Efficacy and Tolerability of Oral Zolmitriptan
Efficacy and Tolerability of Oral Zolmitriptan
Background: Approximately 60% of female migraineurs report experiencing migraine in association with menstruation, while 7% to 25% experience attacks almost exclusively with menstruation.
Objective: To examine the efficacy and tolerability of oral zolmitriptan in the acute treatment of menstrually associated migraine. In this study, menstrually associated migraine was defined as migraine that consistently occurred from 72 hours before to 5 days after onset of menses.
Methods: Participants were women with regular menstrual cycles, aged 18 to 55 years, who had experienced migraine with at least two thirds of prior menstrual cycles. Subjects were randomized to treat one attack per menstrual cycle for 3 months with either zolmitriptan or placebo. Treatment was intensity based: mild migraines were treated with half of a 2.5-mg zolmitriptan tablet, moderate migraines were treated with zolmitriptan 2.5 mg, and severe migraines were treated with 5 mg (two 2.5-mg tablets) of zolmitriptan, or placebo.
Results: Of the 579 women enrolled in the study, 260 were treated with zolmitriptan and 251 were assigned placebo. Twelve hundred thirty-two attacks were treated, and a 2-hour headache response was achieved in 48% of zolmitriptan-treated attacks as compared with 27% of placebo-assigned attacks (P< .0001). Zolmitriptan was superior to placebo in achieving a headache response as early as 30 minutes (18% versus 14%, P= .03) and at 1 hour (33% versus 23%, P< .001). Drug-related adverse events were reported in 16% of subjects receiving zolmitriptan and 9% of subjects receiving placebo.
Conclusion: Oral zolmitriptan exhibits efficacy and good tolerability in the treatment of menstrually associated migraine. Improvement over placebo was observed as early as 30 minutes following treatment.
Over 60% of women with migraine report that they are more likely to experience an attack in association with menstrual periods, while 7% to 25% report attacks that occur almost exclusively around their menstrual cycle. The pathophysiological basis of menstrual attacks is thought to be related to the decline of sustained estrogen levels that heralds the onset of menses.
Clinically, menstrually associated migraine (MAM) is thought to be of longer duration, more severe intensity, and more refractory to acute treatment than nonmenstrual migraine. A large, 3-month, diary study involving 81 female migraineurs selected from the general population showed an increased risk of migraine without aura, but not migraine with aura, in the 2 days before and after onset of menses. In this group of women, headache intensity was slightly higher in the first 2 days of menses, although other headache characteristics were not demonstrably different.
Retrospective analysis of 4 large placebo-controlled trials showed similar efficacy rates for zolmitriptan 2.5- and 5-mg tablets, regardless of the attacks' relation to menses. These post hoc analyses, however, do not specifically examine efficacy in a prospectively defined subpopulation of women with MAM. One published prospective study reported that subcutaneous sumatriptan was effective in the treatment of MAM; however, response rates were slightly lower than those in previous reports of non-MAM. High recurrence rates of approximately 50% were noted in the subcutaneous sumatriptan study, raising the possibility that this subpopulation may be more refractory to treatment. Oral sumatriptan also was studied prospectively; efficacy was reported at 4 hours, although the standard 2-hour headache response was not reported.
This study was designed to prospectively assess the efficacy of zolmitriptan in the treatment of MAM. Women who qualified for study inclusion had clinically diagnosed MAM occurring from 3 days before to 5 days after onset of menses. An important feature of the study was a 3-month follow-up period (after the 3-month placebo-controlled treatment period) during which participants recorded the frequency of migraine and its relationship to menses. This diary information was used to verify that the study participants truly fulfilled the prospectively defined criteria of MAM, thus validating the diagnosis that was made before study entry.
Background: Approximately 60% of female migraineurs report experiencing migraine in association with menstruation, while 7% to 25% experience attacks almost exclusively with menstruation.
Objective: To examine the efficacy and tolerability of oral zolmitriptan in the acute treatment of menstrually associated migraine. In this study, menstrually associated migraine was defined as migraine that consistently occurred from 72 hours before to 5 days after onset of menses.
Methods: Participants were women with regular menstrual cycles, aged 18 to 55 years, who had experienced migraine with at least two thirds of prior menstrual cycles. Subjects were randomized to treat one attack per menstrual cycle for 3 months with either zolmitriptan or placebo. Treatment was intensity based: mild migraines were treated with half of a 2.5-mg zolmitriptan tablet, moderate migraines were treated with zolmitriptan 2.5 mg, and severe migraines were treated with 5 mg (two 2.5-mg tablets) of zolmitriptan, or placebo.
Results: Of the 579 women enrolled in the study, 260 were treated with zolmitriptan and 251 were assigned placebo. Twelve hundred thirty-two attacks were treated, and a 2-hour headache response was achieved in 48% of zolmitriptan-treated attacks as compared with 27% of placebo-assigned attacks (P< .0001). Zolmitriptan was superior to placebo in achieving a headache response as early as 30 minutes (18% versus 14%, P= .03) and at 1 hour (33% versus 23%, P< .001). Drug-related adverse events were reported in 16% of subjects receiving zolmitriptan and 9% of subjects receiving placebo.
Conclusion: Oral zolmitriptan exhibits efficacy and good tolerability in the treatment of menstrually associated migraine. Improvement over placebo was observed as early as 30 minutes following treatment.
Over 60% of women with migraine report that they are more likely to experience an attack in association with menstrual periods, while 7% to 25% report attacks that occur almost exclusively around their menstrual cycle. The pathophysiological basis of menstrual attacks is thought to be related to the decline of sustained estrogen levels that heralds the onset of menses.
Clinically, menstrually associated migraine (MAM) is thought to be of longer duration, more severe intensity, and more refractory to acute treatment than nonmenstrual migraine. A large, 3-month, diary study involving 81 female migraineurs selected from the general population showed an increased risk of migraine without aura, but not migraine with aura, in the 2 days before and after onset of menses. In this group of women, headache intensity was slightly higher in the first 2 days of menses, although other headache characteristics were not demonstrably different.
Retrospective analysis of 4 large placebo-controlled trials showed similar efficacy rates for zolmitriptan 2.5- and 5-mg tablets, regardless of the attacks' relation to menses. These post hoc analyses, however, do not specifically examine efficacy in a prospectively defined subpopulation of women with MAM. One published prospective study reported that subcutaneous sumatriptan was effective in the treatment of MAM; however, response rates were slightly lower than those in previous reports of non-MAM. High recurrence rates of approximately 50% were noted in the subcutaneous sumatriptan study, raising the possibility that this subpopulation may be more refractory to treatment. Oral sumatriptan also was studied prospectively; efficacy was reported at 4 hours, although the standard 2-hour headache response was not reported.
This study was designed to prospectively assess the efficacy of zolmitriptan in the treatment of MAM. Women who qualified for study inclusion had clinically diagnosed MAM occurring from 3 days before to 5 days after onset of menses. An important feature of the study was a 3-month follow-up period (after the 3-month placebo-controlled treatment period) during which participants recorded the frequency of migraine and its relationship to menses. This diary information was used to verify that the study participants truly fulfilled the prospectively defined criteria of MAM, thus validating the diagnosis that was made before study entry.