Topiramate (Topamax) is an antiepileptic drug recently approved by the U.S. Food and Drug Administration (FDA) for prevention of migraine headache in adults. Its exact mechanism of action is uncertain, but it is known to affect neuronal hyperexcitability,1 which is one probable factor in the development of migraine.
|Name||Starting dosage||Dose form||Approximate monthly cost*|
|Topiramate (Topamax)||25 mg once per day, increasing by 25 mg per week up to the recommended dosage of 50 mg twice per day.||50-mg tablets||$210 for 60 tablets|
|(Dosage should be halved for patients with renal impairment.)|
Clinical trials and experience with topiramate have not identified serious safety concerns. Topiramate markedly lowers serum bicarbonate levels in 10 percent of patients,1 but this is clinically significant only in patients with other risk factors for metabolic acidosis. In three large randomized controlled trials2–4 in which collectively almost 1,000 patients received topiramate,10 patients reported renal calculi, and for three of these patients this resulted in discontinuation of the medication. Topiramate is FDA pregnancy category C, and is excreted in breast milk.1
Topiramate is not tolerated well by some patients. The most common side effects of topiramate compared with placebo are paresthesias (51 versus 6 percent, respectively), fatigue (15 versus 11 percent), nausea (13 versus 8 percent), and difficulty with memory, concentration, or language (15 versus 5 percent).1 Topiramate is associated with a dosage-dependent decrease in body weight. Patients who received 100 mg of topiramate per day lost about 3 percent of their body weight.2,3 In placebo-controlled migraine trials, significantly more patients who received 100 mg per day of topiramate discontinued because of an adverse event than those who received placebo (25 versus 10 percent, respectively).1
Topiramate has been studied in patients age 12 to 65 years who had an average of 5.5 headaches per month at baseline. At a dosage of 50 mg twice per day, topiramate reduced migraine frequency by approximately two headaches per month compared with a reduction of one headache per month with placebo.2–4 At the same dosage, between 37 and 54 percent of patients had at least a 50 percent reduction in monthly headache frequency compared with a 22 percent response rate for patients receiving placebo (number needed to treat = 3 to 7).2–4 The reduction in migraine frequency generally was observed after one month of treatment. A Cochrane review5 of anticonvulsants for migraine prevention, which included topiramate, showed that anticonvulsants as a class reduced migraine frequency by 1.4 attacks per month, similar to the effect seen for topiramate. Topiramate has not been directly compared with other anti-epileptic drugs, tricyclic antidepressants, or calcium channel blockers. However, one study4 included propranolol (Inderal) as an active control. Topiramate and propranolol had similar efficacy, decreasing migraine frequency by 1.6 headaches per month.4
A one-month supply (60 tablets) of 50-mg tablets will cost patients approximately $210, compared with $130 for 100 tablets of divalproex (Depakote ER) and $2.50 to $4.00 for 100 tablets of generic propranolol.
The recommended dosage of topiramate for migraine prevention is 50 mg twice per day. Patients should start with 25 mg once per day, then increase by 25 mg per week up to the recommended dosage. The dosage should be halved for patients with renal impairment (i.e., creatinine clearance less than 70 mL per minute [1.17 mL per second]).1These dosing requirements make topiramate more complicated to use than many other medications for migraine prevention.
Topiramate is more effective than placebo for migraine prevention. Its effectiveness appears to be similar to that of other antiepileptic drugs and beta blockers. Because of the high cost of topiramate and the relative frequency of adverse effects, other approaches to migraine prevention, such as beta blockers, tricyclic antidepressants, or riboflavin, should be used first.6