Oral and subcutaneous sumatriptan in the acute treatment of migraine: an open randomized cress-over study

In an open, randomized cross-over study in 124 patients, we compared the efficacy, safety and patient preference of oral and subcutaneous sum triptan in the acute treatment of migraine. Patients were treated for 3 attacks or 3 months and then crossed over. Primary clinical efficacy was defined as a reduction in headache severity on a four-point self-rating scale from severe (3) or moderate (2) to mild (1) or none (0), or mild (1) to none (0). Efficacy was evaluated 2 h after the administration of subcutaneous and 4h after the administration of oral sumatriptan. Subcutaneous sumatriptan was significantly more effective than oral sumatriptan in relieving headache (over all three attacks 78% vs 61% improvement), improving clinical disability (55% vs 41 % improvement) and relieving nausea (69% vs 53%), vomiting (72% vs 32%) and phono- or photophobia (67% vs 49%). Median time to recurrence was shorter after subcutaneous (12.5 h) than after oral sumatriptan (18 h); the number of patients experiencing a recurrence was similar Patients reported more adverse events after subcutaneous sumatriptan (1.32 per attack) than after the oral form (0.85 per attack), but all adverse events were mild to moderate in intensity and of short duration. Patient opinion was more often positive after subcutaneous sumatriptan. These results may be useful in counselling patients to choose between the available marketed formulations of sumatriptan.     

Oral rizatriptan versus oral sumatriptan: a direct comparative study in the acute treatment of migraine. Rizatriptan 030 Study Group

Rizatriptan is a potent, oral, 5-HT1B/1D agonist with more rapid absorption and higher bioavailability than oral sumatriptan. It was postulated that this would result in more rapid onset of effect. This randomized, double-blind, triple-dummy, parallel-groups study compared rizatriptan 5 mg, rizatriptan 10 mg, sumatriptan 100 mg, and placebo in 1268 outpatients treating a single migraine attack. Headache relief rates after rizatriptan 10 mg were consistently higher than sumatriptan at all time points up to 2 hours, with significance at 1 hour (37% versus 28%, P = 0.010). All active agents were significantly superior to placebo with regard to headache relief and pain freedom at 2 hours (P < or = 0.001). The primary efficacy endpoint of time to pain relief through 2 hours demonstrated that, after adjustment for age imbalance, rizatriptan 10 mg had earlier onset than sumatriptan 100 mg (P = 0.032; hazard ratio 1.21). Rizatriptan 10 mg was also superior to sumatriptan on pain-free response (P = 0.032), reduction in functional disability (P = 0.015), and relief of nausea at 2 hours (P = 0.010). Significantly fewer drug-related clinical adverse events were reported after rizatriptan 10 mg (33%, P = 0.014) compared with sumatriptan 100 mg (41%). We conclude that rizatriptan 10 mg has a rapid onset of action and relieves headache and associated symptoms more effectively than sumatriptan 100 mg.     

Risk factors for headache recurrence after sumatriptan: a study in 366 migraine patients

Headache recurrence (HR) is the major limitation of sumatriptan in the acute treatment of migraine attacks. The risk of HR is mainly patient dependent. We analyzed, in 366 migraine patients, clinical differences between patients who always have HR and patients who never have HR. We found remarkably few differences. HR more frequently occurred in patients with more severe attacks and longer untreated attack duration; in patients who experienced a sensation of a subclinically ongoing attack, despite headache relief after sumatriptan; and in females, mainly with menstruation-related migraine, most probably due to the more severe and longer lasting attacks these patients suffer, rather than due to hormonal factors. The incidence of HR was, among other factors, not related to the (other) clinical effects of sumatriptan, the timing of administration within the attack, the duration of use of sumatriptan, pharmacokinetic factors, or whether patients were experiencing HR after use of ergot alkaloids.     

