Topiramate Reduces Chronic Headache Days

LOS ANGELES – The anticonvulsant drug topiramate significantly eased chronic daily headaches, one of the most intractable forms of headache to treat, in a randomized, placebo-controlled trial conducted at 46 U.S. centers.

Although subjects continued to experience headaches on about half of the days in a given month, the relief they obtained had a significant impact on their daily functioning, reported Dr. Stephen D. Silberstein at the annual meeting of the American Headache Society.

With this multicenter study, topiramate has demonstrated “the best efficacy of any drug [used in the treatment of] chronic daily headache,” he said in an interview following the meeting.

At baseline, patients enrolled in the trial experienced headaches about 20–21 days a month, including 17 days in which their headaches were migraines or had migraine features, including unilateral pain, pulsatility, worsening of pain with movement, and nausea and/or vomiting.

The group of 328 patients included mostly women. On average, they had suffered chronic, near-daily headaches for more than 9 years.

The mean number of days per month patients had migraine or “migrainous” headaches declined by 6.41 days in patients randomized to topiramate, compared with 4.67 days in those on placebo, said Dr. Silberstein, director of the Jefferson Headache Center at Thomas Jefferson University Hospital in Philadelphia.

Patients who took 100 mg/day of topiramate for 3 months after a washout period and a 4-week titration phase had strictly defined migraines less often than did those on placebo: 4.1 days versus 5.6 days, he reported.

Although total average headache severity was not significantly improved by topiramate, peak severity decreased substantially, suggesting that topiramate reduces the migrainous component of headaches, Dr. Silberstein said.

Topiramate, marketed as Topamax, is Food and Drug Administration approved for the prevention of episodic migraine headaches, defined as those occurring less than 15 days/month.

In addition to this pivotal U.S. study, it was the subject of a companion study conducted in Europe that produced similar results in patients with chronic daily headaches, even when those patients suffered from medication overuse headaches.

Dr. Silberstein acknowledged the suggestion by one audience member that the results were “significant but not overly dramatic,” but he noted the limitations of any clinical trial with regard to its clinical application.

“I think it's extremely important to point out that in real life … we'll increase the dose to get significantly higher levels,” he said.

In his clinic, it is not uncommon for patients with severe, long-standing chronic daily headaches to receive 800 mg to 1 g of topiramate per day.

The most common side effect seen in both the U.S. and European trials was paresthesia, seen in about 30% of topiramate patients, especially during titration. Adverse events leading to withdrawal from the trial occurred in 11.3% of the topiramate patients and 6.2% of those receiving placebo. Mental confusion was an uncommon adverse effect. There were no serious adverse events in either group.

Dr. Silberstein disclosed that he receives grant support and serves on the advisory board and as a speaker for Ortho-McNeil Neurologics Inc., the manufacturer of topiramate.

In real life, physicians tend to increase the doses to higher levels than those used in the study. DR. SILBERSTEIN

LOS ANGELES – The anticonvulsant drug topiramate significantly eased chronic daily headaches, one of the most intractable forms of headache to treat, in a randomized, placebo-controlled trial conducted at 46 U.S. centers.

Although subjects continued to experience headaches on about half of the days in a given month, the relief they obtained had a significant impact on their daily functioning, reported Dr. Stephen D. Silberstein at the annual meeting of the American Headache Society.

With this multicenter study, topiramate has demonstrated “the best efficacy of any drug [used in the treatment of] chronic daily headache,” he said in an interview following the meeting.

At baseline, patients enrolled in the trial experienced headaches about 20–21 days a month, including 17 days in which their headaches were migraines or had migraine features, including unilateral pain, pulsatility, worsening of pain with movement, and nausea and/or vomiting.

The group of 328 patients included mostly women. On average, they had suffered chronic, near-daily headaches for more than 9 years.

The mean number of days per month patients had migraine or “migrainous” headaches declined by 6.41 days in patients randomized to topiramate, compared with 4.67 days in those on placebo, said Dr. Silberstein, director of the Jefferson Headache Center at Thomas Jefferson University Hospital in Philadelphia.

Patients who took 100 mg/day of topiramate for 3 months after a washout period and a 4-week titration phase had strictly defined migraines less often than did those on placebo: 4.1 days versus 5.6 days, he reported.

