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Treatment of migraine attacks with subcutaneous sumatriptan: first placebo-controlled study. The Subcutaneous Sumatriptan International Study Group.

The results of the very first large-scale placebo-controlled dose-response trial with the novel selective 5-hydroxytryptamine1-like (5HT1-like) receptor agonist sumatriptan are presented. We studied the efficacy and tolerability of subcutaneous injections of 1 mg, 2 mg and 3 mg of sumatriptan in alleviating migraine attacks in a double-blind, placebo-controlled, parallel-group, multicentre clinical trial. Six-hundred and ninety patients were randomized and 685 received study medication. At 30 min, reduction of headache severity to mild or none (primary efficacy endpoint) was achieved in 22% (95% CI: 15-28%) of placebo-treated patients and in 39% (CI: 31-46%) of patients treated with 1 mg sumatriptan, 44% (CI: 36-51%) treated with 2 mg sumatriptan and 55% (CI: 48-63%) treated with 3 mg sumatriptan. Differences from placebo were 17% (CI: 8-27%) for 1 mg sumatriptan, 22% (CI: 13-32%) for 2 mg sumatriptan and 34% (CI: 24-44%) for 3 mg sumatriptan (p < 0.001 for all three comparisons). Other migraine symptoms were also more effectively treated by sumatriptan than by placebo. Subsequently, an open-label 3 mg dose subcutaneous sumatriptan was given to partial or non-responders. Thirty minutes after this open dose the response rate to sumatriptan had improved to between 70 and 80%. Adverse events after sumatriptan were minor and short-lived. We conclude that subcutaneous sumatriptan is well tolerated in doses up to 3 + 3 mg and may rapidly abort migraine attacks.

Adolescent

A randomized, double-blind comparison of sumatriptan and Cafergot in the acute treatment of migraine. The Multinational Oral Sumatriptan and Cafergot Comparative Study Group.

The efficacy and safety of oral sumatriptan as a 100-mg dispersible tablet was compared with oral Cafergot (2 mg ergotamine tartrate, 200 mg caffeine) in a multicentre, randomized, double-blind, double-dummy, parallel-group trial. In the trial, 580 patients were treated from 47 investigating centres in nine European countries. Sumatriptan was significantly more effective than Cafergot at reducing the intensity of headache from severe or moderate to mild or none; 66% (145/220) of those treated with sumatriptan improved in this way by 2 h, compared with 48% (118/246) of those treated with Cafergot (p less than 0.001). The onset of headache resolution was more rapid with sumatriptan, whereas recurrence of migraine headache within 48 h was lower with Cafergot. Sumatriptan was also significantly more effective at reducing the incidence of nausea (p less than 0.001), vomiting (p less than 0.01) and photophobia/phonophobia (p less than 0.001) 2 h after treatment, and fewer patients on sumatriptan (24%) than on Cafergot (44%, p less than 0.001) required other medication after 2 h. The overall incidence of patients reporting adverse events was 45% after sumatriptan and 39% after Cafergot; the difference was not significant. The most commonly reported events in the sumatriptan-treated patients were malaise or fatigue and bad taste; these were generally mild and transient. Nausea and/or vomiting, abdominal discomfort, and dizziness or vertigo were reported by a greater proportion of Cafergot-treated patients. It is concluded that oral sumatriptan was well tolerated and is a more effective acute treatment for migraine than Cafergot.

Administration, Oral

A placebo-controlled study of intranasal sumatriptan for the acute treatment of migraine. The Finnish Sumatriptan Group and the Cardiovascular Clinical Research Group.