Oral sumatriptan for the acute treatment of probable migraine: first randomized, controlled study

OBJECTIVE: To evaluate the efficacy and tolerability of sumatriptan tablets in adults who meet International Headache Society (IHS) criteria for probable migraine but who do not meet IHS criteria for migraine with or without aura. BACKGROUND: Headaches with some but not all of the features of migraine meet criteria for probable migraine, a form of migraine recognized by the IHS. Probable migraine attacks are also prevalent and frequently underdiagnosed. METHODS: This was a randomized, multicenter, double-blind, placebo-controlled, parallel-group study. Adults (18 to 65 years) with a 1-year history of headaches that met 2004 IHS criteria for probable migraine without aura (same operational definition as 1988 IHS migrainous disorder) were eligible for enrollment. All patients were triptan- and ergot-na?ve and had never been diagnosed with migraine. Patients were randomized in a 1:1:1:1 fashion to receive sumatriptan 25, 50, or 100 mg conventional tablets or matching placebo and were instructed to treat a single moderate or severe probable migraine attack. A post hoc analysis was conducted to evaluate the population of patients who achieved headache relief sustained throughout the immediate posttreatment period. Patients who reported relief within 2 hours and subsequently lost headache relief within 4 hours were considered nonresponders. RESULTS: At 2 hours, more patients treated with sumatriptan achieved headache relief, the primary efficacy measure, compared with placebo, but differences only approached statistical significance for 100 mg (P= .053). The 2-hour headache relief rate in the sumatriptan 25 or 50 mg groups was not significantly different than placebo. The time to use of rescue was significantly shorter in the placebo group compared with the sumatriptan 100 mg group (P= .002). The time to use of rescue in the sumatriptan 25 or 50 mg groups was not significantly different than placebo. More patients treated with placebo (22%) lost headache relief within 4 hours compared with patients treated with sumatriptan 25 mg (17%), 50 mg (14%), or 100 mg (7%). A post hoc analysis demonstrated that at 2 hours, headache relief sustained through 4 hours (S 0-4 hours) was achieved in 44%, 49%, and 57% of patients treated with sumatriptan 25, 50, and 100 mg, respectively, compared with 34% of patients treated with placebo (P < .05 for sumatriptan 50 and 100 mg vs. placebo). All doses of sumatriptan were well tolerated and no serious adverse events were reported. CONCLUSION: These results suggest that oral sumatriptan may be effective and is well tolerated for the acute treatment of probable migraine without aura, however, the difference between sumatriptan and placebo was not statistically significant for the a priori defined primary endpoint.     

Efficacy of sumatriptan nasal spray in recurrent migrainous headache: an open prospective study

OBJECTIVE: To evaluate the effectiveness of sumatriptan 20 mg via nasal spray and 100-mg tablets in treating migrainous headache in patients without a concomitant migraine diagnosis. METHODS: We prospectively investigated the efficacy of sumatriptan 20 mg via nasal spray and 100-mg tablets in patients with a history of at least 5 moderate to severe headache attacks lasting 2 to 72 hours that consistently did not meet the International Headache Society (IHS) criteria for migraine or episodic tension-type headache. RESULTS: Nineteen headache attacks classifiable as migrainous disorder without aura (IHS 1.7) were evaluated in 13 patients using 20-mg sumatriptan nasal spray within a 10-week period. A 2-point decrease in headache severity on a four-point scale was achieved in 74% (95% confidence interval [CI], 50% to 89%) of the attacks within 2 hours. The pain-free incidence (a reduction in headache severity from moderate or severe to none) was 37% (95% CI, 17% to 63%) after 2 hours. Ten patients completed the second part of the study, taking oral sumatriptan for 14 migrainous attacks: a 2-point decrease in headache severity was achieved in 38% (95% CI, 13% to 71%) of the attacks within 2 hours and in 77% (95% CI, 48% to 92%) within 4 hours. CONCLUSION: This is the first prospective study to show that intranasal or oral sumatriptan may be effective in patients experiencing moderate to severe headache attacks which consistently do not fulfill the IHS criteria for migraine or episodic tension-type headache.     

