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Home , Alniditan, Frovatriptan, Zolmitriptan

Triptans for the Treatment of Acute in Adults: A Systematic Review and Network Meta- Analysis (ONLINE APPENDICES)

George Wells, Shannon Kelly, Chris Cameron, Meghan Murphy, Shu-Ching Hsieh, Ahmed Kotb, Joan Peterson, Li Chen, Vijay Shukla, Becky Skidmore

February 2014

30 Bond Street, Toronto ON, M5B 1W8 www.odprn.ca [email protected] 2

APPENDICES

Appendix A: Review of Previous Evidence Syntheses

Author, Interventions Comparators Studies Major Conclusion(s) Notes Publication Date Included (n) Thorlund et al. Oral Oral triptan or 74 Efficacy: appear to Industry-funded 2013(11) placebo offer differing treatment Only included: effects. Double blind RCTs consistently has the highest Oral formulations odds of producing Excluded: relief at 2 hours, freedom Patients with history from pain at 2 hours, of treatment- sustained headache relief at resistant migraines 24 hours, and sustained (i.e. previous poor freedom from pain at 24 response to a hours. triptan) Had other clinical , , and significant high-dose (100 mg) Illnesses also appear effective at two hours, No menstrual whereas only zolmitriptan migraines and high-dose sumatriptan No safety appear to maintain their efficacy at 24 hours.

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Worthington Triptans Varied by Twelve acute Limited literature 2013 (1) comparison, received a strong search with limited mix of recommendation for use in transparency of SR/MA and acute therapy methods, no RCT (, eletriptan, information , , scientist used in the rizatriptan, sumatriptan, literature search zolmitriptan, ASA, ibuprofen, conduct, unsure of naproxen sodium, diclofenac data synthesis potassium, and methods, primary acetaminophen). Four RCTs used only received a weak where existing SR or recommendation for use MA was not (, available (no , codeine- indication of containing combination whether the quality , and - of the SR/MAs used containing combination was assessed), no analgesics). Three of these indirect were not recommended for comparisons routine use (ergotamine, and conducted. codeine- and tramadol- containing medications). Strong recommendations were made to avoid use of butorphanol and butalbital- containing medications. NICE, Triptan Triptan, 19 Offer combination therapy Included 2013(7) antiemetics, with an oral triptan and an adolescents 12 to aspirin, NSAIDs, NSAID, or an oral triptan and 18, Placebo not opioids, acetaminophen, for the included as acetaminophen, acute treatment of migraine, comparator. triptans, ergots taking into account the and person's preference, NMA limited corticosteroids comorbidities and risk of outcomes to: adverse events. For young headache response people aged 12–17 years up to 2 hours; consider a nasal triptan in freedom from pain preference to an oral triptan. up to 2 hours; For women and girls with sustained headache predictable menstrual- response at 24 related migraine that do not hours and sustained respond adequately to freedom from pain standard acute treatment, at 24 hours, change consider treatment with in patient reported frovatriptan (2.5 mg twice a migraine days. day) or zolmitriptans (2.5 mg twice or three times a day) Triptans generally on the days migraine is studied as a class in expected. the NMA, only separately in a few analyses

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Asseburg et al. Oral Triptan at Oral triptan at 56 Efficacy and safety: The Update of a 2012(8) listed dosing listed dosing or highest probability of 2-hour previous review placebo pain-free was estimated for (Ferrari 2000) eletriptan 40 mg and the Two databases lowest probability of searched recurrence was estimated for naratriptan 2.5 mg. The probability of achieving sustained pain-free and no adverse events was estimated to be highest with eletriptan 40 mg. Cochrane Various – Head to head Triptans studied (numerous)(137- single drug with similar or individually 150) formulation placebo or combination Helfand 2009(9, Triptans (oral, Triptans (oral, 98 There is no consistent NMA only 10) nasal, and nasal, and evidence that one triptan has conducted where injectable injectable or any particular advantage or there were no head- placebo disadvantage over another in to-head any subgroup based on age, comparisons and race, gender, prophylactic where there was a treatment, or menstruation- common associated migraine. intervention across studies. Otherwise standard meta- analysis and qualitative review done.

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Appendix B: Detailed Literature Search Strategy Triptans – Acute Migraines – Final Strategies 2013 Oct 6

Database: Embase Classic+Embase <1947 to 2013 October 04>, Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) <1946 to Present> Search Strategy: ------1 exp Migraine Disorders/ (66228) 2 (migrain* or migran*).tw. (89392) 3 (anti-migrain* or antimigrain* or anti-migran* or antimigran*).tw. (2360) 4 sick headache*.tw. (31) 5 or/1-4 (106437) 6 exp / (86272) 7 (tryptamin* or tryptomin* or triptan* or indolylethylamine* or NSC 73938 or NSC73938).tw. (10838) 8 ("BRN 0125513" or CCRIS 8959 or EINECS 200-510-5 or Indol-3-ethylamine or UNII-422ZU9N5TV).tw. (0) 9 Tryptamines.rn. (4631) 10 (almotriptan* or Almogran or Almotrex or Amignul or Axert or PNU 180638E or PNU-180638E or UNII- PJP312605E).tw. (681) 11 almotriptan.rn. (1149) 12 (eletriptan* or Relpax or Relert or Relepax or "UK 116044" or "UK 116,044" or "UK-116044" or "UK-116,044" or UNII-22QOO9B8KI).tw. (686) 13 eletriptan.rn. (1281) 14 (frovatriptan* or Allegro or Frova or Frovelan or Migard or Miguard or SB 209509 or VML-251 or VML251).tw. (927) 15 frovatriptan.rn. (872) 16 (naratriptan* or Amerge or Colatan or Naragran or Naramig or UNII-QX3KXL1ZA2).tw. (841) 17 naratriptan.rn. (1619) 18 (rizatriptan* or Risatriptan* or "L 705,126" or "L 705126" or "L-705,126" or "L-705126" or Maxalt or "MK 0462" or MK 462 or MK-0462 or MK-462 or rizalief or rizalt or rizaliv or UNII-51086HBW8G).tw. (1299) 19 rizatriptan.rn. (2190) 20 (sumatriptan* or Arcoiran or Alsuma or BRN 6930870 or Diletan or Dolmigral or GR 43175 or GR 43175X or GR-43175 or HSDB 7742 or Imigran* or Imiject or Imitrex or micranil or Migril or Novelian or Sumigrene or Suminat or Sumatran or Sumatriptanum or Sumax or UNII-8R78F6L9VO or Zecuity).tw. (6824) 21 sumatriptan.rn. (8795) 22 (Zolmitriptan* or AscoTop or Flezol or Rapimelt or UNII-2FS66TH3YW or Zolmitriptan or Zomig or Zomig-ZMT or Zomigon or Zomigoro).tw. (1407) 23 Zolmitriptan.rn. (2644) 24 (Treximet or Trexima).tw. (60) 25 or/6-24 (102640) 26 5 and 25 (11117) 27 randomized controlled trial.pt. (387867) 28 exp randomized controlled trials as topic/ (142502) 29 random allocation/ (145233) 30 double-blind method/ or single-blind method/ (289667) 31 Placebos/ (277057) 32 (random* or RCT$1 or placebo*).tw. (1760512) 33 ((singl* or doubl* or trebl* or tripl*) and (mask* or blind* or dumm*)).tw. (332772) 34 or/27-33 (2166102) 35 26 and 34 (2796) 36 adult.mp. (9410610)

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37 middle aged.sh. (4500001) 38 age$.tw. (5885873) 39 or/36-38 (14388970) 40 35 and 39 (1651) 41 exp Animals/ not (exp Animals/ and Humans/) (8923948) 42 40 not 41 (1647) 43 (comment or editorial or interview or letter or news).pt. (2770847) 44 42 not 43 (1638) 45 limit 44 to english language (1599) 46 45 use prmz (705) 47 exp migraine/ (66228) 48 (migrain* or migran*).tw. (89392) 49 (anti-migrain* or antimigrain* or anti-migran* or antimigran*).tw. (2360) 50 sick headache*.tw. (31) 51 or/47-50 (106437) 52 derivative/ (2624) 53 triptan derivative/ (1999) 54 (tryptamin* or tryptomin* or triptan* or indolylethylamine* or NSC 73938 or NSC73938).tw,tn. (10838) 55 ("BRN 0125513" or CCRIS 8959 or EINECS 200-510-5 or Indol-3-ethylamine or UNII-422ZU9N5TV).tw,tn. (0) 56 61-54-1.rn. (2370) 57 almotriptan/ (997) 58 (almotriptan* or Almogran or Almotrex or Amignul or Axert or PNU 180638E or PNU-180638E or UNII- PJP312605E).tw,tn. (681) 59 154323-57-6.rn. (986) 60 eletriptan/ (1156) 61 (eletriptan* or Relpax or Relert or Relepax or "UK 116044" or "UK 116,044" or "UK-116044" or "UK-116,044" or UNII-22QOO9B8KI).tw,tn. (686) 62 143322-58-1.rn. (1135) 63 frovatriptan/ (792) 64 (frovatriptan* or Allegro or Frova or Frovelan or Migard or Miguard or SB 209509 or VML-251 or VML251).tw,tn. (927) 65 158747-02-5.rn. (764) 66 naratriptan/ (1470) 67 (naratriptan* or Amerge or Colatan or Naragran or Naramig or UNII-QX3KXL1ZA2).tw,tn. (841) 68 121679-13-8.rn. (1619) 69 rizatriptan/ (1928) 70 (rizatriptan* or Risatriptan* or "L 705,126" or "L 705126" or "L-705,126" or "L-705126" or Maxalt or "MK 0462" or MK 462 or MK-0462 or MK-462 or rizalief or rizalt or rizaliv or UNII-51086HBW8G).tw,tn. (1299) 71 144034-80-0.rn. (1881) 72 sumatriptan/ (8967) 73 (sumatriptan* or Arcoiran or Alsuma or BRN 6930870 or Diletan or Dolmigral or GR 43175 or GR 43175X or GR-43175 or HSDB 7742 or Imigran* or Imiject or Imitrex or micranil or Migril or Novelian or Sumigrene or Suminat or Sumatran or Sumatriptanum or Sumax or UNII-8R78F6L9VO or Zecuity).tw,tn. (6824) 74 103628-46-2.rn. (8795) 75 Zolmitriptan/ (2314) 76 (Zolmitriptan* or AscoTop or Flezol or Rapimelt or UNII-2FS66TH3YW or Zolmitriptan or Zomig or Zomig-ZMT or Zomigon or Zomigoro).tw,tn. (1407) 77 139264-17-8.rn. (2644) 78 naproxen plus sumatriptan succinate/ (23) 79 (Treximet or Trexima).tw,tn. (60) 80 811794-26-0.rn. (0) 81 or/52-80 (25720)

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82 51 and 81 (10907) 83 randomized controlled trial/ (747726) 84 "randomized controlled trial (topic)"/ (39581) 85 Randomization/ (145233) 86 double blind procedure/ or single blind procedure/ or placebo/ (330971) 87 (random* or RCT$1 or placebo*).tw. (1760512) 88 ((singl* or doubl* or trebl* or tripl*) adj (mask* or blind* or dumm*)).tw. (301343) 89 or/83-88 (2139152) 90 82 and 89 (2830) 91 exp animals/ or exp animal experimentation/ or exp models animal/ or exp animal experiment/ or nonhuman/ or exp vertebrate/ (38752497) 92 exp humans/ or exp human experimentation/ or exp human experiment/ (28784180) 93 91 not 92 (9969946) 94 90 not 93 (2826) 95 adult.mp. (9410610) 96 middle aged.sh. (4500001) 97 age$.tw. (5885873) 98 or/95-97 (14388970) 99 94 and 98 (1648) 100 (letter or editorial).pt. (2467327) 101 99 not 100 (1640) 102 limit 101 to english language (1603) 103 102 use emczd (955) 104 46 or 103 (1660) 105 remove duplicates from 104 (1054) TOTAL UNIQUE HITS 106 105 use prmz (644) MEDLINE UNIQUE HITS 107 105 use emczd (410) EMBASE UNIQUE HITS

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Triptans – Network Meta-Analysis Cochrane Strategy

Search Name: Triptans - Network Meta-Analysis Date Run: 06/10/13 14:17:26.40 Description: Ottawa Heart Institute - 2013 Oct 6

ID Search Hits #1 [mh "Migraine Disorders"] 1606 #2 (migrain* or migran*):ti,ab,kw 2899 #3 (anti-migrain* or antimigrain* or anti-migran* or antimigran*):ti,ab,kw 101 #4 (sick next headach*):ti,ab,kw 0 #5 (13-#4) 2907 #6 [mh Tryptamines] 2091 #7 (tryptamin* or tryptomin* or triptan* or indolylethylamine* or "NSC 73938" or NSC73938):ti,ab,kw 415 #8 ("BRN 0125513" or "CCRIS 8959" or "EINECS 200-510-5" or "Indol-3-ethylamine" or "UNII- 422ZU9N5TV"):ti,ab,kw 0 #9 (almotriptan* or Almogran or Almotrex or Amignul or Axert or "PNU 180638E" or "PNU-180638E" or "UNII-PJP312605E"):ti,ab,kw 63 #10 (eletriptan* or Relpax or Relert or Relepax or "UK 116044" or "UK 116,044" or "UK-116044" or "UK- 116,044" or "UNII-22QOO9B8KI"):ti,ab,kw 47

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#11 (frovatriptan* or Allegro or Frova or Frovelan or Migard or Miguard or "SB 209509" or "VML-251" or VML251):ti,ab,kw 40 #12 (naratriptan* or Amerge or Colatan or Naragran or Naramig or "UNII-QX3KXL1ZA2"):ti,ab,kw 51 #13 (rizatriptan* or Risatriptan* or "L 705,126" or "L 705126" or "L-705,126" or "L-705126" or Maxalt or "MK 0462" or "MK 462" or "MK-0462" or "MK-462" or rizalief or rizalt or rizaliv or "UNII-51086HBW8G"):ti,ab,kw 118 #14 (sumatriptan* or Arcoiran or Alsuma or "BRN 6930870" or Diletan or Dolmigral or "GR 43175" or "GR 43175X" or "GR-43175" or "HSDB 7742" or Imigran* or Imiject or Imitrex or micranil or Migril or Novelian or Sumigrene or Suminat or Sumatran or Sumatriptanum or Sumax or "UNII-8R78F6L9VO" or Zecuity):ti,ab,kw 523 #15 (Zolmitriptan* or AscoTop or Flezol or Rapimelt or "UNII-2FS66TH3YW" or Zolmitriptan or Zomig or "Zomig-ZMT" or Zomigon or Zomigoro):ti,ab,kw 106 #16 (Treximet or Trexima):ti,ab,kw 1 #17 (151-#16) 2394 #18 #5 and #17 721

DSR - 18 DARE - 20 CENTRAL – 640 Methods – 8 HTA – 6 NHS EED – 29

Only CENTRAL and DSR records were downloaded

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Appendix C: Included and Excluded Studies Included Studies (with single attack data) n = 133 1. Ahrens SP, Farmer MV, Williams DL, Willoughby E, Jiang K, Block GA, et al. Efficacy and safety of rizatriptan wafer for the acute treatment of migraine. Rizatriptan Wafer Protocol 049 Study Group. Cephalalgia. 1999;19(5):525-30. 2. Allais G, Acuto G, Cabarrocas X, Esbri R, Benedetto C, Bussone G. Efficacy and tolerability of almotriptan versus zolmitriptan for the acute treatment of menstrual migraine. Neurological Sciences. 2006;27 Suppl 2:S193-7, 2006 May.:7. 3. Banerjee M, Findley LJ. Sumatriptan in the treatment of acute migraine with aura. Cephalalgia. 1992;12(1):39-44. 4. Barbanti P, Carpay JA, Kwong WJ, Ahmad F, Boswell D. Effects of a fast disintegrating/rapid release oral formulation of sumatriptan on functional ability in patients with migraine. Current Medical Research and Opinion. 2004;20(12):2021-9. 5. Barbanti P, Fofi L, Dall'Armi V, Aurilia C, Egeo G, Vanacore N, et al. Rizatriptan in migraineurs with unilateral cranial autonomic symptoms: a double-blind trial. J headache pain. 2012;13(5):407-14. 6. Bates D, Ashford E, Dawson R, Ensink FB, Gilhus NE, Olesen J, et al. Subcutaneous sumatriptan during the migraine aura. Sumatriptan Aura Study Group. Neurology. 1994;44(9):1587-92. 7. Bomhof M, Paz J, Legg N, Allen C, Vandormael K, Patel K. Comparison of rizatriptan 10 mg vs. naratriptan 2.5 mg in migraine. European Neurology. 1999;42(3):173-9. 8. Bousser MG, d'Allens H, Richard A. Efficacy of subcutaneous sumatriptan in the acute treatment of early- morning migraine: a placebo-controlled trial. Early-Morning Migraine Sumatriptan Study Group. Journal of Internal Medicine. 1993;234(2):211-6. 9. Brandes JL, Kudrow D, Cady R, Tiseo PJ, Sun W, Sikes CR. Eletriptan in the early treatment of acute migraine: influence of pain intensity and time of dosing. Cephalalgia. 2005;25(9):735-42. 10. Brandes JL, Kudrow D, Stark SR, O'Carroll CP, Adelman JU, O'Donnell FJ, et al. Sumatriptan-naproxen for acute treatment of migraine: a randomized trial. JAMA. 2007;297(13):1443-54. 11. Bussone G, Manzoni GC, Cortelli P, Roncolato M, Fabbri L, Benassuti C. Efficacy and tolerability of sumatriptan in the treatment of multiple migraine attacks. Neurological Sciences. 2000;21(5):272-8. 12. Cady R, Crawford G, Ahrens S, Hairwassers D, Getson A, Visser WH, et al. Long-term efficacy and tolerability of rizatriptan wafers in migraine. Medscape General Medicine. 2001;3(3):1. 13. Cady R, Martin V, Mauskop A, Rodgers A, Hustad CM, Ramsey KE, et al. Efficacy of Rizatriptan 10 mg administered early in a migraine attack. Headache. 2006;46(6):914-24. 14. Cady RC, Ryan R, Jhingran P, O'Quinn S, Pait DG. Sumatriptan injection reduces productivity loss during a migraine attack: results of a double-blind, placebo-controlled trial. Archives of Internal Medicine. 1998;158(9):1013-8. 15. Cady RK, Martin VT, Geraud G, Rodgers A, Zhang Y, Ho AP, et al. Rizatriptan 10-mg ODT for early treatment of migraine and impact of migraine education on treatment response. Headache. 2009;49(5):687-96. 16. Carpay HA, Matthijsse P, Steinbuch M, Mulder PG. Oral and subcutaneous sumatriptan in the acute treatment of migraine: an open randomized cross-over study. Cephalalgia. 1997;17(5):591-5. 17. Carpay J, Schoenen J, Ahmad F, Kinrade F, Boswell D. Efficacy and tolerability of sumatriptan tablets in a

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fast-disintegrating, rapid-release formulation for the acute treatment of migraine: results of a multicenter, randomized, placebo-controlled study. Clinical Therapeutics. 2004;26(2):214-23. 18. Charlesworth BR, Dowson AJ, Purdy A, Becker WJ, Boes-Hansen S, Farkkila M. Speed of onset and efficacy of zolmitriptan nasal spray in the acute treatment of migraine: a randomised, double-blind, placebo- controlled, dose-ranging study versus zolmitriptan tablet. CNS Drugs. 2003;17(9):653-67. 19. Colman SS, Brod MI, Krishnamurthy A, Rowland CR, Jirgens KJ, Gomez-Mancilla B. Treatment satisfaction, functional status, and health-related quality of life of migraine patients treated with almotriptan or sumatriptan. Clinical Therapeutics. 2001;23(1):127-45. 20. Cull RE, Price WH, Dunbar A. The efficacy of subcutaneous sumatriptan in the treatment of recurrence of migraine headache. Journal of Neurology Neurosurgery and Psychiatry. 1997;62(5):490-5. 21. Dahlof C, Diener HC, Goadsby PJ, Massiou H, Olesen J, Schoenen J, et al. Zolmitriptan, a 5-HT(1B/1D) receptor for the acute oral treatment of migraine: a multicentre, dose-range finding study. European Journal of Neurology. 1998;5(6):535-43. 22. Dahlof C, Tfelt-Hansen P, Massiou H, Fazekas A, Almotriptan Study G. Dose finding, placebo-controlled study of oral almotriptan in the acute treatment of migraine. Neurology. 2001;57(10):1811-7. 23. Dahlof CG, Hauge AW, Olesen J. Efficacy and safety of tonabersat, a gap-junction modulator, in the acute treatment of migraine: a double-blind, parallel-group, randomized study. Cephalalgia. 2009;29 Suppl 2:7-16. 24. Dasbach EJ, Carides GW, Gerth WC, Santanello NC, Pigeon JG, Kramer. Work and productivity loss in the rizatriptan multiple attack study. Cephalalgia. 2000;20(9):830-4. 25. Di MV, Nicolodi M, Aloisio A, Del BP, Fonzari M, Grazioli I, et al. Efficacy of a fixed combination of indomethacin, , and caffeine versus sumatriptan in acute treatment of multiple migraine attacks: a multicenter, randomized, crossover trial. Headache. 2003;43(8):835-44. 26. Diamond S, Elkind A, Jackson RT, Ryan R, DeBussey S, Asgharnejad M. Multiple-attack efficacy and tolerability of sumatriptan nasal spray in the treatment of migraine. Archives of Family Medicine. 1998;7(3):234-40. 27. Diener HC. Efficacy of almotriptan 12.5 mg in achieving migraine-related composite endpoints: a double- blind, randomized, placebo-controlled study in patients controlled study in patients with previous poor response to sumatriptan 50 mg. Current Medical Research and Opinion. 2005;21(10):1603-10. 28. Diener HC, Barbanti P, Dahlof C, Reuter U, Habeck J, Podhorna J. BI 44370 TA, an oral CGRP antagonist for the treatment of acute migraine attacks: results from a phase II study. Cephalalgia. 2011;31(5):573-84. 29. Diener HC, Eikermann A, Gessner U, Gobel H, Haag G, Lange R, et al. Efficacy of 1,000 mg effervescent acetylsalicylic acid and sumatriptan in treating associated migraine symptoms. European Neurology. 2004;52(1):50-6. 30. Diener HC, Gendolla A, Gebert I, Beneke M. Almotriptan in migraine patients who respond poorly to oral sumatriptan: a double-blind, randomized trial. Headache. 2005;45(7):874-82. 31. Diener HC, Gendolla A, Gebert I, Beneke M. Almotriptan in migraine patients who respond poorly to oral sumatriptan: a double-blind, randomized trial. European Neurology. 2005;53 Suppl 1:41-8. 32. Diener HC, Jansen JP, Reches A, Pascual J, Pitei D, Steiner TJ, et al. 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. European Neurology. 2002;47(2):99-107. 33. Dodick D, Brandes J, Elkind A, Mathew N, Rodichok L. Speed of onset, efficacy and tolerability of zolmitriptan nasal spray in the acute treatment of migraine: a randomised, double-blind, placebo-controlled

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study. CNS Drugs. 2005;19(2):125-36. 34. Dodick DW. Almotriptan increases sustained pain-free outcomes in acute migraine: results from three controlled clinical trials. Headache. 2002;42(1):21-7. 35. Dowson AJ, Charlesworth BR. Patients with migraine prefer zolmitriptan orally disintegrating tablet to sumatriptan conventional oral tablet. International Journal of Clinical Practice. 2003;57(7):573-6. 36. Dowson AJ, MacGregor EA, Purdy RA, Becker WJ, Green J, Levy SL. Zolmitriptan orally disintegrating tablet is effective in the acute treatment of migraine. Cephalalgia. 2002;22(2):101-6. 37. Dowson AJ, Massiou H, Lainez JM, Cabarrocas X. Almotriptan is an effective and well-tolerated treatment for migraine pain: results of a randomized, double-blind, placebo-controlled clinical trial. Cephalalgia. 2002;22(6):453-61. 38. Dowson AJ, Massiou H, Lainez JM, Cabarrocas X. Almotriptan improves response rates when treatment is within 1 hour of migraine onset. Headache. 2004;44(4):318-22. 39. Eletriptan Steering C. Efficacy and safety of eletriptan 20 mg, 40 mg and 80 mg in Japanese migraineurs. Cephalalgia. 2002;22(6):416-23. 40. Farkkila M, Olesen J, Dahlof C, Stovner LJ, ter Bruggen JP, Rasmussen S, et al. Eletriptan for the treatment of migraine in patients with previous poor response or tolerance to oral sumatriptan. Cephalalgia. 2003;23(6):463-71. 41. Freitag F, Diamond M, Diamond S, Janssen I, Rodgers A, Skobieranda F. Efficacy and tolerability of coadministration of rizatriptan and acetaminophen vs rizatriptan or acetaminophen alone for acute . Headache. 2008;48(6):921-30. 42. Freitag F, Taylor FR, Hamid MA, Rodgers A, Hustad CM, Ramsey KE, et al. Elimination of migraine-associated nausea in patients treated with rizatriptan orally disintegrating tablet (ODT): a randomized, double-blind, placebo-controlled study. Headache. 2008;48(3):368-77. 43. Freitag FG, Cady R, DiSerio F, Elkind A, Gallagher RM, Goldstein J, et al. Comparative study of a combination of isometheptene mucate, dichloralphenazone with acetaminophen and sumatriptan succinate in the treatment of migraine. Headache. 2001;41(4):391-8. 44. Friedman BW, Solorzano C, Esses D, Xia S, Hochberg M, Dua N, et al. Treating headache recurrence after emergency department discharge: a randomized controlled trial of naproxen versus sumatriptan. Annals of Emergency Medicine. 2010;56(1):7-17. 45. Gallagher RM, Dennish G, Spierings EL, Chitra R. A comparative trial of zolmitriptan and sumatriptan for the acute oral treatment of migraine. Headache. 2000;40(2):119-28. 46. Garcia-Ramos G, MacGregor EA, Hilliard B, Bordini CA, Leston J, Hettiarachchi J. Comparative efficacy of eletriptan vs. naratriptan in the acute treatment of migraine. Cephalalgia. 2003;23(9):869-76. 47. Gawel M, Aschoff J, May A, Charlesworth BR, Team RS. Zolmitriptan 5 mg nasal spray: efficacy and onset of action in the acute treatment of migraine--results from phase 1 of the REALIZE Study. Headache. 2005;45(1):7-16. 48. Geraud G, Compagnon A, Rossi A, Group CS. Zolmitriptan versus a combination of acetylsalicylic acid and in the acute oral treatment of migraine: a double-blind, randomised, three-attack study. European Neurology. 2002;47(2):88-98. 49. Gerth WC, Ruggles KH, Stark SR, Davies GM, Santanello NC. Improvement in health-related quality of life with rizatriptan 10mg compared with standard migraine therapy. Clinical Drug Investigation.

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2001;21(12):853-60. 50. Gijsman H, Kramer MS, Sargent J, Tuchman M, Matzura-Wolfe D, Polis A, et al. Double-blind, placebo- controlled, dose-finding study of rizatriptan (MK- 462) in the acute treatment of migraine. Cephalalgia. 1997;17(6):647-51. 51. Goadsby PJ, Ferrari MD, Olesen J, Stovner LJ, Senard JM, Jackson NC, et al. Eletriptan in acute migraine: a double-blind, placebo-controlled comparison to sumatriptan. Eletriptan Steering Committee. Neurology. 2000;54(1):156-63. 52. Goadsby PJ, Massiou H, Pascual J, Diener HC, Dahlof CG, Mateos V, et al. Almotriptan and zolmitriptan in the acute treatment of migraine. Acta Neurologica Scandinavica. 2007;115(1):34-40. 53. Goadsby PJ, Zanchin G, Geraud G, De KN, Diaz-Insa S, Gobel H, et al. Early vs. non-early intervention in acute migraine-'Act when Mild (AwM)'. A double-blind, placebo-controlled trial of almotriptan. Cephalalgia. 2008;28(4):383-91. 54. Gobel H, Winter P, Boswell D, Crisp A, Becker W, Hauge T, et al. Comparison of naratriptan and sumatriptan in recurrence-prone migraine patients. Naratriptan International Recurrence Study Group. Clinical Therapeutics. 2000;22(8):981-9. 55. Goldstein J, Keywood C, Study G. Frovatriptan for the acute treatment of migraine: a dose-finding study. Headache. 2002;42(1):41-8. 56. Goldstein J, Smith TR, Pugach N, Griesser J, Sebree T, Pierce M. A sumatriptan iontophoretic transdermal system for the acute treatment of migraine. Headache. 2012;52(9):1402-10. 57. Gross ML, Kay J, Turner AM, Hallett K, Cleal AL, Hassani H. Sumatriptan in acute migraine using a novel cartridge system self-injector. United Kingdom Study Group. Headache. 1994;34(10):559-63. 58. Gruffyd-Jones K, Kies B, Middleton A, Mulder LJ, Rosjo O, Millson DS. Zolmitriptan versus sumatriptan for the acute oral treatment of migraine: a randomized, double-blind, international study. European Journal of Neurology. 2001;8(3):237-45. 59. Henry P, d'Allens H. Subcutaneous sumatriptan in the acute treatment of migraine in patients using dihydroergotamine as prophylaxis. French Migraine Network Bordeaux-Lyon-Grenoble. Headache. 1993;33(8):432-5. 60. Ho TW, Ferrari MD, Dodick DW, Galet V, Kost J, Fan X, et al. Efficacy and tolerability of MK-0974 (), a new oral antagonist of calcitonin gene-related peptide receptor, compared with zolmitriptan for acute migraine: a randomised, placebo-controlled, parallel-treatment trial. Lancet. 2008;372(9656):2115-23. 61. Ho TW, Mannix LK, Fan X, Assaid C, Furtek C, Jones CJ, et al. Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in acute treatment of migraine. Neurology. 2008;70(16):1304-12. 62. Ishkanian G, Blumenthal H, Webster CJ, Richardson MS, Ames M. Efficacy of sumatriptan tablets in migraineurs self-described or physician-diagnosed as having sinus headache: a randomized, double-blind, placebo-controlled study. Clinical Therapeutics. 2007;29(1):99-109. 63. Jelinski SE, Becker WJ, Christie SN, Ahmad FE, Pryse-Phillips W, Simpson SD. Pain free efficacy of sumatriptan in the early treatment of migraine. Canadian Journal of Neurological Sciences. 2006;33(1):73-9. 64. Jensen K, Tfelt-Hansen P, Hansen EW, Krois EH, Pedersen OS. Introduction of a novel self-injector for sumatriptan. A controlled clinical trial in general practice. Cephalalgia. 1995;15(5):423-9. 65. Kaniecki R, Ruoff G, Smith T, Barrett PS, Ames MH, Byrd S, et al. Prevalence of migraine and response to sumatriptan in patients self-reporting tension/stress headache. Current Medical Research and Opinion.

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2006;22(8):1535-44. 66. Klapper J, Lucas C, Rosjo O, Charlesworth B, group Zs. Benefits of treating highly disabled migraine patients with zolmitriptan while pain is mild. Cephalalgia. 2004;24(11):918-24. 67. Klapper JA, O'Connor S. Rizatriptan wafer--sublingual vs. placebo at the onset of acute migraine. Cephalalgia. 2000;20(6):585-7. 68. Klassen A, Elkind A, Asgharnejad M, Webster C, Laurenza A. Naratriptan is effective and well tolerated in the acute treatment of migraine. Results of a double-blind, placebo-controlled, parallel-group study. Naratriptan S2WA3001 Study Group. Headache. 1997;37(10):640-5. 69. Kramer MS, Matzura-Wolfe D, Polis A, Getson A, Amaraneni PG, Solbach MP, et al. A placebo-controlled crossover study of rizatriptan in the treatment of multiple migraine attacks. Rizatriptan Multiple Attack Study Group. Neurology. 1998;51(3):773-81. 70. Kudrow D, Thomas HM, Ruoff G, Ishkanian G, Sands G, Le VH, et al. Valdecoxib for treatment of a single, acute, moderate to severe migraine headache. Headache. 2005;45(9):1151-62. 71. Landy S, Savani N, Shackelford S, Loftus J, Jones M. Efficacy and tolerability of sumatriptan tablets administered during the mild-pain phase of menstrually associated migraine. International Journal of Clinical Practice. 2004;58(10):913-9. 72. Lipton RB, Dodick DW, Adelman JU, Kaniecki RG, Lener SE, White JD, et al. Consistency of response to sumatriptan/naproxen sodium in a placebo-controlled, crossover study. Cephalalgia. 2009;29(8):826-36. 73. Loder E, Freitag FG, Adelman J, Pearlmand S, Abu-Shakra S. Pain-free rates with zolmitriptan 2.5 mg ODT in the acute treatment of migraine: results of a large double-blind placebo- controlled trial. Current Medical Research and Opinion. 2005;21(3):381-9. 74. Mannix LK, Loder E, Nett R, Mueller L, Rodgers A, Hustad CM, et al. Rizatriptan for the acute treatment of ICHD-II proposed menstrual migraine: two prospective, randomized, placebo-controlled, double-blind studies. Cephalalgia. 2007;27(5):414-21. 75. Mannix LK, Martin VT, Cady RK, Diamond ML, Lener SE, White JD, et al. Combination treatment for menstrual migraine and dysmenorrhea using sumatriptan-naproxen: two randomized controlled trials. Obstetrics and Gynecology. 2009;114(1):106-13. 76. Massiou H, Jamin C, Hinzelin G, Bidaut-Mazel C. Efficacy of oral naratriptan in the treatment of menstrually related migraine. European Journal of Neurology. 2005;12(10):774-81. 77. Mathew NT, Finlayson G, Smith TR, Cady RK, Adelman J, Mao L, et al. Early intervention with almotriptan: results of the AEGIS trial (AXERT Early Migraine Intervention Study). Headache. 2007;47(2):189-98. 78. Mathew NT, Schoenen J, Winner P, Muirhead N, Sikes CR. Comparative efficacy of eletriptan 40 mg versus sumatriptan 100 mg. Headache. 2003;43(3):214-22. 79. Misra M, Sharma T, Kalra J, Goel D, Dhasmana DC. Comparative efficacy and tolerability of sumatriptan, ergotamine, naproxen and rizatriptan in moderate to severe acute attack of migraine. JK Science. 2010;12(4):175-9. 80. Misra UK, Kalita J, Yadav RK. Rizatriptan vs. ibuprofen in migraine: a randomised placebo-controlled trial. J headache pain. 2007;8(3):175-9. 81. Multinational Oral Sumatriptan and Cafergot Comparative Study Group. A randomized, double-blind comparison of sumatriptan and Cafergot in the acute treatment of migraine. The Multinational Oral Sumatriptan and Cafergot Comparative Study Group. European Neurology. 1991;31(5):314-22.

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82. Myllyla VV, Havanka H, Herrala L, Kangasniemi P, Rautakorpi I, Turkka J, et al. rapid release versus sumatriptan in the acute treatment of migraine: comparable effect in a double-blind, randomized, controlled, parallel-group study. Headache. 1998;38(3):201-7. 83. Nappi G, Sicuteri F, Byrne M, Roncolato M, Zerbini O. Oral sumatriptan compared with placebo in the acute treatment of migraine. Journal of Neurology. 1994;241(3):138-44. 84. Nett R, Landy S, Shackelford S, Richardson MS, Ames M, Lener M. Pain-free efficacy after treatment with sumatriptan in the mild pain phase of menstrually associated migraine. Obstetrics and Gynecology. 2003;102(4):835-42. 85. Olesen J, Diener HC, Schoenen J, Hettiarachchi J. No effect of eletriptan administration during the aura phase of migraine. European Journal of Neurology. 2004;11(10):671-7. 86. Oral Sumatriptan and Aspirin plus Metoclopramide Comparative Study Group. A study to compare oral sumatriptan with oral aspirin plus oral metoclopramide in the acute treatment of migraine. The Oral Sumatriptan and Aspirin plus Metoclopramide Comparative Study Group. European Neurology. 1992;32(3):177-84. 87. Oral Sumatriptan Dose-Defining Study Group. Sumatriptan--an oral dose-defining study. The Oral Sumatriptan Dose-Defining Study Group. European Neurology. 1991;31(5):300-5. 88. Oral Sumatriptan International Multiple-Dose Study Group. Evaluation of a multiple-dose regimen of oral sumatriptan for the acute treatment of migraine. The Oral Sumatriptan International Multiple-Dose Study Group. European Neurology. 1991;31(5):306-13. 89. Pascual J, Falk RM, Piessens F, Prusinski A, Docekal P, Robert M, et al. Consistent efficacy and tolerability of almotriptan in the acute treatment of multiple migraine attacks: results of a large, randomized, double- blind, placebo-controlled study. Cephalalgia. 2000;20(6):588-96. 90. Pascual J, Vega P, Diener HC, Allen C, Vrijens F, Patel K. Comparison of rizatriptan 10 mg vs. zolmitriptan 2.5 mg in the acute treatment of migraine. Rizatriptan-Zolmitriptan Study Group. Cephalalgia. 2000;20(5):455- 61. 91. Pfaffenrath V, Cunin G, Sjonell G, Prendergast S. Efficacy and safety of sumatriptan tablets (25 mg, 50 mg, and 100 mg) in the acute treatment of migraine: defining the optimum doses of oral sumatriptan. Headache. 1998;38(3):184-90. 92. Pini LA, Fabbri L, Cavazzuti L. Efficacy and safety of sumatriptan 50 mg in patients not responding to standard care, in the treatment of mild to moderate migraine. The Sumatriptan 50 mg Italian Study Group. International Journal of Clinical Pharmacology Research. 1999;19(2):57-64. 93. Pini LA, Sternieri E, Fabbri L, Zerbini O, Bamfi F. High efficacy and low frequency of headache recurrence after oral sumatriptan. The Oral Sumatriptan Italian Study Group. Journal of International Medical Research. 1995;23(2):96-105. 94. Rapoport A, Ryan R, Goldstein J, Keywood C. Dose range-finding studies with frovatriptan in the acute treatment of migraine. Headache. 2002;42 Suppl 2:S74-83, 2002 Apr.:83. 95. Ryan R, Elkind A, Baker CC, Mullican W, DeBussey S, Asgharnejad M. Sumatriptan nasal spray for the acute treatment of migraine. Results of two clinical studies. Neurology. 1997;49(5):1225-30. 96. Ryan R, Geraud G, Goldstein J, Cady R, Keywood C. Clinical efficacy of frovatriptan: placebo-controlled studies. Headache. 2002;42 Suppl 2:84-92. 97. Sakai F, Iwata M, Tashiro K, Itoyama Y, Tsuji S, Fukuuchi Y, et al. Zolmitriptan is effective and well tolerated in Japanese patients with migraine: a dose-response study. Cephalalgia. 2002;22(5):376-83.

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98. Sandrini G, Cerbo R, Del BE, Ferrari A, Genco S, Grazioli I, et al. Efficacy of dosing and re-dosing of two oral fixed combinations of indomethacin, prochlorperazine and caffeine compared with oral sumatriptan in the acute treatment of multiple migraine attacks: a double-blind, double-dummy, randomised, parallel group, multicentre study. International Journal of Clinical Practice. 2007;61(8):1256-69. 99. Sandrini G, Farkkila M, Burgess G, Forster E, Haughie S, Eletriptan Steering C. Eletriptan vs sumatriptan: a double-blind, placebo-controlled, multiple migraine attack study. Neurology. 2002;59(8):1210-7. 100. Savani N, Brautaset NJ, Reunanen M, Szirmai I, Ashford EA, Hassani H, 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. International Journal of Clinical Practice, Supplement. 1999;105:7-15. 101. Savani N, Pfaffenrath V, Rice L, Boswell D, Black L, Jones M, et al. Efficacy, tolerability, and patient satisfaction with 50- and 100-mg sumatriptan tablets in those initially dissatisfied with the efficacy of 50-mg sumatriptan tablets. Clinical Therapeutics. 2001;23(2):260-71. 102. Schulman EA. Transdermal sumatriptan for acute treatment of migraineurs with baseline nausea. Headache. 2012;52(2):204-12. 103. Schulman EA, Cady RK, Henry D, Batenhorst AS, Putnam DG, Watson CB, et al. Effectiveness of sumatriptan in reducing productivity loss due to migraine: results of a randomized, double-blind, placebo-controlled clinical trial. Mayo Clinic Proceedings. 2000;75(8):782-9. 104. Scott RJ, Aitchison WR, Barker PR, McLaren GI. Oral sumatriptan in the acute treatment of migraine and migraine recurrence in general practice. QJM. 1996;89(8):613-22. 105. Sheftell F, Ryan R, Pitman V, Eletriptan Steering C. 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(3):202-13. 106. Sheftell FD, Dahlof CG, Brandes JL, Agosti R, Jones MW, Barrett PS. Two replicate randomized, double-blind, placebo-controlled trials of the time to onset of pain relief in the acute treatment of migraine with a fast- disintegrating/rapid-release formulation of sumatriptan tablets. Clinical Therapeutics. 2005;27(4):407-17. 107. Silberstein SD, Cady RK, Sheftell FD, Almas M, Parsons B, Albert KS. Efficacy of eletriptan in migraine-related functional impairment: functional and work productivity outcomes. Headache. 2007;47(5):673-82. 108. Silberstein SD, Mannix LK, Goldstein J, Couch JR, Byrd SC, Ames MH, et al. Multimechanistic (sumatriptan- naproxen) early intervention for the acute treatment of migraine. Neurology. 2008;71(2):114-21. 109. Slof J. Cost-effectiveness analysis of early versus non-early intervention in acute migraine based on evidence from the 'Act when mild' study. Applied Health Economics and Health Policy. 2012;10(3):201-15. 110. Smith TR, Sunshine A, Stark SR, Littlefield DE, Spruill SE, Alexander WJ. Sumatriptan and naproxen sodium for the acute treatment of migraine. Headache. 2005;45(8):983-91. 111. Solomon GD, Cady RK, Klapper JA, Earl NL, Saper JR, Ramadan NM. Clinical efficacy and tolerability of 2.5 mg zolmitriptan for the acute treatment of migraine. The 042 Clinical Trial Study Group. Neurology. 1997;49(5):1219-25. 112. Spierings EL, Gomez-Mancilla B, Grosz DE, Rowland CR, Whaley FS, Jirgens KJ. Oral almotriptan vs. oral sumatriptan in the abortive treatment of migraine: a double-blind, randomized, parallel-group, optimum- dose comparison. Archives of Neurology. 2001;58(6):944-50. 113. Spierings EL, Rapoport AM, Dodick DW, Charlesworth B. Acute treatment of migraine with zolmitriptan 5 mg orally disintegrating tablet. CNS Drugs. 2004;18(15):1133-41.