Although total average headache severity was not significantly improved by topiramate, peak severity decreased substantially, suggesting that topiramate reduces the migrainous component of headaches, Dr. Silberstein said.

Topiramate, marketed as Topamax, is Food and Drug Administration approved for the prevention of episodic migraine headaches, defined as those occurring less than 15 days/month.

In addition to this pivotal U.S. study, it was the subject of a companion study conducted in Europe that produced similar results in patients with chronic daily headaches, even when those patients suffered from medication overuse headaches.

Dr. Silberstein acknowledged the suggestion by one audience member that the results were “significant but not overly dramatic,” but he noted the limitations of any clinical trial with regard to its clinical application.

“I think it's extremely important to point out that in real life … we'll increase the dose to get significantly higher levels,” he said.

In his clinic, it is not uncommon for patients with severe, long-standing chronic daily headaches to receive 800 mg to 1 g of topiramate per day.

The most common side effect seen in both the U.S. and European trials was paresthesia, seen in about 30% of topiramate patients, especially during titration. Adverse events leading to withdrawal from the trial occurred in 11.3% of the topiramate patients and 6.2% of those receiving placebo. Mental confusion was an uncommon adverse effect. There were no serious adverse events in either group.

Dr. Silberstein disclosed that he receives grant support and serves on the advisory board and as a speaker for Ortho-McNeil Neurologics Inc., the manufacturer of topiramate.

In real life, physicians tend to increase the doses to higher levels than those used in the study. DR. SILBERSTEIN

LOS ANGELES – The anticonvulsant drug topiramate significantly eased chronic daily headaches, one of the most intractable forms of headache to treat, in a randomized, placebo-controlled trial conducted at 46 U.S. centers.

Although subjects continued to experience headaches on about half of the days in a given month, the relief they obtained had a significant impact on their daily functioning, reported Dr. Stephen D. Silberstein at the annual meeting of the American Headache Society.

With this multicenter study, topiramate has demonstrated “the best efficacy of any drug [used in the treatment of] chronic daily headache,” he said in an interview following the meeting.

At baseline, patients enrolled in the trial experienced headaches about 20–21 days a month, including 17 days in which their headaches were migraines or had migraine features, including unilateral pain, pulsatility, worsening of pain with movement, and nausea and/or vomiting.

The group of 328 patients included mostly women. On average, they had suffered chronic, near-daily headaches for more than 9 years.

The mean number of days per month patients had migraine or “migrainous” headaches declined by 6.41 days in patients randomized to topiramate, compared with 4.67 days in those on placebo, said Dr. Silberstein, director of the Jefferson Headache Center at Thomas Jefferson University Hospital in Philadelphia.

Patients who took 100 mg/day of topiramate for 3 months after a washout period and a 4-week titration phase had strictly defined migraines less often than did those on placebo: 4.1 days versus 5.6 days, he reported.

Although total average headache severity was not significantly improved by topiramate, peak severity decreased substantially, suggesting that topiramate reduces the migrainous component of headaches, Dr. Silberstein said.

Topiramate, marketed as Topamax, is Food and Drug Administration approved for the prevention of episodic migraine headaches, defined as those occurring less than 15 days/month.

In addition to this pivotal U.S. study, it was the subject of a companion study conducted in Europe that produced similar results in patients with chronic daily headaches, even when those patients suffered from medication overuse headaches.

Dr. Silberstein acknowledged the suggestion by one audience member that the results were “significant but not overly dramatic,” but he noted the limitations of any clinical trial with regard to its clinical application.

“I think it's extremely important to point out that in real life … we'll increase the dose to get significantly higher levels,” he said.

In his clinic, it is not uncommon for patients with severe, long-standing chronic daily headaches to receive 800 mg to 1 g of topiramate per day.

The most common side effect seen in both the U.S. and European trials was paresthesia, seen in about 30% of topiramate patients, especially during titration. Adverse events leading to withdrawal from the trial occurred in 11.3% of the topiramate patients and 6.2% of those receiving placebo. Mental confusion was an uncommon adverse effect. There were no serious adverse events in either group.

Dr. Silberstein disclosed that he receives grant support and serves on the advisory board and as a speaker for Ortho-McNeil Neurologics Inc., the manufacturer of topiramate.

In real life, physicians tend to increase the doses to higher levels than those used in the study. DR. SILBERSTEIN