A double-blind, randomized, multicentre, parallel-group study was carried out to compare intranasal sumatriptan with placebo in the treatment of migraine. Seventy-four patients (37 in each treatment group) were recruited into the study. Patients received two insufflations of the same treatment (sumatriptan or placebo) 15 min apart. Sumatriptan (20 mg plus 20 mg) was more effective than placebo at relieving headache, defined as a reduction in severity from moderate (grade 2) or severe (grade 3) to mild (grade 1) or none (grade 0), at 60 and 120 min. At 120 min, 75% of patients in the sumatriptan group reported headache relief, compared with 32% of patients in the placebo group (p less than 0.001); 53% of patients in the sumatriptan group were completely pain-free, compared with 11% in the placebo group. A clinically significant reduction in the incidence of nausea, vomiting and photophobia was observed in the sumatriptan group compared with the placebo group, and sumatriptan was also more effective at reducing the functional disability of the patients. A similar number of patients reported migraine recurrence, within 24 h in both treatment groups. The observed reduction in headache severity, functional disability and nausea following intranasal administration of sumatriptan would appear to obviate the need for a concomitant anti-emetic during a migraine attack. The results support the further development and testing of intranasal sumatriptan.

Absorption

Sumatriptan--an oral dose-defining study. The Oral Sumatriptan Dose-Defining Study Group.

Three oral doses of sumatriptan, 100, 200 and 300 mg, given as dispersible tablets, were compared in the acute treatment of migraine in a double-blind, placebo-controlled, parallel-group study of 1,130 patients from 51 centres in eight countries. Patients treated up to three migraine attacks at home over a 3-month period and recorded the results on a diary card. Safety follow-ups were performed monthly at a clinic. All doses of sumatriptan were significantly (p less than 0.001) more effective than placebo at relieving headache within 2 h of treatment. Response rates, scored on a 4-point scale, were: placebo 27%; 100 mg sumatriptan 67%; 200 mg sumatriptan 73%; and 300 mg sumatriptan 67%. The proportion of patients who required rescue medication within 2 h of treatment was significantly (p less than 0.001) lower in all active treatment groups when compared with placebo. Response rates to sumatriptan were the same irrespective of the type of migraine (with or without aura) or the duration of symptoms prior to treatment (less than or equal to 4 or greater than 4 h). Sumatriptan also provided significant (p less than 0.001) relief from nausea and photophobia as compared with placebo. The majority of adverse events reported were mild to moderate in severity and were transient. The overall incidence of adverse events was dose-related, the percentage of patients reporting adverse events in the first attack treated being 36, 47 and 53% for 100-, 200- and 300-mg doses of sumatriptan, respectively, compared to 17% of placebo patients (p less than 0.001 for each treatment dose compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

Evaluation of a multiple-dose regimen of oral sumatriptan for the acute treatment of migraine. The Oral Sumatriptan International Multiple-Dose Study Group.

In a multinational, placebo-controlled, double-blind, parallel-group study of oral sumatriptan (GR43175), given as a dispersible tablet, in the acute treatment of migraine, 149 patients were randomized to receive 100 mg sumatriptan and 84 to placebo. Each patient was provided with three tablets: one to be taken as soon as possible after headache onset; one to be taken 2 h later if the headache persisted and one to be taken if the headache recurred within 24 h. Patients recorded details of the attack and response to treatment on a diary card. Sumatriptan was significantly more effective than placebo in relieving headache (moderate/severe reduced to mild/none) at 2 h (50 vs. 19%; p less than 0.001) and at 4 h (75 vs. 30%; p less than 0.001). Of the sumatriptan group, 59% took the second dose compared with 80% of the placebo group (p less than 0.001). Compared with placebo, more patients on sumatriptan were pain-free by 2 h (26 vs. 5%; p less than 0.001) and by 4 h (48 vs. 13%; p less than 0.001). Headache improvement was apparent by 1 h in 42% of sumatriptan-treated patients and 17% of patients on placebo. Headache relief was significantly (p less than 0.001) better in patients taking sumatriptan, irrespective of the type of migraine (with or without aura), or the time the drug was taken (less than or more than 4 h after onset). There was no significant difference in the number of patients who took placebo or sumatriptan and whose headache recurred within 24 h of initial resolution (42 vs. 48%; p = 0.535).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Clinical experience with oral sumatriptan: a placebo-controlled, dose-ranging study. Oral Sumatriptan Dose-defining Study Group.