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114. Stark R, Dahlof C, Haughie S, Hettiarachchi J, Eletriptan Steering C. 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(1):23-32. 115. Stark S, Spierings EL, McNeal S, Putnam GP, Bolden-Watson CP, O'Quinn S. Naratriptan efficacy in migraineurs who respond poorly to oral sumatriptan. Headache. 2000;40(7):513-20. 116. Steiner TJ, Diener HC, MacGregor EA, Schoenen J, Muirheads N, Sikes CR. Comparative efficacy of eletriptan and zolmitriptan in the acute treatment of migraine. Cephalalgia. 2003;23(10):942-52. 117. Sumatriptan Auto-Injector Study Group. Self-treatment of acute migraine with subcutaneous sumatriptan using an auto-injector device. The Sumatriptan Auto-Injector Study Group. European Neurology. 1991;31(5):323-31. 118. Sunshine A, Mulhern SA, Olson N, Elkind A, Almas M, Sikes C. Comparative sensitivity of stopwatch methodology and conventional pain assessment measures for detecting early response to triptans in migraine: results of a randomized, open-label pilot study. Clinical Therapeutics. 2006;28(8):1107-15. 119. Taylor FR, Heiring JO, Messina E, Braverman-Panza J, Ames MH, Byrd SC, et al. Sumatriptan/naproxen sodium as early intervention for migraine: Effects on functional ability, productivity, and satisfaction in 2 randomized controlled trials. Journal of Clinical Outcomes Management. 2007;14(4):195-204. 120. Teall J, Tuchman M, Cutler N, Gross M, Willoughby E, Smith B, et al. Rizatriptan (MAXALT) for the acute treatment of migraine and migraine recurrence. A placebo-controlled, outpatient study. Rizatriptan 022 Study Group. Headache. 1998;38(4):281-7. 121. Tepper SJ, Cady R, Dodick D, Freitag FG, Hutchinson SL, Twomey C, et al. Oral sumatriptan for the acute treatment of probable migraine: first randomized, controlled study. Headache. 2006;46(1):115-24. 122. Tepper SJ, Cochran A, Hobbs S, Woessner M. Sumatriptan suppositories for the acute treatment of migraine. S2B351 Study Group. International Journal of Clinical Practice. 1998;52(1):31-5. 123. Tepper SJ, Donnan GA, Dowson AJ, Bomhof MA, Elkind A, Meloche J, et al. A long-term study to maximise migraine relief with zolmitriptan. Current Medical Research and Opinion. 1999;15(4):254-71. 124. Tfelt-Hansen P, Bach FW, Daugaard D, Tsiropoulos I, Riddersholm B. Treatment with sumatriptan 50 mg in the mild phase of migraine attacks in patients with infrequent attacks: a randomised, double-blind, placebo- controlled study. J headache pain. 2006;7(6):389-94. 125. Tfelt-Hansen P, Henry P, Mulder LJ, Scheldewaert RG, Schoenen J, Chazot G. The effectiveness of combined oral acetylsalicylate and metoclopramide compared with oral sumatriptan for migraine. Lancet. 1995;346(8980):923-6. 126. Tfelt-Hansen P, Teall J, Rodriguez F, Giacovazzo M, Paz J, Malbecq W, et al. Oral rizatriptan versus oral sumatriptan: a direct comparative study in the acute treatment of migraine. Rizatriptan 030 Study Group. Headache. 1998;38(10):748-55. 127. Visser WH, Terwindt GM, Reines SA, Jiang K, Lines CR, Ferrari MD. Rizatriptan vs sumatriptan in the acute treatment of migraine. A placebo-controlled, dose-ranging study. Dutch/US Rizatriptan Study Group. Archives of Neurology. 1996;53(11):1132-7. 128. Wang SJ, Fuh JL, Wu ZA. Intranasal sumatriptan study with high placebo response in Taiwanese patients with migraine. Journal of the Chinese Medical Association. 2007;70(2):39-46. 129. Wells N, Hettiarachchi J, Drummond M, Dphil M, Carter D, Parpia T, et al. A cost-effectiveness analysis of eletriptan 40 and 80 mg versus sumatriptan 50 and 100 mg in the acute treatment of migraine. Value in Health. 2003;6(4):438-47.

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130. Wells NEJ. Comparison of the effectiveness of eletriptan, sumatriptan and Cafergot in reducing the time loss associated with migraine attacks. Journal of Medical Economics. 2001;4(157-166):157-66. 131. White WB, Derosier FJ, Thompson AH, Adams BE, Goodman DK. Evaluation of the migraine treatment sumatriptan/naproxen sodium on blood pressure following long-term administration. Journal of Clinical Hypertension (Greenwich, Conn). 2011;13(12):910-6. 132. Winner P, Adelman J, Aurora S, Lener ME, Ames M. Efficacy and tolerability of sumatriptan injection for the treatment of morning migraine: two multicenter, prospective, randomized, double-blind, controlled studies in adults. Clinical Therapeutics. 2006;28(10):1582-91. 133. Winner P, Mannix LK, Putnam DG, McNeal S, Kwong J, O'Quinn S, et al. Pain-free results with sumatriptan taken at the first sign of migraine pain: 2 randomized, double-blind, placebo-controlled studies. Mayo Clinic Proceedings. 2003;78(10):1214-22.

Included studies (no single attack data) n = 69 1. Allais G, Bussone G, D'Andrea G, Moschiano F, d'Onofrio F, Valguarnera F, et al. Almotriptan 12.5 mg in menstrually related migraine: a randomized, double-blind, placebo-controlled study. Cephalalgia. 2011;31(2):144-51. 2. Bartolini M, Giamberardino MA, Lisotto C, Martelletti P, Moscato D, Panascia B, et al. A double-blind, randomized, multicenter, Italian study of frovatriptan versus almotriptan for the acute treatment of migraine. J headache pain. 2011;12(3):361-8. 3. Bartolini M, Giamberardino MA, Lisotto C, Martelletti P, Moscato D, Panascia B, et al. Frovatriptan versus almotriptan for acute treatment of menstrual migraine: analysis of a double-blind, randomized, cross-over, multicenter, Italian, comparative study. J headache pain. 2012;13(5):401-6. 4. Bigal M, Sheftell F, Tepper S, Tepper D, Ho TW, Rapoport A. A randomized double-blind study comparing

rizatriptan, dexamethasone, and the combination of both in the acute treatment of menstrually related migraine: research submission. Headache. 2008;48(9):1286-93. 5. Boureau F, Chazot G, Emile J, Bertin L, d'Allens H. Comparison of subcutaneous sumatriptan with usual acute treatments for migraine. French Sumatriptan Study Group. European Neurology. 1995;35(5):264-9. 6. Boureau F, Kappos L, Schoenen J, Esperanca P, Ashford E. A clinical comparison of sumatriptan nasal spray and dihydroergotamine nasal spray in the acute treatment of migraine. International Journal of Clinical Practice. 2000;54(5):281-6. 7. Cady R, Elkind A, Goldstein J, Keywood C. Randomized, placebo-controlled comparison of early use of frovatriptan in a migraine attack versus dosing after the headache has become moderate or severe. Current Medical Research and Opinion. 2004;20(9):1465-72. 8. Cady R, Martin V, Mauskop A, Rodgers A, Hustad C, Ramsey K, et al. Symptoms of cutaneous sensitivity pre- treatment and post-treatment: results from the rizatriptan TAME studies. Cephalalgia. 2007;27(9):1055-60. 9. Cady RK, Freitag FG, Mathew NT, Elkind AH, Mao L, Fisher AC, et al. Allodynia-associated symptoms, pain intensity and time to treatment: predicting treatment response in acute migraine intervention. Headache. 2009;49(3):350-63. 10. Cady RK, Goldstein J, Silberstein S, Juhasz M, Ramsey K, Rodgers A, et al. Expanding access to triptans: assessment of clinical outcome. Headache. 2009;49(10):1402-13. 11. Christie S, Gobel H, Mateos V, Allen C, Vrijens F, Shivaprakash M, et al. Crossover comparison of efficacy and preference for rizatriptan 10 mg versus ergotamine/caffeine in migraine. European Neurology.

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2003;49(1):20-9. 12. Connor KM, Aurora SK, Loeys T, Ashina M, Jones C, Giezek H, et al. Long-term tolerability of telcagepant for acute treatment of migraine in a randomized trial. Headache. 2011;51(1):73-84. 13. Dahlof CG, Lipton RB, McCarroll KA, Kramer MS, Lines CR, Ferrari MD. Within-patient consistency of response of rizatriptan for treating migraine. Neurology. 2000;55(10):1511-6. 14. Derosier F, Sheftell F, Silberstein S, Cady R, Ruoff G, Krishen A, et al. Sumatriptan-naproxen and butalbital: a double-blind, placebo-controlled crossover study. Headache. 2012;52(4):530-43. 15. Dib M, Massiou H, Weber M, Henry P, Garcia-Acosta S, Bousser MG, et al. Efficacy of oral ketoprofen in acute migraine: a double-blind randomized clinical trial. Neurology. 2002;58(11):1660-5. 16. Diclofenac-K/Sumatriptan Migraine Study Group. Acute treatment of migraine attacks: efficacy and safety of a nonsteroidal anti-inflammatory drug, diclofenac-potassium, in comparison to oral sumatriptan and placebo. The Diclofenac-K/Sumatriptan Migraine Study Group. Cephalalgia. 1999;19(4):232-40. 17. Diener HC, Bussone G, de LH, Eikermann A, Englert R, Floeter T, et al. Placebo-controlled comparison of effervescent acetylsalicylic acid, sumatriptan and ibuprofen in the treatment of migraine attacks. Cephalalgia. 2004;24(11):947-54. 18. Diez FI, Straube A, Zanchin G. Patient preference in migraine therapy. A randomized, open-label, crossover clinical trial of acute treatment of migraine with oral almotriptan and rizatriptan. Journal of Neurology. 2007;254(2):242-9. 19. Dowson A. Can oral 311C90, a novel 5-HT1D agonist, prevent migraine headache when taken during an aura? European Neurology. 1996;36 Suppl 2:28-31, 1996.:31. 20. Dowson A, Ball K, Haworth D. Comparison of a fixed combination of domperidone and (Domperamol) with sumatriptan 50 mg in moderate to severe migraine: a randomised UK primary care study. Current Medical Research and Opinion. 2000;16(3):190-7. 21. Dowson A, Bundy M, Salt R, Kilminster S. Patient preference for triptan formulations: a prospective study with zolmitriptan. Headache. 2007;47(8):1144-51. 22. Dowson AJ, Charlesworth BR, Purdy A, Becker WJ, Boes-Hansen S, Farkkila M. Tolerability and consistency of effect of zolmitriptan nasal spray in a long-term migraine treatment trial. CNS Drugs. 2003;17(11):839-51. 23. Dowson AJ, Massiou H, Aurora SK. Managing migraine experienced by patients who self-report with menstrually related migraine: a prospective, placebo-controlled study with oral sumatriptan. J headache pain. 2005;6(2):81-7. 24. Facchinetti F, Allais G, Nappi RE, Gabellari IC, Di Renzo GC, Genazzani AR, et al. Sumatriptan (50 mg tablets vs. 25 mg suppositories) in the acute treatment of menstrually related migraine and oral contraceptive- induced menstrual migraine: a pilot study. Gynecological Endocrinology. 2010;26(10):773-9. 25. Facchinetti F, Bonellie G, Kangasniemi P, Pascual J, Shuaib A. The efficacy and safety of subcutaneous sumatriptan in the acute treatment of menstrual migraine. The Sumatriptan Menstrual Migraine Study Group. Obstetrics and Gynecology. 1995;86(6):911-6. 26. Geraud G, Olesen J, Pfaffenrath V, Tfelt-Hansen P, Zupping R, Diener HC, et al. Comparison of the efficacy of zolmitriptan and sumatriptan: issues in migraine trial design. Cephalalgia. 2000;20(1):30-8. 27. Goadsby PJ, Zagami AS, Donnan GA, Symington G, Anthony M, Bladin PF, et al. Oral sumatriptan in acute migraine. Lancet. 1991;338(8770):782-3. 28. Goldstein J, Ryan R, Jiang K, Getson A, Norman B, Block GA, et al. Crossover comparison of rizatriptan 5 mg

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and 10 mg versus sumatriptan 25 mg and 50 mg in migraine. Rizatriptan Protocol 046 Study Group. Headache. 1998;38(10):737-47. 29. Gruffydd-Jones K, Hood CA, Price DB. A within-patient comparison of subcutaneous and oral sumatriptan in the acute treatment of migraine in general practice. Cephalalgia. 1997;17(1):31-6. 30. Kolodny A, Polis A, Battisti WP, Johnson-Pratt L, Skobieranda F, Rizatriptan P. Comparison of rizatriptan 5 mg and 10 mg tablets and sumatriptan 25 mg and 50 mg tablets. Cephalalgia. 2004;24(7):540-6. 31. Lainez MJ, Evers S, Kinge E, Allais G, Allen C, Rao NA, et al. Preference for rizatriptan 10-mg wafer vs. eletriptan 40-mg tablet for acute treatment of migraine. Cephalalgia. 2006;26(3):246-56. 32. Lainez MJ, Galvan J, Heras J, Vila C. Crossover, double-blind clinical trial comparing almotriptan and ergotamine plus caffeine for acute migraine therapy. European Journal of Neurology. 2007;14(3):269-75. 33. Lampl C, Huber G, Haas S, Rittberger E, Diener HC. Difference in triptan effect in patients with migraine and early allodynia. Cephalalgia. 2008;28(10):1031-8. 34. Landy SH, McGinnis JE, McDonald SA. Pilot study evaluating preference for 3-mg versus 6-mg subcutaneous sumatriptan. Headache. 2005;45(4):346-9. 35. Lines CR, Vandormael K, Malbecq W. A comparison of visual analog scale and categorical ratings of headache pain in a randomized controlled clinical trial with migraine patients. Pain. 2001;93(2):185-90. 36. Lipton RB, Stewart WF, Cady R, Hall C, O'Quinn S, Kuhn T, et al. 2000 Wolfe Award. Sumatriptan for the range of headaches in migraine sufferers: results of the Spectrum Study. Headache. 2000;40(10):783-91. 37. Loder E, Brandes JL, Silberstein S, Skobieranda F, Bohidar N, Wang L, et al. Preference comparison of rizatriptan ODT 10-mg and sumatriptan 50-mg tablet in migraine. Headache. 2001;41(8):745-53. 38. Loder E, Silberstein SD, Abu-Shakra S, Mueller L, Smith T. Efficacy and tolerability of oral zolmitriptan in menstrually associated migraine: a randomized, prospective, parallel-group, double-blind, placebo-

controlled study. Headache. 2004;44(2):120-30. 39. Mathew NT. Almotriptan increases pain-free status in patients with acute migraine treated in placebo- controlled clinical trials. Headache. 2002;42 Suppl 1:32-7. 40. Mathew NT, Asgharnejad M, Peykamian M, Laurenza A. Naratriptan is effective and well tolerated in the acute treatment of migraine. Results of a double-blind, placebo-controlled, crossover study. The Naratriptan S2WA3003 Study Group. Neurology. 1997;49(6):1485-90. 41. Mathew NT, Kailasam J, Gentry P, Chernyshev O. Treatment of nonresponders to oral sumatriptan with zolmitriptan and rizatriptan: a comparative open trial. Headache. 2000;40(6):464-5. 42. Mathew NT, Landy S, Stark S, Tietjen GE, Derosier FJ, White J, et al. Fixed-dose sumatriptan and naproxen in poor responders to triptans with a short half-life. Headache. 2009;49(7):971-82. 43. Mauskop A, Farkkila M, Hering-Hanit R, Rapoport A, Warner J. Zolmitriptan is effective for the treatment of persistent and recurrent migraine headache. Current Medical Research and Opinion. 1999;15(4):282-9. 44. Mei D, Ferraro D, Zelano G, Capuano A, Vollono C, Gabriele C, et al. and triptans revert chronic migraine with overuse to episodic migraine. Clinical Neuropharmacology. 2006;29(5):269-75. 45. Mitsikostas DD, Vikelis M, Kodounis A, Zaglis D, Xifaras M, Doitsini S, et al. Migraine recurrence is not associated with depressive or anxiety symptoms. Results of a randomized controlled trial. Cephalalgia. 2010;30(6):690-5. 46. Padma MV, Jain S, Maheshwari MC, Misra S, Karak B, Singh AK, et al. Efficacy and tolerability of oral Sumatriptan in Indian patients with acute migraine; a multicentre study. Neurology India. 1998;46(2):105-8.

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47. Pascual J, Bussone G, Hernandez JF, Allen C, Vrijens F, Patel K, et al. Comparison of preference for rizatriptan 10-mg wafer versus sumatriptan 50-mg tablet in migraine. European Neurology. 2001;45(4):275- 83. 48. Pini LA, Guerzoni S, Cainazzo M, Ciccarese M, Prudenzano MP, Livrea P. Comparison of tolerability and efficacy of a combination of paracetamol + caffeine and sumatriptan in the treatment of migraine attack: a randomized, double-blind, double-dummy, cross-over study. J headache pain. 2012;13(8):669-75. 49. Rapoport AM, Ramadan NM, Adelman JU, Mathew NT, Elkind AH, Kudrow DB, et al. Optimizing the dose of zolmitriptan (Zomig, 311C90) for the acute treatment of migraine. A multicenter, double-blind, placebo- controlled, dose range-finding study. The 017 Clinical Trial Study Group. Neurology. 1997;49(5):1210-8. 50. Rapoport AM, Visser WH, Cutler NR, Alderton CJ, Paulsgrove LA, Davis RL, et al. Oral sumatriptan in preventing headache recurrence after treatment of migraine attacks with subcutaneous sumatriptan. Neurology. 1995;45(8):1505-9. 51. Rederich G, Rapoport A, Cutler N, Hazelrigg R, Jamerson B. Oral sumatriptan for the long-term treatment of migraine: clinical findings. Neurology. 1995;45(8 Suppl 7):S15-S20. 52. Russell MB, Holm-Thomsen OE, Rishoj NM, Cleal A, Pilgrim AJ, Olesen J. A randomized double-blind placebo- controlled crossover study of subcutaneous sumatriptan in general practice. Cephalalgia. 1994;14(4):291-6. 53. Ryan, Jr., Diamond S, Giammarco RAM, Aurora SK, Reed RC, Fletcher PE. Efficacy of zolmitriptan at early time-points for the acute treatment of migraine and treatment of recurrence: a randomised, placebo- controlled trial. CNS Drugs. 2000;13(3):215-26. 54. Ryan RE, Elkind A, Goldstein J. Twenty-four-hour effectiveness of BMS 180048 in the acute treatment of migraine headaches. Headache. 1997;37(4):245-8. 55. Salonen R, Ashford EA, Gibbs M, Hassani H. Patient preference for oral sumatriptan 25 mg, 50 mg, or 100 mg in the acute treatment of migraine: a double-blind, randomized, crossover study. Sumatriptan Tablets S2CM11 Study Group. International Journal of Clinical Practice, Supplement. 1999;105:16-24. 56. Santanello NC, Polis AB, Hartmaier SL, Kramer MS, Block GA, Silberstein SD. Improvement in migraine- specific quality of life in a clinical trial of rizatriptan. Cephalalgia. 1997;17(8):867-72. 57. Savi L, Omboni S, Lisotto C, Sances G, Zanchin G, Ferrari MD. Efficacy of frovatriptan in the acute treatment of menstrually-related migraine: Analysis of a double-blind, Randomized, Multicenter, Comparative study vs. Rizatriptan. Cephalalgia. 2011;31 Suppl 1:77-8. 58. Savi L, Omboni S, Lisotto C, Zanchin G, Ferrari MD, Zava D, et al. Efficacy of frovatriptan in the acute treatment of menstrually related migraine: analysis of a double-blind, randomized, cross-over, multicenter, Italian, comparative study versus rizatriptan. J headache pain. 2011;12(6):609-15. 59. Savi L, Omboni S, Lisotto C, Zanchin G, Ferrari MD, Zava D, et al. A double-blind, randomized, multicenter, Italian study of frovatriptan versus rizatriptan for the acute treatment of migraine. J headache pain. 2011;12(2):219-26. 60. Schoenen J, Pascual J, Rasmussen S, Sun W, Sikes C, Hettiarachchi J. Patient preference for eletriptan 80 mg versus subcutaneous sumatriptan 6 mg: results of a crossover study in patients who have recently used subcutaneous sumatriptan. European Journal of Neurology. 2005;12(2):108-17. 61. Seeburger JL, Cady RK, Winner P, MacGregor A, Valade D, Ge Y, et al. Rizatriptan for treatment of acute migraine in patients taking topiramate for migraine prophylaxis. Headache. 2012;52(1):57-67. 62. Seeburger JL, Taylor F, Newman L, Friedman D, Ge YJ, Zhang Y, et al. Efficacy and tolerability of rizatriptan for the treatment of acute migraine in sumatriptan non-responders. HeadacheConference: 52nd Annual

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Scientific Meeting of the American Headache Society Los Angeles, CA United StatesConference Start: 20100624 Conference End: 20100627Conference Publication: (varpagings)50 ()(pp 74), 2010Date of Publication: Augus. 2010. 63. Seeburger JL, Taylor FR, Friedman D, Newman L, Ge Y, Zhang Y, et al. Efficacy and tolerability of rizatriptan for the treatment of acute migraine in sumatriptan non-responders. Cephalalgia. 2011;31(7):786-96. 64. Stronks DL, Tulen JH, Bussmann HB, Mulder LJ, Passchier J. Effects of naratriptan versus naproxen on daily functioning in the acute treatment of migraine: a randomized, double-blind, double-dummy, crossover study. Headache. 2003;43(8):845-52. 65. Touchon J, Bertin L, Pilgrim AJ, Ashford E, Bes A. A comparison of subcutaneous sumatriptan and dihydroergotamine nasal spray in the acute treatment of migraine. Neurology. 1996;47(2):361-5. 66. Tuchman M, Hee A, Emeribe U, Silberstein S. Efficacy and tolerability of zolmitriptan oral tablet in the acute treatment of menstrual migraine. CNS Drugs. 2006;20(12):1019-26. 67. Tullo V, Allais G, Curone M, Ferrari MD, Omboni S, Benedetto C, et al. Frovatriptan versus zolmitriptan for the acute treatment of migraine with aura: a subgroup analysis of a double-blind, randomized, multicenter, Italian study. Neurological Sciences. 2012;33 Suppl 1:S61-S4. 68. Tullo V, Allais G, Ferrari MD, Curone M, Mea E, Omboni S, et al. Frovatriptan versus zolmitriptan for the acute treatment of migraine: a double-blind, randomized, multicenter, Italian study. Neurological Sciences. 2010;31 Suppl 1:S51-S4. 69. Vollono C, Capuano A, Mei D, Ferraro D, Pierguidi L, Evangelista M, et al. Multiple attack study on the available triptans in Italy versus placebo. European Journal of Neurology. 2005;12(7):557-63.

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Excluded Studies n = 210 1. A placebo-controlled study of intranasal sumatriptan for the acute treatment of migraine. The Finnish Sumatriptan Group and the Cardiovascular Clinical Research Group. European Neurology. 1991;31(5):332-8. 2. Treatment of acute with sumatriptan. The Sumatriptan Cluster Headache Study Group. New England Journal of Medicine. 1991;325(5):322-6. 3. A study comparing the efficiency, safety and tolerability of oral sumatriptan 25, 50 and 100 mg doses in the acute treatment of migraine [abstract]. European Journal of Neurology. 1996;3(Suppl 5):149-50. 4. The long-term tolerability and efficacy of oral zolmitriptan (Zomig, 311C90) in the acute treatment of migraine. An international study. The International 311C90 Long-term Study Group. Headache. 1998;38(3):173-83. 5. Sumatriptan + naproxen: Better than either alone for acute migraine? Journal of Family Practice. 2007;56(7):536. 6. Akpunonu BE, Mutgi AB, Federman DJ, Volinsky FG, Brickman K, Davis RL, et al. Subcutaneous sumatriptan for treatment of acute migraine in patients admitted to the emergency department: a multicenter study. Annals of Emergency Medicine. 1995;25(4):464-9. 7. Allais G, Acuto G, Benedetto C, D'Andrea G, Grazzi L, Manzoni GC, et al. Evolution of migraine-associated symptoms in menstrually related migraine following symptomatic treatment with almotriptan. Neurological Sciences. 2010;31 Suppl 1:S115-9, 2010 Jun.:9. 8. Allais G, D'Andrea G, Moschiano F, d'Onofrio F, Valguarnera F, Manzoni G, et al. A randomized, prospective, cross-over, double blind, placebo-controlled multicentre study to assess the efficacy and tolerability of almotriptan 12.5 mg in menstrually-related migraine. Cephalalgia. 2009;29:13. 9. Allais G, Tullo V, Benedetto C, Zava D, Omboni S, Bussone G. Efficacy of frovatriptan in the acute treatment of menstrually related migraine: analysis of a double-blind, randomized, multicenter, Italian, comparative study versus zolmitriptan. Neurological Sciences. 2011;32 Suppl 1:S99-S104. 10. Allais G, Tullo V, Omboni S, Benedetto C, Sances G, Zava D, et al. Efficacy of frovatriptan versus other triptans in the acute treatment of menstrual migraine: pooled analysis of three double-blind, randomized, crossover, multicenter studies. Neurological Sciences. 2012;33 Suppl 1:S65-S9. 11. Anon. Treximet in acute migraine headache: assessing cognitive function. Clinicaltrialsgov [wwwclinicaltrialsgov]. 2009. 12. Aurora SK, Barrodale PM, McDonald SA, Jakubowski M, Burstein R. Revisiting the efficacy of sumatriptan therapy during the aura phase of migraine. Headache. 2009;49(7):1001-4. 13. Azimova I, Tabeeva GR. [Trimigren in stopping migraine attacks: an open prospective multicenter comparative study of rectal suppository and tablet forms of sumatriptan]. Zhurnal nevrologii i psikhiatrii imeni SSKorsakova / Ministerstvo zdravookhraneniia i meditsinsko? promyshlennosti Rossi?sko? Federatsii, Vserossi?skoe obshchestvo nevrologov [i] Vserossi?skoe obshchestvo psikhiatrov. 2009;109(12):71-5. 14. Bakhshayesh B, Seyed Saadat SM, Rezania K, Hatamian H, Hossieninezhad M. A randomized open-label study of sodium vs sumatriptan and metoclopramide for prolonged migraine headache. American Journal of Emergency Medicine. 2013;31(3):540-4. 15. Banks JW, Smith TR, Nicholson RA. A combination of metoclopramide and/or caffeine does not improve the efficacy of frovatriptan in the acute treatment of migraine. CephalalgiaConference: 14th Congress of the International Headache Society Philadelphia, PA United StatesConference Start: 20090910 Conference End: 20090913Conference Publication: (varpagings)29 ()(pp 13-14), 2009Date of Publication: October 20. 2009.

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16. Bell CF, Foley KA, Barlas S, Solomon G, Hu XH. Time to pain freedom and onset of pain relief with rizatriptan 10 mg and prescription usual-care oral medications in the acute treatment of migraine headaches: A multicenter, prospective, open-label, two-attack, crossover study. Clinical Therapeutics. 2006;28(6):872-80. 17. Berges A, Walls C, Lener SE, McDonald SA. and tolerability of sumatriptan after single- dose administration of a fixed-dose combination tablet of sumatriptan/naproxen sodium 85/500 mg followed two hours later by subcutaneous sumatriptan 4- or 6-mg injection: a randomized, open-label, three-period crossover study in healthy volunteers. Clinical Therapeutics. 2010;32(6):1165-77. 18. Bertin L, Brion N, Farkkila M, Gobel H, Wessely P. A dose-defining study of sumatriptan suppositories in the acute treatment of migraine. International Journal of Clinical Practice. 1999;53(8):593-8. 19. Block GA, Goldstein J, Polis A, Reines SA, Smith ME. Efficacy and safety of rizatriptan versus standard care during long-term treatment for migraine. Rizatriptan Multicenter Study Groups. Headache. 1998;38(10):764-71. 20. Block GA, Smith M, Jiang K, Reines S, Teall J. Rizatriptan (MK-0462) for the acute treatment of migraine and migraine recurrence [abstract]. Neurology. 1997;48(3):A68. 21. Boureau F, Chazot G, Emile J. Sumatriptan vs usual acute treatment of migraine [abstract]. Canadian Journal of Neurological Sciences. 1993;20 Suppl 4. 22. Brauneis S, Marzano M, Collini S, Occhigrossi F, Pinto G. [ The administration of sumatriptan in the treatment of migraine and cluster headache. ]. Confin Cephalalgica. 1994;3(4):159-64. 23. Burke R, Pwebster C, Laurenza A, Asgharnejad M. Efficacy of sumatriptan injection for the acute treatment of migraine in a primarily non-caucasian group of patients. Functional Neurology. 1998;2(13):182. 24. Burke-Ramirez P, Asgharnejad M, Webster C, Davis R, Laurenza A. Efficacy and tolerability of subcutaneous sumatriptan for acute migraine: a comparison between ethnic groups. Headache. 2001;41(9):873-82. 25. Burkiewicz JS, Chan JD, Alldredge BK. Eletriptan: 5-HT(1B/1D) receptor agonist for the acute treatment of migraine. Formulary. 2000;35(2):129-41. 26. Bussone G, D'Amico D, McCarroll KA, Gerth W, Lines CR. Restoring migraine sufferers' ability to function normally: a comparison of rizatriptan and other triptans in randomized trials. European Neurology. 2002;48(3):172-7. 27. Cabanas A, Rodriguez R, Rosado F, Cruz A. Subcutaneous sumatriptan comparative study versus placebo in migraine attacks. Journal of the Neurological Sciences. 1997;150 Suppl:S303. 28. Cabarrocas X, Almotriptan Study G. Efficacy and tolerability of subcutaneous almotriptan for the treatment of acute migraine: a randomized, double-blind, parallel-group, dose-finding study. Clinical Therapeutics. 2001;23(11):1867-75. 29. Cady R, Sheftell F, Silberstein S, Derosier FJ, Ruoff G, Krishen A, et al. Rescue medication use in a crossover study to evaluate efficacy of a single fixed-dose tablet of sumatriptan and naproxen sodium (sumaRT/Nap) versus butalbital-containing combination medication (BCM) and placebo (PLA) for migraine headache. HeadacheConference: 52nd Annual Scientific Meeting of the American Headache Society Los Angeles, CA United StatesConference Start: 20100624 Conference End: 20100627Conference Publication: (varpagings)50 ()(pp 10-11), 2010Date of Publication: Au. 2010. 30. Cady RC, Ryan R, Jhingran P, Pait G, Watson C, Batenhorst A. Sumatriptan injection reduces productivity loss during a migraine attack: results of a double-blind, placebo-controlled trial. Neurology. 1997;48(3):A121. 31. Cady RK, Dexter J, Sargent JD, Galer B. Sumatriptan for repeated episodes of migraine. Annals of Internal Medicine. 1993;119(Suppl 3):72.

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32. Cady RK, Dexter J, Sargent JD, Markley H, Osterhaus JT, Webster CJ. Efficacy of subcutaneous sumatriptan in repeated episodes of migraine. Neurology. 1993;43(7):1363-8. 33. Cady RK, Diamond ML, Diamond MP, Ballard JE, Lener ME, Dorner DP, et al. Sumatriptan-naproxen sodium for menstrual migraine and dysmenorrhea: satisfaction, productivity, and functional disability outcomes. Headache. 2011;51(5):664-73. 34. Cady RK, Freitag FG, Mathew NT, Elkind AH, Mao L, Fisher AC, et al. Allodynia-associated symptoms, pain intensity and time to treatment: predicting treatment response in acute migraine intervention. Headache. 2009;49(3):350-63. 35. Cady RK, Lipton RB, Hall C, Stewart WF, O'Quinn S, Gutterman D. Treatment of mild headache in disabled migraine sufferers: results of the Spectrum Study. Headache. 2000;40(10):792-7. 36. Cady RK, Rubino J, Crummett D, Littlejohn TW, III. Oral sumatriptan in the treatment of recurrent headache. Archives of Family Medicine. 1994;3(9):766-72. 37. Cady RK, Voirin J, Farmer K, Browning R, Beach ME, Tarrasch J. Two center, randomized pilot study of migraine prophylaxis comparing paradigms using pre-emptive frovatriptan or daily topiramate: research and clinical implications. Headache. 2012;52(5):749-64. 38. Cady RK, Wendt JK, Kirchner JR, Sargent JD, Rothrock JF, Skaggs H, Jr. Treatment of acute migraine with subcutaneous sumatriptan. JAMA. 1991;265(21):2831-5. 39. Campbell J, Harper S, Hu X. Acute migraine therapy with frovatriptan vs. Sumatriptan: Comparison based on sustained pain-free response with no adverse events. CephalalgiaConference: 14th Congress of the International Headache Society Philadelphia, PA United StatesConference Start: 20090910 Conference End: 20090913Conference Publication: (varpagings)29 ()(pp 18-19), 2009Date of Publication: October 20. 2009. 40. Centonze V, Polito MB, Bari M, Fabbri L, Cassiano MA, Bassi A, et al. [Evaluation of the efficacy of oral sumatriptan in the management of migraine attacks. Clinical results]. La Clinica terapeutica. 1995;146(11):721-8. 41. Cerritelli F, Emanuele C, Marcello DV, Luca M, Rina GL, Gabriella M. Is osteopathic manipulative treatment effective in migraine? International Journal of Osteopathic Medicine.16(1):e15-e6. 42. Chatterjee A, Almas M. Migraine attacks during menses: Efficacy of eletriptan and relationship to recurrence after response. NeurologyConference: 64th American Academy of Neurology Annual Meeting New Orleans, LA United StatesConference Start: 20120421 Conference End: 20120428Conference Publication: (varpagings)78 (1 Meeting Abstract) , 2012Date of Publication: 22 Apr. 2012(var.pagings). 43. Chen J, Jiang XG, Jiang WM, Gao XL, Mei N. Intranasal absorption of rizatriptan--in vivo pharmacokinetics and study in humans. Pharmazie. 2005;60(1):39-41. 44. Conner SJ, Rideout S. What are the best therapies for acute migraine in pregnancy? Journal of Family Practice. 2005;54(11):992+5. 45. Cortelli P, Allais G, Tullo V, Benedetto C, Zava D, Omboni S, et al. Frovatriptan versus other triptans in the acute treatment of migraine: pooled analysis of three double-blind, randomized, cross-over, multicenter, Italian studies. Neurological Sciences. 2011;32 Suppl 1:S95-8, 2011 May.:8. 46. Couch JR, Jr., Saper J, Meloche JP. Treatment of migraine with BMS180048: response at 2 hours. North American BMS180048 Study Group. Headache. 1996;36(9):523-30. 47. Creac'H C, Frappe P, Cancade M, Laurent B, Peyron R, Demarquay G, et al. In-patient versus out-patient withdrawal programmes for medication overuse headache: A 2-year randomized trial. Cephalalgia. 2011;31(11):1189-98.

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migraine. Functional Neurology. 1998;2(13):179. 174. Salonen R, Ashford E, Dahlof C, Dawson R, Gilhus NE, Luben V, et al. Intranasal sumatriptan for the acute treatment of migraine. International Intranasal Sumatriptan Study Group. Journal of Neurology. 1994;241(8):463-9. 175. Salonen R, Ashford E, Dahlof C, Dawson R, Gilhus NE, Luben V, et al. Intranasal sumatriptan for the acute treatment of migraine. Journal of Neurology. 1994;241(8):463-9. 176. Sang CN, Ramadan NM, Wallihan RG, Chappell AS, Freitag FG, Smith TR, et al. LY293558, a novel AMPA/GluR5 antagonist, is efficacious and well-tolerated in acute migraine. Cephalalgia. 2004;24(7):596- 602. 177. Sargent J, Kirchner JR, Davis R, Kirkhart B. Oral sumatriptan is effective and well tolerated for the acute treatment of migraine: results of a multicenter study. Neurology. 1995;45(8 Suppl 7):S10-S4. 178. Schoenen J, Bulcke J, Caekebeke J, Dehaene I, Keyser J, Hildebrand G, et al. Self-treatment of acute migraine with subcutaneous sumatriptan using an auto-injector device: comparison with customary treatment in an open, longitudinal study. Cephalalgia. 1994;14(1):55-63. 179. Schoenen J, De KN, Giurgea S, Herroelen L, Jacquy J, Louis P, et al. Almotriptan and its combination with aceclofenac for migraine attacks: a study of efficacy and the influence of auto-evaluated brush allodynia. Cephalalgia. 2008;28(10):1095-105. 180. Scholpp J, Schellenberg R, Moeckesch B, Banik N. Early treatment of a migraine attack while pain is still mild increases the efficacy of sumatriptan. Cephalalgia. 2004;24(11):925-33. 181. Schulman E, O'Neill C, Pierce M, Griesser J, Angelov AS. Efficacy of Zelrix, a novel iontophoretic transdermal sumatriptan patch, in the treatment of acute migraine in patients with nausea. HeadacheConference: 52nd Annual Scientific Meeting of the American Headache Society Los Angeles, CA United StatesConference Start: 20100624 Conference End: 20100627Conference Publication: (varpagings)50 ()(pp 27-28), 2010Date of Publication: Au. 2010. 182. Schulman EA, Dermott KF. Sumatriptan plus metoclopramide in triptan-nonresponsive migraineurs. Headache. 2003;43(7):729-33. 183. Seeburger JL, Cady RK, Winner P, MacGregor A, Valade D, Ge Y, et al. Efficacy and tolerability of rizatriptan for the treatment of acute migraine in patients taking topiramate for migraine prophylaxis. HeadacheConference: 52nd Annual Scientific Meeting of the American Headache Society Los Angeles, CA United StatesConference Start: 20100624 Conference End: 20100627Conference Publication: (varpagings)50 ()(pp 33), 2010Date of Publication: Augus. 2010. 184. Siegel SJ, O'Neill C, Dube LM, Kaldeway P, Morris R, Jackson D, et al. A unique iontophoretic patch for optimal transdermal delivery of sumatriptan. Pharmaceutical Research. 2007;24(10):1919-26. 185. Silberstein S GJ, Mannix LK, Sheftell F, Byrd S,, al. AMe. A new migraine therapy: efficacy and tolerability of a fixed single-tablet formulation of sumatriptan RT Technology™ and naproxen sodium in the early intervention paradigm. Headache 2006; 46:833 [Abstract]. 2006. 186. Silberstein SD, Massiou H, McCarroll KA, Lines CR. Further evaluation of rizatriptan in menstrual migraine: retrospective analysis of long-term data. Headache. 2002;42(9):917-23. 187. Smelt AF, Blom JW, Dekker F, van den Akker ME, Knuistingh NA, Zitman FG, et al. A proactive approach to migraine in primary care: a pragmatic randomized controlled trial. Canadian Medical Association Journal. 2012;184(4):E224-E31. 188. Solbach MP, Waymer RS. Treatment of menstruation-associated migraine headache with subcutaneous

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sumatriptan. Obstetrics and Gynecology. 1993;82(5):769-72. 189. Solomon GD, Cady RK, Klapper JA. 2.5 mg 311C90 (zomig, zolmitriptan) is clinically effective in treating migraine: clinical efficacy and improvement in activity [abstract]. Neurology. 1997;48(3):A67. 190. Spierings EL, Keywood C. Rapid responders to frovatriptan in acute migraine treatment: results from a long- term, open-label study. Pain Medicine. 2009;10(4):633-8. 191. Sramek JJ, Hussey EK, Clements B, Cutler NR. Oral sumatriptan pharmacokinetics in the migraine state. Clinical Drug Investigation. 1999;17(2):137-44. 192. Syrett N, Abu-Shakra S, Yates R. Zolmitriptan nasal spray: advances in migraine treatment. Neurology. 2003;61(8 Suppl 4):S27-S30. 193. Taylor FR, Seeburger JL, Newman L, Friedman D, Ge Y, Zhang Y, et al. Efficacy of rizatriptan for the treatment of acute migraine in sumatriptan non-responders. Journal of Headache and PainConference: 2nd European Headache and Migraine Trust International Congress - EHMTIC Nice FranceConference Start: 20101028 Conference End: 20101031Conference Publication: (varpagings)11 ()(pp S97), 2010Date of Public. 2010. 194. Tazaki Y, Sakai F, Tashiro K, Hirai S, Goto F, Maruyama S, et al. [Clinical Evaluation of SN-308 (Sumatriptan) Tablet on Migraine: Dose Finding Study by Double-Blind Cross-Over Method]. Rinsho Iyaku (Journal of Clinical Therapeutics and Medicines). 1997;13(21):5567-94. 195. Tazaki Y, Sakai F, Tashiro K, Hirai S, Maruyama S, Goto F, et al. [Study on Clinical Usefulness of SN-308 (Sumatriptan) Subcutaneous Injection in Migraine: Dose Finding Study by Envelope Method]. Rinsho Iyaku (Journal of Clinical Therapeutics and Medicines). 1993;9(5):1077-93. 196. Tepper SJ, Millson DS. Zolmitriptan (Zomig, 311C90) is efficacious in migraine on awakening. Journal of the Neurological Sciences. 1997;150 Suppl:S106. 197. Tfelt-Hansen P. The effectiveness of combined oral lysine acetylsalicylate and metoclopramide (Migpriv) in the treatment of migraine attacks. Comparison with placebo and oral sumatriptan. Functional Neurology. 2000;15 Suppl 3:196-201. 198. Tfelt-Hansen P, Goadsby PJ. Naratriptan is effective and well tolerated in the acute treatment of migraine [comment]. Neurology. 1999;52(6):1300-1. 199. Tfelt-Hansen P, Henry P, Mulder LJ, Scheldewaert RG, Schoenen J, Chazot G. [The combination of oral lysine- acetylsalicylate and metoclopramide compared with oral sumatriptan in the treatment of migraine attacks. A randomized, double-blind, placebo-controlled clinical trial]. Ugeskrift for Laeger. 1996;158(45):6435-9. 200. Tietjen GE, Athanas K, Utley C, Herial NA, Khuder SA. The combination of naratriptan and prochlorperazine in migraine treatment. Headache. 2005;45(6):751-3. 201. Utiger D, Eichenberger U, Bernasch D, Baumgartner RW, Bartsch P. Transient minor improvement of high altitude headache by sumatriptan. High Alt Med Biol. 2002;3(4):387-93. 202. Valade D, Seeburger JL, Cady RK, Winner P, MacGregor A, Ge Y, et al. Rizatriptan treatment of acute migraine in patients taking Topiramate for migraine prophylaxis. Journal of Headache and PainConference: 2nd European Headache and Migraine Trust International Congress - EHMTIC Nice FranceConference Start: 20101028 Conference End: 20101031Conference Publication: (varpagings)11 ()(pp S97), 2010Date of Public. 2010. 203. Visser WH, Ferrari MD, Bayliss EM, Ludlow S, Pilgrim AJ. Treatment of migraine attacks with subcutaneous sumatriptan: first placebo-controlled study. The Subcutaneous Sumatriptan International Study Group. Cephalalgia. 1992;12(5):308-13. 204. Visser WH, Jiang K. Effect of rizatriptan versus sumatriptan on migraine associated symptoms [abstract].

