This multicentre, randomised, double-blind study compared oral zolmitriptan 2.5 mg with a combination of oral acetylsalicylic acid 900 mg and metoclopramide 10 mg as acute anti-migraine therapy for 3 migraine attacks. In total, 666 patients took at least one dose of study medication (326 took zolmitriptan and 340 took acetylsalicylic acid plus metoclopramide). The percentage of patients with a 2-hour headache response after the first dose for all 3 attacks (the primary end point) was 33.4% with zolmitriptan and 32.9% with acetylsalicylic acid plus metoclopramide [odds ratio 1.06, 95% confidence interval (CI) 0.77–1.47; p = 0.7228]. For the majority of secondary end points, the two treatments demonstrated comparable efficacy. However, post hoc analysis showed that significantly more patients receiving zolmitriptan were free of pain 2 h after the first dose in all 3 attacks compared with patients receiving acetylsalicylic acid plus metoclopramide (10.7 vs. 5.3%; odds ratio 2.19, 95% CI 1.23–4.03; p = 0.0095). In addition, post hoc analysis showed that the overall 2-hour pain-free response rate was consistently higher with zolmitriptan (34.6%) than with acetylsalicylic acid plus metoclopramide (27.9%) (odds ratio 1.40, 95% CI 1.09–1.78; p = 0.007). Both treatments reduced migraine-associated nausea, vomiting, phonophobia and photophobia. There were no important inter-group differences with respect to the onset of meaningful migraine relief, the frequency of headache recurrence, the usage or efficacy of a second dose of medication or the use of escape medication. However, at the last attack, the proportion of patients who expressed overall satisfaction with the treatment was significantly higher in the zolmitriptan group, i.e. 83.7%, versus 75.0% with acetylsalicylic acid plus metoclopramide (p = 0.0346). Both agents were well tolerated. Adverse events were reported by 40.8% (133/326) of zolmitriptan-treated patients and 29.1% (99/340) of those treated with acetylsalicylic acid plus metoclopramide. The incidence of withdrawals due to adverse events was very low with both zolmitriptan (0.9%) and the combination regimen (1.5%); the latter percentage included 1 patient who withdrew from the study due to phlebitis, which was classified as a serious adverse event. This study showed that zolmitriptan is effective and well tolerated for the acute treatment of moderate to severe migraine. Zolmitriptan was at least as effective as acetylsalicylic acid plus metoclopramide in achieving a 2-hour headache response, but significantly more effective than the combination therapy for other end points, including the 2-hour pain-free response.

Keywords:
Migraine, Zolmitriptan, Acetylsalicylic acid, Metoclopramide, Clinical trial
1.
Osterhaus JT, Townsend RJ, Gandek B, Ware JE: Measuring the functional status and well-being of patients with migraine headache. Headache 1994;34:337–343.
2.
Stewart WF, Lipton RB: The economic and social impact of migraine. Eur Neurol 1994;34(suppl 2):12–17.
3.
Michel P, Dartigues JF, Lindoulsi A, Henry P: Loss of productivity and quality of life in migraine sufferers among French workers: Results from the GAZEL cohort. Headache 1997;37:71–78.
4.
Lipton RB, Stewart WF, von Korff M: Burden of migraine: Societal costs and therapeutic opportunities. Neurology 1997;48(suppl 3):S4–S9.
5.
Solomon GD: Evolution of the measurement of quality of life in migraine. Neurology 1997;48(suppl 3):S10–S15.
6.
Henry P, Michel P, Brochet B, Dartigues JF, Tison S, Salamon R: A nationwide survey of migraine in France: Prevalence and clinical features in adults. GRIM. Cephalalgia 1992;12:229–237.
7.
Stewart WF, Lipton RB, Celentano DD, Reed ML: Prevalence of migraine headache in the United States. JAMA 1992;267:64–69.
8.
Stewart WF, Shechter A, Rasmussen BK: Migraine prevalence. A review of population based studies. Neurology 1994;44(suppl 4):S17–S23.
9.
Rasmussen BK: Epidemiology of headache. Cephalalgia 1995;15:45–68.
10.
Russell BM, Rasmussen BK, Thorvaldsen P, Olesen J: Prevalence and sex ratio of the sub-types of migraine. Int J Epidemiol 1995;24:612–618.
11.
Pfaffenrath V, Scherzer S: Analgesics and NSAIDs in the treatment of the acute migraine attack. Cephalalgia 1995;15(suppl 15):14–20.
12.