Dihydroergotamine, ergotamine, methysergide and sumatriptan - basic science in relation to migraine treatment

The 5-hydroxytryptamine (5-HT) receptor family mediates the effects of several drugs highly effective in migraine primarily by activating 5-HT(1B) , 5-HT(1D) , and 5-HT(1F) receptors. Ergotamine, dihydroergotamine, and methysergide, as well as the "triptan" sumatriptan, are all agonists for these receptors. The receptor profile and degree of selectivity of these four drugs differ, which is reflected by their side effects that limit their use in the acute and prophylactic treatment of migraine. The acute antimigraine efficacy of these remedies is very much dependent on the formulation used where, in general, parenteral formulations are more effective in reliving the symptoms of a migraine attack.     

Patient preference in clinical trials for headache medication: the patient's view

From a clinical point of view, the subjective preference of the patient regarding headache medication is imperative. Consequently, a new trial design for headache medication, the so-called patient preference trial, has been vividly discussed. However, some critical questions have been raised concerning preference trials, such as whether placebos should be used, the necessity of blinding, and how to assess the data if a patient does not prefer medication A over B. As patient preference is the topic, we passed these questions on to headache patients using a questionnaire, which was handed out to 1112 headache patients. Out of 612, 486 returned questionnaires were correctly completed and analysed. Complete pain relief was the most important factor for 61% of patients to qualify a therapy effective. This is in contrast to the literature, where rapid speed of onset of the drug is discussed as the most important factor for migraineurs. Regarding the study design, 80% of the patients want to decide the time-point of taking acute medication themselves. About 60% of the patients would participate in placebo-controlled clinical trials and agree that studies should be blinded. If patients had to decide between two equally effective drugs, most would vote for the drug which is available in different application forms. Furthermore, we used the same questionnaire to ask headache specialists with expertise in performing headache studies the same questions. This was mailed to and completed by 22 experts in Germany. In this article, we discuss the patient preference compared with the expert preference regarding clinic trials and drug therapy.     

Oral sumatriptan and almotriptan--delimiting the MAOI effect

(Headache 2012;52:765‐772) Objectives/Background.— (1) To investigate whether a parsimonious model for sumatriptan pharmacokinetics can apply to oral administration; (2) for a successful model, whether a monoamine oxidase A inhibitor (MAOI‐A) perturbs it; and (3) whether such a model is generalizable to oral almotriptan. These goals respond to statements in US product labeling. Methods.— Extension of a previous model for subcutaneous sumatriptan. Numerical solutions to 3 concurrent differential equations were found, with prospective criteria for model acceptance based upon comparison with clinically observed data. Results.— The model was successfully extended by inserting a time factor into the absorption phase. This extension was robust: it imitated clinical data for 3 oral sumatriptan dose sizes (both without and with a concomitant MAOI‐A) and also for oral almotriptan. Conclusion.— A model for oral sumatriptan pharmacokinetics can be found using the differential calculus, and it is generalizable to oral almotriptan. The model suggests that an MAOI‐A probably has greater effect on elimination kinetics than first‐pass metabolism, and that this interaction appears to be overstated in product labeling.     

Efficacy of a fixed combination of indomethacin,prochlorperazine, and caffeine versus sumatriptan in acute treatment of multiple migraine attacks: a multicenter,randomized, crossover trial