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Neurology. 1998;50(4 Suppl 4):A375. 205. Visser WH, Klein KB, Cox RC, Jones D, Ferrari MD. 311C90, a new central and peripherally acting 5-HT1D receptor agonist in the acute oral treatment of migraine: a double-blind, placebo-controlled, dose-range finding study. Neurology. 1996;46(2):522-6. 206. Wells NE, Steiner TJ. Effectiveness of eletriptan in reducing time loss caused by migraine attacks. PharmacoEconomics. 2000;18(6):557-66. 207. Wendt J, Cady R, Singer R, Peters K, Webster C, Kori S, et al. A randomized, double-blind, placebo-controlled trial of the efficacy and tolerability of a 4-mg dose of subcutaneous sumatriptan for the treatment of acute migraine attacks in adults. Clinical Therapeutics. 2006;28(4):517-26. 208. Wilkinson M. L-ASA compared to sumatriptan and parenteral placebo in the acute treatment of migraine. Cephalalgia. 1999;19(6):542. 209. Winner P, Ricalde O, Le FB, Saper J, Margul B. A double-blind study of subcutaneous dihydroergotamine vs subcutaneous sumatriptan in the treatment of acute migraine. Archives of Neurology. 1996;53(2):180-4. 210. Zhao YB, Zhang GP, Chen QT, Han DL, Ma XP. [A clinical trial with sumatriptan in patients with acute migraine]. The Chinese Journal of Clinical Pharmacology. 1994;10(3):143-7.

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Appendix D: Detailed Trial Characteristics

Reference Study Details Patients Intervention Outcomes

Ahrens 1999 Study Design: Patient Group: Placebo:wafer Efficacy: p525 RCT o Headache relief within 2 hours Parallel Placebo: Rizatriptan 5mg: wafer o Freedom from pain within 2 Age (mean): 41.6 hours N % Female: 91 Rizatriptan 10mg: wafer o Functional health status Placebo: 185 o Recurrence Rizatriptan 5mg: On experiencing a moderate or severe o Rescue medication Rizatriptan 5mg: Age (mean): 42.7 migraine headache that was not resolving Safety: 182 % Female: 84 spontaneously and provided they had not o Participants with any serious taken any prohibited medications adverse event Rizatriptan 10mg: Rizatriptan 10mg: (monoamine oxidase inhibitors o Withdrawals due to adverse 188 Age (mean): 43.1 any ergot derivative opiate or events % Female: 90 sumatriptan within 24 h antiemetics or any other form of analgesia within 6 h; Menstrual within 1 h) patients were migraine: No instructed to place the wafer on the tongue and to allow it to dissolve prior to swallowing. Banerjee 1992 Study Design: Patient Group: Placebo: oral tablet Efficacy: p39 RCT Age (mean): 35 o Headache relief within 2 hours Parallel % Female: 85 Sumatriptan:200mg oral tablet o Freedom from pain within 2 hours N Placebo: Each patient treated up to three attacks o Rescue medication Placebo: 39 Age (mean): NR with study medication within a period of Safety: % Female: NR three months. The patient was instructed to o Participants with any adverse Sumatriptan take the study medication as the first event 200mg: 37 Sumatriptan treatment as soon as s/he recognized an o Participants with any serious 200mg: attack of migraine with aura. adverse event Age (mean): NR o Withdrawals due to adverse % Female: NR events

Menstrual migraine: No

Barbanti 2012 Study Design: Patient Group: Rizatriptan 10mg: 10mg oral tablet Efficacy: p407 RCT o Headache relief within 2 hours Parallel Rizatriptan 10mg: Placebo:oral tablet o Freedom from pain within 2 Age (mean): 43.95 hours N % Female: 80 Patients were encouraged to take migraine o Sustained headache response Rizatriptan 10mg: medication as soon as their migraine at 24 hours 41 Placebo: headache became moderate or severe. o Sustained freedom from pain Age (mean): 41.41 at 24 hours Placebo: 39 % Female: 87 o Recurrence o Rescue medication Menstrual Safety: migraine: No o Participants with any adverse event o Participants with any serious adverse event

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Reference Study Details Patients Intervention Outcomes

Bates 1994 Study Design: Patient Group: Sumatriptan: 6mg subcutaneous injection Efficacy: p1587 RCT o Headache relief within 2 hours Parallel Sumatriptan 6mg: Placebo:matching placebo o Recurrence Age (mean): 40 Safety: N years The study medication was administered o Participants with any adverse Sumatriptan % Female: 72 using a novel cartridge-system self- event 6mg: 90 injector.I6 The device delivered the contents o Participants with any serious Placebo: of a 0.5-ml prefilled syringe as a adverse event Placebo: 87 Age (mean): 40 subcutaneous injection. At the onset of o Withdrawals due to adverse years aura, patients received either 6 mg events % Female: 75 subcutaneous sumatriptan or matching placebo (double-blind). Menstrual migraine: No Bomhof 1999 Study Design: Patient Group: Rizatriptan 10mg:10mg tablet Efficacy: p173 RCT o Headache relief within 2 hours Parallel Rizatriptan Naratriptan 2.5mg: 2.5mg tablet o Freedom from pain within 2 10mg:Age (mean): hours N 38.9 Placebo: tablets o Functional health status Rizatriptan 10mg: % Female: 87 o Recurrence 201 Patients took a single dose of study o Rescue medication Naratriptan medication for a migraine headache that Safety: Naratriptan 2.5mg: was not resolving spontaneously and was of o Participants with any adverse 2.5mg: 214 Age (mean): 39.5 moderate or severe intensity on a 4-point event % Female: 82 headache severity scale. o Participants with any serious Placebo: 107 adverse event Placebo: o Withdrawals due to adverse Age (mean): 39.1 events % Female: 81

Menstrual migraine: No Bousser 1993 Study Design: Patient Group: Sumatriptan: 12mg ml-1subcutaneous Efficacy: p211 RCT injection o Headache relief within 2 hours Crossover Sumatriptan: o Freedom from pain within 2 Age (mean): 43 Placebo: Placebo as isotonic saline was hours N % Female: 73.5 provided in identical syringe o Recurrence Sumatriptan: 49 o Rescue medication Placebo: The patient was asked to perform a first Safety: Placebo: 47 Age (mean): 39 injection of 6 mg sumatriptan or placebo o Withdrawals due to adverse % Female: 87.8 when awakening with an early-morning events migraine attack. Between 1-24 h later, a Menstrual second optional identical injection was migraine: No firmly recommended for patients who were not pain-free and from 2-24 h after the first dose. Brandes 2005 Study Design: Patient Group: Eletriptan 20mg: 20mg oral tablet Efficacy: p735 RCT o Freedom from pain within 2 Parallel Eletriptan 20mg: Eletriptan 40mg: 40mg oral tablet hours Age (mean): 39.1 o Sustained headache response N % Female: 79 Placebo: Placebo oral tablets at 24 hours Eletriptan 20mg: o Functional health status 183 Group 2 Patients were instructed to take study o Recurrence Age (mean): 38.7 medication as soon as they were sure they o Rescue medication Eletriptan 40mg: % Female: 83 were experiencing a typical migraine Safety: 207 headache, and after the aura phase (if o Participants with any serious Group 3 present) had ended. Patients were adverse event Placebo: 203 Age (mean): 39.1 encouraged, but not required, to take study % Female: 85 medication when headache pain was mild.

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Brandes 2007 Study Design: Patient Group: Sumatriptan/Naproxen Sodium:85mg Efficacy: p1443 – Study RCT sumatriptan tablet + 500mg Naproxen o Headache relief within 2 hours 1 Parallel Sumatriptan/ Sodium tablet o Freedom from pain within 2 Naproxen hours N SodiumAge Sumatriptan: 85mg tablet o Sustained headache response Sumatriptan + (mean): 40.3 at 24 hours Naproxen % Female: 87 Naproxen Sodium: 500mg tablet o Sustained freedom from pain Sodium: 370 at 24 hours Sumatriptan: Placebo: Placebo tablets o Recurrence Sumatriptan: 365 Age (mean): 40.1 o Rescue medication % Female: 86 Patients were instructed to treat a migraine Safety: Naproxen attack with study medication when pain o Participants with any adverse Sodium: 361 Naproxen Sodium: intensity was moderate or severe. Patients event Age (mean): 39.4 were to treat a migraine within 6 weeks of o Participants with any serious Placebo: 365 % Female: 86 the screening visit. adverse event

Placebo: Age (mean): 40.0 % Female: 84

Menstrual migraine: No Brandes 2007 Study Design: Patient Group: Sumatriptan/Naproxen Sodium: 85mg Efficacy: p1443 – Study RCT sumatriptan tablet + 500mg Naproxen o Headache relief within 2 hours 2 Parallel Sumatriptan/ Sodium tablet o Freedom from pain within 2 Naproxen Sodium: hours N Age (mean): 39.4 Sumatriptan: 85mg tablet o Sustained headache response Sumatriptan + years at 24 hours Naproxen % Female: 87% Naproxen Sodium: 500mg tablet o Sustained freedom from pain Sodium: 367 at 24 hours Sumatriptan: Placebo: Placebo tablets o Recurrence Sumatriptan: 370 Age (mean): 40.3 o Rescue medication years Patients were instructed to treat a migraine Safety: Naproxen % Female: 87% attack with study medication when pain o Participants with any adverse Sodium: 371 intensity was moderate or severe. Patients event Naproxen Sodium: were to treat a migraine within 6 weeks of o Participants with any serious Placebo: 387 Age (mean): 40.4 the screening visit. adverse event years % Female: 89%

Placebo: Age (mean): 40.6 years % Female: 89%

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Bussone 2000 Study Design: Patient Group: Sumatriptan:50mg oraltablet Efficacy: p272 RCT Age (mean): 37 o Headache relief within 2 hours Crossover % Female: 79 Placebo: oral tablet o Freedom from pain within 2 hours N Sumatriptan Patients were instructed to take the study o Headache relief within 4 hours Sumatriptan 50mg: medication for the next four attacks. Safety: 50mg: 147 Age (mean): NR o Participants with any serious % Female: NR adverse event Placebo: 53 Placebo: Age (mean): NR % Female: NR

Menstrual migraine: No

Cady 1998 Study Design: Patient Group: Sumatriptan:6mg injection Efficacy: p1013 RCT o Headache relief within 2 hours Parallel Sumatriptan: Placebo: Matching placebo o Functional health status Age (mean): 40.6 o Recurrence N % Female: 85 Patients treated the first migraine occurring o Rescue medication Sumatriptan: 67 after the screening visit with their usual Safety: Placebo: (nonsumatriptan) medication. Patients were o Participants with any adverse Placebo: 68 Age (mean): 39.3 randomized 1:1 during this visit to use event % Female: 85 sumatriptan injection (6mg) or matching o Withdrawals due to adverse placebo in the workplace to treat a events Menstrual moderate or severe migraine occurring migraine: No within the first 4 hours of a minimum 8-hour work shift. Cady 2001 p1 Study Design: Patient Group: Rizatriptan 5mg: wafer Efficacy: RCT o Headache relief within 2 hours Parallel Rizatriptan 5mg: Rizatriptan 10mg:wafer o Freedom from pain within 2 Age (mean): NR hours N % Female: NR Patients took a single dose of study o Sustained headache response Rizatriptan 5mg: medication for a migraine headache that at 24 hours 191 Rizatriptan 10mg: was not resolving spontaneously andwas of o Sustained freedom from pain Age (mean): NR moderate or severe intensity on a 4-grade at 24 hours Rizatriptan 10mg: % Female: NR headache severity scale. o Rescue medication 181 Safety: Menstrual o Participants with any adverse migraine: No event o Participants with any serious adverse event o Withdrawals due to adverse events Cady 2006 Study Design: Patient Group: Rizatriptan: 10mg tablet Efficacy: p914 – Study 1 RCT o Freedom from pain within 2 Parallel Rizatriptan 10mg: Placebo: oral tablet hours Age (mean): 43 o Sustained freedom from pain N % Female: 88.1 A single dose of study medication was used at 24 hours Rizatriptan 10mg: to treat the headache in order to observe o Functional health status 363 Placebo: the impact of a single dose of rizatriptan on o Rescue medication Age (mean): 43 24-hour sustained pain freedom. Safety: Placebo: 179 % Female: 89.3 o Participants with any adverse event Menstrual o Participants with any serious migraine: No adverse event o Withdrawals due to adverse events

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Reference Study Details Patients Intervention Outcomes

Cady 2006 Study Design: Patient Group: Rizatriptan: 10mg oral tablet Efficacy: p914 – Study 2 RCT o Freedom from pain within 2 Parallel Rizatriptan 10mg: Placebo: oral tablet hours Age (mean): 41 o Sustained freedom from pain N % Female: 86.4 A single dose of study medication was used at 24 hours Rizatriptan 10mg: to treat the headache in order to observe o Functional health status 339 Placebo: the impact of a single dose of rizatriptan on o Rescue medication Age (mean): 41 24-hour sustained pain freedom. Safety: Placebo: 173 % Female: 91.1 o Participants with any adverse event Menstrual o Participants with any serious migraine: No adverse event o Withdrawals due to adverse events Cady 2009 Study Design: Patient Group: Rizatriptan 10mg ODT: 10mg orally Efficacy: p687 RCT disintegrating tablet (ODT) o Freedom from pain within 2 Parallel Rizatriptan 10mg hours ODT: Placebo: Matching Placebo o Sustained freedom from pain N Age (mean): 40 at 24 hours Rizatriptan 10mg % Female: 87 Participants treated a single migraine attack o Functional health status ODT: 94 at the earliest time they knew that their Safety: Placebo: headache was a migraine and when the o Participants with any adverse Placebo: 98 Age (mean): 42 headache pain was mild. event % Female: 93 o Participants with any serious adverse event Menstrual o Withdrawals due to adverse migraine: No events Carpay 1997 Study Design: Patient Group: Sumatriptan:100mgfilm-coated tablets Efficacy: p591 RCT o Recurrence Crossover Sumatriptan Subcutaneous sumatriptan: 12mg/mL 100mg: solution in a 0.5mL auto-injector syringe N Age (mean): 37.8 Sumatriptan % Female: 80 Patients were allowed to use sumatriptan at 100mg: 61 an early stage of their migraine, when Subcutaneous headache severity was only mild, but they Subcutaneous sumatriptan: had to be connived that their headache was sumatriptan: 63 Age (mean): 40 a migraine attack. % Female: 83

Menstrual migraine: No Carpay 2004 Study Design: Patient Group: Sumatriptan:50mg tablets Efficacy: p214 RCT o Freedom from pain within 2 Parallel Sumatriptan Sumatriptan: 100mg tablets hours 50mg: o Sustained freedom from pain N Age (mean): 41.5 Placebo: Placebo tablets at 24 hours Sumatriptan % Female: 83.2 Safety: 50mg: 137 They were instructed to treat a migraine o Participants with any adverse Sumatriptan attack within 1 hour of the onset of mild event Sumatriptan 100mg: pain and to treat only while pain was mild. o Participants with any serious 100mg: 142 Age (mean): 39.7 adverse event % Female: 85.9 o Withdrawals due to adverse Placebo: 153 events Placebo: Age (mean): 40.6 % Female: 79.7

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Charlesworth Study Design: Patient Group: Zolmitriptan 5mg: nasal spray Efficacy: 2003 p653 RCT o Headache relief within 2 hours Parallel Zolmitriptan 5mg: Zolmitriptan 2.5mg (spray): nasal spray o Freedom from pain within 2 Age (mean): 40.8 hours N % Female: 84.7 Zolmitriptan 1mg: nasal spray o Headache relief within 4 hours Zolmitriptan o Freedom from pain within 4 5mg: 236 Zolmitriptan Zolmitriptan 2.5mg (oral): oral tablet o Sustained headache response 2.5mg (spray): at 24 hours Zolmitriptan Age (mean): 40.7 Placebo:Placebo o Functional health status 2.5mg (spray): % Female: 76.8 o Recurrence 224 Patients were instructed to treat moderate o Rescue medication Zolmitriptan 1mg: or severe migraine headaches with the Safety: Zolmitriptan Age (mean):39.8 study medication to treat the migraine o Participants with any adverse 1mg: % Female: 86.9 within 12 hours of onset and not to sleep event 238 between administration and the 4 hour post o Participants with any serious Zolmitriptan dose assessment period. adverse event Zolmitriptan 2.5mg (oral): o Withdrawals due to adverse 2.5mg (oral): 233 Age (mean):41.5 events % Female: 82.2 Placebo: 228 Placebo: Age (mean): 40.2 % Female: 86.3

Menstrual migraine: Menstrual subgroup data is only available for 2 attacks combined. Colman 2001 Study Design: Patient Group: Almotriptan: 12.5mg capsules Efficacy: p127 RCT o Headache specific QOL Parallel Almotriptan Sumatriptan: 50mg capsules o Functional health status 12.5mg: N Age (mean): 41.25 The first dose of study medication was Almotriptan % Female: 89 taken at the onset of a moderate or severe 12.5mg: 591 migraine. Sumatriptan Sumatriptan 50mg: 50mg: 582 Age (mean): 40.26 % Female: 89

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Cull 1997 p490 Study Design: Patient Group: Sumatriptan 6mg injection + Sumatriptan Efficacy: RCT 6mg injection: Sumatriptan 6mg o Recurrence Parallel Sumatriptan 6mg subcutaneous injection + Sumatriptan 6mg o Rescue medication injection + subcutaneous injection Safety: N Sumatriptan 6mg o Participants with any adverse Sumatriptan 6mg injection Sumatriptan 6mg injection + placebo: event injection + Age (mean): 41 Sumatriptan 6mg subcutaneous injection + o Participants with any serious Sumatriptan 6mg years placebo adverse event injection: 433 % Female: 81% The patients were randomly allocated to Sumatriptan 6mg Sumatriptan 6mg one of two treatment groups (group 1 and injection + injection + 2). Starting from week 2, patients in both placebo: 438 placebo: groups took 6 mg sumatriptan Age (mean): 40.5 subcutaneously at the onset of a migraine years headache of moderate or severe intensity % Female: 84% (dose 1). For the treatment of headache recurrence only (dose 2) group 1 took 6 mg Menstrual sumatriptan subcutaneously and group 2 migraine: No took placebo. Patients self-administered study medication with a modified Owen Mumford auto-injector. Dahlof 1998 Study Design: Patient Group: Placebo: oral tablet Efficacy: p535 RCT o Headache relief within 2 hours Parallel Placebo: Zolmitriptan: 5mg oral tablet o Freedom from pain within 2 Age (mean): 39.5 hours N % Female: 76 Patients were instructed to take study o Recurrence Placebo: 99 medication within 12 weeks of o Rescue medication Zolmitriptan 5mg: randomization to treat a migraine headache Safety: Zolmitriptan Age (mean): 39.7 of moderate or severe intensity within 6 o Participants with any adverse 5mg: 213 % Female: 82 hours of headache onset. event o Participants with any serious Menstrual adverse event migraine: No

Dahlof 2001 Study Design: Patient Group: Placebo: Oral administration Efficacy: p1811 RCT o Headache relief within 2 hours Parallel Placebo: Almotriptan 6.25mg: Oral administration o Freedom from pain within 2 Age (mean): 39.4 hours N % Female: 86.3 Almotriptan 12.5mg:Oral administration o Rescue medication Placebo: 80 Safety: Almotriptan Almotriptan 25mg:Oral administration o Participants with any adverse Almotriptan 6.25mg: event 6.25mg: 167 Age (mean): 40.9 Patients took a single dose of active drug or o Withdrawals due to adverse % Female: 86.2 placebo at the onset of a migraine attack of events Almotriptan moderate or severe intensity. 12.5mg: 164 Almotriptan 12.5mg: Almotriptan Age (mean): 41.2 25mg: 161 % Female: 83.5

Almotriptan 25mg: Age (mean): 41.5 % Female: 85.7

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Dahlof 2009 p7 Study Design: Patient Group: Placebo: Oral administration Efficacy: RCT o Headache relief within 2 hours Parallel Placebo: Tonabersat 20mg: Oral administration o Freedom from pain within 2 Age (mean): 40.4 hours N % Female: 79.1 Tonabersat 40mg: Oral administration Safety: Placebo: 134 o Participants with any adverse Tonabersat 20mg: Sumatriptan 50mg: Oral administration event Tonabersat Age (mean): 39.6 o Withdrawals due to adverse 20mg: 134 % Female: 85.8 A single oral dose of test drugs or placebo events was taken at the onset of a moderate (grade Tonabersat Tonabersat 40mg: 2) or severe (grade 3) attack (dosing within 40mg: 137 Age (mean): 38.8 6 h after onset of attack). % Female: 83.9 Sumatriptan 50mg: 136 Sumatriptan 50mg: Age (mean): 40.0 % Female: 88.2

Menstrual migraine: No Di Monda 2003 Study Design: Patient Group: Sumatriptan: 25mg suppository Safety: p835 RCT Age (mean): 34.6 o Participants with any serious Crossover % Female: 72 IndoProCaf: Indomethacin 25mg, adverse event prochlorperazine dimaleate 4mg, and N Sumatriptan caffeine 75mg suppository Sumatriptan 25mg: 25mg: 45 Age (mean): NR Patients were instructed to take the study % Female: NR medication as soon as possible at the onset IndoProCaf of headache (not during aura). suppository: 43 IndoProCaf suppository: Age (mean): NR % Female: NR

Menstrual migraine: No Diamond 1998 Study Design: Patient Group: Sumatriptan 20mg: nasal spray Efficacy: p234 RCT o Headache relief within 2 hours Parallel Sumatriptan Sumatriptan 10mg: nasal spray o Functional health status 20mg: Safety: N Age (mean): 40.7 Sumatriptan 5mg: nasal Spray o Withdrawals due to adverse Sumatriptan % Female: 90 events 20mg: 292 Plaebo: nasal spray Sumatriptan Sumatriptan 10mg: Patients were asked to use study medication 10mg: 296 Age (mean): 41.1 to treat up to 3 moderate or severe % Female: 88 migraine attacks on an outpatient basis over Sumatriptan the next 6 months 5mg: 299 Sumatriptan 5mg: Age (mean): 40.8 Placebo: 199 % Female: 86

Placebo: Age (mean): 42 % Female: 87

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Diener 2002 Study Design: Patient Group: Eletriptan 40mg: Oral tablet Efficacy: p99 RCT o Headache relief within 2 hours Parallel Eletriptan 40mg: Eletriptan 80mg: Oral tablet o Freedom from pain within 2 Age (mean): 40 hours % Female: 90 Ergotamine plus Caffeine: Oral tablet o Functional health status N o Recurrence Eletriptan 40mg: Eletriptan 80mg: Placebo: Oral tablet Safety: 210 Age (mean): 40 o Participants with any serious % Female: 86 Each patient initially took 4 tablets adverse event Eletriptan 80mg: according to a double dummy design, 2 to o Withdrawals due to adverse 214 Ergotamine plus match eletriptan 40 mg and 2 to match events Caffeine: Cafergot some or all of which were placebo. Ergotamine plus Age (mean):40 Caffeine: 203 % Female: 86

Placebo: 106 Placebo: Age (mean): 42 % Female: 86

Menstrual migraine: No Diener 2004 Study Design: Patient Group: Acetylsalicylic acid: one 1000mg Efficacy: p50 RCT effervescentcapsules o Headache relief within 2 hours Parallel Acetylsalicylic o Freedom from pain within 2 acid: Sumatriptan:one 50mg hours N Age (mean): 41.8 encapsulatedcapsule o Recurrence Acetylsalicylic % Female: 88.4 o Rescue medication acid: 146 Placebo: one matching placebo capsule Safety: Sumatriptan (effervescent and non-buffered or o Participants with any adverse Sumatriptan 50mg: encapsulated) event 50mg: 135 Age (mean): 43.7 % Female: 82.2 Patients took one dose of study medication Placebo: 152 for the treatment of a moderate or severe Placebo: migraine headache within 6 h of the start of Age (mean): 41.9 headache (or within 6 h of waking if the % Female: 83.6 headache was present on awakening) provided they had been free from any Menstrual previous migraine for at least 24 h. migraine: No Diener 2005 Study Design: Patient Group: Almotriptan: 12.5mg oral dose Efficacy: p874 RCT o Headache relief within 2 hours Parallel Almotriptan Sumatriptan: 50mg oral dose o Freedom from pain within 2 12.5mg: hours N Age (mean): 41.1 Placebo: oral o Sustained freedom from pain Almotriptan % Female: 88 at 24 hours 12.5mg: 108 Patients were instructed to take the first o Rescue medication Sumatriptan dose of study medication as soon as Safety: Sumatriptan 50mg: possible (ie, within 1 hour after onset of the o Participants with any adverse 50mg: 81 Age (mean): 41.1 headache phase of the migraine attack) for event % Female: 86.4 the next attack that resulted in moderate or o Participants with any serious Placebo: 113 severe pain. adverse event Placebo: Age (mean): 41.4 % Female: 85.8

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Diener 2011 Study Design: Patient Group: Placebo: oral tablet Efficacy: p573 RCT o Headache relief within 2 hours Parallel Placebo: BI 44370 TA 50mg: oral tablet o Freedom from pain within 2 Age (mean): 38.2 hours N % Female: 87.1 BI 44370 TA 200mg: oral tablet o Sustained headache response Placebo: 78 at 24 hours BI 44370 TA BI 44370 TA 400mg: oral tablet o Sustained freedom from pain BI 44370 TA 50mg:Age (mean): at 24 hours 50mg: 71 42.8 Eletriptan: 40mg oral tablets o Functional health status % Female: 84.4 o Recurrence BI 44370 TA They were instructed to take study o Rescue medication 200mg: 72 BI 44370 TA medication to treat their next migraine Safety: 200mg: attack when the migraine pain was o Participants with any adverse BI 44370 TA Age (mean): 41.2 moderate or severe, and when no additional event 400mg: 79 % Female: 81.5 requirements were violated (i.e. a treatable migraine attack). Migraine attacks were Eletriptan 40mg: BI 44370 TA defined as non-treatable when they 76 400mg: occurred in the middle of the night or when Age (mean): 41.1 another pain medication was taken within % Female: 75.3 48 hours preceding the attack.

Eletriptan 40mg: Age (mean): 37.9 % Female: 88.4

Menstrual migraine: No Dodick 2005 Study Design: Patient Group: Zolmitriptan: 5mg nasal spray Efficacy: p125 RCT o Headache relief within 2 hours Parallel Zolmitriptan 5mg: Placebo: matching nasal spray o Freedom from pain within 2 Age (mean): 40.7 hours N % Female: 85.1 In the 10 weeks following randomization o Headache relief within 4 hours Zolmitriptan patients were to treat up to two migraine o Freedom from pain within 4 5mg: 935 Placebo: attacks each with a single dose of study hours Age (mean): 40.7 medication. For each attack the study o Sustained headache response Placebo: 934 % Female: 88.3 medication was to be taken within 15 at 24 hours minutes of migraine headache pain o Sustained freedom from pain Menstrual becoming of moderate or severe intensity. at 24 hours migraine: No Headaches with moderate or severe pain o Functional health status upon awakening were not to be treated as o Recurrence part of this study o Rescue medication Safety: o Participants with any adverse event o Participants with any serious adverse event o Withdrawals due to adverse events

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Reference Study Details Patients Intervention Outcomes

Dowson 2002 Study Design: Patient Group: Placebo: orally disintegrating tablet Efficacy: p101 RCT o Headache relief within 2 hours Parallel Placebo: Zolmitriptan ODT: 2.5 mg orally o Freedom from pain within 2 Age (mean): 42 disintegrating tablet hours N % Female: 86 o Sustained headache response Placebo: 240 Patients were instructed to treat only a at 24 hours Zolmitriptan ODT: migraine of moderate or severe intensity, to o Rescue medication Zolmitriptan Age (mean): 41 have had at least 24 h since a previous ODT: 231 % Female: 88 migraine, to take the medication within 4 h Safety: of migraine onset or within 4 h of waking o Participants with any adverse Menstrual with a migraine, and not to sleep within 4 h event migraine: No of dosing. o Participants with any serious adverse event o Withdrawals due to adverse events Dowson 2002 Study Design: Patient Group: Almotriptan 12.5mg: oral administration Efficacy: p453 RCT o Headache relief within 2 hours Parallel Almotriptan Almotriptan 25mg: oral administration o Freedom from pain within 2 12.5mg hours N Age (mean): 42.8 Sumatriptan 100mg: oral administration o Recurrence Almotriptan % Female: 85.9 o Rescue medication 12.5mg: 184 Placebo: oral admnistration Safety: Almotriptan 25mg o Participants with any adverse Almotriptan Age (mean): 41.4 Patients were instructed to take the study event 25mg: 191 % Female: 83.2 medication when the attack was severe or o Withdrawals due to adverse moderate in intensity events Sumatriptan Sumatriptan 100mg: 194 100mg Age (mean): 42.0 Placebo: 99 % Female: 83.5

Placebo Age (mean): 40.2 % Female: 88.9

Menstrual migraine: No Dowson 2003 Study Design: Patient Group: Zolmitriptan: 2.5mg orally disintegrating Safety: p573 RCT Age (median): 45 tablet o Participants with any adverse Parallel % Female: 86 event Sumatriptan: 50mg oral tablet o Participants with any serious N Zolmitriptan adverse event Zolmitriptan 2.5mg ODT: Patients were instructed to take the study 2.5mg ODT: 77 Age (mean): NR medication for the acute treatment of a % Female: NR single migraine of any intensity. Sumatriptan 50mg: 91 Sumatriptan 50mg: Age (mean): NR % Female: NR

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Eletriptan Study Design: Patient Group: Eletriptan 20mg: oral dose Efficacy: Steering RCT o Headache relief within 2 hours Committee in Parallel Eletriptan 20mg: Eletriptan 40mg: oral dose o Freedom from pain within 2 Japan 2002 Age (mean): 35 hours p416 N % Female: 68 Eletriptan 80mg: oral dose o Sustained headache response Eletriptan 20mg: at 24 hours 80 Eletriptan Placebo:oral dose o Rescue medication 40mg:Age (mean): o Recurrence Eletriptan 40mg: 36 Patients were instructed to take the study 80 % Female: 74 medication as soon as possible within 6 h of the onset of their migraine of severe or Safety: Eletriptan 80mg: Eletriptan 80mg: moderate in intensity o Participants with any serious 74 Age (mean): 35 adverse event % Female: 79 o Withdrawals due to adverse Placebo: 84 events Placebo: Age (mean): 36 % Female: 76

Menstrual migraine: No Farkkila 2003 Study Design: Patient Group: Placebo: oral tablet Efficacy: p463 RCT o Headache relief within 2 hours Parallel Placebo: Eletriptan 40mg: oral tablet o Freedom from pain within 2 Age (mean): 40.9 hours N % Female: 91 Eletriptan 80mg: oral tablet o Headache relief within 4 hours Placebo: 81 o Freedom from pain within 4 Eletriptan 40mg: Upon experiencing a typical migraine hours Eletriptan 40mg: Age (mean): 41.4 headache, subjects were instructed to take o Recurrence 179 % Female: 86 their medication as soon as possible and o Rescue medication within 6 h. The migraine headache had to be Safety: Eletriptan 80mg: Eletriptan 80mg: of at least moderate severity and not o Participants with any serious 167 Age (mean): 40.9 decreasing in intensity. adverse event % Female: 85

Menstrual migraine: No Freidman 2010 Study Design: Patient Group: Naproxen: 500mg capsule Efficacy: p7 RCT o Freedom from pain within 2 Parallel Naproxen 500mg: Sumatriptan: 100mg capsule hours Age (mean): 35 o Functional health status N % Female: 94 At discharge from the ED, we gave patients o Rescue medication Naproxen 500mg: vials containing one masked gel capsule and 84 Sumatriptan instructed them to take the medication if 100mg: they believed they needed something to Sumatriptan Age (mean): 35 treat recurrence of headache after 100mg: 82 % Female: 83 discharge.

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Freitag 2001 Study Design: Patient Group: Isometheptene:overencapsulated capsules Efficacy: p391 RCT o Headache relief within 2 hours Parallel Isometheptene: o Headache relief within 4 hours Age (mean): 40.9 Sumatriptan: 25mg overencapsulated o Sustained headache response N % Female: 86.2 capsules at 24 hours Isometheptene: o Functional health status 65 Sumatriptan Patients eligible for the study were o Recurrence 25mg: instructed to begin taking their medication Safety: Sumatriptan Age (mean): 43.3 at the first signs or symptoms that they o Participants with any adverse 25mg: 61 % Female: 91.8 recognized as the beginning of an acute event migraine attack. They were then to take Menstrual additional doses of medication on a hourly migraine: No basis for the next 3 hours.

