Summary

In the treatment of migraine, pethidine is less efficacious than dihydroergotamine plus metoclopramide: it can aggravate nausea, there is a risk of dependence and it has a short duration of effect necessitating additional medication. Its use therefore cannot be substantiated.

Pethidine is a relatively old non-alkaloid opioid agonist. It has a short duration of effect and is an addictive drug. Chronic administration of pethidine can result in substantial accumulation of the active metabolite, norpethidine, which has CNS stimulatory effects and can cause seizures.

The mechanism responsible for the headache of migraine involves a 'neural hypothesis' with possible inflammatory components.1,2 The use of pethidine in the treatment of migraine therefore does not aim at the primary mechanism; it acts as a rather 'nonspecific' analgesic.1 The efficacy of pethidine is not better than that of non-opioid analgesics, it has the potential for aggravating nausea and there is a risk of dependence.

Also, because of its short duration of action resulting in loss of efficacy during an attack of migraine, pethidine can cause the headache to return with the result that the patient requires additional medication.1

There have been a number of randomised double-blind clinical trials in migraine patients in which the efficacy of pethidine, always in combination with an antihistamine such as hydroxyzine, promethazine or dimenhydrinate, was compared with either chlorpromazine or dihydroergotamine plus metoclopramide or non-steroidal anti-inflammatory drugs such as ketorolac. The combination with pethidine was not found to be more efficacious and, in one study3, intravenous dihydroergotamine plus metoclopramide was found to be significantly better than pethidine plus hydroxyzine. These authors recommended that pethidine be replaced by a combination of dihydroergotamine plus metoclopramide. In another study, pethidine produced more adverse effects.4 With the advent of 5HT1 agonists such as sumatriptan for acute treatment, the need for pethidine cannot be substantiated.

There have been several reports of long-term use of opioid analgesics (in particular, codeine) actually promoting headache.5 Since some migraine patients take opioid analgesics (e.g. codeine, dextropropoxyphene) chronically, the risk of dependence and tolerance to pethidine when administered acutely cannot be underestimated.

Pethidine should not be used in the treatment of migraine.

Treatment of acute migraine*
Patients should be advised to rest in a quiet, darkened room. They should avoid movement or any activity including reading or watching television.

Initial therapy
soluble aspirin 600-900 mg 4 hourly
OR
soluble paracetamol 1-1.5 g 4 hourly, to a maximum of 4 g/day

Efficacy may be improved by first giving metoclopramide 10 mg orally.

If nausea or vomiting is prominent, use prochlorperazine suppository (25 mg) rectally, followed, if required, in 6 hours by prochlorperazine 5 mg orally
OR
metoclopramide 10 mg intravenously or intramuscularly

If simple treatment is ineffective
If previous attacks have not responded to aspirin or paracetamol, substitute ergotamine 1-2 mg orally, at the onset of the prodrome or headache, and repeat 1 mg in an hour if necessary.

If vomiting precludes oral therapy, give dihydroergotamine 0.5-1 mg subcutaneously or intramuscularly
OR
ergotamine/caffeine 2/100 mg rectally

Other cases
If the above treatments have failed to relieve previous attacks, sumatriptan can be used. It can be given orally or by injection and should be taken as soon as possible in the course of an attack.

* Based on 'Therapeutic Guidelines: Neurology` by Therapeutic Guidelines Ltd.

References

  1. Goadsby PJ, Olesen J. Diagnosis and management of migraine. Br Med J 1996;312:1279-83.
  2. Moskowitz MA. Drug mechanisms in acute migraine. Prog Pain Res Manag 1994;2:755-64.
  3. Klapper JA, Stanton J. Current emergency treatment of severe migraine headaches. Headache 1993;33:560-2.
  4. Scherl ER, Wilson JF. Comparison of dihydroergotamine with metoclopramide versus meperidine with promethazine in the treatment of acute migraine. Headache 1995;35:256-9.
  5. Olesen J. Analgesic headache [editorial]. Br Med J 1995;310:479-80.