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Curt PracticeSumatriptan is effective in the treatment of menstrual migraine:a review of prospective studies and retrospective analysesR Salonen, J SaiersNctrrdogyndPsych&y7herapeuticevelopmentGroup, Glaxo Wellcume,North Carolina, USA

!&&menR, S aiers J. S umatriptan is eff ective in the treatment of menstrual migraine: a review of prospectivestudies and Hxqxctive ana@es. Cephalalgia 199!$19:1&9. Oslo. ISS N 0333-1024Menstrual migraine may be debil itating, long-lasting and refractory to treatment. because the ef ficacy andtolerability of abortive and prophylactic treatment options for menstrual migraine have generally not beenevahrated in controlled clinical trials, treatment choices are often made on the basis of personal experienceand anecdotal reports. This article reviews evidence from retrospective analyses and prospective studiesshowing that sumatriptan injection and tablets are effective and well tolerated in menstrual migraine.(1) Sumatriptan injection 6 mg was as effective in the treatment of menstrual migraine attacks as it was f ornonmenstrual attacks in a retrospective analysis of data from two randomized, double-blind, placebo-controlled, parallel-group trials (n 51104). In the menstrual migraine group, 80% of women treated withsumatriptan injection 6 mg compared with 19% of placebo-treated patients reported headache relief 1 hpostdose (pt0.001). (2) Sumatriptan injection 6 mg was eff ective in the acute treatment of menstrualmigraine attacks in a prospective, double-blind, placebocontrolled, parallel-group, two-attack study(n = 226). Across the two attacks, 70 - 71% of patients treating menstrual migraine attacks with sumatriptaninj ec&n 6 mg compared with 22-24% of placebo-treated patients reported headache relief 1 h postdose@

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cEPHALALaA19 (1999)

benefits, such as stabilization of serotonin function.The occurrence of menstrual migraine attackscoincides with the fall of estrogen during themenstrual cycle, and premenstrual administrationof estrogen has been shown to delay the occurrenceof migraine. There i s also evidence that abnormalrelease of and/or biochemical responses to otherhormones and neurotransmitters such as p-endor-phin, prostaglandin Fz~ and El, dopamine, andmelatonin are involved in the pathophysiology ofmenstrual migraine. (For more detailed informationon the pathophysiology of menstrual migraine, seeReferences 4, 5, 8 and 9.)Although the pathophysiology of menstrualmigraine and nonmenstrual migraine may differ,treatments typically recommended for menstrualmigraine are the same as those for nonmenstrualmigraine. In their recent review (lo), Granella andcolleagues advocate, based on their clinical experi-ence, a sequential approach to treatment, in whichacute attack medications such as sumatriptan aret&d first, accompanied or followed, if necessary, byintermittent prophylaxis, estrogen gel or patches,and anti-estrogen medications. Abortive therapeuticoptions for menstrual migraine include nonsteroidalanti-inflammatory drugs, ergot derivatives, and5HTr agonists. Prophylactic treatments, the use ofwhich is often prompted by the severity of attacksand their predictability, include beta-blockers andantidepressants. Estrogen has been used in bothacute and prophylactic treatment of menstrualmigraine.With the exception of sumatriptan (see below),these acute and prophylactic treatment options havenot been evaluated in controlled, prospectivechnical trials (1, 10). Evaluation of medications formenstrual migraine i n controlled clinical trialsmay be particularly important given the strongpossibi lity that the pathophysiology of migraineand of menstrual migraine differ. In this case,medications (e.g., the 5HTr agonist triptans) ef fec-tive in nonmenstrual migraine would not necessa-rily be expected to be effective in menstrualmigraine.A retrospective attempt to gauge the effects of thenew 5HTr agonist zolmitriptan (2.5 mg to 10 mg) inmenstrual migraine was made using a subset ofdata from 672 menstruant women from a double-blind, randomized, placebo-controlled, parallel-group study (11). Headache relief (moderate orsevere predose pain reduced to mild or no pain) 2 hpostdose in the active treatment groups wasw by 69 -73% of women treating 118menstrually associated migraines and by 64-71%of women treating 315 nonmenstrually associatedmigraines. Menstrual migraine was defined asoccurring from 2 days before to 3 days after theonset of menstruation. Though these data suggest

Sumatnjdan and mt3drual migraine 17

that zolmitriptan may be effective in the treatmentof menstrual migrame attacks, they lack corrobora-tion in controlled, prospective studies.