Freitag 2008 Study Design: Patient Group: Rizatriptan ODT: 10mg orally disintegrating Efficacy: p368 RCT Age (median): 40 tablet o Headache relief within 2 hours Parallel o Functional health status Rizatriptan Placebo: orally disintegrating tablet Safety: N ODT:Age (mean): o Participants with any adverse Rizatriptan ODT: NR Patients were instructed to take the study event 105 % Female: 89.5 medication at the earliest sign of nausea of o Withdrawals due to adverse a moderate or severe migraine headache. events Placebo: 212 Placebo: Age (mean): NR % Female: 89.7

Menstrual migraine: No Freitag 2008 Study Design: Patient Group: Rizatriptan + Acetaminophen: one Efficacy: p921 RCT rizatriptan 10mg tablet +2 acetaminophen o Headache relief within 2 hours Parallel Rizatriptan + 500mg tablets o Freedom from pain within 2 Acetaminophen: hours N Age (mean): 41.5 Acetaminophen: two 500mgtablets + one o Sustained headache response Rizatriptan + % Female: 85.4 placebo tablet at 24 hours Acetaminophen: o Sustained freedom from pain 49 Acetaminophen Rizatriptan: one 10mg tablet + 2 placebo at 24 hours 1000mg: Age tablets o Functional health status Acetaminophen (mean): 42.0 Safety: 1000mg: 45 % Female: 88.4 Placebo: 3 matching 0mg tablets o Participants with any adverse event Rizatriptan 10mg: Rizatriptan 10mg: Eligible patients treated a single attack of o Participants with any serious 46 Age (mean): 44.3 migraine within 4 h from the onset of pain if adverse event % Female: 83.3 the attack met the following criteria: Placebo: 44 migraine pain was moderate (Grade 2) or Placebo: severe (Grade 3); migraine pain did not Age (mean): 45.2 spontaneously resolve; and migraine was % Female: 94.9 not preceded by any prohibited concurrent medication. All patients were to ingest 3 Menstrual tablets to treat one migraine attack. migraine: No

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Reference Study Details Patients Intervention Outcomes

Gallagher 2000 Study Design: Patient Group: Zolmitriptan 2.5mg: tablet Efficacy: p119 RCT o Headache relief within 2 hours Parallel Zolmitriptan Zolmitriptan 5mg: tablet o Headache relief within 4 hours 2.5mg: o Sustained headache response N Age (mean): 39.9 Sumatriptan 25mg: tablet at 24 hours Zolmitriptan % Female: 84.4 o Recurrence 2.5mg: 327 Sumatriptan 50mg: tablet o Rescue medication Zolmitriptan 5mg: Safety: Zolmitriptan Age (mean): 40.2 Once entered into the trial, patients used o Participants with any adverse 5mg: 337 % Female: 89.8 either zolmitriptan 2.5 mg or 5 mg or event sumatriptan 25 mg or 50 mg to treat their o Participants with any serious Sumatriptan Sumatriptan first migraine. adverse event 25mg: 336 25mg: o Withdrawals due to adverse Age (mean): 39.6 events Sumatriptan % Female: 88.9 50mg: 338 Sumatriptan 50mg: Age (mean): 40.6 % Female: 87.3

Menstrual migraine: No

Garcia-Ramos Study Design: Patient Group: Eleptriptan 40mg: oral tablet Efficacy: 2003 p869 RCT o Headache relief within 2 hours Parallel Eleptriptan 40mg: Naratriptan 2.5mg: oral capsule o Freedom from pain within 2 Age (mean): 36.3 hours N % Female: 79 Placebo: oral tablet or capsule o Functional health status Eleptriptan o Recurrence 40mg: 192 Naratriptan Patients were instructed to take study o Rescue medication 2.5mg: medication when they experienced a typical Safety: Naratriptan Age (mean): 37.5 migraine attack of moderate or severity, and o Participants with any adverse 2.5mg: 199 % Female: 82 within 4 h of the onset of headache pain. event Patients who experienced aura were o Withdrawals due to adverse Placebo: 92 Placebo: instructed to wait until the aura phase events Age (mean): 36.4 ended before taking study treatment. % Female: 82

Menstrual migraine: No Gawel 2005 p7 Study Design: Patient Group: Zolmitriptan: 5mg Nasal Spray Efficacy: RCT o Headache relief within 2 hours Parallel Zolmitriptan 5mg: Placebo: nasal spray o Freedom from pain within 2 Age (mean): 40.9 hours N % Female: 88.7 Patients were permitted to treat a single o Sustained freedom from pain Zolmitriptan attack with any baseline intensity at any at 24 hours 5mg: 464 Placebo: time after onset in order to more duplicate o Functional health status Age (mean): 42.4 clinical practice. Patients could only treat an o Rescue medication Placebo: 451 % Female: 86.3 attack with the study drug if at least 24 Safety: hours had passed since any previous attack o Participants with any adverse Menstrual regardless of whether medication had been event migraine: No taken for that previous attack. o Participants with any serious adverse event o Withdrawals due to adverse events

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Reference Study Details Patients Intervention Outcomes

Geraud 2002 Study Design: Patient Group: Zolmitriptan:2.5mg oral tablets Efficacy: p88 RCT o Headache relief within 2 hours Parallel Zolmitriptan Acetylsalicylic acid + metoclopramide: o Freedom from pain within 2 2.5mg: Acetylsalicylic acid 900mg plus hours N Age (mean): 41.6 metoclopramide 10mg o Recurrence Zolmitriptan % Female: 83.7 o Rescue medication 2.5mg: 326 Patients took one dose of study medication Safety: Acetylsalicylic acid (consisting of active treatment and double- o Participants with any adverse Acetylsalicylic + metoclopramide: dummy placebo) for the treatment of a event acid + Age (mean): 40.9 moderate or severe migraine headache o Participants with any serious metoclopramide: % Female: 86.2 within 6 h of the start of headache (or adverse event 340 within 6 h of waking if the headache was o Withdrawals due to adverse Menstrual present on awakening), provided they had events migraine: No been free from any previous migraine for at least 24 h. Gijsman 1997 Study Design: Patient Group: Rizatriptan 5mg: oral administration Efficacy: p647 RCT Age (mean): 39.2 o Headache relief within 2 hours Parallel % Female: 75.6 Rizatriptan 10mg: oral administration o Freedom from pain within 2 hours N Rizatriptan 5mg: Placebo: oral administration o Functional health status Rizatriptan 5mg: Age (mean): NR o Recurrence 130 % Female: NR Patients were instructed to ingest test o Rescue medication medication only if their headache of Safety: Rizatriptan 10mg: Rizatriptan 10mg: moderate or severity intensity was not o Participants with any serious 145 Age (mean): NR resolving spontaneously. adverse event % Female: NR o Withdrawals due to adverse Placebo: 67 events Placebo: Age (mean): NR % Female: NR

Menstrual migraine: No Goadsby 2000 Study Design: Patient Group: Eletriptan 20mg: oral tablet Efficacy: p156 RCT o Headache relief within 2 hours Parallel Eletriptan 20mg: Eletriptan 40mg: oral tablet o Freedom from pain within 2 Age (mean): 40 hours N % Female: 82 Eletriptan 80mg: oral tablet o Functional health status Eletriptan 20mg: o Recurrence 144 Eletriptan 40mg: Sumatriptan 100mg: oral capsule o Rescue medication Age (mean): 41 Safety: Eletriptan 40mg: % Female: 85 Placebo: oral tablet or capsule o Participants with any adverse 136 event Eletriptan 80mg: Patients were instructed to take study o Participants with any serious Eletriptan 80mg: Age (mean): 40 medication within 6 hours of migraine onset adverse event 141 % Female: 81 or on awakening with a migraine headache that was moderate or severe and was not Sumatriptan Sumatriptan yet improving. 100mg: 129 100mg: Age (mean): 40 Placebo: 142 % Female: 84

Placebo Age (mean): 41 % Female: 80

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Goadsby 2007 Study Design: Patient Group: Almotriptan: 12.5mg oral Efficacy: p34 RCT o Headache relief within 2 hours Parallel Almotriptan Zolmitriptan: 2.5 mg oral o Freedom from pain within 2 12.5mg: hours N Age (mean): 39 Patients were instructed to take a single o Sustained headache response Almotriptan % Female: 86.8 dose of the study drug when migraine at 24 hours 12.5mg: 532 headache pain was moderate to severe. o Sustained freedom from pain Zolmitriptan at 24 hours Zolmitriptan 2.5mg: o Functional health status 2.5mg: 530 Age (mean): 40 o Recurrence % Female: 83.0 o Rescue medication Safety: Menstrual o Participants with any adverse migraine: No event o Withdrawals due to adverse events Goadsby 2008 Study Design: Patient Group: Almotriptan: 12.5mg oral dose Efficacy: p383 RCT o Freedom from pain within 2 Parallel Almotriptan Placebo: oral dose hours 12.5mg: o Sustained freedom from pain N Age (mean): 36.9 Patients were instructed to take the study at 24 hours Almotriptan % Female: 83.3 medication when pain is mild, and within 1 o Recurrence 12.5mg: 225 h of onset; or when pain is moderate or Safety: Placebo : severe. o Participants with any adverse Placebo: 214 Age (mean): 39.6 event % Female: 85.0 o Participants with any serious adverse event Menstrual o Withdrawals due to adverse migraine: No events Gobel 2000 Study Design: Patient Group: Naratriptan: 2.5mg oral tablet Efficacy: p981 RCT Age (mean): 45 o Sustained headache response Cross-over % Female: 91 Sumatriptan: 100mg oral tablet at 24 hours o Rescue medication N Naratriptan Patients were required to treat 1 moderate o Recurrence Naratriptan 2.5mg: or severe migraine attack in a non-clinical Safety: 2.5mg: 164 Age (mean): NR setting with one 2.5-mg naratriptanand 1 o Participants with any adverse % Female: NR attack with one 100-mg sumatriptan tablet event Sumatriptan in predetermined order. 100mg: 181 Sumatriptan 100mg: Age (mean): NR % Female: NR

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Goldstein 2002 Study Design: Patient Group: Placeb: oral tablet Efficacy: p41 RCT o Headache relief within 2 hours Parallel Placebo Frovatriptan 1mg: oral tablet o Freedom from pain within 2 Age (mean): 41.4 hours N % Female: 83 Frovatriptan 2.5mg: oral tablet o Functional health status Placebo: 123 o Recurrence Frovatriptan 1mg: Frovatriptan 5mg: oral tablet o Rescue medication Frovatriptan Age (mean): 42.1 Safety: 1mg: 122 % Female: 88 Patients were required to take the study o Participants with any adverse medication at the onset of a headache of event Frovatriptan Frovatriptan moderate or severe intensity. 2.5mg: 131 2.5mg: Age (mean): 41.5 Frovatriptan % Female: 87 5mg: 126 Frovatriptan 5mg: Age (mean): 40.5 % Female: 83

Menstrual migraine: No Goldstein 2012 Study Design: Patient Group: Sumatriptan: 6.5 mg, patch (iontophoretic Efficacy: p1402 RCT transdermal system) o Headache relief within 2 hours Parallel Sumatriptan: o Freedom from pain within 2 Age (mean): 40.7 Placebo: patch hours N % Female: 84 Safety: Sumatriptan: 234 Patients were required to apply the study o Participants with any adverse Placebo: patch only if their migraine score was ≥ 2 event Placebo: 235 Age (mean): 41.0 (on a 4-point headache o Withdrawals due to adverse % Female: 86 pain scale, where 0 = none, 1 = mild, events 2 = moderate, 3 = severe) . Menstrual migraine: No Gross 1994 Study Design: Patient Group: Sumatriptan: 6 mg (0.5 mL of a 12mL Efficacy: p559 RCT solution, given as the succinate salt), o Headache relief within 2 hours Parallel Placebo s.c. subcutaneous injection o Functional health status Age (mean): 43 o Rescue medication N % Female: 73 Placebo: subcutaneous isotonic saline Safety: Placebo s.c.: 26 o Participants with any adverse Sumatriptan 6mg Patients were instructed to treat their event Sumatriptan s.c.: s.c. migraine attack with the self-injector. The 60 Age (mean): 44 thigh and deltoid area of the arm were % Female: 83 recommended as suitable injection sites.

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Gruffyd-Jones Study Design: Patient Group: Zolmitriptan 2.5mg: oral tablet Efficacy: 2001 p237 RCT o Headache relief within 2 hours Parallel Zolmitriptan Zolmitriptan 5mg: oral tablet o Freedom from pain within 2 2.5mg: hours N Age (mean): 42.1 Sumatriptan 50mg: oral tablet o Sustained freedom from pain Zolmitriptan % Female: 85.4 at 24 hours 2.5mg: 555 Patients were instructed to treat their Safety: Zolmitriptan 5mg: migraine headache of moderate or severe o Participants with any adverse Zolmitriptan Age (mean): 41.7 intensity, provided they had been free of event 5mg: 551 % Female: 86.0 any previous migraine for 24 h and the o Participants with any serious headache was not of >12 h duration (or, if adverse event Sumatriptan Sumatriptan present on waking, present for >12 h since o Withdrawals due to adverse 50mg: 560 50mg: waking). events Age (mean): 41.9 % Female: 84.6

Menstrual migraine: Yes (20%) Henry 1993 Study Design: Patient Group: Sumatriptan: 6mg subcutaneous injection Efficacy: p432 RCT o Headache relief within 2 hours Parallel Sumatriptan: Placebo: subcutaneous isotonic saline o Rescue medication Age (mean): 44 Safety: N % Female: 89.2 Patients were required to treattheir o Participants with any adverse Sumatriptan: 37 migraine headache of moderate or severe event Placebo: intensity (grade 2 or 3) with an auto- Placebo: 38 Age (mean): 42 injector. % Female: 84.6

Menstrual migraine: No Ho 2008 p1304 Study Design: Patient Group: Rizatriptan: 10mg oral tablet Efficacy: RCT o Freedom from pain within 2 Parallel Rizatriptan 10mg: Placebo: oral tablet hours Age (mean): 40.2 o Sustained headache response N % Female: 82.4 Patients were instructed to take study at 24 hours Rizatriptan 10mg: medication as soon as they experienced a o Sustained freedom from pain 41 Placebo: moderate or severe migraine headache. at 24 hours Age (mean): 42.2 o Rescue medication Placebo: 143 % Female: 90.4 Safety: o Participants with any adverse Menstrual event migraine: No o Participants with any serious adverse event Ho 2008 p2115 Study Design: Patient Group: Zolmitriptan: 5mg oral tablet Efficacy: RCT o Headache relief within 2 Parallel Zolmitriptan 5mg: Placebo: oral tablet hours Age (mean): 41.7 o Freedom from pain within 2 N % Female: 86 Patients were instructed to take study hours Zolmitriptan medication when they had a moderate or o Sustained headache response 5mg: 376 Placebo: severe migraine attack. at 24 hours Age (mean): 42.3 o Sustained freedom from pain Placebo: 383 % Female: 84 at 24 hours o Headache specific QOL Menstrual o Functional health status migraine: No Safety: o Participants with any adverse event o Participants with any serious adverse event

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Reference Study Details Patients Intervention Outcomes

Ishkanian 2007 Study Design: Patient Group: Sumatriptan: 50mg oral tablet Efficacy: p99 RCT o Headache relief within 2 hours Parallel Sumatriptan Placebo: oral tablet o Rescue medication 50mg: Safety: N Age (mean): 39.6 Patients were instructed to wait until o Participants with any adverse Sumatriptan % Female: 71 moderate or severe head pain was event 50mg: 108 experienced before administering study o Participants with any serious Placebo: medication. adverse event Placebo: 108 Age (mean): 41.0 o Withdrawals due to adverse % Female: 69 events

Menstrual migraine: no Jelinski 2006 Study Design: Patient Group: Placebo: oral tablet Efficacy: p73 RCT o Freedom from pain within 2 Parallel Placebo: Sumatriptan 50mg: oral tablet hours Age (mean): 40.7 o Sustained freedom from pain N % Female: 83 Sumatriptan 100mg: oral tablet at 24 hours Placebo: 111 o Recurrence Sumatriptan Patients were instructed to treat their next Safety: Sumatriptan 50mg: migraine attack within two hours of the first o Participants with any adverse 50mg: 126 Age (mean): 39.8 sign of migraine pain, while the pain was event % Female: 87 still considered to be 1 (mild) on a four point o Participants with any serious Sumatriptan scale (0=no pain, 1=mild pain, 2=moderate adverse event 100mg: 127 Sumatriptan pain, 3=severe pain). If the patient 100mg: experienced moderate to severe migraine Age (mean): 39.8 pain at the onset of the attack, they were % Female: 86 instructed not to treat that migraine with the study medication. Menstrual migraine: no Jensen 1995 Study Design: Patient Group: Placebo: subcutaneous self-injector Efficacy: p423 RCT Age (mean): 43 o Headache relief within 2 hours Crossover % Female: 90 Sumatriptan: 6mg subcutaneous self- Safety: injector o Participants with any serious N Placebo: adverse event Placebo: Age (mean): NR Each patient received two trial medications Treated N=55 % Female: NR due to the crossover design; one sumatriptan 6mg and one placebo. Sumatriptan 6mg Sumatriptan 6mg subcutaneous: subcutaneous: Treated N=63 Age (mean): NR % Female: NR

Menstrual migraine: No Kaniecki 2006 Study Design: Patient Group: Sumatriptan: 100mg oral tablet Efficacy: p1535 RCT o Headache relief within 2 hours Parallel Sumatriptan Placebo: oral tablet o Freedom from pain within 2 100mg: hours N Age (mean): 37.3 Patients were instructed to treat moderate o Sustained headache response Sumatriptan % Female: 94 or severe pain within 1 h of its becoming at 24 hours 100mg: 131 moderate or severe. o Sustained freedom from pain Placebo: at 24 hours Placebo: 127 Age (mean): 37.4 o Rescue medication % Female: 90 Safety: o Participants with any serious Menstrual adverse event migraine: no

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Reference Study Details Patients Intervention Outcomes

Klapper 2000 Study Design: Patient Group: Rizatriptan: 10 mg wafer for sublingual use Efficacy: p585 RCT o Time to freedom from pain Parallel Rizatriptan 10mg: Placebo: wafer for sublingual use o Headache relief within 2 hours Age (mean): NR N % Female: NR Patients were instructed to sublingually use Rizatriptan 10mg: the wafer at the onset of their acute 16 Placebo: migraine attack. Age (mean): NR Placebo: 14 % Female: NR

Menstrual migraine: no Klapper 2004 Study Design: Patient Group: Zolmitriptan: 2.5 mg oral tablet Efficacy: p918 RCT o Freedom from pain within 2 Parallel Zolmitriptan Placebo: oral tablet hours 2.5mg: o Functional health status N Age (mean): 41.4 Patients were instructed to treat a single o Rescue medication Zolmitriptan % Female: 82.6 migraine headache during the mild intensity Safety: 2.5mg: 138 phase, within 4 h of onset; the time to o Participants with any adverse Placebo: treatment was recorded. event Placebo: 142 Age (mean): 42.0 o Withdrawals due to adverse % Female: 89.4 events

Menstrual migraine: no Klassen 1997 Study Design: Patient Group: Naratriptan 1mg: oral tablet Efficacy: p640 RCT o Functional health status (2hr Parallel Naratriptan 1mg: Naratriptan 2.5mg: oral tablet & 4hr) Age (mean): 38.2 o Recurrence N % Female: 84 Placebo: oral tablet o Rescue medication Naratriptan 1mg: Safety: 117 Naratriptan Patients were instructed to take the study o Participants with any adverse 2.5mg: medication for the acute treatment of one event Naratriptan Age (mean): 40.5 moderate or severe migraine attack at o Withdrawals due to adverse 2.5mg: 127 % Female: 90 home. events

Placebo: 122 Placebo: Age (mean): 39.9 % Female: 88

Menstrual migraine: no Kramer 1998 Study Design: Patient Group: Placebo: oraltablets Efficacy: p773 RCT Age (mean): 40.6 o Headache relief within 2 hours Crossover % Female: 84 Rizatriptan: 10mg oral tablets o Headache relief within 4 hours o Freedom from pain within 2 N Placebo: Outpatients were instructed to ingest one hours Placebo: Age (mean): NR tablet of test medication when they o Freedom from pain within 4 Treated N=83 % Female: NR developed a moderate or severe migraine hours headache that did not start to resolve o Functional health status Rizatriptan 10mg: Rizatriptan 10mg: spontaneously. Safety: Treated N=324 Age (mean): NR o Withdrawals due to adverse % Female: NR events

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Kudrow 2005 Study Design: Patient Group: Placebo: oral tablet Efficacy: p1151 RCT o Headache relief within 2 hours Parallel Placebo: Valdecoxib: 20mg or 50mg oral tablet o Recurrence Age (mean): 39.0 o Rescue medication N % Female: 87.9 Sumatriptan: 50mg oral tablet Safety: Placebo: 141 o Participants with any adverse Valdecoxib: Patients were required to contact the study event Valdecoxib: 289 Age (mean): 41.1 coordinator, who would ascertained % Female: 94.1 whether the episode was of moderate to Sumatriptan: 144 severe intensity and if their clinical status Sumatriptan: conformed to study requirements, and then Age (mean): 41.1 take an initial dose of study medication % Female: 90.3 within 6 hours of headache onset.

Menstrual migraine: No Landy 2004 Study Design: Patient Group: Sumatriptan 50mg: oral tablet Efficacy: p913 RCT o Sustained freedom from pain Parallel Sumatriptan Sumatriptan 100mg: oral tablet at 24 hours 50mg: o Functional health status N Age (mean): 37.8 Placebo: oral tablet o Rescue medication Sumatriptan % Female: 100 Safety: 50mg: 151 Patients were instructed to treat a o Participants with any serious Sumatriptan menstrually associated migraine within 1 h adverse event Sumatriptan 100mg: of onset of mild pain and to treat only while 100mg: 148 Age (mean): 37.9 pain was mild. % Female: 100 Placebo: 148 Placebo: Age (mean): 37.6 % Female: 100

Menstrual migraine: Yes (100%) Lipton 2009 Study Design: Patient Group: Placebo: single fast-disintegrating tablet Efficacy: p826 – Study 1 RCT Age (mean): 41.5 o Freedom from pain within 2 Crossover % Female: 89 Sumatriptan/Naproxen: combination single hours fast-disintegrating, rapid-release, fixed dose o Sustained freedom from pain N Placebo: tablet of sumatriptan/naproxen sodium at 24 hours Placebo: 123 Age (mean): NR 85/500 mg o Rescue medication % Female: NR Safety: Sumatriptan/ Patients were instructed to use the study o Participants with any adverse Naproxen: 447 Sumatriptan/ medication within 1h of onset of migraine event Naproxen: head pain while the pain remained mild. o Withdrawals due to adverse Age (mean): NR events % Female: NR

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Lipton 2009 Study Design: Patient Group: Placebo: single fast-disintegrating tablet Efficacy: p826 – Study 2 RCT Age (mean): 40.9 o Freedom from pain within 2 Crossover % Female: 90 Sumatriptan/Naproxen: combination single hours fast-disintegrating, rapid-release, fixed dose o Sustained freedom from pain N Placebo: tablet of sumatriptan/naproxen sodium at 24 hours Placebo: 107 Age (mean): NR 85/500 mg o Rescue medication % Female: NR Safety: Sumatriptan/ Patients were instructed to use the study o Participants with any adverse Naproxen: 458 Sumatriptan/ medication within 1h of onset of migraine event Naproxen: head pain while the pain remained mild. o Withdrawals due to adverse Age (mean): NR events % Female: NR

Menstrual migraine: No Loder 2005 Study Design: Patient Group: Zolmitriptan: 2.5 mg orallydisintegrating Efficacy: p381 RCT tablets (ODT) o Recurrence Parallel Zolmitriptan Safety: 2.5mg: Placebo: ODT o Participants with any adverse N Age (mean): 40.0 event Zolmitriptan % Female: 84.0 Zolmitriptan ODT is uniquely formulated to o Participants with any serious 2.5mg: 281 dissolve on the tongue.Patients were adverse event Placebo: instructed to take a single oral dose of trial o Withdrawals due to adverse Placebo: 285 Age (mean): 42.7 medication as soon as possible at the onset events % Female: 86.6 of a migraine headache. The headache pain could be mild, moderate, or severe in Menstrual intensity. migraine: No Mannix 2007 Study Design: Patient Group: Rizatriptan: 10mg oral tablet Efficacy: p414 – Study 1 RCT o Headache relief within 2 hours Parallel Rizatriptan 10mg: Placebo: oral tablet o Sustained headache response Age (median): 38.0 at 24 hours N % Female: 100 Patients were instructed to take the study o Functional health status Rizatriptan 10mg: medication to treat a single menstrual o Rescue medication 251 Placebo: migraine (MM) attack when the pain was Safety: Age (mean): 37.0 moderate (Grade 2) or severe (Grade 3). o Participants with any adverse Placebo: 130 % Female: 100 event o Participants with any serious Menstrual adverse event migraine: Yes o Withdrawals due to adverse (100%) events Mannix 2007 Study Design: Patient Group: Rizatriptan: 10mg oral tablet Efficacy: p414 – Study 2 RCT o Headache relief within 2 hours Parallel Rizatriptan 10mg: Placebo: oral tablet o Sustained headache response Age (median): 37.0 at 24 hours N % Female: 100 Patients were instructed to take the study o Functional health status Rizatriptan 10mg: medication to treat a single menstrual o Rescue medication 257 Placebo: migraine (MM) attack when the pain was Safety: Age (mean): 37.5 moderate (Grade 2) or severe (Grade 3). o Participants with any adverse Placebo: 118 % Female: 100 event o Participants with any serious Menstrual adverse event migraine: Yes o Withdrawals due to adverse (100%) events

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Reference Study Details Patients Intervention Outcomes

Mannix 2009 Study Design: Patient Group: Sumatriptan/Naproxen:oral sumatriptan 85 Efficacy: p106 – Study 1 RCT mg, as the succinate salt, formulated with o Freedom from pain within 2 Parallel Sumatriptan/ RT technology, and 500mg naproxen sodium hours Naproxen: tablet o Sustained freedom from pain N Age (mean): 36 at 24 hours Sumatriptan/ % Female: 100 Placebo: oral tablet o Recurrence Naproxen:161 Safety: Placebo: Participants were instructed to treat their o Participants with any serious Placebo: 168 Age (mean): 36 next menstrual migraine attack during the adverse event % Female: 100 mild pain phase (within 1 hour of onset). o Withdrawals due to adverse events Menstrual migraine: Yes (100%) Mannix 2009 Study Design: Patient Group: Sumatriptan/Naproxen:oral sumatriptan 85 Efficacy: p106 – Study 2 RCT mg, as the succinate salt, formulated with o Freedom from pain within 2 Parallel Sumatriptan/ RT technology,and 500mg naproxen sodium hours Naproxen: tablet o Sustained freedom from pain N Age (mean): 37 at 24 hours Sumatriptan/ % Female: 100 Placebo: oral tablet o Recurrence Naproxen:162 Safety: Placebo: Participants were instructed to treat their o Participants with any serious Placebo: 173 Age (mean): 38 next menstrual migraine attack during the adverse event % Female: 100 mild pain phase (within 1 hour of onset). o Withdrawals due to adverse events Menstrual migraine: Yes (100%) Massiou 2005 Study Design: Patient Group: Naratriptan: 2.5mgoral tablet Efficacy: p774 RCT o Freedom from pain within 2 Parallel Naratriptan Placebo: oral tablet hours 2.5mg: o Freedom from pain within 4 N Age (mean): NR Patients were instructed to ingest one tablet hours Naratriptan % Female: 100% for a mild headache and within 1 h after the o Sustained freedom from pain 2.5mg: 128 start of a menstrually related migraine. at 24 hours Placebo: o Functional health status Placebo: 129 Age (mean): NR o Recurrence % Female: 100% Safety: o Participants with any adverse Menstrual event migraine: Yes (100%)

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Reference Study Details Patients Intervention Outcomes

Mathew 2007 Study Design: Patient Group: Amlotriptan: 12.5mg oraltablet Efficacy: p189 RCT o Headache relief within 2 hours Parallel Amlotriptan Placebo: matching oral tablet o Headache relief within 4 hours 12.5mg: o Freedom from pain within 2 Almotriptan Age (mean): 40.7 Patients self administered medication at the hours 12.5mg: 174 % Female: 88.3 earliest onset of headache pain of any o Freedom from pain within 4 intensity, typical of their usual migraine, hours Placebo: 173 Placebo: within 1 hour of onset. o Sustained headache response Age (mean): 40.2 at 24 hours % Female: 85.2 o Sustained freedom from pain at 24 hours Menstrual o Functional health status migraine: No o Recurrence o Rescue medication Safety: o Participants with any adverse event (within treatment and 24 hrs post) o Participants with any serious adverse event o Withdrawals due to adverse events Mathew 2003 Study Design: Patient Group: Eletriptan: 40mg film coated oral tablet Efficacy: p214 RCT o Headache relief within 2 hours Parallel Eletriptan 40mg: Sumatriptan:100mg oralgelatin capsule o Freedom from pain within 2 Age (mean): 41.1 hours N % Female: 87 Placebo: matching film coated tablet or o Sustained headache response Eletriptan 40mg: gelatin capsule at 24 hours 835 Sumatriptan o Functional health status 100mg:Age Patients were instructed to take study o Recurrence Sumatriptan (mean): 41.8 medication within 6 hours of the onset of a o Rescue medication 100mg: 849 % Female: 86 migraine of moderate or severe intensity Safety: that was not improving. o Participants with any adverse Placebo: 429 Placebo: event Age (mean): 41.6 o Participants with any serious % Female: 87 adverse event

Menstrual migraine: No Mellor 1991 Study Design: Patient Group: Placebo: Three dispersible tablets Efficacy: p306 RCT o Headache relief within 2 hours Parallel Placebo: Sumatriptan 100mg: three dispersible o Headache relief within 4 hours Age (mean): 40 tablets o Freedom from pain within 2 N % Female: 83 hours Placebo: 84 Patients were instructed to use one tablet o Freedom from pain within 4 Sumatriptan to treat their next migraine attack as soon hours Sumatriptan 100mg: as possible after headache onset; one to be o Recurrence 100mg: 149 Age (mean): 42 taken 2h later if persisted and one if o Rescue medication % Female: 86 headache recurred within 24h. Safety: o Participants with any adverse Menstrual event migraine: No

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Reference Study Details Patients Intervention Outcomes

Misra 2007 Study Design: Patient Group: Rizatriptan 10mg: oral administration Efficacy: p175 RCT o Headache relief within 2 hours Parallel Rizatriptan 10mg: Ibuprophen 400mg: oral administration o Freedom from pain within 2 Age (mean): 29.2 hours N % Female: 68 Placebo:oral administration o Recurrence Rizatriptan 10mg: o Rescue medication 53 Ibuprophen Patients were advised to take study Safety: 400mg: medication if the headache was moderate o Participants with any adverse Ibuprophen Age (mean): 30.5 to severe. event 400mg: 53 % Female: 73 o Participants with any serious adverse event Placebo:53 Placebo: o Withdrawals due to adverse Age (mean): 31.8 events % Female: 80

Menstrual migraine: No Misra 2010 Study Design: Patient Group: Naproxen:500mgoral administration Efficacy: p175 RCT Age (mean): 32.6 o Headache relief within 2 hours Parallel % Female: 67.5 Sumatriptan: 50mg oral administration o Sustained freedom from pain at 24 hours N Naproxen 500mg: Rizatriptan: 10mgoral administration o Functional health status Naproxen Age (mean): NR o Recurrence 500mg:11 % Female: NR Ergotamine tartrate + caffeine + cyclizine Safety: HCL: oral administration of 2mg ergotamine o Participants with any adverse Sumatriptan Sumatriptan + 100mg caffeine + 50mg cyclizine HCL event 50mg:11 50mg: o Participants with any serious Age (mean):NR Patients were advised to take a single dose adverse event Rizatriptan 10mg: % Female: NR of study drug during a moderate to severe 11 migraine attack. Rizatriptan 10mg: Ergotamine Age (mean): NR tartrate + % Female: NR caffeine + cyclizine HCL: 10 Ergotamine tartrate + caffeine + cyclizine HCL: Age (mean): NR % Female: NR

Menstrual migraine: No MOSCC Group Study Design: Patient Group: Sumatriptan: one 100mg dispersible tablet Efficacy: (Kirkham) 1991 RCT o Headache relief within 2 hours p314 Parallel Sumatriptan Cafergot: 2mg ergotamine tartrate capsule o Recurrence 100mg: plus a 200mg caffeine capsule o Rescue medication N Age (mean): 39 (encapsulated) Safety: Sumatriptan % Female: 81.6 o Participants with any adverse 100mg: 290 Patients were asked to treat a total of three event Cafergot: attacks, or remain in the active phase of the o Withdrawals due to adverse Cafergot: 290 Age (mean): 40 trial for 12 weeks, whichever occurred first. events % Female: 84.4

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Myllyla 1998 Study Design: Patient Group: Tolfenamic acid: 200mgrapid-relief oral Efficacy: p201 RCT tablet o Headache relief within 2 hours Parallel Tolfenamic acid o Freedom from pain within 2 200mg: Placebo: oral tablet hours N Age (mean): 39 o Recurrence Tolfenamic acid % Female: 91 Sumatriptan: 100mgoral tablet o Rescue medication 200mg:47 Safety: Placebo: Patients were instructed to take the dose at o Participants with any adverse Placebo: 48 Age (mean): 39 the first symptoms of a migraine. event % Female: 94 Sumatriptan 100mg: 46 Sumatriptan 100mg: Age (mean): 40 % Female: 85

Menstrual migraine: No Nappi 1994 Study Design: Patient Group: Sumatriptan: 100 mgfilm coated tablet Efficacy: p138 RCT o Headache relief within 2 hours Parallel Sumatriptan Placebo: film coated tablet o Headache relief within 4 hours 100mg: o Recurrence N Age (mean): 38 Patients were instructed to take the first o Rescue medication Sumatriptan % Female: 76 dose at the earliest sign of migraine. Safety: 100mg: 162 o Participants with any adverse Placebo: event Placebo: 88 Age (mean): 38 o Participants with any serious % Female: 79 adverse event o Withdrawals due to adverse Menstrual events migraine: No Nett 2003 p835 Study Design: Patient Group: Sumatriptan 50mg: oral tablet Efficacy: RCT o Sustained freedom from pain Parallel Sumatriptan Sumatriptan 100mg: oral tablet at 24 hours 50mg: o Functional health status N Age (mean): 35.5 Placebo: oral tablet o Rescue medication Sumatriptan % Female: 100 Safety: 50mg: 124 Patients were instructed to treat a o Participants with any adverse Sumatriptan menstrually-associated migraine within 1 h event Sumatriptan 100mg: of onset of mild pain and to treat only while o Participants with any serious 100mg: 122 Age (mean): 37.3 pain was mild. adverse event % Female: 100 Placebo: 123 Placebo: Age (mean): 36.9 % Female: 100

Menstrual migraine: Yes (100%) Olesen 2004 Study Design: Patient Group: Eletriptan: 80mgoral tablet Efficacy: p671 RCT o Rescue medication Parallel Eletriptan 80mg: Placebo:oral tablet Safety: Age (mean): 40 o Withdrawals due to adverse N % Female: 74 Patients self dosed with 2 tablets of events Eletriptan 80mg: Eletriptan 40 mg or placebo within 30 min of 43 Placebo: the onset of typical aura provided no Age (mean): 40 migraine had started at the time of dosing Placebo: 44 % Female: 82 and onset of aura was not during sleep.

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

OSDD Group Study Design: Patient Group: Placebo: three tablets Efficacy: (Edwards) 1991 RCT o Headache relief within 2 hours p300 Parallel Placebo: Sumatriptan: three tablets (appropriate Safety: Age (mean): 41 combination of 100mg sumatriptan and o Participants with any adverse N % Female: 83 placebo tablets) event Placebo: 212 o Withdrawals due to adverse Sumatriptan Patients were instructed to take their events Sumatriptan 100mg: treatment at the earliest sign of an attack 100mg: 313 Age (mean): 40 provided 48h had elapsed since the previous % Female: 84 study treatment.

Menstrual migraine: No Pascual 2000 Study Design: Patient Group: Placebo:tablet Efficacy: p455 RCT o Headache relief within 2 hours Parallel Placebo: Rizatriptan: 10 mg tablet o Freedom from pain within 2 Age (mean): 38.2 hours N % Female: 81 Zolmitriptan: 2.5 mgtablet o Sustained freedom from pain Placebo: 154 at 24 hours Rizatriptan 10mg: Patients took a single dose of study o Functional health status Rizatriptan 10mg: Age (mean): 38.5 medication for a migraine that was not o Recurrence 308 % Female: 84 resolving spontaneously and was of o Rescue medication moderate or severe intensity. Safety: Zolmitriptan Zolmitriptan o Participants with any adverse 2.5mg: 304 2.5mg: event Age (mean): 39.4 o Participants with any serious % Female: 84 adverse event o Withdrawals due to adverse Menstrual events migraine: No Pascual 2000 Study Design: Patient Group: Placebo: oral tablet Efficacy: p588 RCT o Headache relief within 2 hours Parallel Placebo: Almotriptan 6.25mg: oral tablet o Freedom from pain within 2 Age (mean): 41.2 hours N % Female: 81.8 Almotriptan 12.5mg: oral tablet o Sustained headache response Placebo: 176 at 24 hours Almotriptan Patients were instructed to take a dose of Safety: Almotriptan 6.25mg: study medication at the onset of a o Participants with any adverse 6.25mg:360 Age (mean): 40.8 moderate-to-severe migraine. event % Female: 89.4 o Participants with any serious Almotriptan adverse event 12.5mg: 374 Almotriptan o Withdrawals due to adverse 12.5mg: events Age (mean): 41.9 % Female: 86.3

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Pfaffenrath Study Design: Patient Group: Placebo: matching tablet Efficacy: 1998 p184 RCT o Headache relief within 2 hours Parallel Placebo: Sumatriptan 25mg: white film coated tablet o Sustained headache response Age (mean): 40 at 24 hours N % Female: 80 Sumatriptan 50mg: white film coated tablet o Sustained freedom from pain Placebo: 99 at 24 hours Sumatriptan Sumatriptan 100mg: white film coated o Functional health status Sumatriptan 25mg: tablet o Recurrence 25mg: 303 Age (mean): 39 Safety: % Female: 83 Patients used the initial dose of study o Participants with any adverse Sumatriptan medication as the first treatment of a event 50mg: 303 Sumatriptan migraine and the second dose in the event o Withdrawals due to adverse 50mg: Age (mean): of recurrence within 24 hrs. events Sumatriptan 40 100mg: 298 % Female: 88

Sumatriptan 100mg: Age (mean): 40 % Female: 84

Menstrual migraine: No Pini 1995 p96 Study Design: Patient Group: Sumatriptan: 100 mgoral dispersible tablet Efficacy: RCT Age (mean): 37 o Freedom from pain within 4 Parallel % Female: 78 Placebo: oral administration hours o Functional health Sumatriptan Sumatriptan Patients took the medication at the earliest o Recurrence 100mg: 151 100mg: sign of a migraine. o Rescue medication Age (mean): NR Safety: Placebo: 87 % Female: NR o Participants with any adverse event Placebo: Age (mean): NR % Female: NR

Menstrual migraine: No Pini 1999 p64 Study Design: Patient Group: Sumatriptan: 50 mg oraltablet Efficacy: RCT % Female: 80 o Headache relief within 4 hours Parallel Placebo: oral tablet o Recurrence Sumatriptan o Rescue medication N 50mg: Patients were instructed to treat the next Safety: Age (mean): 38 mild or moderate attack. o Participants with any adverse Sumatriptan % Female: NR event 50mg:137 o Participants with any serious Placebo: adverse event Placebo:82 Age (mean): 36 % Female: NR

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Rapoport 2002 Study Design: Patient Group: Placebo: oral tablet Efficacy: pS74 RCT o Headache relief within 2 hours Parallel Placebo: Frovatriptan 0.5mg: oral tablet o Freedom from pain within 2 Age (mean): 39.8 hours N % Female: 84 Frovatriptan 1.0mg: oral tablet o Headache relief within 4 hours Placebo: 199 o Freedom from pain within 4 Frovatriptan Frovatriptan 2.5mg: oral tablet hours Frovatriptan 0.5mg: o Functional health status Recurrence 0.5mg: 114 Age (mean): 40.8 Frovatriptan 5mg: oral tablet o % Female: 84 Safety: Participants with any adverse Frovatriptan Frovatriptan 10mg: oral tablet o Frovatriptan event 1.0mg: 107 1.0mg: Frovatriptan 20mg: oral tablet Frovatriptan Age (mean): 41.6 % Female: 91 2.5mg: 219 Frovatriptan 40mg: oral tablet

Frovatriptan Frovatriptan Study medication was taken at the onset of 2.5mg: 5mg: 212 a moderate or severe migraine. Age (mean): 41.6

% Female: 87 Frovatriptan

10mg:192 Frovatriptan 5mg: Age (mean): 40.8 Frovatriptan % Female: 87 20mg: 203 Frovatriptan Frovatriptan 10mg: 40mg: 207 Age (mean): 40.3 % Female: 86

Frovatriptan 20mg: Age (mean): 40.1 % Female: 85

Frovatriptan 40mg: Age (mean): 40.4 % Female: 84

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Ryan 1997 Study Design: Patient Group: Placebo: oral administration Efficacy: p245 RCT o Headache relief within 2 hours Parallel Placebo: Avitriptan 75mg: oral administration o Freedom from pain within 2 Age (mean): NR hours N % Female: NR Avitriptan 150mg: oral administration o Headache relief within 4 hours Placebo:31 o Freedom from pain within 4 Avitriptan 75mg: Avitriptan 200mg: oral administration hours Avitriptan Age (mean): NR o Sustained headache response 75mg:60 % Female: NR Patients were given one dose of study at 24 hours medication for outpatient use to treat the o Recurrence Avitriptan Avitriptan 150mg: next migraine headache of moderate or o Rescue medication 150mg: 66 Age (mean): NR severe pain. % Female: NR Avitriptan 200mg:59 Avitriptan 200mg: Age (mean): NR % Female: NR

Menstrual migraine: No Ryan 2002 Study Design: Patient Group: Frovatriptan: 2.5mg oral tablet Efficacy: pS84 – Study 1 RCT o Headache relief within 2 hours Parallel Frovatriptan Placebo:oral tablet o Headache relief within 4 hours 2.5mg: o Freedom from pain within 2 N Age (mean): 42.3 A single dose of study medication was taken hours Frovatriptan % Female: 87 to treat an initial moderate or severe o Freedom from pain within 4 2.5mg: 214 migraine. hours Placebo: o Recurrence Placebo: 108 Age (mean): 40.2 % Female: 86

Menstrual migraine: No Ryan 2002 Study Design: Patient Group: Frovatriptan: 2.5mg oral tablet Efficacy: pS84 – Study 2 RCT o Headache relief within 2 hours Parallel Frovatriptan Placebo:oral tablet o Headache relief within 4 hours 2.5mg: o Freedom from pain within 2 N Age (mean): 41.2 A single dose of study medication was taken hours Frovatriptan % Female: 90 to treat an initial moderate or severe o Freedom from pain within 4 2.5mg: 760 migraine. hours Placebo: o Recurrence Placebo: 388 Age (mean): 41.4 % Female: 86

Menstrual migraine: No Ryan 2002 Study Design: Patient Group: Frovatriptan: 2.5mg oral tablet Efficacy: pS84 – Study 3 RCT o Headache relief within 2 hours Parallel Frovatriptan Placebo:oral tablet o Headache relief within 4 hours 2.5mg: o Freedom from pain within 2 N Age (mean): 41.1 A single dose of study medication was taken hours Frovatriptan % Female: 85 to treat an initial moderate or severe o Freedom from pain within 4 2.5mg: 480 migraine. hours Placebo: o Recurrence Placebo: Age (mean): 40.3 Treated N = 244 % Female: 85

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

SAI Group Study Design: Patient Group: Placebo: isotonic saline auto-injector Efficacy: (Cleal) 1991 RCT syringe o Headache relief within 2 hours p323 Parallel Placebo: o Freedom from pain within 2 Age (mean): 41 Sumatriptan 6mg subcutaneous: 0.5ml hours N % Female: 85 isotonic solution containing 12mg/ml as the o Functional health status Placebo: 80 succinate salt in a 0.5mL auto-injector o Recurrence Sumatriptan 6mg syringe o Rescue medication Sumatriptan 6mg sc: Safety: subcutaneous: Age (mean): 41 Patients were asked to use the auto-injector o Participants with any adverse 155 % Female: 80 to treat their next moderate or severe event migraine attack. o Participants with any serious Menstrual adverse event migraine: No o Withdrawals due to adverse events Sakai 2002 Study Design: Patient Group: Placebo: oral administration Efficacy: p376 RCT o Headache relief within 2 hours Parallel Placebo: Zolmitriptan 1mg: oral administration o Freedom from pain within 2 Age (mean): 37.5 hours N % Female: 71.4 Zolmitriptan 2.5mg: oral administration o Headache relief within 4 hours Placebo: 59 o Sustained headache response Zolmitriptan 1mg: Zolmitriptan 5mg: oral administration at 24 hours Zolmitriptan Age (mean): 38.4 o Recurrence 1mg: 52 % Female: 76.6 Patients were requested to treat only o Rescue medication moderate or severe migraine headaches Safety: Zolmitriptan Zolmitriptan with study medication. o Participants with any adverse 2.5mg: 61 2.5mg: event Age (mean): 37.6 o Participants with any serious Zolmitriptan % Female: 68.5 adverse event 5mg: 57 Zolmitriptan 5mg: Age (mean): 39.6 % Female: 80.8

Menstrual migraine: No Sandrini 2002 Study Design: Patient Group: Placebo: matching placebo tablet or Efficacy: p1210 RCT matching gelatin capsule o Headache relief within 2 hours Parallel Placebo: o Freedom from pain within 2 Age (mean): 37.5 Eletriptan 40mg: oral tablet hours N % Female: 89 o Sustained headache response Placebo:84 Eletriptan 80mg: oral tablet at 24 hours Eletriptan 40mg: o Sustained freedom from pain Eletriptan 40mg: Age (mean): 38.0 Sumatriptan 50mg: oral gelatin capsule at 24 hours 175 % Female: 88 o Functional health status Sumatriptan 100mg: oral gelatin capsule o Rescue medication Eletriptan 80mg: Eletriptan 80mg: Safety:

164 Age (mean): 39.9 o Participants with any serious % Female: 87 Patients were instructed to takea dose of adverse event study medication as soon as possible and Sumatriptan o Withdrawals due to adverse 50mg: 181 Sumatriptan within 6hours of onset if the headachewas events moderate to severe in intensity and was not 50mg: decreasing in intensity. Sumatriptan Age (mean): 37.4 100mg: 170 % Female: 90

Sumatriptan 100mg: Age (mean): 38.2 % Female: 87

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Sandrini 2007 Study Design: Patient Group: Indoprocaf coated: oral administration Efficacy: p1256 RCT ofone effervescent tablet containing o Headache relief within 2 hours Parallel Indoprocaf coated: indomethacin 25mg, prochlorperazine 2mg o Freedom from pain within 2 Age (mean): 35 and caffeine 75mg and one placebo capsule hours N % Female: 86 o Sustained headache response Indoprocaf Indoprocaf effervescent: oral at 24 hours coated: 72 Indoprocaf administration ofone encapsulated tablet o Sustained freedom from pain effervescent: containing indomethacin 25mg, at 24 hours Indoprocaf Age (mean): 34 prochlorperazine 2mg and caffeine 75mg o Recurrence effervescent: 71 % Female: 72 and one placebo effervescent tablet o Rescue medication Safety: Sumatriptan Sumatriptan Sumatriptan 50mg: oral administration o Participants with any adverse 50mg: 139 50mg: ofone encapsulated tablet containing event Age (mean): 36 sumatriptan 50mg and one placebo o Participants with any serious % Female: 78 effervescent tablet adverse event o Withdrawals due to adverse Menstrual The first dose was to be taken as soon as events migraine: No possible when the headache of moderate severity occurred. Savani 1999 p7 Study Design: Patient Group: Sumatriptan: 50 mgoral tablet Efficacy: RCT o Headache relief within 2 hours Parallel Sumatriptan Placebo: oral tablet o Freedom from pain within 2 50mg: hours N Age (mean): N/A Recurrent headache 4 to 24 hrs after dosing o Freedom from pain within 4 Sumatriptan % Female: N/A could be treated by a second dose of hours 50mg: 332 randomized medication. o Sustained headache response Placebo: at 24 hours Placebo: 156 Age (mean): N/A o Functional health status % Female: N/A o Recurrence o Rescue medication Menstrual Safety: migraine: No o Participants with any adverse event Savani 2001 Study Design: Patient Group: Sumatriptan 50mg: oral tablets Efficacy: p260 RCT o Headache relief within 2 hours Parallel Sumatriptan Sumatriptan 100mg: oral tablets o Freedom from pain within 2 50mg: hours N Age (mean): 37.6 o Sustained headache response Sumatriptan % Female: 82 at 24 hours 50mg: 123 Safety: Sumatriptan o Participants with any serious Sumatriptan 100mg: adverse event 100mg: 108 Age (mean): 36.0 o Withdrawals due to adverse % Female: 86 events

Menstrual migraine: No Schulman 2012 Study Design: Patient Group: Sumatriptan: transdermal, single-use, Efficacy: p204 RCT disposable patch that delivers sumatriptan o Headache relief within 2 hours Parallel Sumatriptan: by applying a mild electrical current to the o Freedom from pain within 2 Age (mean): 40.7 skin hours N % Female: 84 Safety: Sumatriptan: 234 Placebo: patch o Participants with any serious Placebo: adverse event Placebo: 235 Age (mean): 41.0 Patients were instructed to treat a single o Withdrawals due to adverse % Female: 86 moderate to severe migraine headache. events

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Scott 1996 Study Design: Patient Group: Placebo: oral tablet Efficacy: p613 RCT o Headache relief within 4 hours Parallel Placebo: Sumatriptan: 100mg oral tablet o Recurrence Age (mean): 41.4 N % Female: 83.8 Patients were instructed to take a Placebo: 669 tablet of sumatriptan 100mg at the onset of Sumatriptan a migraine attack of severe or moderate Sumatriptan 100mg: intensity (dose 1) and 4 h after the first dose 100mg: 680 Age (mean): 40.7 all patients took a randomized second tablet % Female: 86.4 of either sumatriptan 100 mg or placebo.