Gilkey SJ, Ramadan NM: Use of over-the-counter drugs in migraine – issues in self-medication. CNS Drugs 1996;6:83–89.
13.
Chabriat H, Joire J, Danchot J, Grippon P, Bousser MG: Combined oral lysine acetylsalicylate and metoclopramide in the acute treatment of migraine: A multicentre double-blind placebo-controlled study. Cephalalgia 1994;14:297–300.
14.
Lance JW: Current concepts of migraine pathogenesis. Neurology 1993;43(suppl 3):S11–S15.
15.
Ferrari MD, Saxena PR: 5HT1 receptors in migraine pathophysiology and treatment. Eur J Neurol 1995;2:5–21.
16.
Martin GR: Pre-clinical pharmacology of zolmitriptan (Zomig™; formerly 311C90), a centrally and peripherally acting 5HT1B/1D agonist for migraine. Cephalalgia 1997;17(suppl 18):4–14.
17.
Goadsby PJ, Hoskin KL: Inhibition of trigeminal neurones by intravenous administration of the serotonin (5HT)1B/1D receptor agonist zolmitriptan (311C90): Are brain stem sites therapeutic targets in migraine? Pain 1996;67:355–359.
18.
Goadsby PJ, Knight YE: Direct evidence for central sites of action of zolmitriptan (311C90): An autoradiography study in cat. Cephalalgia 1997;17:153–158.
19.
Rapoport AM, Ramadan NM, Adelman JU, Mathew NT, Elkind AH, Kudrow DB, Earl NL: 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;49:1210–1218.
20.
Ferrari MD: 311C90: Increasing the options for therapy with effective acute antimigraine 5HT1B/1D receptor agonists. Neurology 1997;48(3 suppl 3):S21–S24.
21.
Ryan RE 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. CNS Drugs 2000;13:215–226.
22.
Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Headache Classification Committee of the International Headache Society. Cephalalgia 1988;8(suppl 7):1–96.
23.
Goadsby PJ: A triptan too far? J Neurol Neurosurg Psychiatry 1998;64:143–147.
24.
Ferrari MD: Migraine. Lancet 1998;351:1043–1051.
25.
Tfelt-Hansen P: Methodology of treatment trials for acute migraine attacks; in Olesen J, Tfelt-Hansen P (eds): Headache Treatment. Trial Methodology and New Drugs. Philadelphia, Lippincott-Raven, 1997, pp 111–118.
26.
Thompson CJ: A study to compare oral sumatriptan with oral aspirin plus oral metoclopramide in the acute treatment of migraine. Eur Neurol 1992;32:177–184.
27.
The Multinational Oral Sumatriptan and Cafergot Comparative Study Group: A randomised, double-blind comparison of sumatriptan and cafergot in the acute treatment of migraine. Eur Neurol 1991;31:314–322.
28.
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;49:1219–1225.
29.
Lipton RB, Stewart WF, Stone AM, Láinez MJA, Sawyer JPC: Stratified care vs step care strategies for migraine: The Disability in Strategies of Care (DISC) Study: A randomized trial. JAMA 2000;284:2599–2605.
30.
Tfelt-Hansen P, Henry P, Mulder LJ, Scheldewaert RG, Schoenen J, Chazot G: The effectiveness of combined oral lysine acetylsalicylate and metoclopramide compared with sumatriptan for migraine. Lancet 1995;346:923–926.
31.
Geraud G: Evaluation of the long-term safety and efficacy of zolmitriptan (311C90) in the treatment of migraine. Eur Neurol 1996;36(suppl 2):24–27.
32.
Schoenen J, Sawyer J: Zolmitriptan (Zomig™, 311C90), a novel dual central and peripheral 5HT1B/1D agonist: An overview of efficacy. Cephalalgia 1997;17(suppl 18):28–40.
33.
Tuchman M, Edvinsson L, Geraud G, Korczyn A, Mauskop A, Pfaffenrath V: Zolmitriptan provides consistent migraine relief when used in the long-term. Curr Med Res Opin 1999;15:272–281.
34.
Edmeads JG, Millson DS: Tolerability profile of zolmitriptan (Zomig; 311C90), a novel dual central and peripherally acting 5HT1B/1D agonist. International clinical experience based on >3000 subjects treated with zolmitriptan. Cephalalgia 1997;17(suppl 18):41–52.
35.
Simmons VE, Blakeborough P: The safety profile of sumatriptan. Rev Contemp Pharmacother 1994;5:319–328.
© 2002 S. Karger AG, Basel
2002
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.