Pethidine is inappropriate for migraine
- Andrew A. Somogyi
- Aust Prescr 1997;20:71
- 1 July 1997
- DOI: 10.18773/austprescr.1997.061
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*
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
If simple treatment is ineffective
If vomiting precludes oral therapy, give dihydroergotamine 0.5-1 mg subcutaneously or intramuscularly
* Based on 'Therapeutic Guidelines: Neurology` by Therapeutic Guidelines Ltd.
Associate Professor, Department of Clinical and Experimental Pharmacology, University of Adelaide
Experimental Pharmacology, University of Adelaide
Department of Clinical Pharmacology, Royal Adelaide Hospital, Adelaide