Prophylaxis of Migraine

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Chapter: Essential pharmacology : 5Hydroxytryptamine, Its Antagonists And Drug Therapy Of Migraine

Regular medication to reduce the frequency and/or severity of attacks is recommended for moderate to severe migraine when 2–3 or more attacks occur per month.



Regular medication to reduce the frequency and/or severity of attacks is recommended for moderate to severe migraine when 2–3 or more attacks occur per month. Diverse classes of drugs are used but none is effective in all cases, and none abolishes the attacks totally. It may be prudent to discontinue pophylaxis every 6 months to check whether its continuation is needed or not. It is important to avoid the precipitating factor(s).


Β-Adrenergic blockers


Propranolol is the most commonly used drug: reduces frequency as well as severity of attacks in upto 70% patients. Effect is generally seen in 4 weeks and is sustained during prolonged therapy. The starting dose is 40 mg BD, which may be increased upto 160 mg BD if required. The mechanism of action is not clear; that it is due to β adrenergic blockade has been questioned. Other nonselective (timolol) and β1 selective (metoprolol, atenolol) agents are also effective, but pindolol and others having intrinsic sympathomimetic action are not useful.


Tricyclic antidepressants


Many tricyclic compounds of which amitriptyline has been most extensively tried (25–50 mg at bed time) reduce migraine attacks. It is effective in many patients but produces more side effects than propranolol. It is not known whether its 5HT (and other monoamine) uptake blocking property is causally related to the prophylactic effect. The antimigraine effect is independent of antidepressant property, but this class of drugs are better suited for patients who also suffer from depression.


Calcium Channel Blockers


Verapamil was found to reduce migraine attacks, but was judged inferior to propranolol. Flunarizine is a relatively weak Ca2+ channel blocker that also inhibits Na+ channels. It is claimed to be as effective as propranolol, but convincing proof is lacking. Frequency of attacks is often reduced, but effect on intensity and duration of attacks is less well documented. It is claimed to be a cerebroselective Ca2+ channel blocker; may benefit migraine by reducing intracellular Ca2+ overload due to brain hypoxia and other causes. Side effects are sedation, constipation, dry mouth, hypotension, flushing, weight gain and rarely extrapyramidal symptoms.


Dose: 10–20 mg OD, children 5 mg OD, NOMIGRAIN, FLUNARIN 5 mg, 10 mg caps/tab.




Valproic acid (400–1200 mg/day) and gabapentin (300–1200 mg/day) have some prophylactic effect in migraine. The newer drug topiramate has recently been approved for migrain prophylaxis. A 50% reduction in the number of attacks in half of the patients was noted in 2 randomized trials. Start with 25 mg OD and gradually increase to 50 mg OD or BD. Efficacy of anticonvulsants in migraine is lower than that of β blockers. They are indicated in patients refractory to other drugs or when propranolol is contraindicated.


5HT   Antagonists 


The   prophylactic   effect   of methysergide and cyproheptadine is less impressive than β blockers. They are seldom used now for migraine.


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