Imigran (imitrex, sumatriptan)

Sumatriptan is the generic name of the drug traded under the brands names Imigran and Imitrex. As its name indicates, it is prescribed for the treatment of migraine headaches. It works on migraine whether or not there is an aura (visual disturbances) and can also treat cluster headache attacks. Imigran does not reduce the number of attacks experienced but reduces the pain and make the headache’s duration shorter. Since migraine is believed to be caused by tightening of certain blood vessels in the head, Imigran works by shrinking these vessels back to their normal size, thus relieving the pain quickly and effectively. The drug belongs to a class of medications called serotonin agonists and can be taken orally or injected. It is preferred that it is not combined with other painkillers or migraine therapies.

Prescrire Int. 2005 Apr;14(76):45-7.
Nasal sumatriptan: new dosage. For adolescents with migraine: too little benefit.
[No authors listed]

(1) The reference first-line drug therapy for migraine attacks in adolescents is a non specific analgesic such as paracetamol or a nonsteroidal antiinflammatory drug like ibuprofen. Two specific analgesics are authorised for use in this setting in France, namely ergotamine and dihydroergotamine. (2) Nasal sumatriptan is the first triptan to be licensed for this age group in France. (3) Evaluation data includes three flawed placebo-controlled trials. (4) Effects were modest at best. Only one of the three trials showed that sumatriptan was more likely than placebo to give complete pain relief within two hours. The three trials fail to show that sumatriptan is effective against symptoms such as nausea and vomiting, photophobia and phonophobia. (5) The principal known adverse effects of sumatriptan are chest tightness, flushing, and increased blood pressure. (6) In the only trial report containing relevant information, unpleasant taste was the only adverse effect more commonly associated with sumatriptan than with placebo. (7) Postmarketing follow-up revealed a number of serious adverse effects, including stroke, myocardial infarction and loss of vision. (8) The packs containing 6 or 12 spray vials carry a risk of overuse and self-induced headache. (9) In practice, sumatriptan must not be used to treat migraine attacks in adolescents.

Expert Rev Neurother. 2004 Mar;4(2):199-209.
Sumatriptan: a decade of use and experience in the treatment of migraine.
Sheftell FD, Bigal ME, Tepper SJ, Rapoport AM.
The New England Center for Headache, PC 778 Long Ridge Road, Stamford, CT 06902 1251, USA. Ninotores1@aol.com

The migraine-specific triptans have revolutionized the treatment of migraine and are usually the drugs of choice to treat a migraine attack in progress. Sumatriptan (Imitrex) has been available for the longest time within the class, is most flexible in form and has been given successfully to the most number of patients. It is useful for the full range of attacks experienced by a migraine suffer. The aim of this review is to provide an overview of the first 10 years of the use of sumatriptan.

Am Fam Physician. 2005 Feb 15;71(4):717-24.
Management of cluster headache.
Beck E, Sieber WJ, Trejo R.
Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, California, USA. ebeck@ucsd.edu

Cluster headache, an excruciating, unilateral headache usually accompanied by conjunctival injection and lacrimation, can occur episodically or chronically, and can be difficult to treat. Existing effective treatments may be underused because of underdiagnosis of the syndrome. Oxygen and sumatriptan have been demonstrated to be effective in the acute treatment of cluster headaches. Verapamil has been shown to be effective for prophylaxis. For cluster headache completely refractory to all treatments, surgical modalities and newer interventions such as the implantation of stereotactic electrodes may be useful. Patients should be encouraged to avoid possible triggers such as smoking or alcohol consumption, especially during the duster period. The intensity of duster headache pain leads to ethical concerns among researchers over the use of placebo, making randomized controlled trials difficult. As new technology and genetic studies clarify the etiology of duster headache, it is possible that more specific therapies will emerge.

