Pharmacy & Therapeutics- August 2008 - (Page 481) CONTINUING EDUCATION CREDIT Table 1 Prophylactic Pharmacotherapies for Migraine Headache Drug Class Beta blockers Agent, Dose Range Propranolol (Inderal)* 40–240 mg/day in divided doses or LA q.d. Nadolol (Corgard) 20–120 mg q.d. or b.i.d. Timolol (Blocadren)* 20–60 mg q.d. or b.i.d. Atenolol (Tenormin) 25–100 mg q.d. Metoprolol (Toprol) 50–200 mg b.i.d. Tricyclic agents • Amitriptyline 10–150 mg h.s. • Nortriptyline (Pamelor) 10–150 mg h.s. • Doxepin (Sinequan) 10–200 mg h.s. • Desipramine (Norpramin) 25–150 mg h.s. MAOIs: Phenelzine (Nardil) 15–60 mg t.i.d. SSRIs: Fluoxetine (Prozac) 10–80 mg q.d. Valproic acid (Depakene):* start 250 mg h.s. or b.i.d., titrate dose to 1,500 daily in divided doses Divalproex sodium 1,000 mg q.d. • Depakote valproate sodium • Depakene solution Topiramate (Topamax)* 100–400 mg b.i.d.–t.i.d. daily Verapamil (Calan) 240–360 mg daily in divided doses Monitoring Parameter Side effects • Heart rate • Blood pressure • Sexual dysfunction (males) Drug interactions Efficacy Side effects • Anticholinergic • Cardiac status/predose ECG in some patients • Weight gain Drug interactions Efficacy Side effects • Sedation/fatigue • Liver enzymes • Complete blood count Drug interactions Efficacy Cognitive effects Side effects • Heart rate • Blood pressure • Sexual dysfunction (males) Drug interactions Efficacy Side effects • Renal function • Signs and symptoms of bleeding Antidepressants Anticonvulsants Calcium-channel blockers NSAIDs Naproxen sodium (Naprosyn) 550–1,100 mg daily in divided doses Ketoprofen 150 mg daily in divided doses *These agents are FDA-approved for migraine prophylaxis. b.i.d. = twice daily; ECG = electrocardiogram; ER = extended-release; h.s. = at bedtime; LA = long-acting; MAOI = monoamine oxidase inhibitor; NSAID = nonsteroidal anti-inflammatory drug; q.d. = once daily; t.i.d. = three times daily. Adapted from references 1, 2, 4, and 34. ous antihypertensive agents. One reported drug interaction with propranolol that might be significant in migraine patients who are using triptans that are metabolized by the monoamine oxidase A (MAO-A) pathway—including sumatriptan (Imitrex, GlaxoSmithKline), almotriptan (Axert, Ortho-McNeil), and others—is propranolol’s inhibition of triptan metabolism and a potentially greater risk of side effects. The concurrent use of these triptans with propranolol should be monitored carefully. Lower doses of these triptans should be used, or they should be avoided in favor of an alternative agent.36,37 Beta blockers are considered a drug of choice for migraine prevention, especially in patients without absolute contraindications. They offer an excellent choice for patients with other morbidities, including hypertension and coronary artery disease. Beta blockers should be initiated at low doses along with monitoring of heart rate and blood pressure. An adequate trial of 3 to 12 months with continued assessment of efficacy and tolerability is recommended.11,13,35 Antidepressants Tricyclic Agents Although various classes of antidepressants have been studied and used to prevent migraine headache, more data are available for the tricyclic antidepressants (TCAs) (Table 1).4,38,39 Their proposed mechanism of action is thought to involve the inhibition of central cortical depression and sympathetic activity associated with migraine pathophysiology.40,41 Clinical trials with the TCA amitriptyline have reported a 50% to 70% reduction in the number and in intensity of migraine attacks, with doses ranging from 10 to 100 mg daily.38,42 Trials comparing amitriptyline with the beta blocker propranolol have reported similar efficacy.43 The side-effect profile of the TCAs includes dry mouth, constipation, urinary retention, and weight gain along with central effects (sedation, weakness, fatigue, and tremor), which may limit their use in some patients. The secondary-amine TCAs nortriptyline (Pamelor, Mallinckrodt) and desipramine (Nor- Vol. 33 No. 8 • August 2008 • P&T® 481
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