26.07 Prophylactic Treatment of Migraine
Drugs used in prophylactic treatment of migraine include β-adrenoceptor antagonists, 5-HT2 receptor antagonists, anticonvulsants and calcium channel antagonists. The type of prophylactic drug is chosen on the basis of factors such as contraindications, co-morbid conditions and tolerability. Even when used, only 50% of sufferers can expect a reduction in migraine frequency.
b-adrenoceptor antagonists such as propranolol and metoprolol have been used successfully in the prophylactic treatment of migraine. The mechanism of prophylaxis is unknown, but it may be due to vasoconstrictor effects. These drugs are contraindicated in respiratory diseases such as asthma, and side effects include fatigue and bronchoconstriction.
5-HT2 antagonists such as pizotifen, cyproheptadine and methysergide act by preventing 5-HT2 receptor-induced vasodilation, secondary to nitric oxide production, and consequent inflammation. Adverse effects include weight gain and methysergide is now rarely used owing to the risk of retroperitoneal fibrosis and renal failure with long-term use.
Anticonvulsants such as sodium valproate, gabapentin and topiramate are thought to prevent migraine by increasing inhibitory GABAergic and Ca2+ channel activity, thus reducing cortical excitability and possibly the threshold for triggering migraine attacks. These drugs may reduce cortical spreading excitation, hence depression, and trigeminal neurotransmission, however they are teratogens thus their use is excluded during pregnancy and lactation.
Finally, calcium channel antagonists like nifedipine and verapamil have shown some efficacy, and act to decrease cellular excitability by reducing Ca2+ entry into cells.
The need remains for improved drugs, with greater selectivity and fewer side effects, for treatment of migraine. Drugs that act selectively on 5-HT1D/1F receptors would remove 5-HT1B-induced constriction of coronary and cerebral arteries. The role of CGRP in regulation of vascular tone and in the pathogenesis of migraine is being increasingly recognised, and CGRP antagonists such as olcegepant.