J Neurol. 2005 Mar 11.
The use of multiattribute decision models in evaluating triptan treatment options in migraine.
Ferrari MD, Goadsby PJ, Lipton RB, Dodick DW, Cutrer FM, McCrory D, Williams P.
Dept. of Neurology, Leiden University Medical Centre, 9600, 2300, RC Leiden, The Netherlands, M.D.Ferrari@LUMC.NL.

BACKGROUND : The physician treating patients with migraine is now able to choose from among seven triptans-almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan. These differ, to greater or lesser degrees, on a range of clinical attributes important for treatment selection. OBJECTIVE : To outline the basic principles of Multiattribute Decision Making (MADM) and describe how one such method-TOPSIS (Technique for Order Preference by Similarity to the Ideal Solution)-can be applied to evaluate the currently available triptans. METHODS : In an example application, summary data from a recent meta-analysis of 53 published and unpublished placebo-controlled trials of the oral triptans were combined in TOPSIS models with computer-generated attribute importance weights representing the entire range of possible values, That is, the relative performance of the triptans was explored across all logically possible combinations of relative importance of the treatment attributes available from the meta-analysis, and uncertainty was assessed based on the confidence intervals from the meta-analysis. RESULTS : When compared across the entire range of values for relative attribute importance, almotriptan, eletriptan and rizatriptan were more similar to a hypothetical ideal triptan and were more likely to appear in the top three closest to the hypothetical ideal, than were naratriptan, sumatriptan, and zolmitriptan. CONCLUSION : Using the TOPSIS model, almotriptan, eletriptan and rizatriptan were more likely to appear in the top three closest to the hypothetical ideal triptan.

Curr Med Res Opin. 2004 Dec;20(12):2021-9.
Effects of a fast disintegrating/rapid release oral formulation of sumatriptan on functional ability in patients with migraine.
Barbanti P, Carpay JA, Kwong WJ, Ahmad F, Boswell D.
Department of Neurological Sciences, La Sapienza University, Rome, Italy.

BACKGROUND: A new oral form of sumatriptan has been developed to facilitate tablet disintegration and drug dispersion and to mitigate the effects of gastric stasis that can accompany migraine. OBJECTIVE: To evaluate the effects on functional ability of the new fast disintegrating/rapid release formulation of sumatriptan. METHODS: Sumatriptan 50 mg (n = 137), 100 mg (n = 142), or placebo (n = 153) was administered early when pain was mild for the acute treatment of a single migraine attack in a randomized, double-blind, parallel-group, placebo-controlled clinical trial. For this report, main health-outcomes endpoints (which were secondary endpoints for this clinical trial that was primarily designed to assess pain-free efficacy) included functional ability measured through 2 h postdose on a 5-point scale and lost time equivalents, a composite measure of migraine-associated time missed from activities, and reduced effectiveness at activities through 24 h postdose. RESULTS: Normal functional ability was restored in a significantly (p < 0.05) greater percentage of patients treated with sumatriptan than placebo beginning 45 min postdose for sumatriptan 100 mg and 1 h postdose for sumatriptan 50 mg. During the 24 h after initial dosing, the median (range) lost time equivalents for the combination of paid work activities and activities outside of paid work were significantly lower in the groups treated with sumatriptan (1.1 [0-10] sumatriptan 100 mg; 0.8 [0-36] sumatriptan 50 mg) compared with placebo (2.9 [0-24]) (p < or = 0.01 each sumatriptan group versus placebo). The corresponding mean +/- SD values for lost time equivalents were 1.9 +/- 2.3 and 2.5 +/- 4.7 for sumatriptan 100 mg and 50 mg, respectively, compared with 3.5 +/- 4.3 for placebo. CONCLUSION: A new oral sumatriptan formulation confers rapid, sustained restoration of functional ability in the acute treatment of migraine so that patients can return rapidly to normal functioning at work and outside of work.

