Zolmitriptan for Menstrually Associated Migraine
(2004)Objective
To evaluate the efficacy and tolerability of oral zolmitriptan for the acute treatment of menstrually associated migraine (MAM).
Study Summary
• Patients treated one migraine attack per menstrual cycle for three months with either zolmitriptan or placebo, using an intensity-based dosing regimen (1.25 mg for mild, 2.5 mg for moderate, 5 mg for severe attacks).
• Zolmitriptan was significantly more effective than placebo, with a 2-hour headache response rate of 48% versus 27% (p<.0001).
• Efficacy was seen as early as 30 minutes, and the treatment was well-tolerated.
Intervention
Oral zolmitriptan (1.25 mg, 2.5 mg, or 5 mg based on headache intensity) versus a matching placebo for the acute treatment of one menstrually associated migraine attack per month for a total of three months.
Study Design
Arms: Zolmitriptan (intensity-based dosing: 1.25 mg mild, 2.5 mg moderate, 5 mg severe) vs Placebo (n=287 vs n=292)
Outcome
• Zolmitriptan was also superior at 30 minutes (18% vs. 14% response) and 1 hour (33% vs. 23% response).
• The rate of 2-hour pain-free response was 26% with zolmitriptan vs. 10% with placebo.
• Treatment-related adverse events were more common with zolmitriptan (16% vs. 9%).
Bottom Line
Oral zolmitriptan is an effective and well-tolerated acute treatment for menstrually associated migraine, providing significantly better headache response than placebo as early as 30 minutes after administration.
Major Points
- This was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled 579 women with a history of menstrually associated migraine (MAM).
- A unique feature was the intensity-based dosing: mild migraines were treated with zolmitriptan 1.25 mg, moderate with 2.5 mg, and severe with 5 mg (or matching placebo).
- The primary endpoint, headache response at 2 hours, was achieved in 48% of zolmitriptan-treated attacks versus 27% of placebo-treated attacks (P<.0001).
- Zolmitriptan demonstrated superiority to placebo as early as 30 minutes post-treatment (18% vs. 14% response, P=.03).
- The treatment was well-tolerated, with 16% of subjects receiving zolmitriptan reporting drug-related adverse events compared to 9% on placebo.
- A 3-month post-treatment follow-up confirmed that the study population consistently experienced MAM, validating the initial diagnosis.
Study Design
- Study Type
- Multicenter, double-blind, randomized, parallel-group, placebo-controlled, multiple-attack study
- Randomization
- Yes
- Blinding
- Double-blind
- Sample Size
- 579
- Follow-up
- A 3-month treatment period, followed by a 3-month observational follow-up period.
- Centers
- 18
- Countries
- United States, Canada
Primary Outcome
Definition: Headache response at 2 hours, defined as a reduction in headache intensity from moderate or severe to mild or no pain, or from mild pain to no pain.
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 27% | 48% | - (2.09 to 3.75) | <.0001 |
Limitations & Criticisms
- The overall efficacy rates for zolmitriptan were lower than reported in some previous non-MAM trials, which may be partly due to the low dose (1.25 mg) used for mild attacks being subtherapeutic.
- The study population may have been more refractory to treatment, as suggested by the very low placebo response rate (27%) compared to other migraine trials.
- The inclusion of mild headaches and the intensity-based dosing strategy, while reflective of clinical practice, was an unusual design for a triptan trial.
- Recurrence rates were reported descriptively but not formally analyzed for statistical significance.
Citation
Headache 2004;44:120-130