Menstrual migraine: No Sheftell 2003 Study Design: Patient Group: Placebo: oral tablet Efficacy: p202 RCT o Headache relief within 2 hours Parallel Placebo Eletriptan 20mg: oral tablet o Sustained headache response Age (mean): 42 at 24 hours N % Female: 88 Eletriptan 40mg: oral tablet o Sustained freedom from pain Placebo: 292 at 24 hours Eletriptan Eletriptan 80mg: oral tablet o Functional health status Eletriptan 20mg: o Recurrence 20mg: 290 Age (mean): 41 Patients were instructed to take a dose of o Rescue medication % Female: 85 study medication within 6 hours of onset of Safety: Eletriptan a migraine attack, provided that the o adverse event 40mg: 296 Eletriptan headache was moderate to severe in o Participants with any serious 40mg intensity and was not improving. adverse event Eletriptan Age (mean): 42 o Withdrawals due to adverse 80mg: 312 % Female: 85 events

Eletriptan 80mg Age (mean): 42 % Female: 90

Menstrual migraine: No Sheftell 2005 Study Design: Patient Group: Placebo: oral tablet Efficacy: p407 – Study 1 RCT o Headache relief within 2 hours Parallel Placebo: Sumatriptan 50mg: fast-disintegrating/ o Freedom from pain within 2 Age (mean): 41.2 rapid-release tablet hours N % Female: 88 o Sustained headache response Placebo: 513 Sumatriptan 100mg: fast-disintegrating/ at 24 hours Sumatriptan rapid-release tablet o Sustained freedom from pain Sumatriptan 50mg: at 24 hours 50mg: 517 Age (mean): 41.6 Patients were instructed to take the study o Recurrence % Female: 85 medication to treat a single migraine attack o Rescue medication Sumatriptan characterized by moderate or severe pain. Safety: 50mg: 512 Sumatriptan o Withdrawals due to adverse 100mg: events Age (mean): 41.5 % Female: 84

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Sheftell 2005 Study Design: Patient Group: Placebo: tablet Efficacy: p407 – Study 2 RCT o Headache relief within 2 hours Parallel Placebo: Sumatriptan 50mg: fast-disintegrating/ o Freedom from pain within 2 Age (mean): 39.2 rapid-release tablet hours N % Female: 87 o Sustained headache response Placebo: 505 Sumatriptan 100mg: fast-disintegrating/ at 24 hours Sumatriptan rapid-release tablet o Sustained freedom from pain Sumatriptan 50mg: at 24 hours 50mg: 511 Age (mean): 39.9 Patients were instructed to take the study o Recurrence % Female: 85 medication to treat a single migraine attack o Rescue medication Sumatriptan characterized by moderate or severe pain. Safety: 50mg: 495 Sumatriptan o Withdrawals due to adverse 100mg: events Age (mean): 40.2 % Female: 82

Menstrual migraine: No Shulman 2000 Study Design: Patient Group: Sumatriptan 6mg: subcutaneous injection Efficacy: p782 RCT o Functional health status Parallel Sumatriptan 6mg: Placebo: subcutaneous injection o Recurrence Age (mean): 40.9 o Rescue medication N % Female: 93 Patients were instructed to self-treat the Safety: Sumatriptan next moderate or severe migraine that o Participants with any adverse 6mg: 80 Placebo: occurred in the workplace, during the first 4 event Age (mean): 38.6 hours of an 8 hour workday, using o Participants with any serious Placebo: 40 % Female: 85 medication identical to that administered at adverse event a previous in clinic practice treatment. o Withdrawals due to adverse Menstrual events migraine: No Silberstein Study Design: Patient Group: Placebo: matching placebo tablet Efficacy: 2008 p114 – RCT o Freedom from pain within 2 Study 1 Parallel Placebo: Sumatriptan/Naproxen: fixed dose single- hours Age (mean): 40.8 tablet formulation of sumatriptan 85mg, o Sustained freedom from pain N % Female: 87 formulated with RT technology/naproxen at 24 hours Placebo: 297 sodium 500mg o Rescue medication Sumatriptan/ Safety: Sumatriptan/ Naproxen: Patients were instructed to treat their next o Participants with any adverse Naproxen: 283 Age (mean): 39.3 migraine while the pain was mild but not event % Female: 88 more than 1 hour after the onset of o Participants with any serious migraine head pain. adverse event Menstrual migraine: No Silberstein Study Design: Patient Group: Placebo: matching placebo tablet Efficacy: 2008 p114 – RCT o Freedom from pain within 2 Study 2 Parallel Placebo: Sumatriptan/Naproxen: fixed dose single- hours Age (mean): 41.0 tablet formulation of sumatriptan 85mg, o Sustained freedom from pain N % Female: 90 formulated with RT technology/naproxen at 24 hours Placebo: 264 sodium 500mg o Rescue medication Sumatriptan/ Safety: Sumatriptan/ Naproxen: Patients were instructed to treat their next o Participants with any adverse Naproxen: 278 Age (mean): 40.8 migraine while the pain was mild but not event % Female: 91 more than 1 hour after the onset of o Participants with any serious migraine head pain. adverse event Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Smith 2005 Study Design: Patient Group: Placebo: one placebo capsule and one Efficacy: p983 RCT placebo tablet. o Headache relief within 2 hours Parallel Placebo: o Headache relief within 4 hours Age (mean): 41.2 Naproxen Sodium: one placebo capsule o Freedom from pain within 2 N % Female: 88.4 (matching the sumatriptan 50mg-E capsule) hours Placebo: 241 and one tablet of naproxen sodium 500 mg. o Freedom from pain within 4 Naproxen Sodium: hours Naproxen Age (mean): 42.1 Sumatriptan: one sumatriptan 50mg-E o Sustained headache response Sodium: 250 % Female: 89.2 (encapsulated) capsule and one placebo at 24 hours tablet (matching the naproxen sodium o Sustained freedom from pain Sumatriptan: 229 Sumatriptan: tablet). at 24 hours Age (mean): 41.2 o Recurrence Sumatriptan/ % Female: 90.8 Sumatriptan/Naproxen:one sumatriptan o Rescue medication Naproxen: 251 50mg-E capsule and one tablet of naproxen Safety: Sumatriptan/ sodium 500mg. o Participants with any adverse Naproxen: event Age (mean): 42.5 Patients were instructed to take the study o Participants with any serious % Female: 93.6 medication following the onset of a adverse event moderate-to-severe migraine attack. o Withdrawals due to adverse Menstrual events migraine: No Solomon 1997 Study Design: Patient Group: Placebo: oral dose Efficacy: p1219 RCT o Headache relief within 2 hours Parallel Placebo: Zolmitriptan: 2.5mg oral c o Headache relief within 4 hours Age (mean): 40.2 o Freedom from pain within 2 N % Female: 85 Each patient treated a single moderate or hours Placebo: 101 severe migraine headache within 12 hours o Freedom from pain within 4 Zolmitriptan of headache onset. hours Zolmitriptan 2.5mg: o Sustained headache response 2.5mg: 200 Age (mean): 40.7 at 24 hours % Female: 85 o Functional health status o Recurrence Menstrual o Rescue medication migraine: Yes- Safety: subgroup data o Participants with any adverse available event o Withdrawals due to adverse events Spierings 2001 Study Design: Patient Group: Sumatriptan Succinate: single 50mg oral Efficacy: p944 RCT capsule o Headache relief within 2 hours Parallel Sumatriptan o Freedom from pain within 2 Succinate: Almotriptan Malate: single 12.5mg oral hours N Age (mean): 40.3 capsule o Recurrence Sumatriptan % Female: 89 o Rescue medication Succinate: 582 Patients treated a migraine headache of Safety: Almotriptan moderate or severe intensity within 60 days o Participants with any adverse Almotriptan Malate: of screening. event Malate: 591 Age (mean): 41.2 o Participants with any serious % Female: 89 adverse event

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Spierings 2004 Study Design: Patient Group: Placebo: oral disintegrating tablet Efficacy: p1133 RCT o Recurrence Parallel Placebo: Zolmitriptan: 5mg oral disintegrating tablet o Rescue medication Age (mean): 41.9 Safety: N % Female: 87.7 Patients were asked to place the study o Participants with any adverse Placebo: 342 medication on the tongue and allow the event Zolmitriptan 5mg: tablet to dissolve without the ingestion of o Participants with any serious Zolmitriptan Age (mean): 42.2 water. adverse event 5mg: 329 % Female: 85.4 o Withdrawals due to adverse events Menstrual migraine: No Stark 2000 Study Design: Patient Group: Naratriptan: 2.5mg oral tablet Efficacy: p513 RCT o Headache relief within 2 hours Parallel Naratriptan 2.5mg Placebo: oral tablet o Headache relief within 4 hours Age (mean): 41.5 o Freedom from pain within 2 N % Female: 90 Patients who did not respond to hours Naratriptan sumatriptan therapy were instructed to take o Freedom from pain within 4 2.5mg: 99 Placebo their randomized treatment (placebo or hours Age (mean): 40.3 naratriptan) for their next attack. o Functional health status (2hr Placebo: 107 % Female: 90 & 4hrs) o Safety: Menstrual o Participants with any adverse migraine: No event o Participants with any serious adverse event o Withdrawals due to adverse events Stark 2002 p23 Study Design: Patient Group: Placebo: oral tablet Efficacy: RCT o Headache relief within 2 hours Parallel Placebo: Eletriptan 40mg: oral tablet o Freedom from pain within 2 Age (mean): 42 hours N % Female: 81 Eletriptan 80mg: oral tablet o Functional health status Placebo: 238 o Recurrence Eletriptan 40mg: Patients were instructed to take the study o Rescue medication Eletriptan 40mg: Age (mean): 42 drug as soon as possible but within 6h of 453 % Female: 83 onset of the attack, provided that the headache was moderate or severe, that the Eletriptan 80mg: Eletriptan 80mg: headache had not spontaneously improved, 462 Age (mean): 42 and provided that any aura phase had % Female: 85 ended.

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Steiner 2003 Study Design: Patient Group: Eletriptan 40mg: oral tablet Efficacy: p942 RCT o Headache relief within 2 hours Parallel Eletriptan 40mg: Eletriptan 80mg: oral tablet o Freedom from pain within 2 Age (mean): 40.3 hours N % Female: 88 Zolmitriptan 2.5mg: thin gelatin capsule o Sustained headache response Eletriptan 40mg: containing zolmitriptan at 24 hours 392 Eletriptan 80mg: o Sustained freedom from pain Age (mean): 40.4 Placebo: thin gelatin capsule containing at 24 hours Eletriptan 80mg: % Female: 83 inactive substance OR oral tablet o Functional health status 396 o Recurrence Zolmitriptan Patients were instructed to treat, within 4h o Rescue medication Zolmitriptan 2.5mg: of its onset but after resolution of any aura, Safety: 2.5mg: 405 Age (mean): 40.1 one attack of migraine headache of o Participants with any adverse % Female: 83 moderate or severe intensity and not event Placebo: 144 improving at the time of treatment. o Participants with any serious Placebo: adverse event Age (mean): 39.9 % Female: 86

Menstrual migraine: No Sunshine 2006 Study Design: Patient Group: Eletriptan 40mg: oral administration Efficacy: p1107 RCT o Headache relief within 2 hours Parallel Eletriptan 40mg: Eletriptan 80mg: oral administration o Headache relief within 4 hours Age (mean): 39.2 N % Female: 84.6 Rizatriptan 10mg: oral administration Eletriptan 40mg: 26 Eletriptan 80mg: Patients were instructed to take the study Age (mean): 36.5 drug within 4 hours of the onset of a Eletriptan 80mg: % Female: 65.4 moderate to severe migraine headache 26 provided that any aura phase had ended. Rizatriptan 10mg: Rizatriptan 10mg: Age (mean): 37.3 27 % Female: 85.2

Menstrual migraine: No Taylor 2007 Study Design: Patient Group: Sumatriptan/Naproxen sodium: Efficacy: p195 – Study 1 RCT combination tablet containing sumatriptan o Functional health status Parallel Sumatriptan/ 85mg formulated with RT technology and (2hrs& 4hrs) Naproxen sodium: naproxen sodium 500mg o Rescue medication N Age (mean): 39.3 Safety: Sumatriptan/ % Female: 88 Placebo: oral tablet o Participants with any serious Naproxen adverse event sodium: 280 Placebo: Patients were instructed to treat a migraine Age (mean): 40.8 attack within 1 hour of onset of mild pain Placebo: 296 % Female: 87 and to treat only while pain was mild.

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Taylor 2007 Study Design: Patient Group: Sumatriptan/Naproxen sodium: Efficacy: p195 – Study 2 RCT combination tablet containing sumatriptan o Functional health status (2hrs Parallel Sumatriptan/ 85mg formulated with RT technology and &4hrs) Naproxen sodium: naproxen sodium 500mg o Rescue medication N Age (mean): 40.8 Safety: Sumatriptan/ % Female: 91 Placebo: oral tablet o Participants with any serious Naproxen adverse event sodium: 276 Placebo: Patients were instructed to treat a migraine Age (mean): 41.0 attack within 1 hour of onset of mild pain Placebo: 259 % Female: 90 and to treat only while pain was mild.

Menstrual migraine: No Teall 1998 p281 Study Design: Patient Group: Placebo: oral administration Efficacy: RCT o Headache relief within 2 hours Parallel Placebo: Rizatriptan 5mg: oral administration o Recurrence Age (mean): 40.6 Safety: N % Female: 85 Rizatriptan 10mg: oral administration o Participants with any adverse Placebo: 458 event Rizatriptan 5mg: Patients were instructed to take the study o Participants with any serious Rizatriptan 5mg: Age (mean): 40.5 medication on experiencing a moderate or adverse event 456 % Female: 86 severe headache that was not resolving spontaneously. Rizatriptan 10mg: Rizatriptan 10mg: 304 Age (mean): 40.7 % Female: 88

Menstrual migraine: No Tepper 1998 Study Design: Patient Group: Placebo: suppository Efficacy: p31 RCT o Headache relief within 2 hours Parallel Placebo: Sumatriptan: 25mg suppository o Freedom from pain within 2 Age (mean): 40 hours N % Female: 90 Patients randomly assigned to use a o Functional health status Placebo: 60 sumatriptan suppository or placebo at home o Recurrence Sumatriptan for treating a moderate or severe migraine Safety: Sumatriptan 25mg: attack. o Participants with any adverse 25mg: 66 Age (mean): 41.6 event % Female: 92 o Withdrawals due to adverse events Menstrual migraine: No Tepper 1999 Study Design: Patient Group: Placebo: two oral tablets Efficacy: p254 RCT o Headache relief within 2 hours Parallel Placebo: Zolmitriptan 2.5mg: one placebo tablet plus o Freedom from pain within 2 Age (mean): 41.6 one 2.5mg zolmitriptan tablet hours N % Female: 83 Safety: Placebo: 550 Zolmitriptan 5mg: two oral 2.5mg o Participants with any adverse Zolmitriptan zolmitriptan tablets event Zolmitriptan 2.5mg: o Participants with any serious 2.5mg: 550 Age (mean): 41.5 Patients who did not respond to the 1st adverse event % Female: 85 2.5mg zolmitritpan therapy at 2hrs were Zolmitriptan instructed to take their next randomized 5mg: 543 Zolmitriptan 5mg: treatment. Age (mean): 41.3 % Female: 85

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Tepper 2006 Study Design: Patient Group: Placebo: conventional tablet Efficacy: p115 RCT o Headache relief within 2 hours Parallel Placebo: Sumatriptan 25mg: conventional tablet o Headache relief within 4 hours Age (mean): 37.8 o Freedom from pain within 2 N % Female: 80 Sumatriptan 50mg: conventional tablet hours Placebo: 138 Safety: Sumatriptan Sumatriptan 100mg: conventional tablet o Participants with any adverse Sumatriptan 25mg: event 25mg: 150 Age (mean): 37.9 Patients were instructed to treat a single o Participants with any serious % Female: 68 moderate or severe probable migraine adverse event Sumatriptan attack with one tablet. o Withdrawals due to adverse 50mg: 141 Sumatriptan events 50mg: Sumatriptan Age (mean): 39.1 100mg: 152 % Female: 74

Sumatriptan 100mg: Age (mean): 39.3 % Female: 73

Menstrual migraine: No Tfelt-Hansen Study Design: Patient Group: Placebo: oral tablet Efficacy: 1995 p923 RCT o Headache relief within 2 hours Parallel Placebo: Sumatriptan 100mg: oral tablet o Recurrence Age (mean): 39 o Rescue medication N % Female: 77 LAS+MTC (900mg aspirin + 10mg Safety: Placebo: 126 metoclopramide): oral tablet o Participants with any adverse Sumatriptan event Sumatriptan 100mg: Patients were instructed to treat two o Withdrawals due to adverse 100mg: 122 Age (mean): 39 consecutive attacks with the study events % Female: 78 medication as soon as the headache LAS+MTC: 137 severity reached 2-3 (moderate to severe LAS+MTC: pain). Age (mean): 40 % Female: 78

Menstrual migraine: No Tfelt-Hansen Study Design: Patient Group: Placebo: three placebo tablets Efficacy: 1998 p748 RCT o Headache relief within 2 hours Parallel Placebo: Rizatriptan 5mg: one active tablet and two o Freedom from pain within 2 Age (mean): 38.3 placebo tablets hours N % Female: 82 o Functional health status Placebo: 160 Rizatriptan 10mg: one active tablet and two o Recurrence Rizatriptan 5mg: placebo tablets o Rescue medication Rizatriptan 5mg: Age (mean):38.3 Safety: 164 % Female: 84 Sumatriptan 100mg: one active tablet and o Participants with any adverse two placebo tablets event Rizatriptan 10mg: Rizatriptan 10mg: o Participants with any serious 387 Age (mean): 37 Patients took the study medication for a adverse event % Female: 82 migraine that was not resolving o Withdrawals due to adverse Sumatriptan spontaneously and was of moderate or events 100mg: Sumatriptan severe intensity. 388 100mg: Age (mean): 39.2 % Female: 80

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Tfelt-Hansen Study Design: Patient Group: Placebo: oral administration Efficacy: 2006 p389 RCT o Freedom from pain within 2 Parallel Placebo: Sumatriptan: 50mg oral administration hours Age (mean): 38 o Sustained freedom from pain N % Female: 83 Patients were instructed to treat a single at 24 hours Placebo: 48 migraine attack within one hour after the o Rescue medication Sumatriptan attack started, but only if the attack was still Safety: Sumatriptan 50mg: in the mild headache phase. o Participants with any adverse 50mg: 53 Age (mean): 37.1 event % Female: 74

Menstrual migraine: No Thompson Study Design: Patient Group: Sumatriptan: one 100mg dispersible tablet Efficacy: 1992 p177 RCT o Headache relief within 2 hours Parallel Sumatriptan Aspirin + Metoclopramide: 3 soluble 300mg o Freedom from pain within 2 100mg: aspirin tablets plus one 10mg hours N Age (mean): 42 metoclopramide tablet o Recurrence Sumatriptan % Female: 75 o Rescue medication 100mg: 175 Patients were instructed to take the study Safety: Aspirin + medication for up to three attacks. o Participants with any adverse Aspirin + Metoclopramide: event Metoclopramide: Age (mean): 39 o Withdrawals due to adverse 183 % Female: 84.2 events

Menstrual migraine: No Tuchman 2006 Study Design: Patient Group: Placebo: oral tablet Safety: p1019 RCT o Participants with any adverse Parallel Placebo: Zolmitriptan 2.5mg: oral tablet event Age (mean): 38.7 N % Female: 100 Patients were instructed to acutely treat at Placebo: 161 least one, but no more than two, moderate Zolmitriptan to severe menstrual migraine attacks per Zolmitriptan 2.5mg: menstrual period over 3 months, each with 2.5mg: 175 Age (mean): 38.3 a single dose of study medication. % Female: 100

Menstrual migraine: Yes (100%) Visser 1996 Study Design: Patient Group: Placebo: oral capsule Efficacy: p1132 RCT o Headache relief within 2 hours Parallel Placebo: Rizatriptan 10mg: oral capsule o Freedom from pain within 2 Age (mean): 39 hours N % Female: 93 Rizatriptan 20mg: oral capsule o Functional health status Placebo: 85 o Recurrence Rizatriptan 10mg: Sumatriptan succinate 100mg: oral capsule Safety: Rizatriptan 10mg: Age (mean): 40 o Participants with any adverse 89 % Female: 87 Patients were instructed to take study event medication during a moderate or severe o Withdrawals due to adverse Rizatriptan 20mg: Rizatriptan 20mg: migraine attack that had not started to events 82 Age (mean): 40 resolve spontaneously. % Female: 90 Sumatriptan succinate 100mg: Sumatriptan 72 succinate 100mg: Age (mean): 41 % Female: 90

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Wang 2007 p39 Study Design: Patient Group: Placebo: intranasalspray Efficacy: RCT o Headache relief within 2 hours Parallel Placebo: Sumatriptan: 20mgintranasalspray o Freedom from pain within 2 Age (mean): 37.4 hours N % Female: 78.6 Patients were instructed to administer a o Recurrence Placebo: 29 single intranasal dose at the onset of a Safety: Sumatriptan nasal moderate or severe migraine attack, with or o Participants with any adverse Sumatriptan spray 20mg: without aura. event nasal spray Age (mean): 37 o Participants with any serious 20mg: 29 % Female: 92.9 adverse event

Menstrual migraine: No Wells 2001 Study Design: Patient Group: Eletriptan 40mg: oral dose Efficacy: p157 & Wells RCT o Headache relief within 2 hours 2003 p438 Parallel Eletriptan 40mg: Eletriptan 80mg: oral dose Age (mean): NR N % Female: 85.7 Sumatriptan 50mg: oral dose Eletriptan 40mg: 93 Eletriptan 80mg: Sumatriptan 100mg: oral dose Age (mean): NR Eletriptan 80mg: % Female: 89 The treatment was taken following onset of 83 migraine headache of severe or moderate Sumatriptan intensity Sumatriptan 50mg: 50mg: 181 Age (mean): NR % Female: 89.9 Sumatriptan 100mg: 179 Sumatriptan 100mg: Age (mean): NR % Female: 86.7

Menstrual migraine: No White 2011 Study Design: Patient Group: Sumatriptan 85mg/Naproxen sodium Safety: p910 RCT 500mg: oral tablets o Participants with any adverse Parallel Sumatriptan event 85mg/Naproxen Sumatriptan 85mg: oral tablets o Withdrawals due to adverse N sodium 500mg: events Sumatriptan Age (mean): 38.9 Naproxen Sodium 500mg: oral tablets 85mg/Naproxen % Female: 77 sodium 500mg: Patients were asked to use the study 127 Sumatriptan medication to treat migraine episodes 85mg: during the ensuing 6 months. Sumatriptan Age (mean): 39.7 85mg: 120 % Female: 87

Naproxen Naproxen Sodium Sodium 500mg: 500mg: 127 Age (mean): 39.2 % Female: 83

Menstrual migraine: No

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Reference Study Details Patients Intervention Outcomes

Winner 2003 Study Design: Patient Group: Placebo: oral tablets Efficacy: p1214 – Study RCT o Freedom from pain within 2 1 Parallel Placebo: Sumatriptan 50mg: oral tablets hours Age (mean): 40.7 o Freedom from pain within 4 N % Female: 87 Sumatriptan 100mg: oral tablets hours Placebo: 121 o Rescue medication Sumatriptan Patients were instructed to treat their next Safety: Sumatriptan 50mg: migraine at the first sign of pain, while pain o Participants with any adverse 50mg: 123 Age (mean): 39.8 was mild, but not more than 2 hours after event % Female: 88 the onset of pain. o Participants with any serious Sumatriptan adverse event 100mg: 118 Sumatriptan 100mg: Age (mean): 40.5 % Female: 89

Menstrual migraine: No Winner 2003 Study Design: Patient Group: Placebo: oral tablets Efficacy: p1214 – Study RCT o Freedom from pain within 2 2 Parallel Placebo: Sumatriptan 50mg: oral tablets hours Age (mean): 42.7 o Freedom from pain within 4 N % Female: 91 Sumatriptan 100mg: oral tablets hours Placebo: 123 o Rescue medication Sumatriptan Patients were instructed to treat their next Safety: Sumatriptan 50mg: migraine at the first sign of pain, while pain o Participants with any adverse 50mg: 115 Age (mean): 43.5 was mild, but not more than 2 hours after event % Female: 85 the onset of pain. o Participants with any serious Sumatriptan adverse event 100mg: 116 Sumatriptan 100mg: Age (mean): 41.7 % Female: 90

Menstrual migraine: No Winner 2006 Study Design: Patient Group: Control: inactive vehicle injection Efficacy: p1582 – Study RCT o Freedom from pain within 2 1 Parallel Control: Sumatriptan: 6mg subcutaneous injection hours Age (mean): 41.4 o Sustained freedom from pain N % Female: 82 Patients were instructed to treat a morning at 24 hours Control: 153 migraine within 1 hr of awakening with o Functional health status Sumatriptan 6mg: moderate or severe pain. o Rescue medication Sumatriptan Age (mean): 40.2 Safety: 6mg: 146 % Female: 84 o Participants with any serious adverse event Menstrual o Withdrawals due to adverse migraine: No events Winner 2006 Study Design: Patient Group: Control: inactive vehicle injection Efficacy: p1582 – Study RCT o Freedom from pain within 2 2 Parallel Control: Sumatriptan: 6mg subcutaneous injection hours Age (mean): 39.3 o Sustained freedom from pain N % Female: 81 Patients were instructed to treat a morning at 24 hours Control: 139 migraine within 1 hr of awakening with o Functional health status Sumatriptan 6mg: moderate or severe pain. o Rescue medication Sumatriptan Age (mean): 38.8 Safety: 6mg: 149 % Female: 93 o Participants with any serious adverse event Menstrual o Withdrawals due to adverse migraine: No events

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Appendix E: Risk of Bias Assessment Summary

INCOMPLETE INCOMPLETE OUTCOME ADEQUATE BLINDING OF OUTCOME DATA ALLOCATION DATA AUTHOR/YEAR (pg reference) SEQUENCE OUTCOMES ADDRESSED – FOR CONCEALMENT? ADDRESSED – GENERATION? ASSESSMENT? EFFICACY FOR SAFETY OUTCOMES? OUTCOMES? Ahrens 1999 p525 Unclear Unclear Unclear Unclear Low Banerjee 1992-39 Unclear Unclear Unclear High Unclear Barbanti 2012 p407 Low Low Low Low Low Bates 1994-1587 Unclear Unclear Low Low Low Bomhof 1999 p173 Unclear Unclear Unclear Unclear Unclear Bousser 1993 p211 Low Unclear Unclear Unclear Unclear Brandes 2005-735 + Unclear Unclear Unclear Low Low Silberstein 2007-673 Brandes 2007-1443-S1 Unclear Unclear Unclear Low Low Brandes 2007-1443-S2 Unclear Unclear Unclear Low Low Bussone 2000 p272 Unclear Unclear Unclear Unclear High Cady 1998 p1013 Unclear Unclear Unclear Low Low Cady 2001 p1 Unclear Unclear Unclear High Low Cady 2006-914-S1 Low Low Unclear Low Low Cady 2006-914-S2 Low Low Unclear Low Low Cady 2009-687 Low Low Low Low Low Carpay 1997 p591 Unclear Unclear High Unclear Unclear Carpay 2004 p214 Unclear Unclear Unclear Low Low

Charlesworth 2003 p653 Low Unclear Low Low Low Colman 2001 p127 Unclear Unclear Low Low Unclear Cull 1997 p490 Unclear Unclear Unclear Unclear Low Dahlof 1998 p535 Low Unclear Low Unclear Unclear Dahlof 2001 p1811 Unclear Unclear Unclear Low Low Dahlof 2009-7 Low Low Unclear High Unclear Di Monda 2003 p835 Low Unclear High Unclear High Diamond 1998 p234 Unclear Unclear Unclear Unclear Unclear Diener 2002 p99 Low Low Unclear Unclear Unclear Diener 2004 p50 Low Unclear Low Unclear Unclear Diener 2005-874+Diener 2005- Unclear Unclear Unclear Low Low 1603+Diener 2005-41 Diener 2011-573 Low Low Low Low Low Dodick 2005 p125 Unclear Unclear High Low Low Dowson 2002 p101 Unclear Low Low Low Low Dowson 2002-453 Unclear Unclear Unclear Low Low Dowson 2003-573 Unclear Unclear High Unclear Low Eletriptan Steering Committee in Low Low Unclear Low Low Japan 2002-416 Farkkila 2003 p463 Low Low Low Low Low Freidman 2010 p7 Low Unclear Low High High Freitag 2001 p391 Unclear Unclear Low Unclear Unclear

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INCOMPLETE INCOMPLETE OUTCOME ADEQUATE BLINDING OF OUTCOME DATA ALLOCATION DATA AUTHOR/YEAR (pg reference) SEQUENCE OUTCOMES ADDRESSED – FOR CONCEALMENT? ADDRESSED – GENERATION? ASSESSMENT? EFFICACY FOR SAFETY OUTCOMES? OUTCOMES? Freitag 2008 p921 Low Unclear Unclear Low Low Freitag 2008-368 Low Low Unclear Low Low Gallagher 2000 p119 Unclear Unclear Low Unclear Unclear Garcia-Ramos 2003 p869 Unclear Unclear Low Low Low Gawel 2005 p7 Unclear Unclear Low Low Low Geraud 2002 p88 Low Unclear Unclear Unclear Unclear Gijsman 1997 p647 Unclear Unclear Unclear Unclear Unclear Goadsby 2000 p156 Low Unclear Low Low Low Goadsby 2007 p34 Unclear Unclear Low Unclear Unclear Goadsby 2008-383 Unclear Unclear Unclear Low Low Gobel 2000 p981 Unclear Unclear Unclear Unclear Unclear Goldstein 2002 p41 Unclear Unclear Unclear Unclear Unclear Goldstein 2012 p1402 Unclear Unclear Low Low Low Gross 1994-559 Unclear Unclear Unclear Low Low Gruffyd-Jones 2001 p237 Low Unclear Low Low Low Henry 1993-432 Unclear Unclear Unclear Low Low Ho 2008 p1304 Unclear Unclear Unclear High High Ho 2008-2115 Low Low Low Low Low Ishkanian 2007-99 Low Low Low Low Low Jelinski 2006 p73 Low Unclear Unclear Low Low Jensen 1995 p423 Unclear Unclear Unclear High High Kaniecki 2006 p1535 Unclear Unclear Unclear Low Low Klapper 2000 p585 Unclear Unclear Low Unclear Unclear Klapper 2004 p918 Unclear Unclear Low Low Low Klassen 1997 p640 Unclear Unclear Unclear Low Low Kramer 1998 p773 Low Low Unclear Unclear Unclear Kudrow 2005 p1151 Unclear Unclear Low Low Low Landy 2004 p913 Unclear Unclear Unclear Low Low Lipton 2009 p826 Unclear Unclear Unclear Unclear Low Loder 2005 p381 Unclear Unclear Low Low Low Mannix 2007-414-S1 Low Low Low Low Low Mannix 2007-414-S2 Low Low Low Low Low Mannix 2009-106-S1 Low Low Unclear Low Low Mannix 2009-106-S2 Low Low Unclear Low Low Massiou 2005 p774 Unclear Unclear Unclear Low Low Mathew 2003 p214 Unclear Unclear Low Low Low Mathew 2007-189 Unclear Unclear Low Low Low Mellor 1991 p306 Unclear Unclear Unclear Low Low Misra 2007 p175 Low Low High Low Low Misra 2010-175 Low Unclear Low Low Low Myllyla 1997 p201 Unclear Unclear Low Low Low

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INCOMPLETE INCOMPLETE OUTCOME ADEQUATE BLINDING OF OUTCOME DATA ALLOCATION DATA AUTHOR/YEAR (pg reference) SEQUENCE OUTCOMES ADDRESSED – FOR CONCEALMENT? ADDRESSED – GENERATION? ASSESSMENT? EFFICACY FOR SAFETY OUTCOMES? OUTCOMES? Nappi 1994-138 Unclear Unclear Unclear Low Low Olesen 2004 p671 Unclear Unclear Low Low Low Pascual 2000 p455 Unclear Unclear Unclear Low Low Pascual 2000 p588 Low Low Low Low High Pfaffenrath 1998 p184 Unclear Unclear Low Unclear Unclear Pini 1995 Unclear Unclear Unclear Low Low Pini 1999-57 Unclear Unclear Unclear High Low Rapoport 2002 pS74 Unclear Unclear Unclear Low Low Ryan 1997-1225-S1 Unclear Unclear Unclear Low Low Ryan 1997-1225-S2 Unclear Unclear Unclear Low Low Ryan 2002-S84-S1 Unclear Unclear Unclear Low Unclear Ryan 2002-S84-S2 Unclear Unclear Unclear Low Unclear Ryan 2002-S84-S3 Unclear Unclear Unclear Low Unclear Sakai 2002 p376 Unclear Unclear Unclear Low Low Sandrini 2002 p1210 Unclear Unclear Low Unclear Low Sandrini 2007 p1256 Low Unclear Low Low Low Savani 1999 p7 Unclear Unclear Unclear Low Low Savani 2001 p260 Unclear Unclear Unclear Low Low Schulman 2012-204 Unclear Unclear Unclear Low Unclear Scott 1996 p613 Unclear Unclear Unclear Low Low Sheftell 2003 p202 Low Low Low Low Low Sheftell 2005 407-S1 Low Low Unclear Unclear Low Sheftell 2005 407-S2 Low Low Unclear Unclear Low Schulman 2000 p782 Unclear Low Low Unclear Unclear Silberstein 2008-114-S1 Low Unclear Low Low Low Silberstein 2008-114-S2 Low Unclear Low Unclear Unclear Smith 2005 p983 Unclear Unclear Low Low Low Solomon 1997 p1219 Unclear Low Low Low Low Spierings 2001 p944 Unclear Unclear Low Low Low Spierings 2004 p1133 Unclear Unclear Low Low Low Stark 2000-513 Unclear Unclear Low Low Low Stark 2002-23 Unclear Unclear Unclear Low High Steiner 2003 p942 Low Low Low Low Low Sunshine 2006 p1107 Low High High Low Unclear Taylor 2007 p195-S1 Unclear Unclear Unclear Low Low Taylor 2007 p195-S2 Unclear Unclear Unclear Low Low Teall 1998 p281 Unclear Unclear Low Low Low Tepper 1998 p31 Unclear Unclear Unclear Low Low Tepper 1999 p254 Low Low Low Low Low Tepper 2006 p115 Unclear Unclear Low Low Low Tfelt-Hansen 1995 p923 Unclear Unclear Unclear Low Low Tfelt-Hansen 1998 p748 Low Low Low Low Low Tfelt-Hansen 2006 p389 Unclear Unclear Unclear Low Low

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INCOMPLETE INCOMPLETE OUTCOME ADEQUATE BLINDING OF OUTCOME DATA ALLOCATION DATA AUTHOR/YEAR (pg reference) SEQUENCE OUTCOMES ADDRESSED – FOR CONCEALMENT? ADDRESSED – GENERATION? ASSESSMENT? EFFICACY FOR SAFETY OUTCOMES? OUTCOMES? The Multinational Oral Sumatriptan and Cafergot Low Unclear Low Low Low Comparative Study Group (MOSCC) 1991-314 The Oral Sumatriptan Dose- Defining Study Group (OSDD) Unclear Unclear Low Low Low 1991-300 The Sumatriptan Auto-Injection Low Unclear Low Unclear Low Study Group(SAI) 1991-323 Thompson 1992 p177 Low Low Low Low Low Tuchman 2006 p1019 Unclear Unclear Unclear Unclear Low Visser 1996 p1132 Low Unclear Low Low Low Wang 2007-39 Low Unclear Low Low Low Wells 2001 p157 Unclear Unclear Unclear Low Unclear White 1011 p910 Unclear Unclear Unclear High Low Winner 2003-1214-S1 Low Low Low Low Low Winner 2003-1214-S2 Low Low Low Low Low Winner 2006-1582-S1 Low Low Low Unclear Unclear Winner 2006-1582-S2 Low Low Low Unclear Unclear

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Appendix F: Summary of Results – Random and Fixed Effects Models

Table F.1: 2 hour headache relief: odds ratios, relative risks and percent of patients with 2 hour headache relief for each treatment compared to placebo – random-effects and fixed effects models

Fixed-effects Model Random-effects Model - Informative Priors % Patients with % Patients with OR RR* OR RR* headache relief headache relief at 2 h (95% at 2 h* (95% (95% CrI) (95% CrI) (95% CrI) (95% CrI) CrI)* CrI)

Placebo 27% 27.4% NA NA NA NA (26%,28%) (26.5%,28.4%)

