Abstract
Objectives
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.
Methods
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.
Results
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.
Conclusions
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.
Similar content being viewed by others
References
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):782–789
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):258–267
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):453–461
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):3–20
Diener HC (1994) A review of current treatments for migraine. Eur Neurol 34(Suppl 2):18–25
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):99–107
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):1219–1225
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):764–771
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):309–312
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):113
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):715–725
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):126–130
Moskowitz MA, Cutrer FM (1993) SUMATRIPTAN: a receptor-targeted treatment for migraine. Annu Rev Med 44:145–154
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–S14
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):633–658
Ashcroft DM, Millson D (2004) Naratriptan for the treatment of acute migraine: meta-analysis of randomised controlled trials. Pharmacoepidemiol Drug Saf 13(2):73–82
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):965–978
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):221–235
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):125–136
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):13–18
Ferrari MD (2002) Tripstar: a comprehensive patient-based approach to compare triptans. Headache 42(Suppl 1):18–25
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):88–100
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):234–240
Antonaci F, Chimento P, Diener HC, Sances G, Bono G (2007) Lessons from placebo effects in migraine treatment. J Headache Pain 8(1):63–66
Dahlof C et al (2001) Dose finding, placebo-controlled study of oral almotriptan in the acute treatment of migraine. Neurology 57(10):1811–1817
Antonaci F, Ghiotto N, Wu S, Pucci E, Costa A (2016) Recent advances in migraine therapy. Springerplus 5:637
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):464–469
Maas HJ, Danhof M, Pasqua OED (2009) Analysis of the relationship between age and treatment response in migraine. Cephalalgia 29(7):772–780
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):99–105
Ferrari MD, Loder E, McCarroll K, Lines CR (2001) Meta-analysis of rizatriptan efficacy in randomized controlled clinical trials. Cephalalgia 21(2):129–136
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):31–44
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):6–38
Acknowledgments
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).
Funding
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).
Author information
Authors and Affiliations
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.
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no competing interests.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
ESM 1
(DOCX 732 kb)
Rights and permissions
About this article
Cite this article
Hou, M., Liu, H., Li, Y. et al. Efficacy of triptans for the treatment of acute migraines: a quantitative comparison based on the dose-effect and time-course characteristics. Eur J Clin Pharmacol 75, 1369–1378 (2019). https://doi.org/10.1007/s00228-019-02748-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00228-019-02748-4