Nippon Rinsho. 2004 Sep;62(9):1749-56.
Improvement of QOL by drug delivery systems
Okada H, Takashima Y.
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, Tokyo University of Pharmacy and Life Science.
The objectives of the medical advancements made in recent years are i) the cure of diseases and relief of their symptoms, ii) expansion of life expectancy, iii) improvement of QOL (quality of life), and iv) prevention of diseases. Most importantly, the therapy should maintain the dignity of patients. DDS is defined as a highly-functional dosage form for improving the medical usefulness of drugs by potentiating their efficacy, reducing their toxicity, and making them a 'patient-friendly medicine'. DDS is strongly expected for achieving 1) the controlled release, 2) new alternative mucosal absorption, and 3) targeting to the action site of drugs. The improvements of QOL by devising novel DDS such as Lupron Depot, Imigran Nasal Spray, Durotep Patch and Pegasys were reviewed.

Neuropsychobiology. 2004;50(3):200-5.
Serotonergic dissection of obsessive compulsive symptoms: a challenge study with m-chlorophenylpiperazine and sumatriptan.
Gross-Isseroff R, Cohen R, Sasson Y, Voet H, Zohar J.
Division of Psychiatry, Chaim Sheba Medical Center, Tel Hashomer, Israel. risseroff@yahoo.com
We have conducted a pharmacological challenge experiment in 10 medication-free obsessive compulsive (OC) disorder (OCD) patients. We used a placebo-controlled paradigm for m-chlorophenylpiperazine (mCPP) and sumatriptan challenges. Endocrine, physiological and behavioral variables were assessed at baseline and over a 3-hour period after the challenge. Both cortisol and prolactin were significantly elevated in OCD patients following mCPP administration. Both mCPP and sumatriptan caused significant OC symptom exacerbation with the response to sumatriptan being more robust. We conclude that the 5-HT(1Dbeta) receptor may play a role in the pathophysiology of OCD. Copyright 2004 S. Karger AG, Basel

J Toxicol Clin Toxicol. 2004;42(3):309-11.
Oral sumatriptan-induced myocardial infarction.
Hack JB.
Pitt County Memorial Hospital, East Carolina University, Greenville, NC 27850, USA. hackj@mail.ecu.edu
BACKGROUND: Sumatriptan has been used in the treatment of migraine and other vascular headaches since 1993 in the United States. Its side effects include chest pains in 3% to 8% of patients who have known cardiac risk factors. This is a case report of a 45-year-old woman with no history of cardiac risk factors who had a myocardial infarction after her monthly dose of oral sumatriptan. METHODS: The patient was examined in the emergency room, evaluated by electrocardiography, and serial evaluations of cardiac enzymes over the next 24 h. She was admitted to the cardiology ward. A cardiac catherization and additional laboratory studies were performed the following day. RESULTS: The catherization revealed normal heart function, but a 60% to 70% non-flowing stenosis within the first septal perforator. Laboratory indices for cardiac risk were within normal ranges. CONCLUSIONS: Patients without cardiac risk factors may experience myocardial infarction following an oral dose of sumatriptan.

Funct Neurol. 2004 Apr-Jun;19(2):73-81.
Cluster headache: the history of the Cluster Club and a review of recent clinical research.
Ekbom K, Waldenlind E.
Department of Neurology, Karolinska Institute Karolinska, University Hospital, Stockholm, Sweden. karl.ekbom@kus.se
In September 2003, a scientific meeting was held in Rome to revive the International Cluster Headache Research Group (or "Cluster Club") tradition. This group of specialists was originally formed in the late 1970s by Ottar Sjaastad in order to promote research ideas, and to generate papers and other important information in this field. Its meetings, the last of which had taken place in 1994, had been informal events at which there was ample time for lively discussion. The last decade of the 20th century brought a significant increase in clinical and experimental research into cluster headache (CH), and this review summarizes some of the results of this research. The male preponderance of CH has been shown to be progressively decreasing over the years. Revised clinical criteria and a modern classification have been presented. First-degree relatives of probands with CH have been shown to have an increased risk of suffering from CH compared with the general population. Genetic analysis suggests that an autosomal dominant gene plays a role in some families. Functional neuroimaging has contributed to a better understanding of the pathophysiology of the condition. Positron emission tomography during provoked attacks has shown activation of the ipsilateral inferior posterior hypothalamus and it has been suggested that CH might be a functional neurovascular disorder of pacemaker or circadian regions in the hypothalamic grey matter. Subcutaneously administered sumatriptan has emerged as a highly effective acute treatment, but, in our opinion, the emphasis should be on attack prevention. Deep brain stimulation of the inferior posterior hypothalamic grey matter seems to be very promising as a novel treatment targeting the presumed central origin of pain attacks.