A double-blind, placebo-controlled multicentre study was carried out to evaluate the efficacy and tolerability of 100, 200 and 300 mg sumatriptan, a selective 5-hydroxytryptamine (5-HT)1-like receptor agonist, given in an oral dispersible form in the acute treatment of migraine attacks. A total of 1130 patients were recruited from 51 centres in eight countries and the efficacy results are presented from an interim analysis of 538 cases. Tolerability was evaluated in 227 patients. At 2 h, an improvement in headache severity from moderate or severe to mild or none was reported by 67% of patients who received 100 mg sumatriptan, 75% receiving 200 mg and 69% of patients receiving 300 mg sumatriptan, compared with 22% of patients who received placebo (P less than 0.001 all doses sumatriptan vs placebo). Adverse events were generally mild and transient, and appeared to be dose-related; the adverse event profile of 100 mg sumatriptan was similar to that of placebo. Overall, nausea/vomiting and "bitter taste" were the most common complaints. The proportion of patients withdrawn due to adverse events was similar in the placebo and 100 mg sumatriptan treatment groups (2% and 3%, respectively). It is concluded that 100 mg sumatriptan given orally is well tolerated with an anti-migraine efficacy comparable to that provided by the two higher doses.

Acute Disease

Self-treatment of acute migraine with subcutaneous sumatriptan using an auto-injector device. The Sumatriptan Auto-Injector Study Group.

The efficacy and safety of sumatriptan, a selective 5-HT1-like receptor agonist, were studied in a randomized, double-blind, placebo-controlled, parallel-group, multicentre, multinational clinical trial of 235 patients suffering a moderate to severe migraine attack. Patients were randomized to treat a single migraine attack at home with 6 mg sumatriptan or placebo using an auto-injector. If the migraine had not improved at 1 h, patients had the option of taking a second identical injection. The primary measure of treatment efficacy was based on a comparison of the number of patients in the two treatment groups who had a reduction in headache severity from severe or moderate to mild or none at 1 and 2 h. At 1 h, 77% of patients treating with 6 mg sumatriptan compared to 26% treating with placebo (p less than 0.001) had mild headache or none. At 2 h, the response rates for all patients had risen to 83 and 30%, respectively. Of those patients requiring a second dose at 1 h, improvement to mild or no headache at 2 h was achieved in 61% of patients receiving sumatriptan compared to 15% of those receiving placebo. Other migraine symptoms were more effectively treated by sumatriptan and patients were able to return to work or normal activities earlier. Migraine recurrence within 48 h was a feature of 46% of attacks treated by patients with either treatment. Adverse events were more frequent using sumatriptan but were minor and transient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Subcutaneous sumatriptan in the acute treatment of migraine. Sumatriptan International Study Group.

Two double-blind, randomized, placebo-controlled multicentre studies were carried out to assess the efficacy and tolerability of subcutaneous (s.c.) injections of 1-3 mg and 1-8 mg sumatriptan, respectively, in the acute treatment of migraine. Data are presented from a total of 519 patients. In both studies, the primary endpoint of efficacy was a reduction in headache severity from severe or moderate to mild or no headache. All doses of sumatriptan were significantly more effective than placebo in relieving symptoms, and the response appeared to be dose-related; an effective response to treatment was achieved within 30 min in 73% of patients treated with 6 mg sumatriptan and 80% of patients treated with 8 mg sumatriptan s.c., compared with 22% for placebo. Sumatriptan was well tolerated and the majority of adverse events were mild and transient. The most frequent complaint was irritation and pain at the site of injection. No changes in laboratory values were noted and ECG readings were unaltered by treatment. On the basis of these results, the 6 mg subcutaneous dose has been selected for further evaluation in large-scale studies.

Adult

A study to compare oral sumatriptan with oral aspirin plus oral metoclopramide in the acute treatment of migraine. The Oral Sumatriptan and Aspirin plus Metoclopramide Comparative Study Group.