OBJECTIVE: To compare the efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine suppositories with sumatriptan suppositories in the treatment of 2 consecutive migraine attacks of moderate or severe intensity in a multicenter, randomized, crossover study. BACKGROUND: A fixed combination of indomethacin, prochlorperazine, and caffeine is the most commonly used drug for the acute treatment of migraine in Italy. No studies have been published comparing the efficacy of this combination with sumatriptan, the most widely prescribed of the triptans. METHODS: One hundred twelve patients with migraine with or without aura according to the diagnostic criteria of the International Headache Society were randomized to treat 2 migraine attacks with a fixed combination of indomethacin, prochlorperazine, and caffeine and 2 migraine attacks with sumatriptan. Both drugs were rectally administered in a single dose for each attack. Patients were asked to take study medication as soon as possible at the onset of a headache. RESULTS: Of the 112 patients, 88 were compliant to the protocol. More attacks became pain-free at 2 hours postdose (primary end point) on the combination than on sumatriptan (49% versus 34%; P<.01), while there was no difference in the relief of headache at 2 hours postdose (71% versus 65%). The combination was statistically superior to sumatriptan in the time to a pain-free response (a higher percentage of attacks became pain-free from 0.5 hours postdose to 5 hours postdose), in alleviation of nausea, and in a sustained pain-free response (pain-free at 2 hours postdose with no use of rescue medication or relapses within 48 hours). Moreover, a significant consistent response was achieved for the combination compared with sumatriptan across (higher percentage of patients pain-free at 2 hours postdose in the first, second, third, and fourth treated attack) and within patients (pain-free in 2 of 2 treated attacks in 35% of patients taking the combination and 20% of patients on sumatriptan). Both drugs were well-tolerated. CONCLUSIONS: This study, analyzed according to the more recent guidelines for controlled trials in migraine, showed that a fixed combination of indomethacin, prochlorperazine, and caffeine is significantly more effective than sumatriptan in the acute treatment of migraine attacks. It is notable that the combination is less expensive than sumatriptan per unit dose.     

A comparative trial of zolmitriptan and sumatriptan for the acute oral treatment of migraine

OBJECTIVE: This randomized, double-blind, parallel group multicenter study compared response rates and tolerability of zolmitriptan with sumatriptan in the acute treatment of migraine. METHODS: A sample consisting of 1445 outpatients with an established diagnosis of migraine was randomized to zolmitriptan, 2.5 mg or 5 mg, or sumatriptan, 25 mg or 50 mg. Patients took 1 tablet for moderate/severe migraine and a second identical tablet, if necessary, for recurrent headache of moderate/severe intensity 4 to 24 hours after the initial dose. Up to six attacks were treated during a 6-month period. The primary outcome measure was headache response 2 hours after the initial dose. Secondary end points included 1-hour and 4-hour headache response and pain relief over 24 hours. RESULTS: A headache response at 2 hours was noted in 67.1% of patients taking zolmitriptan, 2.5 mg, and 64.8% of those taking zolmitriptan, 5 mg, versus 59.6% of patients taking sumatriptan, 25 mg, and 63.8% of those taking sumatriptan, 50 mg. At 2 and 4 hours, the differences between zolmitriptan, 2.5 mg, and sumatriptan, 25 mg, were statistically significant (odds ratio=1.49 and 1.67, respectively; both P<.001). Statistically significant differences between zolmitriptan, 2.5 mg, and sumatriptan, 50 mg, were seen at 2 and 4 hours post dose (odds ratio=1.21 and 1.23, respectively; both P<.05). At 1 hour post dose, the headache response rate for zolmitriptan, 2. 5 mg, was numerically higher than response rates for sumatriptan, 25 mg and 50mg (odds ratio=1.16, odds ratio=1.06, though they failed to reach statistical significance; P=.061, P=.461 respectively). Differences between zolmitriptan, 5 mg, and sumatriptan, 25 mg, were statistically significant at 1, 2, and 4 hours (odds ratio=1.43, 1. 46, and 1.78, respectively; all P<.001) and at 1 and 4 hours versus sumatriptan, 50 mg (odds ratio=1.28, P=.002; odds ratio=1.29, P=.012, respectively). Although not statistically significant at 2 hours, more patients responded to zolmitriptan, 5 mg, than to sumatriptan, 50 mg (odds ratio=1.16, P=.064). Patients receiving zolmitriptan, 2. 5 mg or 5 mg, achieved more pain relief over 24 hours than patients receiving sumatriptan, 25 mg (odds ratio=1.47, and 1.54 respectively, both P<.001) or sumatriptan, 50 mg (odds ratio=1.17, P=.021; odds ratio=1.22, P=.005, respectively). All treatments were well tolerated. CONCLUSIONS: Zolmitriptan, 2.5 mg and 5 mg, was at least as effective as sumatriptan, 25 mg or 50 mg, for all parameters studied. Zolmitriptan, 2.5 mg, was significantly more effective than sumatriptan, 50 mg, in terms of headache response at 2 and 4 hours. Patients taking zolmitriptan were significantly more likely to have pain relief over 24 hours than those taking sumatriptan.     