Eur Neurol. 2004;52(1):50-6. Epub 2004 Jul 05.
Efficacy of 1,000 mg effervescent acetylsalicylic acid and sumatriptan in treating associated migraine symptoms.
Diener HC, Eikermann A, Gessner U, Gobel H, Haag G, Lange R, May A, Muller-Schwefe G, Voelker M.
Department of Neurology, University of Essen, Hufelandstrasse 55, DE-45147 Essen, Germany. h.diener@uni-essen.de
Recently a new effervescent acetylsalicylic acid (ASA) tablet with high buffering capacity has been developed. In this double-blind, 3-arm, multicenter, parallel-group study, 433 patients were treated either with 1,000 mg effervescent ASA or 50 mg encapsulated sumatriptan or placebo. The primary endpoint was the percentage of patients with complete remission of the 3 accompanying symptoms nausea, photophobia and phonophobia within 2 h after intake of the study drug. 43.8% of patients treated with ASA, 43.7% of patients treated with sumatriptan and 30.9% of patients treated with placebo showed complete remission of all 3 accompanying symptoms (p < 0.05 for ASA and sumatriptan vs. placebo). Both active treatments were superior to placebo regarding the individual symptoms photophobia and phonophobia, but not for nausea. The percentage of patients with reduction in headache severity from moderate or severe to mild or no pain (secondary objective) was 49.3% for ASA, 48.8% for sumatriptan and 32.9% for placebo. All active treatments were superior to placebo (p < 0.05). 25.3, 24.4 and 14.5% of patients treated with ASA, sumatriptan or placebo were pain free at 2 h. Drug-related adverse events were reported in 3.9, 4.7 and 6.7% of patients treated with placebo, ASA or sumatriptan. The study showed that administration of effervescent ASA leads to remission of the migraine symptoms nausea, photophobia and phonophobia, reduces migraine headache and is comparable to sumatriptan. Copyright 2004 S. Karger AG, Basel

J Manag Care Pharm. 2004 May-Jun;10(3):259-65.
A comparison of the cost-effectiveness of almotriptan and sumatriptan in the treatment of acute migraine using a composite efficacy/tolerability end point.
Williams P, Reeder CE.
PAREXEL International, The Quays, 101-105 Oxford Rd., Uxbridge, Middlesex, UB8 1LZ, UK. paul.williams@parexel.com
OBJECTIVE: To use a composite efficacy/tolerability end point to compare the cost-effectiveness, from the perspective of a U.S. health care payer, of almotriptan and sumatriptan in the treatment of an acute migraine attack. METHODS: The composite end point.Sustained pain free and No Adverse Events. (SNAE) was created from the sustained pain free and adverse event rates obtained in a meta-analysis of 53 placebo-controlled trials of oral triptans. The total direct cost of treating a single migraine attack was calculated from published sources. RESULTS: In the base-case analysis, the average cost-effectiveness ratios (CERs) were 82 US dollars , 133 US dollars , and 138 US dollars (per attack at which SNAE is achieved, 2004 prices) for almotriptan 12.5 mg, sumatriptan 50 mg, and sumatriptan 100 mg, respectively; the incremental CERs for almotriptan 12.5 mg were 12 US dollars and 16 US dollars (compared with sumatriptan 50 mg and sumatriptan 100 mg, respectively) per incremental attack at which SNAE is achieved. Sensitivity analyses were conducted to explore the impact of (1) relaxing the base-case assumptions (independence of efficacy and tolerability, uniform apportionment of health service use costs across attacks, number of tablets used to treat 1 attack); (2) varying input costs; and (3) uncertainty in the efficacy and tolerability estimates from the meta-analysis. In all of these sensitivity analyses, almotriptan 12.5 mg remained cost effective compared with sumatriptan 50 mg and 100 mg. CONCLUSION: Almotriptan was economically superior to sumatriptan in the treatment of a migraine attack.

