2002) Triptans (serotonin, 5-HT1B/1D agonists) in migraine: detailed results and methods of a meta-analysis of 53 trials. Cephalalgia 22(8):633–658CrossRefGoogle Scholar
  16. 16.
    Ashcroft DM, Millson D (2004) Naratriptan for the treatment of acute migraine: meta-analysis of randomised controlled trials. Pharmacoepidemiol Drug Saf 13(2):73–82CrossRefGoogle Scholar
  17. 17.
    Thorlund K, Toor K, Wu P, Chan K, Druyts E, Ramos E, Bhambri R, Donnet A, Stark R, Goadsby PJ (2017) Comparative tolerability of treatments for acute migraine: a network meta-analysis. Cephalalgia 37(10):965–978CrossRefGoogle Scholar
  18. 18.
    Cameron C, Kelly S, Hsieh SC, Murphy M, Chen L, Kotb A, Peterson J, Coyle D, Skidmore B, Gomes T, Clifford T, Wells G (2015) Triptans in the acute treatment of migraine: a systematic review and network meta-analysis. Headache 55(Suppl 4):221–235CrossRefGoogle Scholar
  19. 19.
    Dodick D, Brandes J, Elkind A, Mathew N, Rodichok L (2005) Speed of onset, efficacy and tolerability of zolmitriptan nasal spray in the acute treatment of migraine: a randomised, double-blind, placebo-controlled study. CNS Drugs 19(2):125–136CrossRefGoogle Scholar
  20. 20.
    Diamond S, Freitag FG, Feoktistov A, Nissan G (2007) Sumatriptan 6 mg subcutaneous as an effective migraine treatment in patients with cutaneous allodynia who historically fail to respond to oral triptans. J Headache Pain 8(1):13–18CrossRefGoogle Scholar
  21. 21.
    Ferrari MD (2002) Tripstar: a comprehensive patient-based approach to compare triptans. Headache 42(Suppl 1):18–25CrossRefGoogle Scholar
  22. 22.
    Cady RK, McAllister PJ, Spierings ELH, Messina J, Carothers J, Djupesland PG, Mahmoud RA (2015) A randomized, double-blind, placebo-controlled study of breath powered nasal delivery of sumatriptan powder (AVP-825) in the treatment of acute migraine (The TARGET Study). Headache 55(1):88–100CrossRefGoogle Scholar
  23. 23.
    Diamond S, Elkind A, Jackson RT, Ryan R, DeBussey S, Asgharnejad M (1998) Multiple-attack efficacy and tolerability of sumatriptan nasal spray in the treatment of migraine. Arch Fam Med 7(3):234–240CrossRefGoogle Scholar
  24. 24.
    Antonaci F, Chimento P, Diener HC, Sances G, Bono G (2007) Lessons from placebo effects in migraine treatment. J Headache Pain 8(1):63–66CrossRefGoogle Scholar
  25. 25.
    Dahlof C et al (2001) Dose finding, placebo-controlled study of oral almotriptan in the acute treatment of migraine. Neurology 57(10):1811–1817CrossRefGoogle Scholar
  26. 26.
    Antonaci F, Ghiotto N, Wu S, Pucci E, Costa A (2016) Recent advances in migraine therapy. Springerplus 5:637CrossRefGoogle Scholar
  27. 27.
    Akpunonu BE, Mutgi AB, Federman DJ, Volinsky FG, Brickman K, Davis RL, Gilbert § C, Asgharnejad M (1995) Subcutaneous sumatriptan for treatment of acute migraine in patients admitted to the emergency department: a multicenter study. Ann Emerg Med 25(4):464–469CrossRefGoogle Scholar
  28. 28.
    Maas HJ, Danhof M, Pasqua OED (2009) Analysis of the relationship between age and treatment response in migraine. Cephalalgia 29(7):772–780CrossRefGoogle Scholar
  29. 29.
    Franconi F, Finocchi C, Allais G, Omboni S, Tullo V, Campesi I, Reggiardo G, Benedetto C, Bussone G (2014) Gender and triptan efficacy: a pooled analysis of three double-blind, randomized, crossover, multicenter, Italian studies comparing frovatriptan vs. other triptans. Neurol Sci 35(1 Supplement):99–105CrossRefGoogle Scholar
  30. 30.
    Ferrari MD, Loder E, McCarroll K, Lines CR (2001) Meta-analysis of rizatriptan efficacy in randomized controlled clinical trials. Cephalalgia 21(2):129–136CrossRefGoogle Scholar
  31. 31.
    Menshawy A, Ahmed H, Ismail A, Abushouk AI, Ghanem E, Pallanti R, Negida A (2018) Intranasal sumatriptan for acute migraine attacks: a systematic review and meta-analysis. Neurol Sci 39(1):31–44CrossRefGoogle Scholar
  32. 32.
    Tfelt-Hansen P, Pascual J, Ramadan N, Dahlöf C, D'Amico D, Diener HC, Hansen JM, Lanteri-Minet M, Loder E, McCrory D, Plancade S, Schwedt T, International Headache Society Clinical Trials Subcommittee (2012) Guidelines for controlled trials of drugs in migraine: third edition. A guide for investigators. Cephalalgia 32(1):6–38CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Mengyuan Hou
    • 1
  • Hongxia Liu
    • 1
  • Yunfei Li
    • 1
  • Ling Xu
    • 1
  • Yingchun He
    • 1
  • Yinghua Lv
    • 1
  • Qingshan Zheng
    • 1
    Email author
  • Lujin Li
    • 1
    Email author
  1. 1.Center for Drug Clinical ResearchShanghai University of Traditional Chinese MedicineShanghaiChina

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