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Drug Treatments for Migraine


Bandolier has been stimulated by a number of papers on different treatments for migraine to try and put together a league table of relative effectiveness. In an ideal world this would be created from all the available evidence from systematic reviews. The problem is that the systematic reviews either have not yet been done, or anyway Bandolier couldn't find any.

In these circumstances the choice is either to forget it, or to press on with what evidence is available. Bandolier , you will not be surprised to learn, chose the latter course. So this section comes with the health warning that it is not complete - it is a "Saturday night special" review. Perhaps migraine treatment, which is now a big industry, is one of those topics about which people should write to ask for a Health Technology Assessment.

Sumatriptan

A review of the controlled clinical trials of sumatriptan up to 1993 was published by Peer Tfelt-Hansen from Copenhagen [1]. It contained data from an impressive number of randomised studies of sumatriptan given by subcutaneous and oral routes, and with impressive numbers of patients. Data from these papers has been extracted to calculate NNTs.

Subcutaneous sumatriptan

Five studies of subcutaneous sumatriptan 6 mg against placebo were highlighted in the Tfelt-Hansen review, with over 2000 patients. The primary outcome measure was the effect on migraine headache. Patients rated their headache on a four-point scale (severe, moderate, mild or none) and the definition of a successful response was the decrease of a severe or moderate headache to mild or none.

The results at two hours after treatment are shown in the L'Abbé plot; the risk ratio was 2.5 (2.3 - 2.8) and the NNT was 2 (1.8 - 2.2).

This means that one of every two patients with a migraine attack treated with subcutaneous sumatriptan will have their headache cured or substantially improved, who would not have done had they been treated with placebo.

Oral sumatriptan

Four reports of oral sumatriptan 100 or 200 mg were highlighted in the Tfelt-Hansen review, and one other was taken from a comparison with aspirin/metoclopramide [2]. Data from five studies and over 1100 patients were available.

Using the same outcome measures as for subcutaneous sumatriptan, the results at two hours after treatment are showed a risk ratio of 2.6 (2.1 - 3.1) and an NNT of 2.7 (2.3 - 3.2).

This means that one of every three patients with a migraine attack treated with oral sumatriptan will have their headache cured or substantially improved, who would not have done had they been treated with placebo.

Oral aspirin/metoclopramide

Two large randomised controlled trials have been reported in this last year [2,3]. One used a combination of lysine acetylsalicylate (equivalent to 900 mg of aspirin) plus 10 mg metoclopramide [2] and the other 900 mg aspirin plus 10 mg metoclopramide [3]. Both used the same outcome measure as for sumatriptan, namely headache at two hours after treatment with no or mild pain.

Combining the two studies, which had very similar results, 145/260 patients had resolution of headache with aspirin/metoclopramide compared with 61 of 255 patients with placebo. The risk ratio was 2.3 (1.8 - 3.0) and the NNT was 3.1 (2.5 - 4.2).

This means that one of every three patients with a migraine attack treated with oral aspirin/metoclopramide will have their headache cured or substantially improved, who would not have done had they been treated with placebo.

Intranasal lignocaine

A trial reported in JAMA in July 1996 demonstrated effectiveness for intranasal lignocaine in migraine [4]. The theoretical site of action is the sphenopalatine ganglion which lies a few millimetres below the nasal mucosa.

In this solitary randomised trial patients received either a 4% solution of lignocaine or normal saline. Patients lay supine with the head extended and rotated towards the side of the headache, and 0.5 mL of solution was dripped into a nostril over 30 seconds. The outcome measure was the reduction of headache pain to none or mild, and at least 50% reduction in initial pain intensity.

By 15 minutes after the intranasal application, 29 of 53 patients given intranasal lignocaine had pain relief, compared with 6 of 28 given saline. The risk ratio was 2.6 (1.2 - 5.4) and the NNT 3.0 (1.9 - 7.7).

This means that one of every three patients with a migraine attack treated with intranasal lignocaine will have their headache cured or substantially improved, who would not have done had they been treated with placebo.

Anticonvulsant prophylaxis

A systematic review of anticonvulsants in chronic pain [5] identified three randomised trials where prophylactic use of anticonvulsants (carbamazepine, clonazepam or valproate) was compared with placebo in migraine. Two studies had dichotomous outcomes (improvement in number of migraine attacks), and 63 of 74 patients benefited with anticonvulsants compared with 17 of 77 given placebo.

The risk ratio was 3.9 (2.5 - 5.9) and the NNT was 1.6 (1.3 - 2.0).

This means that one of two patients suffering from migraine and treated prophylactically with anticonvulsants will have their headache frequency reduced, who would not have done had they been treated with placebo.

Relative effectiveness



The relative effectiveness of these interventions can be seen in the figure below. Lower NNTs means greater treatment-specific effectiveness.

Intranasal lignocaine should probably be regarded as an experimental (and inconvenient) treatment. Prophylactic anticonvulsants carry minor adverse effects as frequently as effectiveness, and with only three small randomised trials their use can also be regarded as experimental; no anticonvulsant is licensed for use in migraine prophylaxis.

While subcutaneous sumatriptan is clearly the most effective of the other three treatments, it is also the most expensive at about £20 per treatment. Oral sumatriptan is the next most effective treatment, and quite expensive at about £8 per treatment. Oral aspirin/metoclopramide has similar efficacy to oral sumatriptan, and is the cheapest at about £0.33 per treatment.

References:

  1. P Tfelt-Hansen. Sumatriptan for the treatment of migraine attacks - a review of controlled clinical trials. Cephalalgia 1993 13: 238-44.
  2. P Tfelt-Hansen, P Henry, L Mulder et al. The effectiveness of combined oral lysine acetylsalicylate and metoclopramide compared with oral sumatriptan for migraine. Lancet 1995 346: 923-6.
  3. P Henry, O Hiesse-Provost, A Dillenschneider, H Ganry, I Insuasty. Efficacité et tolérance de l'association effervescente aspirine - metoclopramide dans le traitement de la crise de migraine sans aura. La Presse Médicale 1995 24: 254-8.
  4. M Maizels, B Scott, W Cohen, W Chen. Intranasal lidocaine for treatment of migraine. Journal of the American Medical Association 1996 276: 319-21.
  5. H McQuay, D Carroll, A Jadad, P Wiffen, A Moore. Anticonvulsant drugs for management of pain: a systematic review. British Medical Journal 1995 311:1047-52.




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