Schweiz Rundsch Med Prax. 2004 May 26;93(22):943-7.
Drug exposure during pregnancy: a differentiated approach
Rousso P.
Swiss Teratogen Information Service (STIS), Division de pharmacologie et toxicologie cliniques, CHUV, Lausanne. philippe.rousso@chuv.hospvd.ch
Numerous drug exposures do occur unintentionally at the beginning of pregnancy. On the other hand, pursuing drug treatment may be necessary in women who wish to be pregnant. In these situations risk evaluation has to be done in a precise and differentiated manner, taking into account at the same time the risk for the fetus and maternal health. Teratovigilance services are able to give a thorough information enabling to avoid unwarranted drug arrests or pregnancy terminations. In return, physician's catamnesis about the outcome of the pregnancy exposed to one or several therapeutic agents will increase the bulk of knowledge health professionals and pregnant women have at their disposal.

Curr Med Res Opin. 2004 Jun;20(6):803-9.
Pharmacokinetic profile of a new form of sumatriptan tablets in healthy volunteers.
Walls C, Lewis A, Bullman J, Boswell D, Summers SJ, Dow A, Sidhu J.
GlaxoSmithKline, Harlow and Stockley Park, UK. christine.walls@gsk.com
OBJECTIVE: Rapid delivery of migraine-specific medication to its site(s) of action is thought to be crucial in preventing or minimizing sensitization of central pain pathways and thereby in optimizing pain-free outcomes in patients with migraine. Sumatriptan has been developed as a new tablet formulation to enhance the rate of systemic drug delivery by improving tablet disintegration and drug dispersion relative to those of conventional tablets. These enhanced formulation characteristics may be beneficial during occurrences of the gastric stasis that can accompany migraine. METHODS: This randomized, open-label, 4-way crossover study (n = 32) was conducted to determine whether the new formulation of sumatriptan 50 and 100 mg is bioequivalent to sumatriptan conventional tablets and to compare the pharmacokinetic profiles of the new formulation and the conventional tablet during the early (0-2 h) postdose interval in healthy volunteers. Pharmacokinetics during the early post-dose interval are important in determining a drug's onset of action, an important parameter to patients with migraine. RESULTS: The results confirm that the new formulation of sumatriptan and sumatriptan conventional tablets are bioequivalent as demonstrated by the finding that the 90% confidence intervals for the sumatriptan area under the concentration time curve to infinity and to the last evaluable time point (AUC(0- infinity ) and AUC(0-t), respectively) and maximum plasma concentration (C(max)) fell within the predetermined bounds defining bioequivalence (0.80-1.25) for both doses. Pharmacokinetic parameters measured early (0-2 h) after dosing reveal slightly faster absorption, on average, of the new sumatriptan formulation than sumatriptan conventional tablets although high intersubject variability was observed. For the new sumatriptan formulation, AUC(0-2) (AUC up to 2 h post dose) was, on average, 1% greater (50 mg) and 8% greater (100 mg) and maximal sumatriptan levels were attained, on average, 10 min earlier (50 mg) and 15 min earlier (100 mg) compared with the conventional tablet. Other measures including AUC(0-0.5) (AUC to 30 min post-dose), times to achieve sumatriptan concentrations of 5 and 10 ng/mL, and mean percentage C(max) 15, 20 and 30 min post-dose demonstrate an observable improvement in rate of drug absorption for the new form of sumatriptan compared with conventional tablets. CONCLUSION: The new form of sumatriptan is bioequivalent to sumatriptan conventional tablets and is absorbed more quickly than conventional tablets.

