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Therapeutics

Lysine acetylsalicylate combined with metoclopramide was as effective as sumatriptan for migraine

ACP J Club. 1996 Mar-April;124:36. doi:10.7326/ACPJC-1996-124-2-036


Source Citation

Tfelt-Hansen P, Henry P, Mulder LJ, et al. The effectiveness of combined oral lysine acetylsalicylate and metoclopramide compared with oral sumatriptan for migraine. Lancet. 1995 Oct 7;346:923-6. [PubMed ID: 7564725]


Abstract

Objective

To compare the efficacy of lysine acetylsalicylate plus metoclopramide with that of oral sumatriptan and with that of placebo in patients with migraine.

Design

Randomized, double-blind, controlled trial with 8-week follow-up.

Setting

56 centers in Europe.

Patients

421 patients (mean age 39 y, 78% women) with the International Headache Society diagnostic criteria for migraine with or without aura who had had migraine for ≥ 1 year, with 2 to 6 attacks per month within the past 3 months. 91% were included in the analysis of the first migraine attack.

Intervention

145 patients were allocated to lysine acetylsalicylate (equivalent to 900 mg of aspirin) plus 10 mg of metoclopramide, 139 patients were allocated to 100 mg of oral sumatriptan, and 137 patients were allocated to placebo. Patients were treated as soon as the headache reached grade 2 to 3 on a 4-point severity scale (3 = severe, 2 = moderate, 1 = mild, 0 = no pain).

Main Outcome Measures

Decrease in headache grade to 0 or 1 at 2 hours after treatment of the first attack, decrease of headache grade for the second treated attack, use of escape medication, effect on nausea and vomiting, number of attacks completely resolved within 24 hours, recurrence of migraine attack within 24 hours, and adverse effects.

Main Results

For the first attack, lysine acetylsalicylate plus metoclopramide led to an improvement in headache severity after 2 hours that was similar to the improvement seen with sumatriptan {P = 0.50}* and was greater than that seen with placebo {P < 0.001}* (Table). Lysine acetylsalicylate plus metoclopramide and sumatriptan were superior to placebo for treating the second attack (P ≤ 0.006) (Table), with no difference between the 2 active treatments (P = 0.08). Rescue medication was taken more frequently in the placebo group. Lysine acetylsalicylate plus metoclopramide was more effective in treating nausea than was sumatriptan (P < 0.001) and was better tolerated (adverse effects 18% vs 28%, P < 0.05). The active drugs led to more attacks being completely resolved within 2 hours than did placebo. No difference was seen between treatment groups in the recurrence of migraine attack within 24 hours.

Conclusion

Lysine acetylsalicylate combined with metoclopramide was as effective as sumatriptan and more effective than placebo in treating migraine attacks.

Source of funding: Not stated.

For article reprint: Dr. P. Tfelt-Hansen, Glostrup Hospital, University of Copenhagen, Department of Neurology, DK-2600 Glostrup, Denmark. FAX 45-43-23-39-26.

*Numbers calculated from data in article.


Table. Lysine acetylsalicylate combined with metoclopramide or sumatriptan for the treatment of migraine†

Outcomes Comparisons Event rates RBI (95% CI) NNT (CI)
Improvement (1st attack)† Lysine vs placebo 57% vs 24% 136% (69 to 236) 3 (2 to 5)
Sumatriptan vs placebo 53% vs 24% 119% (55 to 214) 3 (2 to 6)
Improvement (2nd attack)† Lysine vs placebo 43% vs 25% 71% (16 to 156) 6 (3 to 19)
Sumatriptan vs placebo 55% vs 25% 117% (50 to 221) 3 (2 to 6)

†Abbreviations defined in Glossary; RBI, NNT, and CI calculated from data in article.
†Decrease in headache grade to 0 to 1 at 2 hours after treatment of attack.


Commentary

This study by Tfelt-Hansen and colleagues reminds us that well-established medications, such as salicylates, should not be abandoned in the midst of enthusiasm over newer antimigraine drugs such as sumatriptan. Sumatriptan is expensive and has potentially serious side effects. Salicylates are inexpensive, and their risks are well known. Why, then, does clinical experience suggest that these results will not be replicated in clinical practice? The answer has to do with the many differences between patients who participate in clinical trials and those who are encountered in clinical practice.

First, the design of this study minimized the clinically powerful effect of the preconceived expectations of benefit. Patients and physicians were unaware of which drug was used to treat a particular headache. In practice, patients and physicians know which drug is being used, and simple analgesics have the disadvantage of being perceived as less powerful than sumatriptan and other drugs because they are familiar and easily obtained. Perhaps the addition of metoclopramide both augments salicylatic action and could convince patients that they are getting something better.

Second, patients with migraine whose headaches respond to salicylates or related drugs generally discover this without the benefit of a medical consultation. The portion of patients who consult a physician frequently report resistance to salicylates. A few of these patients have used an inadequate dose or used the medication too late to benefit; some find that the addition of metoclopramide is helpful. For many more patients, however, overuse of salicylates or other analgesics with rebound headaches is a large part of the headache problem. Still others have nausea and vomiting too severe to use oral medications at all.

Third, it is likely that migraine is a genetically heterogeneous disease. Patients whose headaches are clinically indistinguishable may have different neurochemical causes for their headaches. This study reminds us that both alternatives should be considered. Patients who respond to both drugs should be encouraged to use salicylates. Sumatriptan is an important option, however, for patients who do not respond to salicylates or who cannot safely use them.

Elizabeth Loder, MD
The Spalding HospitalBoston, Massachusetts, USA