NSAID 2.62 1.82 49.2% 2.24 1.67 45.9% (1.96,3.53) (1.55,2.1) (42.1%,56.6%) (1.95,2.58) (1.55,1.8) (42.5%,49.3%)

Acetaminophen 2.93 1.92 52% 2.89 1.9 52.2% (1.08,7.84) (1.06,2.77) (28.7%,74.3%) (1.36,6.28) (1.24,2.57) (34%,70.3%)

Aspirin 2.33 1.72 46.3% 2.3 1.7 46.5% (1.11,4.89) (1.08,2.39) (29.1%,64.3%) (1.53,3.45) (1.34,2.07) (36.6%,56.5%) SD Eletriptan 3.42 2.07 55.8% 3.64 2.11 57.9% Tablet (2.73,4.28) (1.85,2.28) (50.3%,61.1%) (3.28,4.05) (2.01,2.22) (55.4%,60.4%)

SD Sumatriptan 2.67 1.84 49.7% 2.6 1.81 49.5% Tablet (2.25,3.18) (1.68,2.01) (45.5%,53.9%) (2.4,2.81) (1.73,1.89) (47.6%,51.4%)

SD Rizatriptan 3.65 2.13 57.4% 3.59 2.1 57.6% Tablet (2.85,4.67) (1.9,2.36) (51.4%,63.3%) (3.17,4.07) (1.98,2.22) (54.6%,60.5%)

SD Frovatriptan 2.01 1.58 42.6% 2.03 1.59 43.4% Tablet (1.39,2.91) (1.26,1.92) (34%,51.8%) (1.72,2.4) (1.44,1.74) (39.4%,47.6%)

SD Almotriptan 2.55 1.8 48.5% 2.47 1.76 48.2% Tablet (1.87,3.48) (1.52,2.09) (41%,56.2%) (2.15,2.83) (1.63,1.89) (44.9%,51.6%)

SD Zolmitriptan 2.72 1.86 50.2% 2.54 1.78 48.9% Tablet (2.14,3.47) (1.63,2.09) (44.2%,56.2%) (2.29,2.81) (1.69,1.89) (46.4%,51.4%)

SD Naratriptan 2.13 1.63 44.1% 2.03 1.58 43.3% Tablet (1.35,3.41) (1.23,2.07) (33.2%,55.7%) (1.58,2.6) (1.36,1.81) (37.4%,49.4%)

SD BI 44370 TA 3.33 2.04 55.2% 3.38 2.05 56% Tablet (1.41,8.01) (1.27,2.78) (34.2%,74.7%) (1.87,6.13) (1.51,2.55) (41.4%,69.8%)

HD Sumatriptan 3.03 1.96 52.8% 3 1.94 53.1% Tablet (2.55,3.6) (1.79,2.13) (48.6%,57%) (2.76,3.26) (1.85,2.02) (51.2%,55.1%)

SD Rizatriptan 5.84 2.53 68.3% 6.15 2.55 69.9% ODT (3.65,9.35) (2.12,2.9) (57.6%,77.4%) (4.53,8.49) (2.29,2.8) (63.2%,76.1%)

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SD Sumatriptan 2.99 1.95 52.5% 3.09 1.97 53.9% Nasal Spray (1.89,4.73) (1.52,2.36) (41.2%,63.5%) (2.42,3.99) (1.74,2.2) (47.8%,60%)

SD Sumatriptan Subcutanous 8.72 2.83 76.3% 8.44 2.78 76.1% Injection (5.53,13.94) (2.47,3.14) (67.3%,83.6%) (5.97,12.13) (2.5,3.03) (69.6%,81.8%)

SD Sumatriptan 2.55 1.8 48.5% 2.59 1.8 49.4% patch (1.41,4.64) (1.27,2.35) (34.3%,63.2%) (1.91,3.55) (1.53,2.09) (41.9%,57.2%)

SD Zolmitriptan 2.91 1.92 51.8% 2.75 1.86 51% Nasal Spray (1.48,5.69) (1.31,2.51) (35.3%,67.8%) (2.02,3.76) (1.58,2.14) (43.2%,58.6%)

SD Zolmitriptan 5.3 2.45 66.2% 5.28 2.43 66.6% ODT (2.34,11.98) (1.72,3.03) (46.4%,81.6%) (3.55,7.95) (2.09,2.75) (57.3%,74.9%)

Ergots 1.53 1.34 36.1% 1.68 1.42 38.8% (0.92,2.51) (0.94,1.79) (25.4%,48.1%) (1.31,2.14) (1.21,1.63) (33.2%,44.6%) Aspirin with 2.81 1.89 51% 2.64 1.82 49.9% antiemetic (1.77,4.52) (1.46,2.32) (39.5%,62.5%) (2.1,3.32) (1.61,2.04) (44.3%,55.6%)

Triptan with 10.93 2.97 80.1% 10.82 2.93 80.3% Acetaminophen (3.54,38.39) (2.1,3.48) (56.7%,93.4%) (4.3,31.82) (2.25,3.39) (61.9%,92.3%)

Triptan with 4.59 2.33 62.9% 4.23 2.24 61.5% NSAID (3.12,6.78) (1.98,2.66) (53.6%,71.5%) (3.6,4.97) (2.09,2.39) (57.6%,65.3%)

Acetaminophen, dichloralphenazo 1.67 1.41 38.1% 1.57 1.36 37.2% ne, and (0.55,5.01) (0.62,2.41) (16.9%,64.9%) (0.72,3.37) (0.78,2.05) (21.3%,56%) isometheptene

LD Eletriptan 3.45 2.08 56.1% 3.32 2.03 55.6% Tablet (2.27,5.26) (1.69,2.46) (45.7%,66%) (2.68,4.12) (1.83,2.23) (50.4%,60.8%)

LD Sumatriptan 2.16 1.65 44.4% 2.04 1.59 43.5% Tablet (1.46,3.18) (1.3,2.01) (35.1%,54%) (1.72,2.42) (1.43,1.75) (39.4%,47.8%)

LD Rizatriptan 2.89 1.91 51.6% 2.77 1.87 51.1% Tablet (1.9,4.39) (1.53,2.3) (41.3%,61.8%) (2.28,3.37) (1.68,2.05) (46.3%,55.9%)

LD Frovatriptan 1.02 1.02 27.4% 1.04 1.03 28.1% Tablet (0.57,1.84) (0.64,1.5) (17.3%,40.5%) (0.72,1.49) (0.78,1.31) (21.3%,36%)

LD Almotriptan 2.12 1.63 43.9% 1.96 1.55 42.5% Tablet (1.27,3.56) (1.18,2.11) (31.9%,56.8%) (1.54,2.48) (1.34,1.77) (36.8%,48.3%)

LD Zolmitriptan 2.15 1.64 44.3% 2.03 1.58 43.4% Tablet (0.91,5.14) (0.93,2.43) (25.2%,65.5%) (1.08,3.81) (1.06,2.16) (29%,58.9%)

LD BI 44370 TA 1.52 1.34 36% 1.55 1.35 36.9% Tablet (0.62,3.71) (0.69,2.14) (18.7%,57.7%) (0.81,2.88) (0.85,1.9) (23.4%,52%)

HD Eletriptan 5.22 2.44 65.9% 5.11 2.4 65.9% Tablet (4.04,6.73) (2.21,2.66) (59.9%,71.3%) (4.5,5.8) (2.28,2.53) (63%,68.6%)

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HD Rizatriptan 4.89 2.39 64.4% 4.76 2.34 64.3% Tablet (2.22,10.8) (1.67,2.97) (45.2%,79.9%) (2.86,8) (1.89,2.75) (52%,75.1%)

HD Frovatriptan 1.85 1.5 40.6% 1.87 1.51 41.3% Tablet (1.06,3.21) (1.05,2.01) (28.2%,54.2%) (1.39,2.5) (1.25,1.78) (34.4%,48.6%)

HD Almotriptan 2.79 1.88 50.8% 2.68 1.84 50.3% Tablet (1.67,4.65) (1.41,2.35) (38.2%,63.1%) (2.05,3.51) (1.59,2.08) (43.7%,56.9%)

HD Zolmitriptan 2.91 1.92 51.8% 2.58 1.8 49.4% Tablet (2.13,4) (1.63,2.22) (44.1%,59.5%) (2.27,2.93) (1.68,1.92) (46.2%,52.5%)

HD BI 44370 TA 4.24 2.26 61% 4.31 2.26 62% Tablet (1.81,9.91) (1.49,2.92) (40.1%,78.5%) (2.44,7.65) (1.75,2.72) (48.1%,74.2%)

SD Tonaberstat 1.2 1.14 30.6% 1.17 1.12 30.6% (0.56,2.55) (0.63,1.8) (17%,48.5%) (0.74,1.81) (0.8,1.48) (22%,40.6%)

LD Tonaberstat 1.07 1.05 28.3% 1.05 1.03 28.3% (0.5,2.3) (0.57,1.7) (15.5%,45.9%) (0.66,1.64) (0.73,1.39) (20%,38.1%) LD Rizatriptan 3.59 2.11 57% 3.71 2.13 58.4% ODT (1.9,6.84) (1.53,2.66) (41.3%,71.6%) (2.6,5.36) (1.8,2.45) (49.6%,66.9%)

LD Sumatriptan 1.94 1.55 41.8% 2.01 1.58 43.2% Nasal Spray (1.19,3.16) (1.13,2) (30.6%,53.8%) (1.55,2.63) (1.34,1.82) (36.9%,49.8%)

LD Sumatriptan 6.6 2.63 70.9% 6.66 2.61 71.6% Suppositories (2.35,19.1) (1.72,3.26) (46.5%,87.5%) (3.11,14.87) (1.97,3.11) (54.1%,84.8%)

LD Zolmitriptan 2.55 1.8 48.6% 2.43 1.74 47.8% Nasal Spray (1.3,5.02) (1.2,2.41) (32.4%,65%) (1.78,3.32) (1.47,2.03) (40.2%,55.7%)

HD Zolmitriptan 4.52 2.32 62.6% 4.23 2.24 61.5% Nasal Spray (2.98,6.92) (1.94,2.67) (52.3%,71.9%) (3.67,4.88) (2.11,2.38) (57.9%,64.9%)

HD Sumatriptan Subcutanous 6.39 2.6 70.2% 6.42 2.58 70.8% Injection (2.04,20.91) (1.59,3.3) (42.9%,88.5%) (2.65,16.67) (1.82,3.17) (50.1%,86.2%)

Residual 286.9 versus 271 597.8 versus 271 Deviance data points data points Deviance Information 1958.2 2182.02

Criteria

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Table F.2: 2 hour freedom from pain: odds ratios, relative risks and percent of patients with 2 hour freedom from pain for each treatment compared to placebo – random-effects and fixed effects models

Fixed-effects Model Random-effects Model - Informative Priors % Patients with % Patients with OR RR* OR RR* freedom from freedom from pain at 2 h pain at 2 h* (95% CrI) (95% CrI) (95% CrI) (95% CrI) (95% CrI)* (95% CrI)

10.6% 11% Placebo NA NA NA NA (10%,11.3%) (10.5%,11.7%)

2.35 2.05 21.8% 2.12 1.89 20.9% NSAID (1.79,3.11) (1.65,2.55) (17.6%,26.8%) (1.78,2.53) (1.64,2.17) (18.2%,23.8%)

2.41 2.09 22.2% 2.32 2.02 22.4% Acetaminophen (0.85,6.57) (0.87,4.14) (9.2%,43.7%) (0.95,5.41) (0.96,3.65) (10.7%,40.1%)

2.66 2.26 24% 2.67 2.26 24.9% Aspirin (1.33,5.28) (1.28,3.64) (13.7%,38.4%) (1.64,4.32) (1.53,3.17) (16.9%,34.9%)

SD Eletriptan 5.43 3.69 39.2% 5.29 3.59 39.6% Tablet (4.31,6.89) (3.18,4.28) (34.1%,44.7%) (4.6,6.06) (3.27,3.92) (36.7%,42.7%)

SD Sumatriptan 3.22 2.61 27.7% 3.1 2.51 27.8% Tablet (2.73,3.82) (2.3,2.96) (24.6%,31%) (2.81,3.41) (2.33,2.71) (26%,29.6%)

SD Rizatriptan 4.86 3.45 36.6% 4.51 3.25 35.9% Tablet (3.88,6.15) (2.96,4.01) (31.7%,42%) (3.92,5.21) (2.95,3.58) (32.9%,39.1%)

SD Frovatriptan 4.48 3.27 34.7% 4.47 3.23 35.7% Tablet (2.83,7.28) (2.36,4.4) (25.4%,45.9%) (3.09,6.69) (2.5,4.14) (28%,44.9%)

SD Almotriptan 2.73 2.31 24.5% 2.51 2.15 23.7% Tablet (2.11,3.56) (1.89,2.81) (20.1%,29.6%) (2.17,2.9) (1.92,2.4) (21.3%,26.4%)

SD Zolmitriptan 3.14 2.56 27.1% 2.83 2.35 26% Tablet (2.47,4) (2.13,3.04) (22.7%,32%) (2.49,3.21) (2.13,2.59) (23.7%,28.3%)

SD Naratriptan 1.79 1.65 17.5% 1.73 1.6 17.7% Tablet (1.13,2.84) (1.11,2.38) (11.8%,25%) (1.26,2.35) (1.22,2.05) (13.6%,22.5%)

SD BI 44370 TA 2.86 2.39 25.3% 2.77 2.32 25.6% Tablet (1.15,6.98) (1.13,4.29) (12%,45.2%) (1.31,5.69) (1.26,3.76) (14%,41.2%)

HD Sumatriptan 3.99 3.03 32.1% 3.88 2.94 32.5% Tablet (3.35,4.75) (2.67,3.42) (28.6%,35.8%) (3.49,4.29) (2.72,3.17) (30.5%,34.6%)

SD Rizatriptan 8.49 4.73 50.2% 8.13 4.55 50.2% ODT (4.41,17.04) (3.24,6.37) (34.5%,66.7%) (4.98,13.83) (3.45,5.76) (38.3%,63%)

SD Sumatriptan 2.26 2 21.2% 2.26 1.98 21.9% Nasal Spray (0.57,9.75) (0.6,5.09) (6.4%,53.4%) (0.65,8.68) (0.68,4.71) (7.5%,51.7%)

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SD Sumatriptan 4.87 3.45 36.6% 4.84 3.4 37.5% Subcutanous (2.83,8.45) (2.37,4.74) (25.1%,50%) (3.35,7.06) (2.66,4.24) (29.4%,46.7%) Injection

SD Sumatriptan 2.19 1.94 20.6% 2.17 1.93 21.3% patch (1.24,3.86) (1.21,2.96) (12.9%,31.4%) (1.47,3.27) (1.4,2.62) (15.5%,28.8%)

SD Zolmitriptan 4.87 3.45 36.6% 4.87 3.41 37.7% ODT (2.19,11.11) (1.94,5.38) (20.6%,56.8%) (2.82,9.01) (2.34,4.79) (26%,52.7%)

1.55 1.46 15.5% 1.44 1.38 15.2% Ergots (0.75,3.15) (0.77,2.57) (8.2%,27.1%) (0.84,2.39) (0.86,2.07) (9.5%,22.8%)

Aspirin with 2.01 1.82 19.3% 1.89 1.72 19% antiemetic (1.26,3.22) (1.22,2.61) (13%,27.5%) (1.36,2.62) (1.31,2.22) (14.5%,24.4%)

Triptan with 8.61 4.76 50.5% 8.29 4.59 50.7% Acetaminophen (3.49,22.12) (2.76,6.87) (29.4%,72.3%) (3.91,18.12) (2.95,6.31) (32.8%,69.1%)

Triptan with 4.91 3.47 36.8% 4.86 3.41 37.6% NSAID (3.93,6.16) (2.99,4.01) (31.7%,42.1%) (4.26,5.56) (3.11,3.72) (34.6%,40.8%)

LD Eletriptan 3.35 2.68 28.5% 3.18 2.56 28.3% Tablet (2.2,5.13) (1.95,3.58) (20.8%,37.6%) (2.39,4.22) (2.07,3.12) (23%,34.3%)

LD Sumatriptan 2.79 2.35 24.9% 2.88 2.38 26.3% Tablet (1.48,5.17) (1.41,3.6) (14.9%,38%) (1.9,4.35) (1.73,3.18) (19.1%,35%)

LD Rizatriptan 3.19 2.59 27.5% 2.84 2.36 26.1% Tablet (1.95,5.25) (1.77,3.63) (18.8%,38.2%) (2.05,3.91) (1.83,2.97) (20.4%,32.6%)

LD Frovatriptan 1.21 1.19 12.6% 1.24 1.21 13.3% Tablet (0.5,2.76) (0.53,2.33) (5.6%,24.4%) (0.55,2.58) (0.58,2.2) (6.4%,24.1%)

LD Zolmitriptan 2.24 1.98 21% 2.07 1.85 20.4% Tablet (0.79,6.06) (0.8,3.96) (8.5%,41.7%) (0.82,4.71) (0.83,3.35) (9.2%,36.9%)

LD BI 44370 TA 0.85 0.87 9.2% 0.83 0.84 9.3% Tablet (0.24,2.58) (0.27,2.21) (2.8%,23.4%) (0.26,2.13) (0.28,1.9) (3.1%,20.9%)

HD Eletriptan 7.78 4.53 48% 7.27 4.29 47.4% Tablet (5.93,10.31) (3.87,5.25) (41.5%,54.7%) (6.14,8.58) (3.88,4.72) (43.5%,51.4%)

HD Rizatriptan 8.44 4.72 50.1% 7.89 4.48 49.5% Tablet (4.02,17.92) (3.04,6.45) (32.3%,67.9%) (4.43,13.95) (3.2,5.77) (35.6%,63.3%)

HD Frovatriptan 4.58 3.32 35.2% 4.66 3.32 36.7% Tablet (2.43,8.77) (2.11,4.84) (22.5%,50.7%) (2.81,7.84) (2.33,4.5) (26.1%,49%)

HD Almotriptan 4.04 3.05 32.4% 3.76 2.88 31.8% Tablet (2.53,6.43) (2.17,4.1) (23.1%,43.2%) (2.83,5.03) (2.35,3.49) (26%,38.3%)

HD Zolmitriptan 3.79 2.92 31% 3.24 2.6 28.7% Tablet (2.77,5.27) (2.33,3.64) (24.8%,38.3%) (2.78,3.79) (2.32,2.91) (25.7%,32%)

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HD BI 44370 TA 4.04 3.06 32.4% 3.92 2.96 32.7% Tablet (1.73,9.5) (1.6,5.02) (17.1%,52.8%) (1.99,7.64) (1.79,4.42) (19.8%,48.6%)

0.53 0.55 5.9% 0.5 0.53 5.8% SD Tonaberstat (0.17,1.42) (0.19,1.36) (2%,14.4%) (0.18,1.13) (0.2,1.12) (2.2%,12.3%)

0.64 0.66 7% 0.6 0.63 7% LD Tonaberstat (0.22,1.66) (0.24,1.55) (2.6%,16.3%) (0.24,1.32) (0.26,1.27) (2.9%,14%)

LD Rizatriptan 5.11 3.56 37.8% 4.97 3.45 38.1% ODT (2.55,10.59) (2.19,5.28) (23.2%,55.5%) (2.98,8.63) (2.44,4.71) (27.1%,51.5%)

HD Zolmitriptan 4.3 3.19 33.8% 3.99 3 33.2% Nasal Spray (2.74,6.8) (2.31,4.22) (24.5%,44.7%) (3.3,4.86) (2.63,3.41) (28.9%,37.8%)

LD Sumatriptan 6.8 4.21 44.7% 6.78 4.14 45.7% Suppositories (2.43,20.83) (2.11,6.75) (22.4%,71.1%) (2.87,17.41) (2.38,6.23) (26.4%,68.3%)

LD Almotriptan 1.92 1.75 18.5% 1.72 1.59 17.6% Tablet (1.05,3.52) (1.05,2.78) (11.1%,29.4%) (1.25,2.35) (1.22,2.04) (13.5%,22.6%)

HD Sumatriptan 3.46 2.74 29.1% 3.44 2.71 29.9% Subcutanous (1.13,11.27) (1.12,5.43) (11.9%,57%) (1.3,9.86) (1.26,5) (14%,54.8%) Injection

Residual 249.1 versus 238 380.6 versus 238

Deviance datapoints datapoints

Deviance Information 1621.28 1698.96 Criteria

Table F.3: 24 hour sustained headache relief: odds ratios, relative risks and percent of patients with 24 hour sustained headache relief for each treatment compared to placebo – random-effects and fixed effects models

Random-effects Model - informative priors Fixed-effects Model

% Patients % Patients with OR RR* OR RR* with sustained sustained headache headache relief (95% CrI) (95% CrI) (95% CrI) (95% CrI) relief at 24 h* at 2 h (95% CrI)* (95% CrI)

17% 17.1% NA NA NA NA Placebo (15.9%,18.2%) (15.9%,18.2%)

2 1.71 29.1% 1.99 1.7 29% Acetaminophen (1.63,2.47) (1.47,1.98) (25.1%,33.5%) (1.66,2.39) (1.49,1.94) (25.5%,32.7%)

2.02 1.72 29.3% 2.05 1.74 29.7% NSAID (0.92,4.46) (0.93,2.83) (16%,47.5%) (0.95,4.4) (0.96,2.8) (16.5%,47.1%)

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4.37 2.77 47.3% 4.33 2.76 47.1% SD Eletriptan (3.67,5.25) (2.49,3.1) (43.4%,51.3%) (3.71,5.04) (2.51,3.04) (43.8%,50.4%) Tablet

2.41 1.94 33.1% 2.42 1.95 33.3% SD Sumatriptan (2.1,2.77) (1.76,2.15) (30.3%,36%) (2.14,2.74) (1.78,2.13) (30.9%,35.7%) Tablet

2.02 1.72 29.3% 1.99 1.7 29.1% SD Rizatriptan (1.49,2.74) (1.37,2.13) (23.7%,35.5%) (1.5,2.65) (1.38,2.08) (23.9%,34.9%) Tablet

2.71 2.1 35.7% 2.71 2.1 35.8% SD Almotriptan (1.98,3.71) (1.69,2.56) (29.2%,43%) (2.06,3.58) (1.74,2.5) (29.9%,42.1%) Tablet

2.94 2.21 37.6% 2.94 2.21 37.7% SD Zolmitriptan (2.4,3.64) (1.92,2.54) (33.4%,42.2%) (2.45,3.55) (1.95,2.5) (33.9%,41.7%) Tablet

3.06 2.27 38.6% 3.1 2.28 39% SD Naratriptan (2.14,4.34) (1.79,2.79) (30.7%,46.8%) (2.26,4.27) (1.85,2.76) (31.9%,46.5%) Tablet

4.36 2.77 47.2% 4.24 2.73 46.6% SD BI 44370 TA (2.2,8.29) (1.82,3.74) (31.4%,62.6%) (2.25,7.89) (1.85,3.66) (31.9%,61.6%) Tablet

2.75 2.12 36% 2.77 2.13 36.3% HD Sumatriptan (2.34,3.22) (1.89,2.36) (32.7%,39.4%) (2.42,3.17) (1.93,2.34) (33.5%,39.1%) Tablet

0.42 0.46 7.9% 0.41 0.46 7.8% Ergots (0.08,1.91) (0.09,1.66) (1.5%,28.2%) (0.07,1.92) (0.08,1.66) (1.4%,28.3%)

4.93 2.95 50.3% 4.93 2.95 50.4% Triptan with (2.26,11.01) (1.86,4.12) (32.1%,69%) (2.35,10.6) (1.9,4.07) (32.9%,68.2%) Acetaminophen

4.2 2.72 46.2% 4.18 2.71 46.2% Triptan with (3.41,5.18) (2.4,3.06) (41.3%,51.4%) (3.49,5) (2.43,3.01) (42%,50.5%) NSAID

2.95 2.21 37.7% 2.91 2.19 37.4% LD Eletriptan (2.06,4.27) (1.74,2.76) (29.8%,46.5%) (2.11,3.99) (1.77,2.66) (30.4%,44.9%) Tablet

2.07 1.75 29.8% 2.07 1.75 29.9% LD Sumatriptan (1.46,2.91) (1.35,2.2) (23.2%,37.1%) (1.54,2.78) (1.41,2.14) (24.2%,36.2%) Tablet

2.26 1.86 31.7% 2.26 1.86 31.7% LD Rizatriptan (1.53,3.34) (1.4,2.4) (24%,40.4%) (1.6,3.2) (1.45,2.34) (24.9%,39.5%) Tablet

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2.04 1.74 29.5% 2.05 1.74 29.6% LD Almotriptan (1,4.14) (1,2.71) (17.1%,45.6%) (1.03,4.01) (1.02,2.66) (17.5%,45%) Tablet

1.24 1.19 20.3% 1.2 1.16 19.8% LD Zolmitriptan (0.54,2.7) (0.58,2.1) (9.9%,35.4%) (0.52,2.54) (0.57,2.02) (9.7%,34.2%) Tablet

4.98 2.97 50.5% 4.93 2.95 50.3% LD BI 44370 TA (3.98,6.28) (2.61,3.36) (45.4%,55.9%) (4.05,6.02) (2.64,3.3) (45.9%,54.9%) Tablet

3.02 2.25 38.3% 3.03 2.25 38.4% HD Eletriptan (2.35,3.93) (1.9,2.64) (32.7%,44.3%) (2.44,3.79) (1.95,2.59) (33.6%,43.5%) Tablet

HD Zolmitriptan 5.8 3.19 54.3% 5.7 3.16 53.9% Tablet (3.04,11.15) (2.25,4.14) (38.8%,69.2%) (3.14,10.34) (2.29,4.04) (39.5%,67.8%)

4.88 2.94 50% 4.85 2.93 49.9% HD BI 44370 TA (2.97,8.23) (2.22,3.72) (38%,62.6%) (3.05,7.84) (2.25,3.65) (38.7%,61.5%) Tablet

3.44 2.43 41.4% 3.44 2.43 41.4% HD Zolmitriptan (2.6,4.56) (2.04,2.85) (34.6%,48.5%) (2.83,4.2) (2.15,2.72) (36.5%,46.6%) Nasal Spray

82.07 versus 87 84.03 versus 87

Resdeviance datapoints datapoints

612.35 608.40 DIC

Table F.4: 24 hour sustained freedom from pain: odds ratios, relative risks and percent of patients with 24 hour sustained freedom from pain for each treatment compared to placebo – random-effects and fixed effects models

Random-effects Model - Informative Priors Fixed-effects Model % Patients % Patients with sustained with sustained OR RR* OR RR* freedom from freedom from (95% CrI) (95% CrI) (95% CrI) (95% CrI) pain at 24 h pain at 24 h* (95% CrI)* (95% CrI)

9.6% 36.7% Placebo NA NA NA NA (8.9%,10.3%) (0.1%,397.2%)

NSAID 1.85 1.71 16.4% 1.84 1.7 46.5% (1.36,2.52) (1.31,2.2) (12.6%,20.9%) (1.45,2.33) (1.39,2.07) (0.1%,515.1%)

Acetaminophen 1.58 1.5 14.3% 1.59 1.51 47.6% (0.49,4.59) (0.52,3.42) (5%,32.5%) (0.56,4.21) (0.59,3.23) (0.1%,530.9%)

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SD Eletriptan 4.63 3.43 32.9% 4.62 3.43 46.4% Tablet (3.5,6.1) (2.81,4.15) (27.5%,38.7%) (3.72,5.78) (2.92,4.01) (0.1%,496.2%)

SD Sumatriptan 2.79 2.38 22.8% 2.8 2.39 224.3% Tablet (2.31,3.38) (2.05,2.77) (20%,26%) (2.43,3.23) (2.13,2.68) (3.9%,859.2%)

SD Rizatriptan 2.97 2.5 23.9% 2.99 2.51 146.1% Tablet (2.19,3.98) (1.96,3.11) (19%,29.5%) (2.4,3.76) (2.11,2.99) (0.5%,827.6%)

SD Almotriptan 2.48 2.17 20.8% 2.43 2.14 149.8% Tablet (1.77,3.49) (1.64,2.83) (15.9%,26.8%) (1.93,3.09) (1.77,2.58) (1.5%,646.2%)

SD Zolmitriptan 2.74 2.35 22.5% 2.77 2.37 76.9% Tablet (2.04,3.66) (1.85,2.93) (18%,27.6%) (2.28,3.38) (2.02,2.77) (0.2%,653.4%)

SD Naratriptan 2.13 1.92 18.4% 2.2 1.97 84.8% Tablet (1.28,3.5) (1.25,2.83) (12%,26.8%) (1.46,3.3) (1.4,2.71) (0.3%,518.4%)

SD BI 44370 TA 3.83 3.01 28.9% 3.86 3.03 56.3% Tablet (1.57,9.13) (1.49,5.16) (14.4%,49%) (1.71,8.53) (1.6,4.98) (0.1%,519.3%)

HD Sumatriptan 3.65 2.91 27.9% 3.61 2.89 137.2% Tablet (2.9,4.62) (2.44,3.46) (23.8%,32.4%) (3.05,4.29) (2.53,3.29) (0.9%,645.8%)

SD Sumatriptan Subcutanous 2.9 2.45 23.5% 2.9 2.45 101.4% Injection (1.77,4.79) (1.65,3.52) (15.8%,33.6%) (1.94,4.38) (1.78,3.32) (0.3%,663.1%)

Triptan with 3.92 3.06 29.3% 3.93 3.07 257.9% Acetaminophen (1.53,9.86) (1.46,5.37) (14.1%,50.8%) (1.7,9.14) (1.59,5.16) (25.1%,720.2%)

Triptan with 4.55 3.39 32.5% 4.61 3.42 51.8% NSAID (3.68,5.61) (2.91,3.93) (28.3%,37%) (3.94,5.38) (3.05,3.83) (0.1%,432.8%)

LD Eletriptan 3.07 2.56 24.6% 3 2.51 33.6% Tablet (2.08,4.53) (1.88,3.41) (18.3%,32.1%) (2.19,4.08) (1.96,3.17) (0.1%,358.9%)

LD BI 44370 TA 0.7 0.72 7% 0.71 0.73 645.2% Tablet (0.13,2.38) (0.15,2.11) (1.4%,20.1%) (0.15,2.28) (0.16,2.03) (251.1%,1239%)

HD Eletriptan 6 4.05 38.9% 5.9 4.01 116.3% Tablet (4.37,8.27) (3.28,4.94) (32%,46.2%) (4.64,7.51) (3.41,4.69) (0.5%,615%)

HD Zolmitriptan 2.97 2.5 23.9% 2.83 2.41 41.1% Tablet (2.03,4.45) (1.84,3.36) (17.8%,31.8%) (2.22,3.62) (1.98,2.91) (0.1%,403.2%)

HD BI 44370 TA 4.1 3.16 30.3% 4.1 3.16 31.7% Tablet (1.72,9.74) (1.6,5.34) (15.5%,50.6%) (1.91,8.81) (1.75,5.06) (0.1%,352.4%)

HD Zolmitriptan 3.54 2.85 27.3% 3.46 2.8 37.6% Nasal Spray (2.45,5.18) (2.15,3.71) (20.5%,35.5%) (2.81,4.28) (2.39,3.26) (0.1%,409.9%)

117.8 versus 114 144.7 versus 114 Resdeviance datapoints datapoints Deviance Information 775.786 783.92

Criteria

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Table F.5.Use of Rescue medications: odds ratios, relative risks and percent of patients using rescue medications for each treatment to placebo – random-effects and fixed effects models

Random-effects Model - Informative Priors Fixed-effects Model

% Patients % Patients requiring rescue requiring rescue OR (95% CrI) RR (95% CrI) OR (95% CrI) RR (95% CrI) medication (95% medication (95% CrI) CrI) 51.6% 51.3% Placebo NA NA NA NA (50.4%,52.7%) (50.2%,52.4%)

0.55 0.72 36.9% 0.58 0.74 37.8% NSAID (0.42,0.71) (0.6,0.84) (31%,43.1%) (0.5,0.66) (0.68,0.8) (34.7%,40.9%)

0.47 0.65 33.4% 0.46 0.64 32.9% Aspirin (0.24,0.94) (0.39,0.97) (20.2%,50.1%) (0.31,0.7) (0.48,0.82) (24.6%,42.3%)

SD Eletriptan 0.25 0.41 21.1% 0.25 0.4 20.6% Tablet (0.2,0.31) (0.35,0.48) (17.9%,24.7%) (0.22,0.28) (0.37,0.44) (18.9%,22.5%)

SD Sumatriptan 0.48 0.65 33.8% 0.47 0.65 33.2% Tablet (0.4,0.57) (0.58,0.73) (30%,37.8%) (0.43,0.52) (0.61,0.68) (31.4%,35.2%)

SD Rizatriptan 0.4 0.58 30% 0.41 0.59 30.1% Tablet (0.32,0.5) (0.5,0.67) (25.6%,34.8%) (0.36,0.46) (0.54,0.64) (27.6%,32.7%)

SD Frovatriptan 0.42 0.6 31% 0.42 0.6 30.9% Tablet (0.19,0.96) (0.32,0.98) (16.5%,50.6%) (0.25,0.71) (0.41,0.83) (20.9%,42.8%)

SD Almotriptan 0.44 0.62 32% 0.46 0.64 32.8% Tablet (0.33,0.59) (0.5,0.75) (26.1%,38.5%) (0.4,0.54) (0.58,0.7) (29.7%,36%)

SD Zolmitriptan 0.36 0.54 28% 0.39 0.56 29% Tablet (0.28,0.48) (0.44,0.65) (22.8%,33.7%) (0.34,0.45) (0.51,0.62) (26.2%,31.9%)

SD Naratriptan 0.41 0.59 30.3% 0.42 0.6 30.8% Tablet (0.28,0.6) (0.45,0.75) (23%,38.8%) (0.34,0.53) (0.51,0.69) (26.3%,35.6%)

SD BI 44370 TA 0.34 0.52 26.7% 0.34 0.52 26.5% Tablet (0.19,0.61) (0.33,0.76) (17%,39.3%) (0.22,0.52) (0.37,0.69) (19.1%,35.2%)

HD Sumatriptan 0.35 0.53 27.4% 0.36 0.54 27.5% Tablet (0.3,0.42) (0.47,0.6) (24.2%,30.8%) (0.33,0.39) (0.5,0.57) (25.9%,29.3%)

SD Rizatriptan 0.23 0.39 19.9% 0.24 0.39 19.9% ODT (0.06,0.8) (0.12,0.89) (6.2%,46%) (0.07,0.67) (0.14,0.81) (7.2%,41.2%)

SD Sumatriptan 0.29 0.45 23.4% 0.31 0.48 24.9% Subcutanous (0.2,0.41) (0.34,0.58) (17.7%,30.1%) (0.25,0.4) (0.4,0.58) (20.6%,29.6%) Injection

SD Sumatriptan 0.33 0.51 26.2% 0.33 0.51 26% patch (0.14,0.79) (0.25,0.89) (12.9%,45.6%) (0.18,0.6) (0.32,0.75) (16.2%,38.6%)

0.3 0.47 24% 0.32 0.49 25.1% Ergots (0.18,0.5) (0.31,0.67) (15.8%,34.9%) (0.25,0.41) (0.4,0.59) (20.7%,30.2%)

Aspirin with 0.44 0.61 31.7% 0.46 0.64 32.9% antiemetic (0.28,0.68) (0.44,0.81) (23%,41.9%) (0.37,0.59) (0.54,0.75) (27.9%,38.3%)

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Triptan with 0.27 0.43 22.3% 0.27 0.43 22.1% NSAID (0.21,0.34) (0.36,0.52) (18.5%,26.7%) (0.24,0.3) (0.39,0.47) (20.1%,24.3%)

LD Eletriptan 0.3 0.47 24.5% 0.31 0.47 24.3% Tablet (0.22,0.43) (0.36,0.61) (18.7%,31.6%) (0.25,0.37) (0.41,0.55) (20.8%,28.2%)

LD Sumatriptan 0.81 0.9 46.4% 0.81 0.9 46% Tablet (0.43,1.53) (0.61,1.2) (31.5%,62%) (0.59,1.1) (0.75,1.05) (38.3%,53.7%)

LD Rizatriptan 0.49 0.67 34.3% 0.52 0.69 35.3% Tablet (0.3,0.8) (0.47,0.89) (24.3%,45.8%) (0.39,0.69) (0.56,0.82) (29%,42.1%)

LD Zolmitriptan 0.46 0.64 33.1% 0.45 0.63 32.4% Tablet (0.14,1.35) (0.26,1.14) (13.2%,58.8%) (0.15,1.13) (0.27,1.06) (14%,54.3%)

LD BI 44370 TA 0.89 0.94 48.6% 0.88 0.94 48.2% Tablet (0.5,1.59) (0.67,1.22) (34.8%,62.8%) (0.58,1.35) (0.74,1.14) (38.2%,58.6%)

HD Eletriptan 0.21 0.35 18.1% 0.19 0.33 16.9% Tablet (0.16,0.27) (0.28,0.43) (14.5%,22.3%) (0.17,0.22) (0.29,0.37) (14.9%,19.1%)

HD Frovatriptan 0.45 0.63 32.3% 0.45 0.63 32.2% Tablet (0.2,1.01) (0.33,1.01) (17.3%,51.8%) (0.26,0.75) (0.42,0.86) (21.8%,44.2%)

HD Almotriptan 0.36 0.54 28% 0.39 0.56 28.9% Tablet (0.22,0.59) (0.37,0.75) (19.3%,38.6%) (0.29,0.51) (0.46,0.68) (23.5%,34.9%)

HD Zolmitriptan 0.47 0.65 33.4% 0.45 0.63 32.4% Tablet (0.29,0.76) (0.46,0.87) (23.9%,44.6%) (0.34,0.6) (0.52,0.75) (26.7%,38.5%)

HD BI 44370 TA 0.25 0.4 20.9% 0.25 0.4 20.6% Tablet (0.14,0.44) (0.25,0.62) (12.9%,32%) (0.16,0.37) (0.28,0.55) (14.6%,28.1%)

HD Zolmitriptan 0.27 0.43 22% 0.28 0.45 22.9% Nasal Spray (0.16,0.43) (0.29,0.61) (14.9%,31.4%) (0.24,0.33) (0.39,0.5) (20.2%,25.9%)

HD Sumatriptan 0.32 0.49 25.5% 0.32 0.49 25.2% Subcutanous (0.11,0.95) (0.2,0.97) (10.1%,50.2%) (0.13,0.77) (0.23,0.87) (11.9%,44.9%) Injection

LD Frovatriptan 0.54 0.71 36.7% 0.55 0.71 36.6% tablet (0.24,1.23) (0.4,1.1) (20.4%,56.7%) (0.32,0.91) (0.5,0.96) (25.5%,49%)

LD Naratriptan 0.51 0.68 35.3% 0.52 0.69 35.4% Tablet (0.24,1.07) (0.4,1.04) (20.7%,53.4%) (0.32,0.83) (0.5,0.91) (25.5%,46.7%)

HD Zolmitriptan 0.51 0.68 35% 0.5 0.67 34.5% Subcutaneous (0.09,2.72) (0.18,1.44) (9.1%,74.1%) (0.11,2.32) (0.2,1.39) (10.1%,70.7%) injection

HD Zolmitriptan 0.3 24.4% 0.32 0.49 25% ODT (0.18,0.51) (16%,35.1%) (0.24,0.41) (0.4,0.59) (20.4%,30.2%)

Residual 251.2 versus 235 449.1 versus 235 deviance datapoints datapoints

DIC 1680.90 1810.17

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Appendix G: Assessment of Inconsistency

Two analyses wee conducted, one using the standard consistency model and the other using an inconsistency model. The residual deviance and DIC statistics of the consistency and inconsistency models were then compared. To help identify the loops in which inconsistency is present, the posterior mean deviance of the individual data points in the inconsistency model were plotted against their posterior mean deviance in the consistency model.

In general, the consistency model has a lower posterior mean of the residual deviance and DIC and hence is a better fit than the inconsistency model for all outcomes.