Rinsho Shinkeigaku. 2004 Feb;44(2):96-101.
Postpartum cerebral angiopathy--a case report the vasculopathy associated with co-administration of two vasoconstrictives, methylergometrine maleate and sumatriptan
Sato S, Shimizu M, Endo K, Homma M, Yamamoto T.
Department of Neurology, Fukushima Medical University School of Medicine.
A 25-year-old woman (gravida 1, para 0) who had no history indicating the toxemia of pregnancy developed hypertension and severe throbbing headache after the delivery of her first child by the cesarean section. Generalized tonic-clonic seizure ensued 5 days after the delivery, after which she did not fully regain her consciousness. Her head T2-weighted and FLAIR MRIs showed areas of multiple high intensities in the basal ganglia and cerebral white matter. Her cerebral MRA revealed the segmental stenosis and irregular wall of the major vessels, in particular of the right MCA trunk. Three weeks later, these abnormalities in the neuroimages disappeared and she was free of any symptoms. The history disclosed that obstetricians had used methylergometrine maleate for uterine contraction after delivery and then sumatriptan for her throbbing headache. We speculate that these vasoconstrictive agents might have induced the postpartum cerebral angiopathy. Postpartum cerebral angiopathy may be distinct from reversible posterior leukoencephalopathy in that the abnormalities are not restricted to the posterior lobes and that the vascular changes are apparent on neuroimagings. However, this entity might have a common underlying physiology, which is the abnormally elevated blood pressure that occurs in the setting of early postpartum period. Caution should be exercised when vasoconstrictives are to be used in postpartum period.

Cephalalgia. 2004 Jul;24(7):586-95.
The sumatriptan/naratriptan aggregated patient (SNAP) database: aggregation, validation and application.
Barrows C, Saunders W, Austin R, Putnam G, Mansbach H; SNAP Study Group.
GlaxoSmithKline, Research Triangle Park, North Carolina 27709, USA. cathy.f.barrows@gsk.com
Pooled data from multiple clinical trials can provide information for medical decision-making that typically cannot be derived from a single clinical trial. By increasing the sample size beyond that achievable in a single clinical trial, pooling individual-patient data from multiple trials provides additional statistical power to detect possible effects of study medication, confers the ability to detect rare outcomes, and facilitates evaluation of effects among subsets of patients. Data from pharmaceutical company-sponsored clinical trials lend themselves to data-pooling, meta-analysis, and data mining initiatives. Pharmaceutical company-sponsored clinical trials are arguably among the most rigorously designed and conducted of studies involving human subjects as a result of multidisciplinary collaboration involving clinical, academic and/or governmental investigators as well as the input and review of medical institutional bodies and regulatory authorities. This paper describes the aggregation, validation and initial analysis of data from the sumatriptan/naratriptan aggregate patient (SNAP) database, which to date comprises pooled individual-patient data from 128 clinical trials conducted from 1987 to 1998 with the migraine medications sumatriptan and naratriptan. With an extremely large sample size (>28000 migraineurs, >140000 treated migraine attacks), the SNAP database allows exploration of questions about migraine and the efficacy and safety of migraine medications that cannot be answered in single clinical trials enrolling smaller numbers of patients. Besides providing the adequate sample size to address specific questions, the SNAP database allows for subgroup analyses that are not possible in individual trial analyses due to small sample size. The SNAP database exemplifies how the wealth of data from pharmaceutical company-sponsored clinical trials can be re-used to continue to provide benefit.