In a double-blind, placebo-controlled study, the efficacy, safety and tolerability of 100 mg oral sumatriptan, given as a dispersible tablet, was compared with that of 900 mg oral aspirin plus 10 mg oral metoclopramide in the acute treatment of migraine. A total of 358 patients treated up to three migraine attacks within 3 months, recording clinical information on a diary card. In attack 1, headache relief after 2 h, defined as a reduction in severity from severe or moderate pain to mild or no pain, was recorded in 56% (74/133) of patients who took sumatriptan and 45% (62/138) of patients who took aspirin plus metoclopramide (p = 0.078). This analysis of the primary efficacy end point was not statistically significant. However, for attacks 2 and 3 (secondary end points), headache relief was achieved in 58 versus 36% of patients (p = 0.001) and 65 versus 34% of patients (p less than 0.001), respectively. Relief from nausea, vomiting, photophobia and phonophobia was similar in both treatment groups. Rescue medication was required by fewer patients treated with sumatriptan than by those who received aspirin plus metoclopramide (attack 1, 34 versus 56%, p less than 0.001; attack 2, 32 versus 51%, p = 0.001, and attack 3, 35 versus 54%, p = 0.001). Sumatriptan also produced a faster improvement and resolution of migraine attacks. Comparing the sumatriptan and aspirin plus metoclopramide treatment groups, complete resolution of the attack occurred within 6 h in 32 versus 19% (attack 1), 35 versus 23% (attack 2) and 32 versus 20% of patients (attack 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

Agonist activity of sumatriptan and metergoline at the human 5-HT1D beta receptor: further evidence for a role of the 5-HT1D receptor in the action of sumatriptan.

We have recently cloned a novel human 5-HT1D receptor subtype termed 5-HT1D beta. CHO K1 cells expressing the human serotonin 5-HT1D beta receptor were assayed to determine the second messenger system of this receptor. Cyclic AMP radioimmunoassays revealed that the 5-HT1D beta receptor is negatively coupled to adenylate cyclase in this cell system. A maximum of 50% inhibition of forskolin stimulated cAMP production was obtained with 5-HT1 receptor agonists which was blocked by the non-selective 5-HT receptor antagonist methiothepin (pKB = 100 nM). The novel anti-migraine drug sumatriptan, a putative 5-HT1D selective compound, acted as an agonist at the 5-HT1D beta receptor. Most notably metergoline, a putative 5-HT1 receptor antagonist, did not block the effects of 5-HT and was found to be acting as a full agonist at the 5-HT1D beta receptor. The ability of metergoline to act as an agonist at the 5-HT1D beta receptor may explain why it does not inhibit 5-HT and sumatriptan induced contraction of dog saphenous vein and other large conducting arteries. These results suggest that the 5-HT1D beta receptor may be the site of action of sumatriptan in preventing migraine, and that metergoline's actions on the dog saphenous vein are not contradictory to that hypothesis, as previously reported.

Cells, Cultured

Dose ranging efficacy and safety of subcutaneous sumatriptan in the acute treatment of migraine. US Sumatriptan Research Group.

Sumatriptan, a specific serotonin1-like receptor agonist, was studied in the acute treatment of migraine. Two hundred forty-two adult migraineurs participated in a randomized, double-blind study in which one dose of 1, 2, 3, 4, 6, or 8 mg of subcutaneous sumatriptan succinate was evaluated in sequential ascending fashion. At each dose level, a placebo group was included. Efficacy was defined as reduction of moderate or severe pain to mild or no pain, without the use of rescue medication. Headache relief rates showed an approximate dose-response relationship and at 1 hour were as follows: placebo, 24%; 1 mg, 43%; 2 mg, 57%; 3 mg, 57%; 4 mg, 50%; 6 mg, 73%; and 8 mg, 80%. Relief of nausea and improvement in clinical disability were also approximately dose related. Adverse events were dose related; the most common types were injection site reactions and tingling. The 6-mg dose was as effective as the 8-mg dose but was associated with fewer adverse effects and so is optimal.

Adult

Treatment of migraine attacks with sumatriptan.

