Table 1.
Randomized placebo-controlled trials of perimenstrual prophylaxis.
| Trial | Study design | Sample size | Rx | No. of cycles | Treatment start | Primary endpoint | Results |
| Naproxen | |||||||
| Sances et al. [1990] | Parallel | 35 | 550 mg bd | 3 | 7 days before expected menses through 6th day of menstrual flow | Pain Total Index no. of attacks (duration X severity) | NS |
| Estradiol | |||||||
| De Lignieres et al. [1986] | Cross-over | 18 | 1.5 mg | 3 | 2 days before expected menses for 7 days | Presence of migraine | Estradiol 30.8% PCB 96.3% (p50.01) |
| Dennerstein et al. [1988] | Cross-over | 18 | 1.5mg | 4 | 2 days before expected migraine for 7 days | Days of moderate to severe migraine during treatment | Estradiol 47 days PCB 86 days (p50.001) |
| Pfaffenrath [1993] | Cross-over | 41 | 50 mcg | 4 | 2 days before expected migraine Duration not stated | Reduction in headache duration, intensity and impairment | NS |
| Smits et al. [1994] | Cross-over | 20 | 50 mcg | 3 | 2 days before expected menses for 8 days | Percentage of treatment periods with migraine | NS |
| MacGregor et al. [2006] | Cross-over | 35 | 1.5 mg | 6 | 9 days after LH surge (approx day −5/−6) until 2nd full day of menses (approx 8 days) | Reduction in migraine days during treatment | 22% RR0.78 95% CI 0.62–0.99 (p=0.04) |
| Frovatriptan | |||||||
| Silberstein et al. [2004] | Cross-over | 445 | 2.5mg bd 2.5mg od | 3 | 2 days before expected migraine for 6 days | Incidence of migraine during each treatment period | bd 43% od 52% PCB 69% (p50.0001) vs PCB |
| Brandes et al. [in press] | Parallel | 410 | 2.5mg bd 2.5mg od | 3 | 2 days before expected migraine for 6 days | No. of headache-free treatment periods | bd 0.92 od 0.69 PCB 0.42 (p50.001 and p50.02) vs PCB |
| Naratriptan | |||||||
| Newman et al. [2001] | Parallel | 206 | 1mg bd 2.5mg bd | 4 | 2 days before expected menses for 5 days | Percentage headachefree treatment periods per patient Mean no. of migraines | 1mg bd 50% PCB 25% (p=0.003) 2.0 vs 4.0 (p50.05) 2.5mg NS |
| Mannix et al. [2007] | Parallel | Study 1: 218 | 1mg bd | 4 | 3 days before expected menses for 6 days | Mean percentage of treatment periods without migraine per patient | Study 1: naratriptan 40% PCB 27% (p50.05) |
| Study 2: 273 | Study 2: naratriptan 37% PCB 24% (p50.05) | ||||||
| Zolmitriptan | |||||||
| Tuchman et al. [2008] | Parallel | 217 | 2.5mg bd 2.5mg tds | 3 | 2 days before expected menses for 7 days | ≥50% reduction in migraine | tds 58.6% bd 54.7% PCB 37.8% (p=0.0007 and p=0.002) vs PCB |
bd, twice daily; NS, not sigficant vs placebo; od, once daily; PCB, placebo; RCT, randomized controlled trial; RR, relative risk; tds, three times daily.