Efficacy and adverse events of subcutaneous, oral, and intranasal sumatriptan used for migraine treatment: a systematic review based on number needed to treat

Objectives : To evaluate the efficacy, speed of onset, and adverse events of 6 mg subcutaneous, 100 mg oral, and 20 mg intranasal sumatriptan in the treatment of migraine attacks. Design : Systematic review of placebo-controlled randomized clinical trials. Data sources : Thirty trials up to April 1997 retrieved from a systematic literature search (Medline, review papers, handsearching of journals, congress proceedings, manufacturer's database); no restriction on language. Outcome parameters : Numbers needed to treat (NNT) were calculated for relief of headache and for adverse events (when data were available). Therapeutic gain was used to evaluate speed of onset of action. Results : Subcutaneous sumatriptan was more efficacious, combined number needed to treat 2.0 at 1 h, than oral (3.0 at 2 h) and intranasal sumatriptan (3.1 at 2 h). For adverse events, the NNT was 3.0 for subcutaneous and 8.3 for oral sumatriptan. Only limited data on adverse events for intranasal sumatriptan were available. Therapeutic gain analysis during the first 2 h showed that subcutaneous sumatriptan was the fastest-acting form of administration. Conclusions : Subcutaneous sumatriptan in a dose of 6 mg is significantly more efficacious than 100 mg of oral sumatriptan, but causes more adverse events than oral sumatriptan. Subcutaneous sumatriptan is the form with the quickest onset of action. Intranasal sumatriptan has the same efficacy as oral sumatriptan and a quicker onset of action than the oral form, but with a limited therapeutic effect for the first 30 min after administration.     

Early migraine intervention with sumatriptan 100 mg in patients with a history of nonresponse to sumatriptan 50 mg: an open-label, prospective study of multiple attacks

Background

Early treatment with sumatriptan tablets (50 and 100 mg) has been shown to be effective in retrospective and prospective study designs. Despite the efficacy of sumatriptan 50 mg and early intervention, however, some patients continue not to respond completely to this dose. New evidence with a scientific basis for early intervention suggests that some patients may need to treat early to prevent the establishment of central sensitization. Also, patients cite complete pain relief as the most important attribute of a migraine medication.

Objective

The primary objective of this study was to determine the 2-hour efficacy of sumatriptan 100 mg in achieving complete pain relief in patients with a history of nonresponse to sumatriptan 50 mg in an early-intervention treatment paradigm. Secondary end points included complete pain relief at 4 hours, consistency of complete relief in at least 2 of 3 attacks, sustained complete relief over 24 hours, satisfaction with the 100-mg dose, and relief of associated symptoms.

Methods

This open-label, prospective study was conducted at the Wesley Headache Clinic (Memphis, Tennessee). Male and female patients between the ages of 18 and 65 years who fulfilled International Headache Society classification criteria for migraine, and who had a documented history of nonresponse to sumatriptan 50 mg at 2 hours after dosing when treating in the early, mild-pain phase in at least 2 of 3 migraine attacks were eligible for the study. Patients were instructed to receive one 100-mg sumatriptan tablet at the earliest sign of pain, while still mild, in 3 subsequent migraine attacks. After each treated attack, patients were to record a detailed diary entry.

Results

Twenty patients (17 women, 3 men; mean age, 44 years) treated all 3 migraines during the early, mild-pain phase and completed the study. Of the 60 attacks treated, 48 (80%) were pain free at 2 hours, 56 (93%) were pain free at 4 hours, and 45 (75%) were pain free at 2 hours and continued to be pain free at 24 hours (sustained pain-free response). Sumatriptan 100 mg was well tolerated; none of the patients reported any adverse events.