BACKGROUND: The headache in migraine attacks may be caused by dilatation of certain cranial arteries or arteriovenous anastomoses, by neurogenic dural plasma extravasation, or by both of these mechanisms. Sumatriptan, a novel selective agonist of 5-hydroxytryptamine-like receptors, blocks these phenomena. We investigated its efficacy in migraine. METHODS: We studied 639 patients with migraine attacks in a randomized, double-blind, placebo-controlled, parallel-group clinical trial. We assessed the effect of subcutaneous injections of 6 or 8 mg of sumatriptan or placebo on the severity of headache and associated migrane symptoms 30, 60, and 120 minutes after treatment. Patients who were not free of pain after 60 minutes subsequently received placebo if they had initially received placebo or 8 mg of sumatriptan, and 6 mg of sumatriptan or placebo if they had initially received 6 mg of sumatriptan. RESULTS: After 60 minutes, the severity of headache was decreased in 72 percent (95 percent confidence interval, 68 to 76 percent) of the 422 patients given 6 mg of sumatriptan, 79 percent (95 percent confidence interval, 71 to 87 percent) of the 109 patients given 8 mg of sumatriptan, and 25 percent (95 percent confidence interval, 17 to 33 percent) of the 105 patients given placebo (data on 3 patients could not be evaluated). As compared with the placebo group, 47 percent (95 percent confidence interval, 38 to 57 percent) more patients who had received 6 mg of sumatriptan and 54 percent (95 percent confidence interval, 43 to 65 percent) more patients who had received 8 mg of sumatriptan had a decrease in the severity of headache (P less than 0.001 for both comparisons). After 120 minutes, 86 to 92 percent of the 511 patients treated with sumatriptan (202 assigned to 6 mg plus placebo, 203 to 6 mg plus 6 mg, and 106 to 8 mg plus placebo) had improvement in the severity of headache, as compared with only 37 percent of the 104 patients who received placebo once or twice (P less than 0.001 for all comparisons). Twenty-one patients were excluded from the analysis because of missing data (19) or protocol violations (2). The response rates did not differ significantly among the sumatriptan regimens. Adverse events were minor and transient in all groups. CONCLUSIONS: We conclude that a single 6-mg dose of sumatriptan given subcutaneously is a highly effective, rapid-acting, and well-tolerated treatment for migrane attacks. The administration of a second dose 60 minutes later to patients not responding well to an initial dose affords little additional benefit.

Adolescent

Sumatriptan: a selective 5-hydroxytryptamine receptor agonist for the acute treatment of migraine.

OBJECTIVE: The clinical pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and associated drug interactions of the novel antimigraine drug sumatriptan are reviewed. DATA SOURCES: English-language publications pertaining to sumatriptan were identified via a search of the MEDLINE computerized database. STUDY SELECTION: Open and controlled clinical studies were reviewed in assessing clinical efficacy, although only the results of controlled, randomized trials from the basis for the conclusions pertaining to the effectiveness of sumatriptan. DATA EXTRACTION: The primary measure of drug effectiveness in all clinical studies was significant improvement in headache severity scores. Secondary measures included functional ability, time to relief, rescue medication use, associated symptoms of nausea/vomiting and photo/phonophobia, and, in some studies, headache recurrence rate. These data were obtained from each published clinical trial and used in the overall analysis of sumatriptan efficacy. DATA SYNTHESIS: Sumatriptan is a serotonin agonist that has been studied for the acute treatment of migraine and cluster headache. The drug appears to work via specific serotonin receptors to mediate selective vasoconstriction within the cranial vasculature and to prevent the release of inflammatory mediators from trigeminal nerve terminals. The recommended dose of sumatriptan is 6 mg given subcutaneously at the onset of headache; an oral formulation is under investigation. In the published clinical trials of the oral and subcutaneous dosage forms to date, sumatriptan was effective in reducing headache severity from moderate/severe to mild/absent in approximately 70-80 percent of patients treated with active drug, compared with only 20-30 percent in the placebo groups, and 48 percent in the oral ergotamine tartrate/caffeine (Cafergot)-treated group. Secondary measures of effectiveness also favored sumatriptan. There may be a higher rate of headache recurrence with sumatriptan compared with placebo or Cafergot, although further study is necessary to confirm this observation. Adverse effects associated with sumatriptan administration generally were mild and transient and included tingling, warm/hot sensations, and pressure and tightness in the chest and neck. No significant drug interactions have yet been identified. CONCLUSIONS: Sumatriptan appears to represent a safe and effective alternative to the ergot alkaloids for the abortive treatment of acute migraine. However, further clinical trials, especially those yielding comparative data with current antimigraine agents, are needed to determine the full therapeutic contribution of sumatriptan.