Sumatriptan in menstrual migraineSumatriptan is the most thoroughly studied acutemigraine therapy in patients with menstrualmigraine and menstruation-associated migraine. Itis the only triptan to be evaluated for eff icacy andtolerability in menstrual migraine in controlled,prospective studies as well as retrospective ana-lyses.Retrospective analysis

Solbach and colleagues (12) retrospectivelyassessed the effi cacy of sumatriptan inj ection 6 mgin the treatment of menstrual migraine using datafrom Glaxo Wellcome studies S2B 305 and S2B306.These studies were randomized, double-bl ind,placebo-controlled, parallel-group trials originallyconducted to compare the eff icacy and tolerabilityof sumatriptan inj ection 6 mg with those of placebo.Of the 1104 patients in the two studies, 157 womenwere retrospectively determined to have treated amenstrual migraine (defined as beginning 1 daybefore to 4 days after the onset of menstruation),and 512 women were determined to have treated anonmenstrual migraine. Data from the remainingpatients were excluded from the retrospectiveanalyses because patients were male (n =123),women who had been hysterectomized (n =260),or women with missing data (n =52).The results demonstrate that sumatriptan inj ec-tion was as effective in the treatment of menstrualmigraine attacks as it was in nonmenstrual attacks.In the menstrual migraine group, 80% of womentreated with sumatriptan inj ection 6 mg comparedwith 19% of placebo-treated patients reportedheadache relief (moderate or severe pain reducedto mild or no pain) 2 h postdose (p

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18 R Salonen, J Saks CEPHALALGIA 19 (1999)of women treated with sumatriptan injection 6 mgcompared with 20% of placebo-treated patientsreported headache relief 2 h postdose (p

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CEPHALALGIA 19 (1999)

m Sumatr ip tan ab le ts 100 mg

Ins ids menstrua l Outs ide menstrua lw i n d o w * w i n d o w

.7.

Fig. 3. Percentage of women reporting relief of migraines insideand outside the menstrual window 4 h postdose (prospective 8.study). *De&ted a s t h e 8 days commencing 3 days prior to theonset of menstruation. TDefi ned as days excluding the 8 days 9.commencing 3 days prior to the onset of menstruation.10.

triptan injection and tablets are effective and welltolerated in the acute treatment of menstrual 11.migraine. Sumatriptan also remains the only triptanwhich has been rigorously assessed in this migrainesubtype. The therapeutic gain with sumatriptan 12*over placebo is as large among patients treatingmenstrual migraine as it is among patients treating 13.rrorunenstrual migraine. Sumatriptan tablets orinj&ion may provide a useful treatment option 14for women suffering from this debilitating, refrac- .tory migraine subtype.

15.References

Dalessio DJ, Brown DL, Solb ach P, Adelman JR, Elkind AH,Stark SR Oral 311C90 i s effective in treatment of menstrualmigraine. Cephalalgia 1996;16:400- 1Sol bach MP, Waymer RS. Treatment of menstruation-associated migraine headache with subcutaneous sumatrip-tan. Obstet Gynecol 1993;82:769 -72The Sub cutaneous Sumatriptan International Study Group.Treatment of migraine attacks with sumatriptan. N EnglJ Med 1991;325:316-21Cady RR, Wendt JR, Kirchner J F, Sargent JD, Rothrock JF,Skaggs H. Treatment of acute migraine with subcutaneoussumatriptan. JAMA 1991;2652831-5Fac&inetti F, Bonelli e G, Kangasniemi P, et al. The effi cacyand safety of subcutaneous sumatriptan in the acutetreatment of menstrual migraine. Obstet Gynecol 1995;86:911-61. Bousser MG, Massiou H. Migra ine i n t he reproductive cycle. 16. Gross MLP, Barrie M, Bates D, Dowson A, Ehington G. TheIn: Gksen J, Tfel t-Hansen P, Welch KMA, editors. Th e efficacy of oral sumatriptan in menstrual migraine-aheadaches. New York: Raven Press, 1993:413-g prospective study. Poster presented at the 7th International2. Johannes CR, Linet MS, Stewart WF, Celentano DD, Lipton Headache Congress, 16-20 September, 1995, Toronto,TB, Szkl o M. Relationshi p of headache to phase of the Canada.

Sumat riptan and menstrual migraine 19menstrual cycle among young women: a daily diary study.Neurology 1995;45: 1076 - 82Granella F, Sances G, Zanferrari C, Costa A, Marlignoni E,Manzoni GC. Migraine without aura and reproductive lifeevents: a clinical epidemiologi cal study in 1300 women.Headache 1993;33385 - 9Fettes 1. Menstrual migraine: methods of prevention andcontrol. Postgrad Med 1997;101:67 - 75Kornstein SG, Parker AJ. Menstrual migraines: etiology,treatment, and relationship to premenstrual syndrome. CurrOpin Obstet Gynecol1997,9:154-9Robbi ns L. Menstrual migraine with features of clusterheadache. A report of 10 cases. Headache 1996%:X6-7Si lberstein S D. Migraine and women: the link betweenheadache and hormones. Postgrad Med 1995;97:147-53Welch KMA. Migraine and ovarian steroid hormones.Cephalalgia 1997;17 Suppl20:12-6Benedetto C, Allais G, Ciochetto D, De Lorenzo C.Pathophysiological aspects of menstrual migraine. Cephalal-gia 1997;17 Suppl20:32-4Granella F, Sances G, Messa G, de Marinis M, Manzoni GC.Treatment of menstrual migraine. Cephalalgia 1997;17 Suppl20:35 - 8