Conclusions

In this study of migraineurs with a history of nonresponse to sumatriptan 50 mg at 2 hours after dosing in the early, mild-pain phase of migraine, increasing the dose of sumatriptan from 50 mg to 100 mg in the early-intervention paradigm, in most attacks complete pain relief was achieved for up to 24 hours. Because patients have indicated that becoming pain free was their therapeutic goal, based on the results of this study, physicians may want to consider increasing the dose of sumatriptan to 100 mg at the first sign of pain if the patient has consistently not responded to sumatriptan 50 mg in the early-intervention model.     

Self-treatment of acute migraine with subcutaneous sumatriptan using an auto-injector device: comparison with customary treatment in an open, longitudinal study

In a multicenter open longitudinal clinical trial where 479 patients suffering from migraine with or without aura were recruited, patients treated at home one to three migraine attacks with their customary treatment, and subsequently, over a 3-month period, one to three migraine attacks with (5 mg sumatriptan sc using an auto-injector. The headache response to customary treatment was 19% at 1 h and 30.5% at 2 h, and was not significantly different when only attacks treated "adequately" according to accepted treatment recommendations were considered: 16% at 1 h and 35% at 2 h. In contrast, 69% and 82% of patients treated with 6 mg sumatriptan sc had mild headache or no headache at 1 and 2 h respectively, regardless of migraine type or duration of symptoms prior to treatment. Other migraine symptoms (nausea, vomiting, photo- and phonophobia) were effectively treated with sumatriptan. Recurrence of migraine was observed in 31% of patients and was well controlled by a second injection of sumatriptan. It is concluded that 6 mg sumatriptan sc, self-administered using an auto-injector, is well tolerated and more effective than most currently used acute treatments for migraine in a population of severely affected patients consulting a neurologist.     

Transcranial Doppler in migraine attacks before and after treatment with oral zolmitriptan or sumatriptan

BACKGROUND: Intracranial blood flow velocity (BFV) changes in migraine have been studied fairly extensively. Although a number of investigations have been performed in migraineurs with nitroglycerin-induced attacks, there has been no reported transcranial study involving such attack treated with zolmitriptan or sumatriptan. METHODS: With ultrasound, we studied the BFV and pulsatility index (PI) changes in the middle cerebral artery in 45 symptom free, otherwise healthy, unmedicated patients with migraine without aura, and in 15 age- and sex-matched controls before nitroglycerin, at the time of maximum head pain induced by nitroglycerin and every 30 minutes for 2 hours after zolmitriptan (15 subjects) or sumatriptan (15 subjects) administration. Headache was rated on a 4-point scale. RESULTS: During headache attacks, BFV decreased significantly (36.7+/-3.3, 38.4+/-3.4, and 37.4+/-4 cm/sec, respectively, in the zolmitriptan, sumatriptan, and nontreated migraine groups, but not in the controls who were migraine free (P <.01). These abnormalities disappeared 1 hour after zolmitriptan or sumatriptan administration (49.7+/-3.7 and 48.9+/-3.9 cm/sec, respectively). There were no significant changes in PI. CONCLUSION: Our data indicate that nitroglycerin-induced headache in individuals with migraine without aura is associated with BFV changes that are reversed by administration of an oral triptan.     

Resolution of concentration-response differences in onset of effect between subcutaneous and oral sumatriptan