Cephalalgia. 2004 Jul;24(7):540-6.
Comparison of rizatriptan 5 mg and 10 mg tablets and sumatriptan 25 mg and 50 mg tablets.
Kolodny A, Polis A, Battisti WP, Johnson-Pratt L, Skobieranda F; Rizatriptan Protocol 052 Study Group.
Merck & Co., Inc., West Point, PA 19486, USA.
This randomized, double-blind, two-attack, placebo-controlled, crossover study explored the efficacy and tolerability of rizatriptan 10 mg compared with sumatriptan 50 mg as well as rizatriptan 5 mg compared with sumatriptan 25 mg in the acute treatment of migraine. Following randomization to one of six possible treatment sequences, patients (n = 1447) treated two sequential attacks, of moderate or severe intensity, separated by at least 5 days. Patients assessed pain severity, migraine-associated symptoms, and functional disability at 0.5, 1, 1.5, and 2 h post treatment. Compared with placebo, all treatments were effective. On the primary endpoint of time to pain relief, rizatriptan 10 mg was not statistically different from sumatriptan 50 mg [odds ratio (OR) 1.10, P = 0.161], and rizatriptan 5 mg was statistically superior to sumatriptan 25 mg (OR 1.22, P = 0.007). In general, rizatriptan 10 mg and 5 mg treatment resulted in improvement compared with the corresponding doses of sumatriptan on measures of pain severity, migraine symptoms, and functional disability and the 5-mg dose reached statistical significance on almost all measures. All treatments were generally well tolerated.

Cephalalgia. 2004 Jul;24(7):515-21.
Effect of high-dose intravenous eletriptan on coronary artery diameter.
Goldstein JA, Massey KD, Kirby S, Gibson M, Hettiarachchi J, Rankin AJ, Jackson NC.
William Beaumont Hospital, Royal Oak, MI 48073, USA. jgoldstein@beaumont.edu
The goal of this study was to evaluate the coronary vasoconstrictive effects of high doses of eletriptan compared with a standard dose of sumatriptan. Patients with no clinically significant coronary artery disease were randomized to receive high-dose intravenous eletriptan (n = 24) vs a standard dose of sumatriptan (n = 18; 6 mg subcutaneously) vs placebo (n = 18). Serial angiograms were obtained. The primary non-inferiority analysis found equivalence between the mean maximum change in left anterior descending coronary artery diameter for eletriptan, -22%[95% confidence interval (CI) -26, -19], and sumatriptan, -19% (95% CI -22, -16). The change due to placebo was -16% (95% CI -20, -12). No individual cases of clinically significant vasoconstriction were observed. The results confirm that eletriptan has a broad cardiovascular safety margin, with plasma concentrations comparable to three to five times the Cmax of an oral 80-mg dose associated with modest vasoconstriction equivalent to standard therapeutic doses of sumatriptan.

Neuroreport. 2004 Jun 28;15(9):1409-12.
The anti-migraine agent sumatriptan induces a calcium-dependent discharge in meningeal sensory neurons.
Strassman AM, Levy D.
Department of Anesthesia and Critical Care, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA. Andrew.Strassman@bidmc.harvard.edu
The anti-migraine agent sumatriptan constricts cerebral blood vessels, and also blocks neuropeptide release from meningeal sensory neurons. We investigated whether sumatriptan can also affect neuronal discharge, by recording the activity of dural primary afferent neurons during dural application of sumatriptan in anesthetized rats. Sumatriptan (0.24-24 microM) induced a concentration-dependent increase in ongoing discharge. The discharge occurred only in the presence of calcium. The suppressive effect of calcium removal was not a result of a general decrease in excitability, because calcium removal produced a pronounced increase in mechanically evoked discharge. The excitatory effect on dural afferent discharge might underlie the initial worsening of the headache that can occur following sumatriptan administration, prior to the subsequent onset of headache relief.

