Preventive Treatment Of Migra... Health Article

The mechanism of action of β-blockers is not clear but it could occur by the inhibition of β 1 -mediated mechanisms [16]. β-Blockers, the most widely used class of prophylactic migraine drug, are ∼50% effective at producing a >50% reduction in attack frequency and include propranolol, nadolol, atenolol, metoprolol and timolol [17]. The relative efficacy of β-blockers has not been established; choice is based on β-selectivity, convenience, AEs and patient reactions. β-Blockers with intrinsic sympathomimetic activity (e.g. acebutolol, alprenolol, oxprenolol and pindolol) are not effective for migraine prevention. β-Blockers can produce behavioral AEs such as drowsiness, fatigue, lethargy, sleep disorders, nightmares, depression, memory disturbance and hallucinations, and should be avoided when patients are depressed. Decreased exercise tolerance limits their use by athletes. Less common AEs include impotence, orthostatic hypotension and bradycardia [18].

There are several different classes of antidepressant that have different mechanisms of action. In animal pain models, antidepressants potentiate the effects of co-administered opioids [16]. Amitriptyline (a tricyclic antidepressant) is the only antidepressant with consistent support for efficacy [17]. AEs include increased appetite, weight gain, dry mouth and sedation; cardiac toxicity and orthostatic hypotension occasionally occur. Selective 5-HT-reuptake inhibitors (SSRIs) are probably not effective at preventing migraine, whereas the results of open and smaller studies indicate that selective norepinephrine-reuptake inhibitors (SNRIs) are effective [19]. The mechanism by which antidepressants prevent headache is unclear but it does not result from treating masked depression.

Ca ²⁺ channel antagonists were introduced for the treatment of migraine on the assumption that they prevent hypoxia of cerebral neurons, contraction of vascular smooth muscle and inhibition of the Ca ²⁺ -dependent enzymes involved in prostaglandin formation. Perhaps it is their ability to block 5-HT release, interfere with neurovascular inflammation or interfere with the initiation and propagation of SD that is crucial [16]. The discovery that an abnormality in an α 1A subunit (P/Q channel) can produce familial hemiplegic migraine has led to a search for more-fundamental associations [20].

Of the drugs in this class [17] , flunarizine is effective at preventing migraine, whereas nimodipine and nifedipine are probably not. The efficacy of verapamil, despite its wide use in the USA (because flunarizine is unavailable), is uncertain, and its most common AE is constipation. The AEs of flunarizine include parkinsonism, depression and weight gain. These are typical of dopamine antagonists and indicate an alternative mechanism of action.