OBJECTIVE: To investigate whether the concentration-response relationships for onset of effect of oral and subcutaneous (s.c.) sumatriptan differ, and if so, then to explore whether a single model for the onset of effect can nonetheless be found for multiple dose sizes and both routes of administration. METHODS: Active and placebo response rates and mean plasma concentrations were collected from the literature for 0 < or =t < or = 2 hours. Plasma concentration-response relationships were plotted. Logarithmic models for the onset of effect (ie, active response rates), characterized by convexity factor A and location parameter B were constructed from the same data. RESULTS: The concentration-response relationships for s.c. and oral sumatriptan are qualitatively different. A single logarithmic model for the onset of effect provides good estimates of observed response rates during the first 2 hours post-dose for multiple dose sizes after both oral and s.c. routes of administration. The precision of this model resides in both its variables. Location parameters for this model differ for similar absolute doses by the two routes of administration. However, curve convexity (representing rate of onset of effect) is related to absolute dose (and hence plasma concentration) in the same way for sumatriptan tablets and injections. CONCLUSIONS: No simple plasma concentration-response relationship exists that is sufficiently robust to apply to both s.c. and oral sumatriptan. There are separate pharmacokinetic-pharmacodynamic relationships for rate of onset and extent of effect. The design of exploratory clinical trials for new acute therapies for migraine may be more efficient when these factors are considered, and these factors may help to describe the gap between experimental and ordinary clinical environments.     

Almotriptan in migraine patients who respond poorly to oral sumatriptan: a double-blind, randomized trial

OBJECTIVE: To investigate the efficacy and tolerability of almotriptan 12.5 mg in migraine patients who respond poorly to sumatriptan 50 mg. BACKGROUND: Poor response to sumatriptan therapy for acute migraine attacks has been documented in the literature, but few controlled trials have investigated the efficacy of an alternative triptan in this subgroup of patients. METHODS: Patients with an International Headache Society diagnosis of migraine who self-described as experiencing at least two unsatisfactory responses to sumatriptan treated their first migraine attack with open-label sumatriptan 50 mg. Patients who did not achieve 2-hour pain relief (improvement of headache from moderate/severe to mild/no headache) were then randomized to treat their second attack with almotriptan 12.5 mg or placebo under double-blind conditions. RESULTS: In the first attack, 221 of 302 participants (73%) did not achieve 2-hour pain relief with sumatriptan and were randomized to treatment of their second attack with almotriptan 12.5 mg or placebo. Of the 198 sumatriptan nonresponders who treated their second attack (99 almotriptan; 99 placebo), 70% had severe headache pain at baseline. Two-hour pain-relief rates were significantly higher with almotriptan compared to placebo (47.5% vs 23.2%; P<.001). A significant treatment effect for almotriptan was also seen in pain-free rates at 2 hours (33.3% vs 14.1%; P<.005) and sustained freedom from pain (20.9% vs 9.0%; P<.05). In the second attack, 7.1% of patients in the almotriptan group experienced adverse events compared to 5.1% in the placebo group (P=.77). CONCLUSIONS: Almotriptan 12.5 mg is an effective and well-tolerated alternative for patients who respond poorly to sumatriptan 50 mg. A poor response to one triptan does not predict a poor response to other agents in that class.     

Amplifying effect of sumatriptan on noradrenaline venoconstriction in migraine patients

The venoconstrictive activity of sumatriptan and its interaction with noradrenaline (NA)- and 5-hydroxy-tryptamine (5HT) venoconstriction was studied in vivo in the hand vein of migraineurs. Sumatriptan, injected at increasing doses into the vein, caused local venoconstriction after a 500 mg dose, comparable to that induced by 0.5–1 mg of 5HT. This venoconstriction was completely inhibited by low doses of ketanserin (5 mg). Subcutaneous sumatriptan (6 mg) provoked a minor increase in vein tone, lasting less than 30 min. Non-venoconstrictive doses of sumatriptan (10–100 mg), injected in the hand vein, produced an amplification of NA-venoconstriction but not of 5HT-induced venoconstriction. A similar increased effect was displayed by subcutaneous sumatriptan (6 mg) for at least 1 h. Sumatriptan appears to cause peripheral venoconstriction only at high doses locally applied (in the hand vein), by acting on 5HT2 receptors. Clinical subcutaneous doses (6 mg) do not show significant venoconstrictive effects. The amplifying effect on NA venoconstriction, also caused by 5HT, ergotamine and dihydroergotamine in human cranial arteries, may be important in explaining the therapeutic action of sumatriptan in migraine attacks.