Neurology -- Correspondence for Silberstein et al., 63 (2) 261-269

Correspondence published:

A randomized trial of frovatriptan for the intermittent prevention of menstrual migraine: James U. Adelman, Anne Calhoun (28 October 2004)

Reply to Adelman et al: Stephen D. Silberstein, MD (28 October 2004)

A randomized trial of frovatriptan for the intermittent prevention of menstrual migraine 28 October 2004

James U. Adelman,
Headache Wellness Center
301 E. Wendover Ave. Greensboro, NC 27401,
Anne Calhoun
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Re: A randomized trial of frovatriptan for the intermittent prevention of menstrual migraine

jadelman{at}triad.rr.com James U. Adelman, et al.

Silberstein et al's article [1] is a good example of how evidenced- based treatment may lead not only to substandard but also expensive care.
To be included in this frovatriptan study, women had to have regular menstrual cycles and be able to predict the onset of their MRM. Despite this selection, the benefit was modest: MRM persisted in 52% of the group receiving frovatriptan 2.5mg qd, 41% of those receiving 2.5mg bid, and 67% of the placebo group. The authors accurately conclude that frovatriptan 2.5mg given prophylactically twice daily for six days was effective in reducing the incidence of MRM.
This form of preventive treatment presents as many problems as benefits. How are these 41% of breakthrough MRMs to be treated? The most effective acute treatment of migraine is a rapid-acting triptan. However, this option cannot be used because of safety concerns of mixing triptans. In this large group of patients in whom acute treatment will be needed, it is unlikely that NSAIDS, analgesics or combination agents will provide adequate relief.
This treatment, at a cost of over $2200 per year, had a therapeutic gain of only 26% in reducing the incidence of MRM compared to placebo. This reduction is from approximately eight MRMs per year to about five per year at a cost of approximately $700 for each MRM prevented. As one-third of women selected for predictable cycles were inaccurate in their predictions, the treatment success in clinical practice may even be lower.
Alternatives exist which are comparable to those demonstrated with frovatriptan but permit use of the most effective acute care migraine treatment (rapidly acting triptans) and at very favorable cost/benefit ratios. These alternative preventive treatments of MRM include hormonal strategies of continuous oral contraceptives or placebo-week augmentation of estrogen[2] or the episodic use of NSAIDs. Probably because of their low cost, quality evidence of double-blind placebo-controlled clinical trials is lacking.
Evidence-based parameters are rapidly becoming the standard by which we are expected to practice. Largely funded by the pharmaceutical industry, this evidence too often reflects marketing needs rather than best practice.
References
1. Silberstein SD, Elkind AH, Schreiber C, Keywood C. A randomized trial of frovatriptan for the intermittent prevention of menstrual migraine. Neurology, 2004. 63:261-269.
2. Calhoun A. A novel specific prophylaxis for menstrual-associated migraine. South Med J. 2004;97.

Reply to Adelman et al 28 October 2004

Stephen D. Silberstein, MD,
Jefferson Headache Center
111 S. 11th Street, 8130 Gibbon, Philadelphia, PA 19107
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Re: Reply to Adelman et al

stephen.silberstein{at}jefferson.edu Stephen D. Silberstein, MD

Our study was not intended to be an economic study, but a scientific study to examine whether or not frovatriptan prohylaxis was effective in preventing MAM. We cannot comment on how much this treatment would cost when it becomes available to patients because the product is not yet licensed for the indication. The final dosing and cost per treatment are unknown.
The basis of scientific medicine is placebo-controlled double-blind studies. What is the scientific evidence for the statement that NSAIDs and oral contraceptives are effective prophylaxis of MAM? In the past, lower levels of evidence have led to bizarre magical headache concoctions. During the Middle Ages, the vulture was prized as the agent of healing. The vulture's head bones, wrapped in deerskin, will cure any pain and headache. Its brain, mixed with the best of oil and put in the nose, will expel all ailments of the head.(Incipit Epistula Vulturis, 800 AD)
We believe that the basis of headache treatment is stratified care. If a patient responds to low-end medication or the intermittent use of triptans, there is no need for any type of short-term prevention. If this is not the case, short-term prevention is justified to prevent the disability of disabling MAM.
I agree with Adelman et al's contention that we need more trials of older generic medications but using unproven medications simply because they cost less is not appropriate. I disagree with the statement that it is unlikely that NSAIDs, analgesics or combination agents will provide adequate relief. There is scientific evidence and clinical trials suggesting that NSAIDs in combination with triptans are more effective than either drug alone, and preliminary evidence suggests that NSAIDs may work in patients with central sensitization in whom triptans fail.