Clinical Trials as Topic

Sumatriptan: a new drug for vascular headache.

The role of serotonin in the pathogenesis of migraine is discussed, and the chemistry, pharmacology, pharmacokinetics, efficacy, adverse effects, and dosage and administration of sumatriptan are reviewed. Sumatriptan, which is structurally related to the neurotransmitter serotonin, is a serotonin type-1-like-receptor agonist that has a selective but heterogeneous effect on the carotid arterial system. Sumatriptan has a rapid onset of action and a large volume of distribution. Its subcutaneous bioavailability approaches 100%, and its mean terminal half-life is two hours. Studies have shown that both subcutaneous sumatriptan and oral sumatriptan are superior to placebo in relieving migraine and cluster headaches. Studies comparing oral sumatriptan with either ergotamine tartrate plus caffeine (Cafergot) or aspirin plus metoclopramide indicated that sumatriptan relieved headache more quickly and effectively; however, the dosages of these other agents may have been suboptimal. Sumatriptan is generally well tolerated by patients, and most dose-related effects are mild and transient. The most common adverse effect is pain at the injection site. No drug interactions have been identified so far. Subcutaneous sumatriptan 6 mg and oral sumatriptan 100 mg seem to offer the best benefit-to-risk ratio, although dosage and administration information is limited. Subcutaneous and oral sumatriptan are effective in aborting moderate to severe migraine and cluster headaches and their associated symtpoms. However, more studies are necessary to compare sumatriptan's efficacy with that of other treatments before it can be recommended as first-line therapy for migraine.

Cluster Headache

Treatment of acute cluster headache with sumatriptan.

BACKGROUND: Attacks of cluster headache are difficult to treat. Sumatriptan, an agonist of 5-hydroxytryptamine1-like receptors, has proved effective in the treatment of migraine. The clinical similarities between migraine and cluster headache and positive results from an open pilot study in patients with cluster headache indicated that sumatriptan should be evaluated more rigorously in the treatment of this condition. METHODS: We conducted a randomized, double-blind, placebo-controlled crossover study to assess the efficacy and tolerability of sumatriptan in 49 patients with cluster headache. The patients received, in random order, a subcutaneous injection of 6 mg of sumatriptan for one cluster-headache attack and placebo for another attack. The results for the two attacks could be fully evaluated for 39 patients. A response to treatment was defined as complete or almost complete relief of headache (no pain or mild pain) within 15 minutes after the injection. RESULTS: In the 39 patients, the severity of headache decreased in 74 percent of the attacks within 15 minutes of treatment with sumatriptan, as compared with 26 percent of the attacks for which placebo was given (P less than 0.001). Thirty-six percent of the patients were free of pain within 10 minutes after the administration of sumatriptan, as compared with 3 percent after placebo (P less than 0.001); by 15 minutes these numbers had increased to 46 percent and 10 percent, respectively (P less than 0.001). Thirteen percent of the patients required oxygen as an additional treatment 15 minutes after receiving sumatriptan, as compared with 49 percent of those who received placebo. The severity of functional disability and the incidence of ipsilateral conjunctival injection also decreased more in response to sumatriptan than placebo. Sumatriptan was well tolerated, and there were no serious adverse events. CONCLUSIONS: Sumatriptan is an effective and well-tolerated treatment for acute attacks of cluster headache.

Acute Disease

Sumatriptan. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the acute treatment of migraine and cluster headache.

