26.06 Acute Treatment of Migraine
It is important to distinguish between drugs that are used to treat acute migraine attacks, and drugs used in migraine prophylaxis, required for cases of at least two migraine attacks per month.
Acute attacks are treated with non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and paracetamol, ergotamines, and more commonly, triptans. NSAIDs are usually effective for mild attacks and when taken shortly after the onset of pain.
For over 70 years ergotamines such as ergotamine tartrate and dihydroergotamine were the classical treatment for migraine. These drugs can relieve the pain of migraine even when taken more than four hours after onset. Ergotamines are partial agonists at 5-HT1D receptors, thus blocking trigeminal nerve transmission, however they act at many additional monoamine receptors, including 5-HT1B, 5-HT2, dopamine D1 and D2, noradrenergic α1 and α2 receptors. Subsequently, their usefulness is limited by their propensity to cause vasoconstriction, including of the coronary vessels, and foetal damage. They also cause nausea and vomiting due to activation of area postrema.
Triptans have become first line treatment for acute severe migraine, replacing ergotamines. A number of triptans are available, including sumaptriptan (the prototype), zolmitriptan, almotriptan and naratriptan. The differences between these drugs lie in their plasma half life and time to peak plasma levels. Moreover, sumatriptan does not cross the blood brain barrier, while the other drugs do. Up to 80% of patients respond to triptans within two hours of administration, and up to 40% experience headache recurrence within 24 hours of initial relief.
All triptans are 5-HT1B/1D agonists, and their effects on migraine are numerous. Activation of these receptors on trigeminal ganglia and trigeminal nucleus caudalis cells inhibits transmission of nociceptive information from the blood vessels and meninges to the brainstem and central pain pathways. Additionally, stimulation of presynaptic 5-HT1B/1D autoreceptors on trigeminal cell bodies inhibits release of neuropeptides from trigeminal ganglia cells, thus reducing neurogenic inflammation. Moreover, on extracerebral blood vessels, activation of 5HT1B/1D receptors causes vasoconstriction, thus facilitating restoration of normal vascular tone. Finally, triptans relieve the nausea associated with migraine. One drawback, however, is their ability to cause vasoconstriction of coronary arteries via 5-HT1B receptors, thus they are contraindicated in cardiovascular disease.