Table G.1: Summary of the goodness of fit of the consistency and inconsistency models

Outcome Measure Consistency Model Inconsistency Model 2 hour relief Deviance 290.6 versus 271 299.4 versus 271 datapoints datapoints DIC 1941.35 1959.83 2 hour freedom from pain Deviance 237.6 versus 228 253.6 versus 228 datapoints datapoints DIC 1553.57 1575.91 24 hour relief Deviance 88.98 versus 93 90.71 datapoints versus 93 datapoints DIC 654.33 661.357 24 hour freedom from Deviance 117.4 versus 114 120.6 versus 114 datapoints pain datapoints DIC 777.162 782.309 Rescue medication Deviance 243 versus 232 datapoints 266.8 versus 232 datapoints DIC 1660.51 1672.07

For most outcomes, the posterior mean deviance contributions are very similar and close to 1, for both models and there is limited evidence of inconsistency. However, a few data points in the 2 hour relief analysis have higher values of the posterior mean deviance in the consistency model than the inconsistency model. These five points (circled below) in the lower right hand quadrant correspond to arms in the Sunrshine 2006 (SD Eletriptan Tablet, SD Rizatriptan ODT), Misra 2010 (NSAID), Goadsby 2000 (HD Eletriptan Tablet), and Wells 2001-2003 (SD Eletriptan Tablet) studies. Similarly, there were six points for rescue medication and the studies correspond to the MOSCC group 1991 (HD Sumatriptan and Ergots), Thompson 1992 (HD Sumatriptan and Aspirin+ with antiemetic), and Silberstein 2008 (Placebo and Ergots). (50, 67, 106, 152, 153)

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Figure G.1: 2 hour headache relief - Plot of posterior mean deviance of the individual data points in the inconsistency model against their posterior mean deviance in the consistency model

Figure G.2: 2 hour freedom from pain - Plot of posterior mean deviance of the individual data points in the inconsistency model against their posterior mean deviance in the consistency model

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Figure G.3: 24 hour sustained headache relief - Plot of posterior mean deviance of the individual data points in the inconsistency model against their posterior mean deviance in the consistency model

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Figure G.4: 24 hour sustained freedom from pain - Plot of posterior mean deviance of the individual data points in the inconsistency model against their posterior mean deviance in the consistency model

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Figure G.5: Use of rescue medication - Plot of posterior mean deviance of the individual data points in the inconsistency model against their posterior mean deviance in the consistency model

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Appendix H: Pairwise Meta-analysis of 2 Hour and 24 Hour Headache Relief and Freedom from Pain Outcomes 2 Hour Headache Relief

SD Eletriptan Tablet

Triptan Placebo Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 1.1.1 SD Eletriptan Tablet Diener 2002p99 111 210 21 106 7.9% 4.54 [2.62, 7.86] Diener 2010-573 39 76 13 78 5.2% 5.27 [2.50, 11.12] ESC-Janpan 2002-416 51 80 40 84 6.7% 1.93 [1.04, 3.62] Farkkila 2003p463 91 179 22 81 7.5% 2.77 [1.57, 4.91] Garcia-Ramos 2003p869 108 192 28 92 8.3% 2.94 [1.73, 4.98] Goadsby 2000p156 76 136 30 142 8.3% 4.73 [2.79, 8.00] Mathew 2003p214 522 835 105 429 14.9% 5.15 [3.96, 6.68] Sandrini 2002p1210 108 175 25 84 7.7% 3.80 [2.18, 6.65] Sheftell p202 184 296 64 292 12.0% 5.85 [4.07, 8.42] Stark 2002-23 267 453 44 238 11.6% 6.33 [4.34, 9.23] Steiner 2003p942 229 392 30 144 9.9% 5.34 [3.41, 8.37] Subtotal (95% CI) 3024 1770 100.0% 4.41 [3.62, 5.37] Total events 1786 422 Heterogeneity: Tau² = 0.05; Chi² = 19.28, df = 10 (P = 0.04); I² = 48% Test for overall effect: Z = 14.72 (P < 0.00001)

Total (95% CI) 3024 1770 100.0% 4.41 [3.62, 5.37] Total events 1786 422 Heterogeneity: Tau² = 0.05; Chi² = 19.28, df = 10 (P = 0.04); I² = 48% 0.01 0.1 1 10 100 Test for overall effect: Z = 14.72 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 1.1.1 SD Eletriptan Tablet Diener 2002p99 111 210 21 106 7.6% 2.67 [1.78, 4.00] Diener 2010-573 39 76 13 78 5.6% 3.08 [1.79, 5.30] ESC-Janpan 2002-416 51 80 40 84 10.1% 1.34 [1.01, 1.77] Farkkila 2003p463 91 179 22 81 8.0% 1.87 [1.27, 2.75] Garcia-Ramos 2003p869 108 192 28 92 9.0% 1.85 [1.32, 2.58] Goadsby 2000p156 76 136 30 142 8.6% 2.65 [1.86, 3.76] Mathew 2003p214 522 835 105 429 12.3% 2.55 [2.15, 3.04] Sandrini 2002p1210 108 175 25 84 8.7% 2.07 [1.46, 2.94] Sheftell p202 184 296 64 292 11.0% 2.84 [2.24, 3.58] Stark 2002-23 267 453 44 238 10.1% 3.19 [2.42, 4.21] Steiner 2003p942 229 392 30 144 9.0% 2.80 [2.02, 3.90] Subtotal (95% CI) 3024 1770 100.0% 2.36 [2.01, 2.78] Total events 1786 422 Heterogeneity: Tau² = 0.05; Chi² = 30.95, df = 10 (P = 0.0006); I² = 68% Test for overall effect: Z = 10.28 (P < 0.00001)

Total (95% CI) 3024 1770 100.0% 2.36 [2.01, 2.78] Total events 1786 422 Heterogeneity: Tau² = 0.05; Chi² = 30.95, df = 10 (P = 0.0006); I² = 68% 0.01 0.1 1 10 100 Test for overall effect: Z = 10.28 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

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SD Sumatriptan Tablet

Triptan Placebo Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 1.1.2 SD Sumatriptan Tablet Brandes 2007-1443-S1 200 365 102 365 7.6% 3.13 [2.30, 4.25] Brandes 2007-1443-S2 182 370 109 387 7.7% 2.47 [1.83, 3.34] Bussone 2000p272 87 147 14 53 4.0% 4.04 [2.02, 8.08] Dahlof 2009-7 70 136 6 134 2.9% 22.63 [9.34, 54.83] Diener 2004p50 66 135 50 152 5.8% 1.95 [1.21, 3.15] Goadsby 2000p156 63 129 30 142 5.3% 3.56 [2.10, 6.06] Ishkanian 2007-99 75 108 46 108 5.0% 3.06 [1.75, 5.36] Kudrow 2005p1151 60 144 42 141 5.7% 1.68 [1.03, 2.75] Nett/Landy2003/2004Study1 60 138 20 132 4.9% 4.31 [2.41, 7.72] Nett/Landy2003/2004Study2 55 116 30 118 5.1% 2.64 [1.52, 4.59] Pfaffenrath 1993p184 176 303 29 99 5.7% 3.35 [2.05, 5.46] Sandrini 2002p1210 88 181 25 84 5.1% 2.23 [1.29, 3.87] Savani 1999p7 147 332 33 156 6.2% 2.96 [1.91, 4.60] Sheftell 2005 407-S1 310 517 208 513 8.2% 2.20 [1.71, 2.82] Sheftell 2005 407-S2 293 511 167 505 8.1% 2.72 [2.11, 3.51] Smith 2005p983 111 229 65 241 6.8% 2.55 [1.73, 3.74] Tepper 2006p115 75 141 65 138 5.9% 1.28 [0.80, 2.04] Subtotal (95% CI) 4002 3468 100.0% 2.76 [2.31, 3.31] Total events 2118 1041 Heterogeneity: Tau² = 0.09; Chi² = 47.44, df = 16 (P < 0.0001); I² = 66% Test for overall effect: Z = 10.98 (P < 0.00001)

Total (95% CI) 4002 3468 100.0% 2.76 [2.31, 3.31] Total events 2118 1041 Heterogeneity: Tau² = 0.09; Chi² = 47.44, df = 16 (P < 0.0001); I² = 66% 0.01 0.1 1 10 100 Test for overall effect: Z = 10.98 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 1.1.2 SD Sumatriptan Tablet Brandes 2007-1443-S1 200 365 102 365 7.6% 1.96 [1.62, 2.37] Brandes 2007-1443-S2 182 370 109 387 7.6% 1.75 [1.44, 2.11] Bussone 2000p272 87 147 14 53 3.9% 2.24 [1.40, 3.58] Dahlof 2009-7 70 136 6 134 1.9% 11.50 [5.17, 25.55] Diener 2004p50 66 135 50 152 6.1% 1.49 [1.12, 1.98] Goadsby 2000p156 63 129 30 142 5.1% 2.31 [1.61, 3.33] Ishkanian 2007-99 75 108 46 108 6.6% 1.63 [1.27, 2.10] Kudrow 2005p1151 60 144 42 141 5.7% 1.40 [1.02, 1.92] Nett/Landy2003/2004Study1 60 138 20 132 4.1% 2.87 [1.84, 4.48] Nett/Landy2003/2004Study2 55 116 30 118 5.1% 1.86 [1.30, 2.68] Pfaffenrath 1993p184 176 303 29 99 5.6% 1.98 [1.44, 2.73] Sandrini 2002p1210 88 181 25 84 5.1% 1.63 [1.14, 2.34] Savani 1999p7 147 332 33 156 5.6% 2.09 [1.51, 2.90] Sheftell 2005 407-S1 310 517 208 513 8.4% 1.48 [1.30, 1.68] Sheftell 2005 407-S2 293 511 167 505 8.2% 1.73 [1.50, 2.00] Smith 2005p983 111 229 65 241 6.7% 1.80 [1.40, 2.30] Tepper 2006p115 75 141 65 138 6.9% 1.13 [0.89, 1.43] Subtotal (95% CI) 4002 3468 100.0% 1.81 [1.60, 2.04] Total events 2118 1041 Heterogeneity: Tau² = 0.04; Chi² = 57.52, df = 16 (P < 0.00001); I² = 72% Test for overall effect: Z = 9.56 (P < 0.00001)

Total (95% CI) 4002 3468 100.0% 1.81 [1.60, 2.04] Total events 2118 1041 Heterogeneity: Tau² = 0.04; Chi² = 57.52, df = 16 (P < 0.00001); I² = 72% 0.01 0.1 1 10 100 Test for overall effect: Z = 9.56 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

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SD Rizatriptan Tablet

Triptan Placebo Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 1.1.3 SD Rizatriptan Tablet Ahrens 1999-525 139 188 52 185 8.9% 7.26 [4.59, 11.46] Bomhof 1999p173 138 201 24 107 8.1% 7.58 [4.40, 13.04] Freitag 2008-368 130 212 50 105 8.7% 1.74 [1.09, 2.80] Freitag 2008p921 33 46 18 44 5.4% 3.67 [1.52, 8.83] Gijsman 1997p647 69 145 12 67 6.7% 4.16 [2.06, 8.42] Kramer 1998p773 246 324 30 83 8.3% 5.57 [3.33, 9.33] Mannix 2007-414-S1 164 251 65 130 9.1% 1.89 [1.22, 2.90] Mannix 2007-414-S2 179 257 52 118 9.0% 2.91 [1.86, 4.57] Pascual 2000p455 206 308 43 154 9.2% 5.21 [3.41, 7.97] Teall 1998p281 323 456 106 304 10.2% 4.54 [3.33, 6.19] Tfelt-Hansen 1998p748 258 387 64 160 9.6% 3.00 [2.05, 4.39] Visser 1996p1132 46 89 15 85 6.8% 4.99 [2.49, 10.01] Subtotal (95% CI) 2864 1542 100.0% 3.94 [2.98, 5.20] Total events 1931 531 Heterogeneity: Tau² = 0.17; Chi² = 43.42, df = 11 (P < 0.00001); I² = 75% Test for overall effect: Z = 9.67 (P < 0.00001)

Total (95% CI) 2864 1542 100.0% 3.94 [2.98, 5.20] Total events 1931 531 Heterogeneity: Tau² = 0.17; Chi² = 43.42, df = 11 (P < 0.00001); I² = 75% 0.01 0.1 1 10 100 Test for overall effect: Z = 9.67 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 1.1.3 SD Rizatriptan Tablet Ahrens 1999-525 139 188 52 185 9.1% 2.63 [2.06, 3.36] Bomhof 1999p173 138 201 24 107 7.4% 3.06 [2.13, 4.41] Freitag 2008-368 130 212 50 105 9.4% 1.29 [1.03, 1.62] Freitag 2008p921 33 46 18 44 6.9% 1.75 [1.18, 2.61] Gijsman 1997p647 69 145 12 67 5.2% 2.66 [1.55, 4.56] Kramer 1998p773 246 324 30 83 8.4% 2.10 [1.57, 2.81] Mannix 2007-414-S1 164 251 65 130 9.8% 1.31 [1.08, 1.59] Mannix 2007-414-S2 179 257 52 118 9.5% 1.58 [1.27, 1.97] Pascual 2000p455 206 308 43 154 8.8% 2.40 [1.84, 3.12] Teall 1998p281 323 456 106 304 10.2% 2.03 [1.72, 2.39] Tfelt-Hansen 1998p748 258 387 64 160 9.7% 1.67 [1.36, 2.04] Visser 1996p1132 46 89 15 85 5.6% 2.93 [1.77, 4.83] Subtotal (95% CI) 2864 1542 100.0% 1.96 [1.66, 2.32] Total events 1931 531 Heterogeneity: Tau² = 0.06; Chi² = 52.55, df = 11 (P < 0.00001); I² = 79% Test for overall effect: Z = 7.94 (P < 0.00001)

Total (95% CI) 2864 1542 100.0% 1.96 [1.66, 2.32] Total events 1931 531 Heterogeneity: Tau² = 0.06; Chi² = 52.55, df = 11 (P < 0.00001); I² = 79% 0.01 0.1 1 10 100 Test for overall effect: Z = 7.94 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

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SD Frovatriptan Tablet

Triptan Placebo Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 1.1.4 SD Frovatriptan Tablet Goldstein 2002p41 48 131 30 123 9.7% 1.79 [1.04, 3.09] Rapoport 2002pS74 80 219 43 199 15.1% 2.09 [1.35, 3.23] Ryan 2002-S84-S1 83 214 24 108 10.2% 2.22 [1.30, 3.77] Ryan 2002-S84-S2 350 760 109 388 41.3% 2.19 [1.68, 2.84] Ryan 2002-S84-S3 173 480 59 244 23.7% 1.77 [1.25, 2.50] Subtotal (95% CI) 1804 1062 100.0% 2.03 [1.71, 2.40] Total events 734 265 Heterogeneity: Tau² = 0.00; Chi² = 1.24, df = 4 (P = 0.87); I² = 0% Test for overall effect: Z = 8.18 (P < 0.00001)

Total (95% CI) 1804 1062 100.0% 2.03 [1.71, 2.40] Total events 734 265 Heterogeneity: Tau² = 0.00; Chi² = 1.24, df = 4 (P = 0.87); I² = 0% 0.01 0.1 1 10 100 Test for overall effect: Z = 8.18 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 1.1.4 SD Frovatriptan Tablet Goldstein 2002p41 48 131 30 123 9.5% 1.50 [1.02, 2.21] Rapoport 2002pS74 80 219 43 199 14.0% 1.69 [1.23, 2.32] Ryan 2002-S84-S1 83 214 24 108 9.2% 1.75 [1.18, 2.58] Ryan 2002-S84-S2 350 760 109 388 45.1% 1.64 [1.37, 1.96] Ryan 2002-S84-S3 173 480 59 244 22.2% 1.49 [1.16, 1.92] Subtotal (95% CI) 1804 1062 100.0% 1.61 [1.43, 1.81] Total events 734 265 Heterogeneity: Tau² = 0.00; Chi² = 0.78, df = 4 (P = 0.94); I² = 0% Test for overall effect: Z = 7.84 (P < 0.00001)

Total (95% CI) 1804 1062 100.0% 1.61 [1.43, 1.81] Total events 734 265 Heterogeneity: Tau² = 0.00; Chi² = 0.78, df = 4 (P = 0.94); I² = 0% 0.01 0.1 1 10 100 Test for overall effect: Z = 7.84 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

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SD Almotriptan Tablet

Triptan Placebo Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 1.1.5 SD Almotriptan Tablet Dahlof 2001-1811 96 164 26 80 18.1% 2.93 [1.67, 5.14] Diener 2005-874+1603+42 48 99 21 99 16.5% 3.50 [1.88, 6.51] Dowson 2002-453 104 184 42 99 20.1% 1.76 [1.08, 2.89] Mathew 2007-189 68 176 46 173 21.4% 1.74 [1.10, 2.74] Pascual 2000-588 250 374 60 176 23.8% 3.90 [2.67, 5.69] Subtotal (95% CI) 997 627 100.0% 2.61 [1.82, 3.74] Total events 566 195 Heterogeneity: Tau² = 0.11; Chi² = 10.80, df = 4 (P = 0.03); I² = 63% Test for overall effect: Z = 5.20 (P < 0.00001)

Total (95% CI) 997 627 100.0% 2.61 [1.82, 3.74] Total events 566 195 Heterogeneity: Tau² = 0.11; Chi² = 10.80, df = 4 (P = 0.03); I² = 63% 0.01 0.1 1 10 100 Test for overall effect: Z = 5.20 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 1.1.5 SD Almotriptan Tablet Dahlof 2001-1811 96 164 26 80 17.6% 1.80 [1.28, 2.53] Diener 2005-874+1603+42 48 99 21 99 13.1% 2.29 [1.49, 3.52] Dowson 2002-453 104 184 42 99 23.0% 1.33 [1.03, 1.73] Mathew 2007-189 68 176 46 173 19.6% 1.45 [1.07, 1.98] Pascual 2000-588 250 374 60 176 26.7% 1.96 [1.58, 2.44] Subtotal (95% CI) 997 627 100.0% 1.70 [1.41, 2.05]

Total events 566 195 Heterogeneity: Tau² = 0.02; Chi² = 7.94, df = 4 (P = 0.09); I² = 50% Test for overall effect: Z = 5.51 (P < 0.00001)

Total (95% CI) 997 627 100.0% 1.70 [1.41, 2.05] Total events 566 195 Heterogeneity: Tau² = 0.02; Chi² = 7.94, df = 4 (P = 0.09); I² = 50% 0.01 0.1 1 10 100 Test for overall effect: Z = 5.51 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

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Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 1.1.6 SD Zolmitriptan Tablet Charlesworty 2003-653 139 233 69 228 15.1% 1.97 [1.58, 2.47] Ho 2008-2115 193 376 95 383 15.4% 2.07 [1.69, 2.53] Pascual 2000p455 193 304 43 154 14.5% 2.27 [1.74, 2.97] Sakai 2002p376 30 61 18 59 11.7% 1.61 [1.02, 2.56] Solomon 1997p1219 110 200 33 101 14.0% 1.68 [1.24, 2.29] Steiner 2003p942 224 405 30 144 13.7% 2.65 [1.91, 3.69] Tepper 1999p254 161 550 166 550 15.6% 0.97 [0.81, 1.16] Subtotal (95% CI) 2129 1619 100.0% 1.81 [1.35, 2.42] Total events 1050 454 Heterogeneity: Tau² = 0.13; Chi² = 53.68, df = 6 (P < 0.00001); I² = 89% Test for overall effect: Z = 3.98 (P < 0.0001)

Total (95% CI) 2129 1619 100.0% 1.81 [1.35, 2.42] Total events 1050 454 Heterogeneity: Tau² = 0.13; Chi² = 53.68, df = 6 (P < 0.00001); I² = 89% 0.01 0.1 1 10 100 Test for overall effect: Z = 3.98 (P < 0.0001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

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Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 1.1.7 SD Naratriptan Tablet Bomhof 1999p173 103 214 24 107 38.4% 2.15 [1.47, 3.13] Garcia-Ramos 2003p869 84 199 28 92 41.2% 1.39 [0.98, 1.97] Stark 2000-513 25 99 11 107 20.4% 2.46 [1.28, 4.73] Subtotal (95% CI) 512 306 100.0% 1.84 [1.30, 2.62] Total events 212 63 Heterogeneity: Tau² = 0.05; Chi² = 3.87, df = 2 (P = 0.14); I² = 48% Test for overall effect: Z = 3.41 (P = 0.0006)

Total (95% CI) 512 306 100.0% 1.84 [1.30, 2.62] Total events 212 63 Heterogeneity: Tau² = 0.05; Chi² = 3.87, df = 2 (P = 0.14); I² = 48% 0.01 0.1 1 10 100 Test for overall effect: Z = 3.41 (P = 0.0006) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

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2 Hour Freedom from Pain

SD Eletriptan Tablet

Triptan Placebo Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 2.1.1 SD Eletriptan Tablet Brandes+Silberstein2005/7 93 207 43 203 11.6% 3.04 [1.97, 4.69] Diener 2002p99 58 210 5 106 8.0% 7.71 [2.99, 19.88] Diener 2010-573 24 76 6 78 7.9% 5.54 [2.11, 14.51] ESC-Janpan 2002-416 17 80 10 84 8.7% 2.00 [0.85, 4.67] Farkkila 2003p463 54 179 5 81 7.9% 6.57 [2.52, 17.14] Garcia-Ramos 2003p869 64 192 17 92 10.4% 2.21 [1.20, 4.04] Goadsby 2000p156 34 136 8 142 8.9% 5.58 [2.48, 12.58] Mathew 2003p214 280 835 20 429 11.3% 10.32 [6.44, 16.53] Sandrini 2002p1210 52 175 3 84 6.5% 11.41 [3.45, 37.79] Stark 2002-23 138 453 7 238 9.2% 14.46 [6.64, 31.48] Steiner 2003p942 115 392 8 144 9.4% 7.06 [3.35, 14.87] Subtotal (95% CI) 2935 1681 100.0% 5.62 [3.65, 8.66] Total events 929 132 Heterogeneity: Tau² = 0.37; Chi² = 38.04, df = 10 (P < 0.0001); I² = 74% Test for overall effect: Z = 7.85 (P < 0.00001)

Total (95% CI) 2935 1681 100.0% 5.62 [3.65, 8.66] Total events 929 132 Heterogeneity: Tau² = 0.37; Chi² = 38.04, df = 10 (P < 0.0001); I² = 74% 0.01 0.1 1 10 100 Test for overall effect: Z = 7.85 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 2.1.1 SD Eletriptan Tablet Brandes+Silberstein2005/7 93 207 43 203 11.4% 2.12 [1.56, 2.88] Diener 2002p99 58 210 5 106 8.0% 5.86 [2.42, 14.16] Diener 2010-573 24 76 6 78 8.3% 4.11 [1.78, 9.48] ESC-Janpan 2002-416 17 80 10 84 9.1% 1.78 [0.87, 3.66] Farkkila 2003p463 54 179 5 81 8.1% 4.89 [2.03, 11.76] Garcia-Ramos 2003p869 64 192 17 92 10.6% 1.80 [1.12, 2.90] Goadsby 2000p156 34 136 8 142 9.0% 4.44 [2.13, 9.24] Mathew 2003p214 280 835 20 429 10.8% 7.19 [4.64, 11.15] Sandrini 2002p1210 52 175 3 84 6.6% 8.32 [2.68, 25.87] Stark 2002-23 138 453 7 238 8.9% 10.36 [4.93, 21.77] Steiner 2003p942 115 392 8 144 9.2% 5.28 [2.65, 10.54] Subtotal (95% CI) 2935 1681 100.0% 4.21 [2.73, 6.48] Total events 929 132 Heterogeneity: Tau² = 0.40; Chi² = 51.95, df = 10 (P < 0.00001); I² = 81% Test for overall effect: Z = 6.53 (P < 0.00001)

Total (95% CI) 2935 1681 100.0% 4.21 [2.73, 6.48] Total events 929 132 Heterogeneity: Tau² = 0.40; Chi² = 51.95, df = 10 (P < 0.00001); I² = 81% 0.01 0.1 1 10 100 Test for overall effect: Z = 6.53 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

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Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 2.1.2 SD Sumatriptan Tablet Brandes 2007-1443-S1 90 365 33 365 7.7% 2.73 [1.88, 3.95] Brandes 2007-1443-S2 82 370 37 387 7.8% 2.32 [1.62, 3.33] Bussone 2000p272 49 147 6 53 3.6% 2.94 [1.34, 6.47] Carpay 2004-214 70 137 30 153 7.8% 2.61 [1.82, 3.74] Dahlof 2009-7 32 136 8 134 3.9% 3.94 [1.89, 8.24] Diener 2004p50 33 135 22 153 6.2% 1.70 [1.04, 2.77] Jelinski 2006p73 51 126 17 111 6.2% 2.64 [1.63, 4.30] Sandrini 2002p1210 33 181 3 84 2.0% 5.10 [1.61, 16.17] Savani 1999p7 66 332 6 156 3.4% 5.17 [2.29, 11.66] Sheftell 2005 407-S1 180 517 84 513 9.6% 2.13 [1.69, 2.67] Sheftell 2005 407-S2 178 511 53 505 8.9% 3.32 [2.51, 4.40] Smith 2005p983 45 229 14 241 5.3% 3.38 [1.91, 5.99] Tepper 2006p115 39 141 35 138 7.4% 1.09 [0.74, 1.61] Tfelt-hansen 2006p389 20 53 8 48 4.0% 2.26 [1.10, 4.66] Winner 2003-1214-S1 59 123 34 121 8.1% 1.71 [1.22, 2.40] Winner 2003-1214-S2 59 115 35 123 8.2% 1.80 [1.29, 2.51] Subtotal (95% CI) 3618 3285 100.0% 2.38 [1.99, 2.84] Total events 1086 425 Heterogeneity: Tau² = 0.07; Chi² = 39.84, df = 15 (P = 0.0005); I² = 62% Test for overall effect: Z = 9.46 (P < 0.00001)

Total (95% CI) 3618 3285 100.0% 2.38 [1.99, 2.84] Total events 1086 425 Heterogeneity: Tau² = 0.07; Chi² = 39.84, df = 15 (P = 0.0005); I² = 62% 0.01 0.1 1 10 100 Test for overall effect: Z = 9.46 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

Ontario Drug Policy Research Network Ontario Drug Policy Research Network 107

Triptan Placebo Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 2.1.3 SD Rizatriptan Tablet Bomhof 1999p173 90 201 9 107 8.9% 8.83 [4.22, 18.45] Cady 2006-914-S1 200 363 55 179 13.3% 2.77 [1.89, 4.04] Cady 2006-914-S2 195 339 52 173 13.2% 3.15 [2.13, 4.65] Cady 2009-687 61 94 27 98 10.4% 4.86 [2.63, 8.97] Freitag 2008p921 17 46 6 44 6.1% 3.71 [1.30, 10.60] Gijsman 1997p647 40 145 2 67 3.9% 12.38 [2.89, 52.96] Ho 2008p1304 11 41 16 143 7.7% 2.91 [1.23, 6.91] Kramer 1998p773 142 324 6 83 7.7% 10.01 [4.24, 23.64] Misra 2010-175 20 53 1 53 2.2% 31.52 [4.04, 246.08] Pascual 2000p455 126 308 15 154 10.8% 6.42 [3.60, 11.45] Tfelt-Hansen 1998p748 155 387 15 160 10.9% 6.46 [3.66, 11.41] Visser 1996p1132 23 89 3 85 4.9% 9.53 [2.74, 33.11] Subtotal (95% CI) 2390 1346 100.0% 5.34 [3.83, 7.43] Total events 1080 207 Heterogeneity: Tau² = 0.18; Chi² = 27.83, df = 11 (P = 0.003); I² = 60% Test for overall effect: Z = 9.92 (P < 0.00001)

Total (95% CI) 2390 1346 100.0% 5.34 [3.83, 7.43] Total events 1080 207 Heterogeneity: Tau² = 0.18; Chi² = 27.83, df = 11 (P = 0.003); I² = 60% 0.01 0.1 1 10 100 Test for overall effect: Z = 9.92 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 2.1.3 SD Rizatriptan Tablet Bomhof 1999p173 90 201 9 107 8.8% 5.32 [2.80, 10.13] Cady 2006-914-S1 200 363 55 179 12.6% 1.79 [1.41, 2.28] Cady 2006-914-S2 195 339 52 173 12.5% 1.91 [1.50, 2.45] Cady 2009-687 61 94 27 98 11.6% 2.36 [1.65, 3.36] Freitag 2008p921 17 46 6 44 7.1% 2.71 [1.18, 6.24] Gijsman 1997p647 40 145 2 67 3.8% 9.24 [2.30, 37.11] Ho 2008p1304 11 41 16 143 8.4% 2.40 [1.21, 4.76] Kramer 1998p773 142 324 6 83 7.5% 6.06 [2.78, 13.23] Misra 2010-175 20 53 1 53 2.2% 20.00 [2.78, 143.69] Pascual 2000p455 126 308 15 154 10.2% 4.20 [2.55, 6.92] Tfelt-Hansen 1998p748 155 387 15 160 10.2% 4.27 [2.60, 7.02] Visser 1996p1132 23 89 3 85 4.9% 7.32 [2.28, 23.49] Subtotal (95% CI) 2390 1346 100.0% 3.41 [2.47, 4.71] Total events 1080 207 Heterogeneity: Tau² = 0.20; Chi² = 47.66, df = 11 (P < 0.00001); I² = 77% Test for overall effect: Z = 7.45 (P < 0.00001)

Total (95% CI) 2390 1346 100.0% 3.41 [2.47, 4.71] Total events 1080 207 Heterogeneity: Tau² = 0.20; Chi² = 47.66, df = 11 (P < 0.00001); I² = 77% 0.01 0.1 1 10 100 Test for overall effect: Z = 7.45 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

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SD Frovatriptan Tablet

Triptan Placebo Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 2.1.4 SD Frovatriptan Tablet Goldstein 2002p41 19 131 6 123 16.3% 3.31 [1.27, 8.59] Rapoport 2002pS74 27 219 6 199 18.0% 4.52 [1.83, 11.20] Ryan 2002-S84-S1 29 214 2 108 7.0% 8.31 [1.94, 35.51] Ryan 2002-S84-S2 95 760 11 388 36.5% 4.90 [2.59, 9.26] Ryan 2002-S84-S3 43 480 7 244 22.3% 3.33 [1.48, 7.52] Subtotal (95% CI) 1804 1062 100.0% 4.31 [2.94, 6.34] Total events 213 32 Heterogeneity: Tau² = 0.00; Chi² = 1.65, df = 4 (P = 0.80); I² = 0% Test for overall effect: Z = 7.45 (P < 0.00001)

Total (95% CI) 1804 1062 100.0% 4.31 [2.94, 6.34] Total events 213 32 Heterogeneity: Tau² = 0.00; Chi² = 1.65, df = 4 (P = 0.80); I² = 0% 0.01 0.1 1 10 100 Test for overall effect: Z = 7.45 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 2.1.4 SD Frovatriptan Tablet Goldstein 2002p41 19 131 6 123 17.2% 2.97 [1.23, 7.20] Rapoport 2002pS74 27 219 6 199 18.1% 4.09 [1.72, 9.70] Ryan 2002-S84-S1 29 214 2 108 6.7% 7.32 [1.78, 30.10] Ryan 2002-S84-S2 95 760 11 388 36.0% 4.41 [2.39, 8.13] Ryan 2002-S84-S3 43 480 7 244 21.9% 3.12 [1.43, 6.84] Subtotal (95% CI) 1804 1062 100.0% 3.90 [2.70, 5.63] Total events 213 32 Heterogeneity: Tau² = 0.00; Chi² = 1.62, df = 4 (P = 0.80); I² = 0% Test for overall effect: Z = 7.26 (P < 0.00001)

Total (95% CI) 1804 1062 100.0% 3.90 [2.70, 5.63] Total events 213 32 Heterogeneity: Tau² = 0.00; Chi² = 1.62, df = 4 (P = 0.80); I² = 0% 0.01 0.1 1 10 100 Test for overall effect: Z = 7.26 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

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Triptan Placebo Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 2.1.5 SD Almotriptan Tablet Dahlof 2001-1811 62 164 9 80 9.4% 4.80 [2.24, 10.27] Diener 2005-874+1603+42 33 99 14 99 10.9% 3.04 [1.50, 6.13] Dowson 2002-453 51 184 15 99 12.9% 2.15 [1.14, 4.06] Goadsby 2008-383 88 214 42 225 24.1% 3.04 [1.98, 4.69] Mathew 2007-189 60 176 37 173 20.7% 1.90 [1.18, 3.07] Pascual 2000-588 144 374 27 176 22.0% 3.46 [2.18, 5.47] Subtotal (95% CI) 1211 852 100.0% 2.83 [2.21, 3.63] Total events 438 144 Heterogeneity: Tau² = 0.02; Chi² = 6.10, df = 5 (P = 0.30); I² = 18% Test for overall effect: Z = 8.26 (P < 0.00001)

Total (95% CI) 1211 852 100.0% 2.83 [2.21, 3.63] Total events 438 144 Heterogeneity: Tau² = 0.02; Chi² = 6.10, df = 5 (P = 0.30); I² = 18% 0.01 0.1 1 10 100 Test for overall effect: Z = 8.26 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 2.1.5 SD Almotriptan Tablet Dahlof 2001-1811 62 164 9 80 7.8% 3.36 [1.76, 6.41] Diener 2005-874+1603+42 33 99 14 99 10.2% 2.36 [1.35, 4.13] Dowson 2002-453 51 184 15 99 11.6% 1.83 [1.09, 3.08] Goadsby 2008-383 88 214 42 225 26.8% 2.20 [1.61, 3.02] Mathew 2007-189 60 176 37 173 22.7% 1.59 [1.12, 2.27] Pascual 2000-588 144 374 27 176 20.9% 2.51 [1.73, 3.63] Subtotal (95% CI) 1211 852 100.0% 2.14 [1.78, 2.58] Total events 438 144 Heterogeneity: Tau² = 0.01; Chi² = 5.86, df = 5 (P = 0.32); I² = 15% Test for overall effect: Z = 7.97 (P < 0.00001)

Total (95% CI) 1211 852 100.0% 2.14 [1.78, 2.58] Total events 438 144 Heterogeneity: Tau² = 0.01; Chi² = 5.86, df = 5 (P = 0.32); I² = 15% 0.01 0.1 1 10 100 Test for overall effect: Z = 7.97 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

Ontario Drug Policy Research Network Ontario Drug Policy Research Network 110

Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 2.1.6 SD Zolmitriptan Tablet Klapper 2004p918 58 138 25 142 18.8% 2.39 [1.59, 3.58] Pascual 2000p455 103 304 15 154 17.5% 3.48 [2.10, 5.77] Sakai 2002p376 10 61 7 59 12.5% 1.38 [0.56, 3.39] Solomon 1997p1219 39 200 9 101 15.2% 2.19 [1.10, 4.34] Steiner 2003p942 98 405 8 144 15.0% 4.36 [2.17, 8.73] Tepper 1999p254 170 550 140 550 20.9% 1.21 [1.00, 1.47] Subtotal (95% CI) 1658 1150 100.0% 2.23 [1.37, 3.64] Total events 478 204 Heterogeneity: Tau² = 0.29; Chi² = 31.52, df = 5 (P < 0.00001); I² = 84% Test for overall effect: Z = 3.22 (P = 0.001)

Total (95% CI) 1658 1150 100.0% 2.23 [1.37, 3.64] Total events 478 204 Heterogeneity: Tau² = 0.29; Chi² = 31.52, df = 5 (P < 0.00001); I² = 84% 0.01 0.1 1 10 100 Test for overall effect: Z = 3.22 (P = 0.001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

Ontario Drug Policy Research Network Ontario Drug Policy Research Network 111

SD Naratritptan Tablet

Triptan Placebo Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 2.1.7 SD Naratriptan Tablet Bomhof 1999p173 44 214 9 107 37.6% 2.82 [1.32, 6.02] Garcia-Ramos 2003p869 34 199 17 92 41.3% 0.91 [0.48, 1.73] Stark 2000-513 6 99 3 107 21.0% 2.24 [0.54, 9.20] Subtotal (95% CI) 512 306 100.0% 1.68 [0.74, 3.84] Total events 84 29 Heterogeneity: Tau² = 0.32; Chi² = 5.32, df = 2 (P = 0.07); I² = 62% Test for overall effect: Z = 1.24 (P = 0.22)

Total (95% CI) 512 306 100.0% 1.68 [0.74, 3.84] Total events 84 29 Heterogeneity: Tau² = 0.32; Chi² = 5.32, df = 2 (P = 0.07); I² = 62% 0.01 0.1 1 10 100 Test for overall effect: Z = 1.24 (P = 0.22) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 2.1.7 SD Naratriptan Tablet Bomhof 1999p173 44 214 9 107 37.6% 2.44 [1.24, 4.82] Garcia-Ramos 2003p869 34 199 17 92 43.0% 0.92 [0.55, 1.57] Stark 2000-513 6 99 3 107 19.4% 2.16 [0.56, 8.41] Subtotal (95% CI) 512 306 100.0% 1.57 [0.75, 3.31] Total events 84 29 Heterogeneity: Tau² = 0.26; Chi² = 5.50, df = 2 (P = 0.06); I² = 64% Test for overall effect: Z = 1.19 (P = 0.23)

Total (95% CI) 512 306 100.0% 1.57 [0.75, 3.31] Total events 84 29 Heterogeneity: Tau² = 0.26; Chi² = 5.50, df = 2 (P = 0.06); I² = 64% 0.01 0.1 1 10 100 Test for overall effect: Z = 1.19 (P = 0.23) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

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24 Hour Headache Relief

SD Eletriptan Tablet

Triptan Placebo Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 3.1.1 SD Eletriptan Tablet Diener 2010-573 28 76 9 78 7.3% 4.47 [1.94, 10.32] Garcia-Ramos 2003p869 64 192 16 92 12.4% 2.38 [1.28, 4.40] Mathew 2003p214 342 835 58 429 33.2% 4.44 [3.26, 6.05] Sandrini 2002p1210 88 175 18 84 13.0% 3.71 [2.04, 6.75] Sheftell p202 115 296 29 292 20.5% 5.76 [3.68, 9.03] Steiner 2003p942 151 392 14 144 13.5% 5.82 [3.23, 10.47] Subtotal (95% CI) 1966 1119 100.0% 4.39 [3.46, 5.57] Total events 788 144 Heterogeneity: Tau² = 0.02; Chi² = 6.41, df = 5 (P = 0.27); I² = 22% Test for overall effect: Z = 12.18 (P < 0.00001)

Total (95% CI) 1966 1119 100.0% 4.39 [3.46, 5.57] Total events 788 144 Heterogeneity: Tau² = 0.02; Chi² = 6.41, df = 5 (P = 0.27); I² = 22% 0.01 0.1 1 10 100 Test for overall effect: Z = 12.18 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 3.1.1 SD Eletriptan Tablet Diener 2010-573 28 76 9 78 8.2% 3.19 [1.62, 6.31] Garcia-Ramos 2003p869 64 192 16 92 13.8% 1.92 [1.18, 3.12]

Mathew 2003p214 342 835 58 429 29.3% 3.03 [2.35, 3.90] Sandrini 2002p1210 88 175 18 84 16.2% 2.35 [1.52, 3.63] Sheftell p202 115 296 29 292 19.7% 3.91 [2.69, 5.69] Steiner 2003p942 151 392 14 144 12.8% 3.96 [2.37, 6.62] Subtotal (95% CI) 1966 1119 100.0% 2.98 [2.41, 3.69] Total events 788 144 Heterogeneity: Tau² = 0.02; Chi² = 7.61, df = 5 (P = 0.18); I² = 34% Test for overall effect: Z = 10.06 (P < 0.00001)

Total (95% CI) 1966 1119 100.0% 2.98 [2.41, 3.69] Total events 788 144 Heterogeneity: Tau² = 0.02; Chi² = 7.61, df = 5 (P = 0.18); I² = 34% 0.01 0.1 1 10 100 Test for overall effect: Z = 10.06 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

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Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 3.1.2 SD Sumatriptan Tablet Brandes 2007-1443-S1 127 365 64 365 17.2% 1.98 [1.53, 2.58] Brandes 2007-1443-S2 121 370 64 387 16.7% 1.98 [1.51, 2.58] Sandrini 2002p1210 62 181 18 84 6.3% 1.60 [1.01, 2.52] Savani 1999p7 109 332 26 156 8.7% 1.97 [1.34, 2.89] Sheftell 2005 407-S1 154 517 92 513 21.9% 1.66 [1.32, 2.09] Sheftell 2005 407-S2 173 511 69 505 18.7% 2.48 [1.93, 3.18] Smith 2005p983 66 229 41 241 10.6% 1.69 [1.20, 2.39] Subtotal (95% CI) 2505 2251 100.0% 1.93 [1.71, 2.17] Total events 812 374 Heterogeneity: Tau² = 0.00; Chi² = 6.79, df = 6 (P = 0.34); I² = 12% Test for overall effect: Z = 10.94 (P < 0.00001)

Total (95% CI) 2505 2251 100.0% 1.93 [1.71, 2.17] Total events 812 374 Heterogeneity: Tau² = 0.00; Chi² = 6.79, df = 6 (P = 0.34); I² = 12% 0.01 0.1 1 10 100 Test for overall effect: Z = 10.94 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

Ontario Drug Policy Research Network Ontario Drug Policy Research Network 114

SD Rizatriptan Tablet

Triptan Placebo Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 3.1.3 SD Rizatriptan Tablet Freitag 2008p921 23 46 6 44 13.0% 6.33 [2.25, 17.86] Ho 2008p1304 12 41 27 143 19.0% 1.78 [0.80, 3.93] Mannix 2007-414-S1 108 251 41 130 34.6% 1.64 [1.05, 2.56] Mannix 2007-414-S2 113 257 34 118 33.4% 1.94 [1.21, 3.10] Subtotal (95% CI) 595 435 100.0% 2.10 [1.37, 3.21] Total events 256 108 Heterogeneity: Tau² = 0.08; Chi² = 5.60, df = 3 (P = 0.13); I² = 46% Test for overall effect: Z = 3.41 (P = 0.0006)

