Preventative Migraine Treatments

Preventative (prophylactic) medications may be taken daily to prevent or reduce the frequency and severity of migraine attacks in the following situations:

Beta-blockers

Some, but not all, beta-blockers decrease the frequency of migraine attacks. Those that are effective include atenolol, metoprolol, nadolol and propranolol. Beta-blockers may act via the central catecholaminergic system and brain serotonin receptors.^{[1, 2]}

Tricyclic antidepressants

In migraine prophylaxis, tricyclic antidepressants such as amitriptyline are claimed to be especially useful for patients who also have tension-type headaches. The mechanism of action is thought to be unrelated to their antidepressant activity. In migraine, tricyclic antidepressants act by inhibiting noradrenaline and serotonin uptake and attenuating beta-adrenergic and central serotonin receptor function.^{[1, 2]}

Anti-epileptics

Divalproex sodium, sodium valproate and valproic acid are effective for migraine prophylaxis.^{[1, 2]} In addition, study data suggest that topiramate may also be useful for migraine prophylaxis, although some patients experience side effects such as peripheral paraesthesias in the hands and feet.^{[1, 2]}

Calcium channel blockers

Calcium channel blockers have a gradual onset of action with therapeutic effects typically not seen until several weeks after the start of treatment for migraine prophylaxis. These agents are thought to exert their activity in migraine by preventing hypoxia and the cellular influx of calcium ions.^{[1, 2]}

Methysergide

Methysergide (an ergotamine derivative) causes carotid vasoconstriction and inhibition of perivascular neuronal peptide release. It is indicated for severe recurrent migraine attacks that are unresponsive to other medication, although treatment should be interrupted every 6 months for 1-2 months to prevent retroperitoneal fibrosis.^[2]

ACE inhibitors

ACE inhibitors have been shown to have a positive effect on the frequency and severity of migraine attacks.^[3] The angiotensin converting enzyme (ACE) inhibitor lisinopril alters sympathetic activity, inhibits free radical activity, increases prostacyclin synthesis and blocks the degradation of bradykinin, encephalin and substance P. All these pharmacological effects have relevance in the pathophysiology of migraine.^{[1, 4, 5]}

Angiotensin receptor blockers

Angiotensin receptor blockers also appear to reduce the frequency and severity of migraine.^[3] Candesartan cilexetil has demonstrated effective migraine prophylaxis with few side effects.^{[1, 6]} Its mechanism of action as a migraine prophylactic is not yet known. However, the ability of candesartan to reduce the effects of angiotensin II (resulting in vasoconstriction, increased sympathetic discharge and adrenal medullary catecholamine release) may be involved.

References:
1. Modi S, Lowder DM. Medications for migraine prophylaxis. Am Fam Physician 2006;73: 72-8.
2. Pryse-Phillips WE, Dodick DW, Edmeads JG, Gawel MJ, Nelson RF, Purdy RA, et al. Guidelines for the diagnosis and management of migraine in clinical practice. Canadian Headache Society. CMAJ 1997;156: 1273-87.
3. Rahimtoola H, Buurma H, Tijssen CC, Leufkens HG, Egberts AC. Reduction in the therapeutic intensity of abortive migraine drug use during ACE inhibition therapy--a pilot study. Pharmacoepidemiol Drug Saf 2004;13: 41-7.
4. Bigal ME, Rapoport AM, Sheftell FD, Tepper SJ. New migraine preventive options: an update with pathophysiological considerations. Rev Hosp Clin Fac Med Sao Paulo 2002;57: 293-8.
5. Schrader H, Stovner LJ, Helde G, Sand T, Bovim G. Prophylactic treatment of migraine with angiotensin converting enzyme inhibitor (lisinopril): randomised, placebo controlled, crossover study. BMJ 2001;322: 19-22.
6. Tronvik E, Stovner LJ, Helde G, Sand T, Bovim G. Prophylactic treatment of migraine with an angiotensin II receptor blocker: a randomized controlled trial. JAMA 2003;289: 65-9.