Sumatriptan is a serotonin1 (5-HT1) receptor agonist, which is effective in the acute treatment of migraine headache. Its antimigraine activity is believed to derive from selective vasoconstriction of cranial blood vessels which are dilated and distended during migraine headache and/or from inhibition of neurogenically mediated inflammation in the dura mater. In placebo-controlled comparative studies, sumatriptan reduced migraine headache from 'moderate or severe' to 'mild or none' within 2 hours in 50 to 73% of patients following oral administration of 100 or 200 mg, and within 1 hour in 70 to 80% of patients following subcutaneous doses of 6 to 8 mg or intranasal doses 20 mg into each nostril. In addition, sumatriptan alleviated the accompanying symptoms of nausea, vomiting, and photophobia/phonophobia more effectively than placebo, and permitted higher percentages of patients to resume normal daily activities. Sumatriptan 100 mg orally was more effective in the acute treatment of migraine than oral combination therapy consisting of ergotamine 2 mg plus caffeine 200 mg or aspirin 900 mg plus metoclopramide 10 mg. Pooled data from nearly 5000 patients treated with either oral or subcutaneous sumatriptan in clinical trials indicate that it is well tolerated. However, migraine recurrence within 24 or 48 hours of initial symptom resolution developed in approximately 40% of patients treated with sumatriptan, irrespective of route of administration. It is likely that migraine recurrence is related to the short half-life of the drug (approximately 2 hours). Future studies should attempt to ascertain whether additional doses of sumatriptan will help prevent migraine recurrence in patients with attacks of long duration and if so, should determine the optimum interval between dosages. In conclusion, sumatriptan is an important addition to the range of drugs currently available for acute treatment of migraine. It provides rapid relief from debilitating symptoms in a high percentage of patients, particularly after subcutaneous administration. At this stage in its development a number of questions remain to be answered - most notably whether repeat doses will help prevent recurrent attacks and which patients are most likely to respond to therapy. Nevertheless, sumatriptan presently offers a combination of efficacy and tolerability that is unique in this particular clinical setting.

Acute Disease

Effect of sumatriptan, a selective 5-HT1-like receptor agonist, on pial vessel diameter in anaesthetised cats.

The action of sumatriptan, a selective 5-HT1-like receptor agonist that is effective for the acute treatment of migraine, was compared on pial vessel diameter following perivascular or intravenous administration to anaesthetised cats. Sumatriptan (0.01-10 microM), when microinjected perivascularly, caused a decrease in pial artery diameter (maximum change of -19 +/- 9%; mean +/- SD) but had no effect on the diameter of pial veins. Sumatriptan (1 microM)-induced pial artery vasoconstriction was unaffected by coadministration of ketanserin (1 microM) or ondansetron (1 microM) but was significantly (p less than 0.01) attenuated by methiothepin (1 microM). Intravenous infusion of a clinically effective dose of sumatriptan (64 micrograms/kg/10 min) caused selective carotid vasoconstriction (22 +/- 6% increase in carotid vascular resistance with little or no change in blood pressure or heart rate) and no change in pial artery diameter, although sumatriptan (1 microM) administered perivascularly in these animals before and after the infusion caused pial artery vasoconstriction. These results demonstrate that perivascularly administered sumatriptan causes pial artery vasoconstriction via activation of 5-HT1-like receptors. However, intravenously administered sumatriptan does not cause pial artery vasoconstriction, which suggests that sumatriptan does not readily penetrate the cerebrovascular intima.

Animals

Treatment of acute migraine with subcutaneous sumatriptan.

Sumatriptan succinate, a 5-HT1D receptor agonist, constricts human cranial arteries. Two parallel-group trials for treatment of acute migraines were conducted in the United States. Adult patients were randomized and given either 6 mg of sumatriptan succinate subcutaneously (n = 734) or placebo (n = 370). At 1 hour, sumatriptan was significantly more effective than placebo in reducing moderate or severe headache pain to mild or no pain (70% vs 22%), in completely relieving headaches (49% vs 9%), and in improving clinical disability (76% vs 34%). Sumatriptan also reduced nausea and photophobia significantly better than placebo. Patients with residual migraines received another injection; those who had originally received sumatriptan received either a second active injection (n = 187) or placebo (n = 178), while those who had received placebo received a second placebo injection (n = 335). Statistical evidence for benefit of second sumatriptan injection is absent. Adverse events associated with sumatriptan were tingling, dizziness, warm-hot sensations, and injection-site reactions. Sumatriptan is effective and well tolerated in patients with acute migraine.

Acute Disease