Total (95% CI) 595 435 100.0% 2.10 [1.37, 3.21] Total events 256 108 Heterogeneity: Tau² = 0.08; Chi² = 5.60, df = 3 (P = 0.13); I² = 46% 0.01 0.1 1 10 100 Test for overall effect: Z = 3.41 (P = 0.0006) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 3.1.3 SD Rizatriptan Tablet Freitag 2008p921 23 46 6 44 10.6% 3.67 [1.65, 8.14] Ho 2008p1304 12 41 27 143 17.1% 1.55 [0.86, 2.78] Mannix 2007-414-S1 108 251 41 130 37.3% 1.36 [1.02, 1.82] Mannix 2007-414-S2 113 257 34 118 34.9% 1.53 [1.11, 2.09] Subtotal (95% CI) 595 435 100.0% 1.61 [1.21, 2.14] Total events 256 108 Heterogeneity: Tau² = 0.03; Chi² = 5.26, df = 3 (P = 0.15); I² = 43% Test for overall effect: Z = 3.27 (P = 0.001)

Total (95% CI) 595 435 100.0% 1.61 [1.21, 2.14] Total events 256 108 Heterogeneity: Tau² = 0.03; Chi² = 5.26, df = 3 (P = 0.15); I² = 43% 0.01 0.1 1 10 100 Test for overall effect: Z = 3.27 (P = 0.001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

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SD Almotriptan Tablet

Triptan Placebo Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 3.1.5 SD Almotriptan Tablet Pascual 2000-588 170 374 42 176 100.0% 2.66 [1.78, 3.97] Subtotal (95% CI) 374 176 100.0% 2.66 [1.78, 3.97] Total events 170 42 Heterogeneity: Not applicable Test for overall effect: Z = 4.77 (P < 0.00001)

Total (95% CI) 374 176 100.0% 2.66 [1.78, 3.97] Total events 170 42 Heterogeneity: Not applicable 0.01 0.1 1 10 100 Test for overall effect: Z = 4.77 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 3.1.5 SD Almotriptan Tablet Pascual 2000-588 170 374 42 176 100.0% 1.90 [1.43, 2.54] Subtotal (95% CI) 374 176 100.0% 1.90 [1.43, 2.54] Total events 170 42 Heterogeneity: Not applicable Test for overall effect: Z = 4.41 (P < 0.0001)

Total (95% CI) 374 176 100.0% 1.90 [1.43, 2.54] Total events 170 42 Heterogeneity: Not applicable 0.01 0.1 1 10 100 Test for overall effect: Z = 4.41 (P < 0.0001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

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Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 3.1.6 SD Zolmitriptan Tablet Dowson 2002-453 92 231 29 240 32.2% 3.30 [2.26, 4.80] Sakai 2002p376 25 61 11 59 16.7% 2.20 [1.19, 4.05] Solomon 1997p1219 84 200 22 101 29.7% 1.93 [1.29, 2.89] Steiner 2003p942 125 405 14 144 21.4% 3.17 [1.89, 5.33] Subtotal (95% CI) 897 544 100.0% 2.61 [1.96, 3.46] Total events 326 76 Heterogeneity: Tau² = 0.03; Chi² = 4.53, df = 3 (P = 0.21); I² = 34% Test for overall effect: Z = 6.60 (P < 0.00001)

Total (95% CI) 897 544 100.0% 2.61 [1.96, 3.46] Total events 326 76 Heterogeneity: Tau² = 0.03; Chi² = 4.53, df = 3 (P = 0.21); I² = 34% 0.01 0.1 1 10 100 Test for overall effect: Z = 6.60 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

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Triptan Placebo Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 3.1.7 SD Naratriptan Tablet Garcia-Ramos 2003p869 47 199 16 92 100.0% 1.47 [0.78, 2.76] Subtotal (95% CI) 199 92 100.0% 1.47 [0.78, 2.76] Total events 47 16 Heterogeneity: Not applicable Test for overall effect: Z = 1.19 (P = 0.23)

Total (95% CI) 199 92 100.0% 1.47 [0.78, 2.76] Total events 47 16 Heterogeneity: Not applicable 0.01 0.1 1 10 100 Test for overall effect: Z = 1.19 (P = 0.23) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 3.1.7 SD Naratriptan Tablet Garcia-Ramos 2003p869 47 199 16 92 100.0% 1.36 [0.81, 2.26] Subtotal (95% CI) 199 92 100.0% 1.36 [0.81, 2.26] Total events 47 16 Heterogeneity: Not applicable Test for overall effect: Z = 1.17 (P = 0.24)

Total (95% CI) 199 92 100.0% 1.36 [0.81, 2.26] Total events 47 16 Heterogeneity: Not applicable 0.01 0.1 1 10 100 Test for overall effect: Z = 1.17 (P = 0.24) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

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24 Hour Freedom from Pain

SD Eletriptan Tablet

Triptan Placebo Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 4.1.1 SD Eletriptan Tablet Brandes+Silberstein2005/7 77 207 30 203 23.3% 3.42 [2.12, 5.52] Diener 2010-573 15 76 5 78 10.2% 3.59 [1.23, 10.44] ESC-Janpan 2002-416 14 80 7 84 11.7% 2.33 [0.89, 6.12] Garcia-Ramos 2003p869 37 192 10 92 15.9% 1.96 [0.93, 4.14] Sandrini 2002p1210 42 175 3 84 8.6% 8.53 [2.56, 28.41] Sheftell p202 59 296 9 292 16.5% 7.83 [3.80, 16.12] Steiner 2003p942 75 392 6 144 13.7% 5.44 [2.31, 12.80] Subtotal (95% CI) 1418 977 100.0% 3.97 [2.64, 5.97] Total events 319 70 Heterogeneity: Tau² = 0.13; Chi² = 10.65, df = 6 (P = 0.10); I² = 44% Test for overall effect: Z = 6.63 (P < 0.00001)

Total (95% CI) 1418 977 100.0% 3.97 [2.64, 5.97] Total events 319 70 Heterogeneity: Tau² = 0.13; Chi² = 10.65, df = 6 (P = 0.10); I² = 44% 0.01 0.1 1 10 100 Test for overall effect: Z = 6.63 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 4.1.1 SD Eletriptan Tablet Brandes+Silberstein2005/7 77 207 30 203 23.3% 2.52 [1.73, 3.66] Diener 2010-573 15 76 5 78 10.7% 3.08 [1.18, 8.05] ESC-Janpan 2002-416 14 80 7 84 12.4% 2.10 [0.89, 4.93] Garcia-Ramos 2003p869 37 192 10 92 16.3% 1.77 [0.92, 3.41] Sandrini 2002p1210 42 175 3 84 8.5% 6.72 [2.14, 21.05] Sheftell p202 59 296 9 292 15.7% 6.47 [3.27, 12.80] Steiner 2003p942 75 392 6 144 13.2% 4.59 [2.04, 10.31] Subtotal (95% CI) 1418 977 100.0% 3.24 [2.18, 4.80] Total events 319 70 Heterogeneity: Tau² = 0.14; Chi² = 12.46, df = 6 (P = 0.05); I² = 52% Test for overall effect: Z = 5.85 (P < 0.00001)

Total (95% CI) 1418 977 100.0% 3.24 [2.18, 4.80] Total events 319 70 Heterogeneity: Tau² = 0.14; Chi² = 12.46, df = 6 (P = 0.05); I² = 52% 0.01 0.1 1 10 100 Test for overall effect: Z = 5.85 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

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SD Sumatriptan Tablet

Triptan Placebo Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 4.1.2 SD Sumatriptan Tablet Brandes 2007-1443-S1 59 365 30 365 12.8% 2.15 [1.35, 3.43] Brandes 2007-1443-S2 51 370 25 387 11.9% 2.31 [1.40, 3.82] Carpay 2004-214 44 137 15 153 9.0% 4.35 [2.29, 8.27] Jelinski 2006p73 30 126 7 109 5.9% 4.55 [1.91, 10.85] Landy 2004-913 41 138 11 132 7.8% 4.65 [2.27, 9.52] Nett 2003-835 35 116 17 118 8.9% 2.57 [1.34, 4.91] Sandrini 2002p1210 20 181 3 84 3.3% 3.35 [0.97, 11.62] Sheftell 2005 407-S1 85 517 46 513 15.1% 2.00 [1.36, 2.93] Sheftell 2005 407-S2 96 511 21 505 12.2% 5.33 [3.27, 8.70] Smith 2005p983 25 229 12 241 7.8% 2.34 [1.15, 4.77] Tfelt-hansen 2006p389 20 53 8 48 5.2% 3.03 [1.18, 7.76] Subtotal (95% CI) 2743 2655 100.0% 3.00 [2.35, 3.82] Total events 506 195 Heterogeneity: Tau² = 0.06; Chi² = 16.77, df = 10 (P = 0.08); I² = 40% Test for overall effect: Z = 8.83 (P < 0.00001)

Total (95% CI) 2743 2655 100.0% 3.00 [2.35, 3.82] Total events 506 195 Heterogeneity: Tau² = 0.06; Chi² = 16.77, df = 10 (P = 0.08); I² = 40% 0.01 0.1 1 10 100 Test for overall effect: Z = 8.83 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 4.1.2 SD Sumatriptan Tablet Brandes 2007-1443-S1 59 365 30 365 12.8% 1.97 [1.30, 2.98] Brandes 2007-1443-S2 51 370 25 387 11.5% 2.13 [1.35, 3.37] Carpay 2004-214 44 137 15 153 9.4% 3.28 [1.91, 5.61] Jelinski 2006p73 30 126 7 109 5.5% 3.71 [1.70, 8.10] Landy 2004-913 41 138 11 132 7.8% 3.57 [1.92, 6.64] Nett 2003-835 35 116 17 118 9.9% 2.09 [1.25, 3.52] Sandrini 2002p1210 20 181 3 84 2.7% 3.09 [0.95, 10.13] Sheftell 2005 407-S1 85 517 46 513 15.6% 1.83 [1.31, 2.57] Sheftell 2005 407-S2 96 511 21 505 11.6% 4.52 [2.86, 7.13] Smith 2005p983 25 229 12 241 7.1% 2.19 [1.13, 4.26] Tfelt-hansen 2006p389 20 53 8 48 6.2% 2.26 [1.10, 4.66] Subtotal (95% CI) 2743 2655 100.0% 2.55 [2.07, 3.13] Total events 506 195 Heterogeneity: Tau² = 0.04; Chi² = 15.58, df = 10 (P = 0.11); I² = 36% Test for overall effect: Z = 8.92 (P < 0.00001)

Total (95% CI) 2743 2655 100.0% 2.55 [2.07, 3.13] Total events 506 195 Heterogeneity: Tau² = 0.04; Chi² = 15.58, df = 10 (P = 0.11); I² = 36% 0.01 0.1 1 10 100 Test for overall effect: Z = 8.92 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

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SD Rizatriptan Tablet

Triptan Placebo Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 4.1.3 SD Rizatriptan Tablet Cady 2006-914-S1 151 363 41 179 32.9% 2.40 [1.60, 3.60] Cady 2006-914-S2 159 339 42 173 32.7% 2.76 [1.83, 4.14] Cady 2009-687 48 94 17 98 13.1% 4.97 [2.57, 9.63] Freitag 2008p921 10 46 6 44 4.7% 1.76 [0.58, 5.34] Ho 2008p1304 6 41 13 143 5.4% 1.71 [0.61, 4.83] Pascual 2000p455 41 308 10 154 11.1% 2.21 [1.08, 4.54] Subtotal (95% CI) 1191 791 100.0% 2.65 [2.08, 3.38] Total events 415 129 Heterogeneity: Tau² = 0.00; Chi² = 5.19, df = 5 (P = 0.39); I² = 4% Test for overall effect: Z = 7.85 (P < 0.00001)

Total (95% CI) 1191 791 100.0% 2.65 [2.08, 3.38] Total events 415 129 Heterogeneity: Tau² = 0.00; Chi² = 5.19, df = 5 (P = 0.39); I² = 4% 0.01 0.1 1 10 100 Test for overall effect: Z = 7.85 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 4.1.3 SD Rizatriptan Tablet Cady 2006-914-S1 151 363 41 179 35.1% 1.82 [1.35, 2.44] Cady 2006-914-S2 159 339 42 173 37.2% 1.93 [1.45, 2.57] Cady 2009-687 48 94 17 98 13.5% 2.94 [1.83, 4.74] Freitag 2008p921 10 46 6 44 3.6% 1.59 [0.63, 4.02] Ho 2008p1304 6 41 13 143 3.7% 1.61 [0.65, 3.97] Pascual 2000p455 41 308 10 154 6.9% 2.05 [1.06, 3.98] Subtotal (95% CI) 1191 791 100.0% 1.98 [1.66, 2.36] Total events 415 129 Heterogeneity: Tau² = 0.00; Chi² = 3.46, df = 5 (P = 0.63); I² = 0% Test for overall effect: Z = 7.67 (P < 0.00001)

Total (95% CI) 1191 791 100.0% 1.98 [1.66, 2.36] Total events 415 129 Heterogeneity: Tau² = 0.00; Chi² = 3.46, df = 5 (P = 0.63); I² = 0% 0.01 0.1 1 10 100 Test for overall effect: Z = 7.67 (P < 0.00001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

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SD Almotriptan Tablet

Triptan Placebo Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 4.1.5 SD Almotriptan Tablet Diener 2005-874+1603+42 21 99 9 99 23.6% 2.69 [1.17, 6.22] Goadsby 2008-383 76 214 28 225 40.1% 3.87 [2.39, 6.29] Mathew 2007-189 40 174 25 173 36.3% 1.77 [1.02, 3.07] Subtotal (95% CI) 487 497 100.0% 2.67 [1.59, 4.49] Total events 137 62 Heterogeneity: Tau² = 0.11; Chi² = 4.39, df = 2 (P = 0.11); I² = 54% Test for overall effect: Z = 3.72 (P = 0.0002)

Total (95% CI) 487 497 100.0% 2.67 [1.59, 4.49] Total events 137 62 Heterogeneity: Tau² = 0.11; Chi² = 4.39, df = 2 (P = 0.11); I² = 54% 0.01 0.1 1 10 100 Test for overall effect: Z = 3.72 (P = 0.0002) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 4.1.5 SD Almotriptan Tablet Diener 2005-874+1603+42 21 99 9 99 20.7% 2.33 [1.13, 4.84] Goadsby 2008-383 76 214 28 225 42.3% 2.85 [1.93, 4.22] Mathew 2007-189 40 174 25 173 37.0% 1.59 [1.01, 2.50] Subtotal (95% CI) 487 497 100.0% 2.21 [1.49, 3.26] Total events 137 62 Heterogeneity: Tau² = 0.05; Chi² = 3.68, df = 2 (P = 0.16); I² = 46% Test for overall effect: Z = 3.96 (P < 0.0001)

Total (95% CI) 487 497 100.0% 2.21 [1.49, 3.26] Total events 137 62 Heterogeneity: Tau² = 0.05; Chi² = 3.68, df = 2 (P = 0.16); I² = 46% 0.01 0.1 1 10 100 Test for overall effect: Z = 3.96 (P < 0.0001) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

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SD Zolmitriptan Tablet

Triptan Placebo Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 4.1.6 SD Zolmitriptan Tablet Pascual 2000p455 24 304 10 154 51.4% 1.23 [0.57, 2.65] Steiner 2003p942 61 405 6 144 48.6% 4.08 [1.72, 9.65] Subtotal (95% CI) 709 298 100.0% 2.21 [0.67, 7.24] Total events 85 16 Heterogeneity: Tau² = 0.56; Chi² = 4.26, df = 1 (P = 0.04); I² = 77% Test for overall effect: Z = 1.31 (P = 0.19)

Total (95% CI) 709 298 100.0% 2.21 [0.67, 7.24] Total events 85 16 Heterogeneity: Tau² = 0.56; Chi² = 4.26, df = 1 (P = 0.04); I² = 77% 0.01 0.1 1 10 100 Test for overall effect: Z = 1.31 (P = 0.19) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 4.1.6 SD Zolmitriptan Tablet Pascual 2000p455 24 304 10 154 51.7% 1.22 [0.60, 2.48] Steiner 2003p942 61 405 6 144 48.3% 3.61 [1.60, 8.18] Subtotal (95% CI) 709 298 100.0% 2.06 [0.69, 6.12] Total events 85 16 Heterogeneity: Tau² = 0.47; Chi² = 4.05, df = 1 (P = 0.04); I² = 75% Test for overall effect: Z = 1.30 (P = 0.19)

Total (95% CI) 709 298 100.0% 2.06 [0.69, 6.12] Total events 85 16 Heterogeneity: Tau² = 0.47; Chi² = 4.05, df = 1 (P = 0.04); I² = 75% 0.01 0.1 1 10 100 Test for overall effect: Z = 1.30 (P = 0.19) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

Triptan Placebo Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 4.1.7 SD Naratriptan Tablet Garcia-Ramos 2003p869 19 199 10 92 46.9% 0.87 [0.39, 1.94] Massiou 2005p774 48 128 23 129 53.1% 2.77 [1.56, 4.92] Subtotal (95% CI) 327 221 100.0% 1.60 [0.52, 5.00] Total events 67 33 Heterogeneity: Tau² = 0.55; Chi² = 5.26, df = 1 (P = 0.02); I² = 81% Test for overall effect: Z = 0.82 (P = 0.41)

Total (95% CI) 327 221 100.0% 1.60 [0.52, 5.00] Total events 67 33 Heterogeneity: Tau² = 0.55; Chi² = 5.26, df = 1 (P = 0.02); I² = 81% 0.01 0.1 1 10 100 Test for overall effect: Z = 0.82 (P = 0.41) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

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Triptan Placebo Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 4.1.7 SD Naratriptan Tablet Garcia-Ramos 2003p869 19 199 10 92 44.2% 0.88 [0.43, 1.81] Massiou 2005p774 48 128 23 129 55.8% 2.10 [1.36, 3.24] Subtotal (95% CI) 327 221 100.0% 1.43 [0.61, 3.35] Total events 67 33 Heterogeneity: Tau² = 0.29; Chi² = 4.12, df = 1 (P = 0.04); I² = 76% Test for overall effect: Z = 0.82 (P = 0.41)

Total (95% CI) 327 221 100.0% 1.43 [0.61, 3.35] Total events 67 33 Heterogeneity: Tau² = 0.29; Chi² = 4.12, df = 1 (P = 0.04); I² = 76% 0.01 0.1 1 10 100 Test for overall effect: Z = 0.82 (P = 0.41) Favours Placebo Favours Triptan Test for subgroup differences: Not applicable

Rescue Medications

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Triptans Control Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 6.1.1 SD Eletriptan Tablet Brandes+Silberstein2005/7 37 207 89 203 7.0% 0.41 [0.29, 0.57] Diener 2010-573 23 76 44 78 5.6% 0.54 [0.36, 0.79] Diener 2010-573-1 29 76 51 78 7.1% 0.58 [0.42, 0.81] ESC-Janpan 2002-416 18 80 36 84 4.3% 0.53 [0.33, 0.84] Farkkila 2003p463 42 179 51 81 7.5% 0.37 [0.27, 0.51] Garcia-Ramos 2003p869 29 192 45 92 5.6% 0.31 [0.21, 0.46] Goadsby 2000p156 39 136 75 142 7.6% 0.54 [0.40, 0.74] Liptan 2009p826-S2 52 458 43 107 6.7% 0.28 [0.20, 0.40] Mathew 2003p214 164 835 222 429 12.6% 0.38 [0.32, 0.45] Sandrini 2002p1210 26 175 40 84 5.2% 0.31 [0.21, 0.47] Sheftell p202 77 296 166 292 10.6% 0.46 [0.37, 0.57] Stark 2002-23 95 453 136 238 10.8% 0.37 [0.30, 0.45] Steiner 2003p942 76 392 81 144 9.5% 0.34 [0.27, 0.44] Subtotal (95% CI) 3555 2052 100.0% 0.40 [0.36, 0.45] Total events 707 1079 Heterogeneity: Tau² = 0.02; Chi² = 23.29, df = 12 (P = 0.03); I² = 48% Test for overall effect: Z = 15.62 (P < 0.00001)

Total (95% CI) 3555 2052 100.0% 0.40 [0.36, 0.45] Total events 707 1079 Heterogeneity: Tau² = 0.02; Chi² = 23.29, df = 12 (P = 0.03); I² = 48% 0.01 0.1 1 10 100 Test for overall effect: Z = 15.62 (P < 0.00001) Favours Controls Favours Triptans Test for subgroup differences: Not applicable

Triptans Control Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 6.1.2 SD Sumatriptan Tablet Brandes 2007-1443-S1 115 365 192 365 10.3% 0.41 [0.31, 0.56] Brandes 2007-1443-S2 137 370 223 387 10.7% 0.43 [0.32, 0.58] Diener 2004p50 53 135 98 152 5.4% 0.36 [0.22, 0.58] Ishkanian 2007-99 37 108 46 108 4.3% 0.70 [0.40, 1.22] Kudrow 2005p1151 49 152 46 144 5.3% 1.01 [0.62, 1.65] Nett/Landy2003/2004Study1 70 138 92 132 5.1% 0.45 [0.27, 0.74] Nett/Landy2003/2004Study2 70 116 83 118 4.4% 0.64 [0.37, 1.10] Sandrini 2002p1210 50 181 40 84 4.5% 0.42 [0.25, 0.72] Savani 1999p7 83 332 69 156 7.1% 0.42 [0.28, 0.63] Sheftell 2005 407-S1 192 517 257 513 12.7% 0.59 [0.46, 0.75] Sheftell 2005 407-S2 187 511 272 505 12.6% 0.49 [0.38, 0.64] Smith 2005p983 115 229 154 241 8.0% 0.57 [0.39, 0.82] Winner 2003-1214-S1 59 123 80 121 4.8% 0.47 [0.28, 0.79] Winner 2003-1214-S2 65 115 84 123 4.6% 0.60 [0.36, 1.02] Subtotal (95% CI) 3392 3149 100.0% 0.51 [0.45, 0.58] Total events 1282 1736 Heterogeneity: Tau² = 0.02; Chi² = 18.58, df = 13 (P = 0.14); I² = 30% Test for overall effect: Z = 10.46 (P < 0.00001)

Total (95% CI) 3392 3149 100.0% 0.51 [0.45, 0.58] Total events 1282 1736 Heterogeneity: Tau² = 0.02; Chi² = 18.58, df = 13 (P = 0.14); I² = 30% 0.01 0.1 1 10 100 Test for overall effect: Z = 10.46 (P < 0.00001) Favours Controls Favours Triptans Test for subgroup differences: Not applicable

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Triptans Control Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 6.1.2 SD Sumatriptan Tablet Brandes 2007-1443-S1 115 365 192 365 8.3% 0.60 [0.50, 0.72] Brandes 2007-1443-S2 137 370 223 387 9.4% 0.64 [0.55, 0.75] Diener 2004p50 53 135 98 152 6.0% 0.61 [0.48, 0.77] Ishkanian 2007-99 37 108 46 108 3.7% 0.80 [0.57, 1.13] Kudrow 2005p1151 49 152 46 144 3.9% 1.01 [0.72, 1.41] Nett/Landy2003/2004Study1 70 138 92 132 7.5% 0.73 [0.60, 0.89] Nett/Landy2003/2004Study2 70 116 83 118 8.0% 0.86 [0.71, 1.04] Sandrini 2002p1210 50 181 40 84 4.0% 0.58 [0.42, 0.80] Savani 1999p7 83 332 69 156 5.6% 0.57 [0.44, 0.73] Sheftell 2005 407-S1 192 517 257 513 10.2% 0.74 [0.64, 0.85] Sheftell 2005 407-S2 187 511 272 505 10.3% 0.68 [0.59, 0.78] Smith 2005p983 115 229 154 241 9.3% 0.79 [0.67, 0.92] Winner 2003-1214-S1 59 123 80 121 6.6% 0.73 [0.58, 0.91] Winner 2003-1214-S2 65 115 84 123 7.5% 0.83 [0.68, 1.01] Subtotal (95% CI) 3392 3149 100.0% 0.71 [0.66, 0.77] Total events 1282 1736 Heterogeneity: Tau² = 0.01; Chi² = 24.59, df = 13 (P = 0.03); I² = 47% Test for overall effect: Z = 8.90 (P < 0.00001)

Total (95% CI) 3392 3149 100.0% 0.71 [0.66, 0.77] Total events 1282 1736 Heterogeneity: Tau² = 0.01; Chi² = 24.59, df = 13 (P = 0.03); I² = 47% 0.01 0.1 1 10 100 Test for overall effect: Z = 8.90 (P < 0.00001) Favours Controls Favours Triptans Test for subgroup differences: Not applicable

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Triptans Control Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 6.1.3 SD Rizatriptan Tablet Ahrens 1999-525 113 188 141 185 9.2% 0.47 [0.30, 0.74] Bomhof 1999p173 81 201 83 107 8.3% 0.20 [0.11, 0.33] Cady 2006-914-S1 123 363 96 179 10.1% 0.44 [0.31, 0.64] Cady 2006-914-S2 113 339 89 173 10.0% 0.47 [0.32, 0.69] Freitag 2008-368 50 212 43 105 8.7% 0.45 [0.27, 0.74] Gijsman 1997p647 10 145 7 67 4.5% 0.63 [0.23, 1.75] Ho 2008p1304 16 41 71 143 6.7% 0.65 [0.32, 1.32] Mannix 2007-414-S1 103 251 61 130 9.4% 0.79 [0.51, 1.21] Mannix 2007-414-S2 100 257 62 118 9.3% 0.58 [0.37, 0.89] Misra 2007p175 14 53 46 53 4.6% 0.05 [0.02, 0.15] Pascual 2000p455 115 308 103 154 9.6% 0.30 [0.20, 0.44] Tfelt-Hansen 1998p748 70 387 51 160 9.5% 0.47 [0.31, 0.72] Subtotal (95% CI) 2745 1574 100.0% 0.42 [0.32, 0.54] Total events 908 853 Heterogeneity: Tau² = 0.16; Chi² = 39.82, df = 11 (P < 0.0001); I² = 72% Test for overall effect: Z = 6.34 (P < 0.00001)

Total (95% CI) 2745 1574 100.0% 0.42 [0.32, 0.54] Total events 908 853 Heterogeneity: Tau² = 0.16; Chi² = 39.82, df = 11 (P < 0.0001); I² = 72% 0.01 0.1 1 10 100 Test for overall effect: Z = 6.34 (P < 0.00001) Favours Controls Favours Triptans Test for subgroup differences: Not applicable

Triptans Control Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 6.1.3 SD Rizatriptan Tablet Ahrens 1999-525 113 188 141 185 11.8% 0.79 [0.68, 0.91] Bomhof 1999p173 81 201 83 107 10.4% 0.52 [0.43, 0.63] Cady 2006-914-S1 123 363 96 179 10.4% 0.63 [0.52, 0.77] Cady 2006-914-S2 113 339 89 173 10.1% 0.65 [0.53, 0.80] Freitag 2008-368 50 212 43 105 7.2% 0.58 [0.41, 0.80] Gijsman 1997p647 10 145 7 67 1.7% 0.66 [0.26, 1.66] Ho 2008p1304 16 41 71 143 5.7% 0.79 [0.52, 1.19] Mannix 2007-414-S1 103 251 61 130 9.5% 0.87 [0.69, 1.11] Mannix 2007-414-S2 100 257 62 118 9.6% 0.74 [0.59, 0.93] Misra 2007p175 14 53 46 53 5.0% 0.30 [0.19, 0.48] Pascual 2000p455 115 308 103 154 10.8% 0.56 [0.47, 0.67] Tfelt-Hansen 1998p748 70 387 51 160 7.7% 0.57 [0.42, 0.77] Subtotal (95% CI) 2745 1574 100.0% 0.63 [0.56, 0.72] Total events 908 853 Heterogeneity: Tau² = 0.03; Chi² = 34.82, df = 11 (P = 0.0003); I² = 68% Test for overall effect: Z = 6.90 (P < 0.00001)

Total (95% CI) 2745 1574 100.0% 0.63 [0.56, 0.72] Total events 908 853 Heterogeneity: Tau² = 0.03; Chi² = 34.82, df = 11 (P = 0.0003); I² = 68% 0.01 0.1 1 10 100 Test for overall effect: Z = 6.90 (P < 0.00001) Favours Controls Favours Triptans Test for subgroup differences: Not applicable

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Triptans Control Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 6.1.4 SD Frovatriptan Tablet Goldstein 2002p41 37 131 59 123 100.0% 0.43 [0.25, 0.72] Subtotal (95% CI) 131 123 100.0% 0.43 [0.25, 0.72] Total events 37 59 Heterogeneity: Not applicable Test for overall effect: Z = 3.21 (P = 0.001)

Total (95% CI) 131 123 100.0% 0.43 [0.25, 0.72] Total events 37 59 Heterogeneity: Not applicable 0.01 0.1 1 10 100 Test for overall effect: Z = 3.21 (P = 0.001) Favours Controls Favours Triptans Test for subgroup differences: Not applicable

Triptans Control Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 6.1.4 SD Frovatriptan Tablet Goldstein 2002p41 37 131 59 123 100.0% 0.59 [0.42, 0.82] Subtotal (95% CI) 131 123 100.0% 0.59 [0.42, 0.82] Total events 37 59 Heterogeneity: Not applicable Test for overall effect: Z = 3.15 (P = 0.002)

Total (95% CI) 131 123 100.0% 0.59 [0.42, 0.82] Total events 37 59 Heterogeneity: Not applicable 0.01 0.1 1 10 100 Test for overall effect: Z = 3.15 (P = 0.002) Favours Controls Favours Triptans Test for subgroup differences: Not applicable

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Triptans Control Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 6.1.5 SD Almotriptan Tablet Dahlof 2001-1811 58 164 47 80 16.2% 0.38 [0.22, 0.66] Diener 2005-874+1603+42 26 99 49 99 13.7% 0.36 [0.20, 0.66] Dowson 2002-453 71 184 55 99 19.9% 0.50 [0.31, 0.82] Mathew 2007-189 45 174 78 173 23.8% 0.42 [0.27, 0.67] Mathew 2007-189-2 64 174 94 173 26.4% 0.49 [0.32, 0.75] Subtotal (95% CI) 795 624 100.0% 0.44 [0.35, 0.55] Total events 264 323 Heterogeneity: Tau² = 0.00; Chi² = 1.16, df = 4 (P = 0.88); I² = 0% Test for overall effect: Z = 7.31 (P < 0.00001)

Total (95% CI) 795 624 100.0% 0.44 [0.35, 0.55] Total events 264 323 Heterogeneity: Tau² = 0.00; Chi² = 1.16, df = 4 (P = 0.88); I² = 0% 0.01 0.1 1 10 100 Test for overall effect: Z = 7.31 (P < 0.00001) Favours Controls Favours Triptans Test for subgroup differences: Not applicable

Triptans Control Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 6.1.5 SD Almotriptan Tablet Dahlof 2001-1811 58 164 47 80 20.4% 0.60 [0.46, 0.79] Diener 2005-874+1603+42 26 99 49 99 10.5% 0.53 [0.36, 0.78] Dowson 2002-453 71 184 55 99 24.3% 0.69 [0.54, 0.89] Mathew 2007-189 45 174 78 173 17.3% 0.57 [0.42, 0.77] Mathew 2007-189-2 64 174 94 173 27.6% 0.68 [0.53, 0.86] Subtotal (95% CI) 795 624 100.0% 0.63 [0.56, 0.71] Total events 264 323 Heterogeneity: Tau² = 0.00; Chi² = 2.18, df = 4 (P = 0.70); I² = 0% Test for overall effect: Z = 7.25 (P < 0.00001)

Total (95% CI) 795 624 100.0% 0.63 [0.56, 0.71] Total events 264 323 Heterogeneity: Tau² = 0.00; Chi² = 2.18, df = 4 (P = 0.70); I² = 0% 0.01 0.1 1 10 100 Test for overall effect: Z = 7.25 (P < 0.00001) Favours Controls Favours Triptans Test for subgroup differences: Not applicable

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Triptans Control Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 6.1.6 SD Zolmitriptan Tablet Klapper 2004p918 64 138 101 142 19.4% 0.35 [0.21, 0.58] Pascual 2000p455 126 304 103 154 28.7% 0.35 [0.23, 0.53] Sakai 2002p376 3 61 13 59 2.7% 0.18 [0.05, 0.68] Solomon 1997p1219 77 200 62 101 19.5% 0.39 [0.24, 0.64] Steiner 2003p942 101 405 81 144 29.7% 0.26 [0.17, 0.39] Subtotal (95% CI) 1108 600 100.0% 0.32 [0.26, 0.40] Total events 371 360 Heterogeneity: Tau² = 0.00; Chi² = 2.81, df = 4 (P = 0.59); I² = 0% Test for overall effect: Z = 10.23 (P < 0.00001)

Total (95% CI) 1108 600 100.0% 0.32 [0.26, 0.40] Total events 371 360 Heterogeneity: Tau² = 0.00; Chi² = 2.81, df = 4 (P = 0.59); I² = 0% 0.01 0.1 1 10 100 Test for overall effect: Z = 10.23 (P < 0.00001) Favours Controls Favours Triptans Test for subgroup differences: Not applicable

Triptans Control Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 6.1.6 SD Zolmitriptan Tablet Klapper 2004p918 64 138 101 142 24.6% 0.65 [0.53, 0.80] Pascual 2000p455 126 304 103 154 27.2% 0.62 [0.52, 0.74] Sakai 2002p376 3 61 13 59 2.1% 0.22 [0.07, 0.74] Solomon 1997p1219 77 200 62 101 22.6% 0.63 [0.50, 0.79] Steiner 2003p942 101 405 81 144 23.5% 0.44 [0.36, 0.55] Subtotal (95% CI) 1108 600 100.0% 0.57 [0.47, 0.68] Total events 371 360 Heterogeneity: Tau² = 0.02; Chi² = 10.40, df = 4 (P = 0.03); I² = 62% Test for overall effect: Z = 6.10 (P < 0.00001)

Total (95% CI) 1108 600 100.0% 0.57 [0.47, 0.68] Total events 371 360 Heterogeneity: Tau² = 0.02; Chi² = 10.40, df = 4 (P = 0.03); I² = 62% 0.01 0.1 1 10 100 Test for overall effect: Z = 6.10 (P < 0.00001) Favours Controls Favours Triptans Test for subgroup differences: Not applicable

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Triptans Control Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 6.1.7 SD Naratriptan Tablet Bomhof 1999p173 99 214 83 107 32.5% 0.25 [0.15, 0.42] Garcia-Ramos 2003p869 53 199 45 92 34.0% 0.38 [0.23, 0.63] Klassen 1997p640 39 127 68 122 33.5% 0.35 [0.21, 0.59] Subtotal (95% CI) 540 321 100.0% 0.32 [0.24, 0.44] Total events 191 196 Heterogeneity: Tau² = 0.00; Chi² = 1.41, df = 2 (P = 0.49); I² = 0% Test for overall effect: Z = 7.37 (P < 0.00001)

Total (95% CI) 540 321 100.0% 0.32 [0.24, 0.44] Total events 191 196 Heterogeneity: Tau² = 0.00; Chi² = 1.41, df = 2 (P = 0.49); I² = 0% 0.01 0.1 1 10 100 Test for overall effect: Z = 7.37 (P < 0.00001) Favours Controls Favours Triptans Test for subgroup differences: Not applicable

Triptans Control Risk Ratio Risk Ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI 6.1.7 SD Naratriptan Tablet Bomhof 1999p173 99 214 83 107 60.3% 0.60 [0.50, 0.71] Garcia-Ramos 2003p869 53 199 45 92 19.5% 0.54 [0.40, 0.74] Klassen 1997p640 39 127 68 122 20.2% 0.55 [0.41, 0.75] Subtotal (95% CI) 540 321 100.0% 0.58 [0.50, 0.66] Total events 191 196 Heterogeneity: Tau² = 0.00; Chi² = 0.38, df = 2 (P = 0.83); I² = 0% Test for overall effect: Z = 7.86 (P < 0.00001)

Total (95% CI) 540 321 100.0% 0.58 [0.50, 0.66] Total events 191 196 Heterogeneity: Tau² = 0.00; Chi² = 0.38, df = 2 (P = 0.83); I² = 0% 0.01 0.1 1 10 100 Test for overall effect: Z = 7.86 (P < 0.00001) Favours Controls Favours Triptans Test for subgroup differences: Not applicable

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Appendix I: Adjustment for Differences in Control Group Response Rate

Table I.1: Comparison of Unadjusted and Adjusted Analyses (OR, 95% CrI)

Random-effect Model - Random-effect Model - unadjusted Adjusted

1 Placebo NA NA

2 NSAID 2.56(2.03,3.27) 2.63(2.11,3.30)

3 Acetaminophen 2.92(1.19,7.27) 4.01(1.79,9.28)

4 Aspirin 2.36(1.29,4.34) 2.54(1.44,4.48)

5 SD Eletriptan Tablet 4.14(3.45,4.97) 3.98(3.37,4.70)

6 SD Sumatriptan Tablet 2.76(2.41,3.16) 2.88(2.54,3.26)

7 SD Rizatriptan Tablet 3.66(3,40.480) 4.42(3.67,5.34)

8 SD Frovatriptan Tablet 2.02(1.51,2.71) 1.84(1.42,2.39)

9 SD Almotriptan Tablet 2.58(2.02,3.30) 2.83(2.26,3.55)

10 SD Zolmitriptan Tablet 2.82(2.35,3.40) 3.01(2.54,3.59)

11 SD Naratriptan Tablet 2.07(1.37,3.16) 2.18(1.48,3.19)

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Random-effect Model - Random-effect Model - unadjusted Adjusted

12 SD BI 44370 TA Tablet 3.70 (1.76,7.81) 3.03(1.53,6.04)

13 HD Sumatriptan Tablet 3.14(2.72,3.62) 3.27(2.87,3.72)

14 SD Rizatriptan ODT 6.23(4.09,9.53) 5.82(3.99,8.51)

15 SD Sumatriptan Nasal Spray 3.05(2.1,4.43) 3.70 (2.66,5.13)

16 SD Sumatriptan Subcutanous Injection 8.96(6.06,13.34) 6.62(4.84,9.17)

17 SD Sumatriptan patch 2.56(1.59,4.11) 1.91(1.24,2.93)

18 SD Zolmitriptan Nasal Spray 2.93(1.71,4.98) 3.20 (1.92,5.34)

19 SD Zolmitriptan ODT 5.27(2.76,10.18) 4.51(2.53,8.05)

20 Ergots 1.68(1.12,2.51) 1.64(1.11,2.41)

21 Aspirin with antiemetic 2.88(1.97,4.21) 2.98(2.07,4.28)

22 Triptan with Acetaminophen 11.0 (3.93,35.37) 15.03(5.84,44.41)

23 Triptan with NSAID 4.59(3.39,6.20) 4.68(3.51,6.27)

24 Acetaminophen, dichloralphenazone, and 1.69(0.65,4.40) 1.85(0.71,4.72) isometheptene

25 LD Eletriptan Tablet 2.89(1.91,4.36) 2.90 (1.96,4.31)

26 LD Sumatriptan Tablet 2.20 (1.62,3.01) 2.40 (1.79,3.23)

27 LD Rizatriptan Tablet 2.88(2.06,4.04) 3.30 (2.40,4.52)

28 LD Frovatriptan Tablet 1.03(0.62,1.68) 0.91(0.57,1.44)

29 LD Almotriptan Tablet 2.11(1.39,3.18) 2.54(1.74,3.74)

30 LD Zolmitriptan Tablet 2.19(1.02,4.67) 2.32(1.11,4.75)

31 LD BI 44370 TA Tablet 1.70 (0.77,3.70) 1.41(0.67,2.88)

32 HD Eletriptan Tablet 5.38(4.41,6.60) 5.18(4.29,6.23)

33 HD Rizatriptan Tablet 4.92(2.52,9.64) 4.78(2.51,9.11)

34 HD Frovatriptan Tablet 1.85(1.18,2.91) 1.64(1.08,2.47)

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Random-effect Model - Random-effect Model - unadjusted Adjusted

35 HD Almotriptan Tablet 2.81(1.86,4.26) 3.32(2.25,4.93)

36 HD Zolmitriptan Tablet 2.90 (2.28,3.71) 2.92(2.33,3.69)

37 HD BI 44370 TA Tablet 4.72(2.29,9.90) 3.91(2.00,7.70)

38 SD Tonaberstat 1.21(0.65,2.27) 1.24(0.67,2.23)

39 LD Tonaberstat 1.09(0.58,2.05) 1.11(0.61,2.02)

40 LD Rizatriptan ODT 3.39(1.83,6.27) 3.42(1.93,6.05)

41 LD Sumatriptan Nasal Spray 1.96(1.31,2.92) 2.37(1.65,3.39)

42 LD Sumatriptan Suppositories 6.65(2.66,17.38) 6.17(2.9,13.37)

43 LD Zolmitriptan Nasal Spray 2.58(1.52,4.40) 2.83(1.7,4.760)

44 HD Zolmitriptan Nasal Spray 4.53(3.28,6.30) 4.92(3.61,6.71)

45 HD Sumatriptan Subcutanous Injection 6.45(2.34,18.70) 5.63(2.47,12.99)

Resdeviance 290.6 versus 271 datapoints 283.1 versus 271 datapoints

DIC 1941.35 1946

Beta NA Beta= -0.58 (-0.41,-0.75)

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