Neurol Neurochir Pol. 2003 Sep-Oct;37(5):1013-23.
Suppressing effect of the serotonin 5HT1B/D receptor agonist rizatriptan on calcitonin gene-related peptide (CGRP) concentration in migraine attacks
Stepien A, Jagustyn P, Trafny EA, Widerkiewicz K.
Kliniki Neurologii Wojskowego Instytutu Medycyny Lotniczej w Warszawie.
Calcitonin gene-related peptide (CGRP) is one of the neuropeptides most abundant in the nervous tissue. Recent studies indicate that local cranial release of CGRP from the trigeminal nerve perivascular endings within arachnoidea plays an important role in the pathophysiology of migraine attacks and cluster headaches. Elevated CGRP levels in cranial venous blood (in the jugular vein) during an acute spontaneous migraine attack have been reported in rather few studies so far. Sumatriptan--a selective serotonin 5HT1B/D receptor agonist, highly effective in terminating migraine attacks, decreases the elevated CGRP level back to normal. The aim of our study was to determine the effect of rizatriptan (a drug from a new generation of triptans) on CGRP release in migraine attacks. In 45 patients suffering from migraine attacks with and without aura, plasma CGRP levels were assessed during an attack twice: before treatment and two hours after rizatriptan administration. In the group under study the plasma CGRP level before treatment was significantly higher than that measured two hours after rizatriptan administration. The decrease in CGRP levels was associated with subsidence of the migraine attack. There was no difference between migraine patients with and without aura. These results suggest that triptans as serotonin 5HT1B/D receptor agonists decrease CGRP plasma concentration in migraine attacks.

Cochrane Database Syst Rev. 2003;(3):CD002915.
Oral sumatriptan for acute migraine.
McCrory DC, Gray RN.
Center for Clinical Health Policy Research, Duke University, 2200 W. Main Street, Suite 220, Durham, NC 27705, USA.
BACKGROUND: Migraine is a common neurovascular disorder characterized by recurrent episodes of disabling headache, autonomic nervous system dysfunction, and, in some patients, neurological aura symptoms. Sumatriptan is one of a class of selective serotonin 5-hydroxytryptamine (5-HT1B/1D) agonists (triptans) thought to relieve migraine attacks by several mechanisms, including cranial vasoconstriction and peripheral and central neural inhibition. OBJECTIVES: To describe and assess the evidence from randomized controlled trials (RCTs) concerning the efficacy and tolerability of oral sumatriptan for the treatment of a single acute attack of migraine in adults. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (Cochrane Library, Issue 4, 2001), MEDLINE (1966 through November 2001), and reference lists of articles and books. SELECTION CRITERIA: We included double-blind RCTs comparing oral sumatriptan (100 mg, 50 mg, 25 mg) with placebo, no intervention, other drug treatments, behavioral therapy, or physical therapy for the treatment of an acute attack of migraine in adults. Trials comparing different doses of sumatriptan or dosing regimens were also included. Outcomes considered were: 2-hour pain-free response, headache relief/headache intensity, and functional disability; headache recurrence; and adverse events. DATA COLLECTION AND ANALYSIS: Data were abstracted by one reviewer and over-read by the other. The two reviewers independently assessed trial quality. Information on adverse events was collected from trial reports. MAIN RESULTS: Twenty-five trials involving 16,200 participants were included. Methodological quality was generally good. Sixteen trials were placebo comparisons and showed that sumatriptan in doses of 100 mg (14 trials), 50 mg (five trials), and 25 mg (three trials) provided significantly better pain-free response (100 mg and 25 mg only), headache relief, and relief of disability at 2 hours. Numbers-needed-to-treat (NNTs) for pain-free response at 2 hours were 5.1 (3.9 to 7.1) for the 100-mg dose (n = 2221) and 7.5 (2.7 to 142) for the 25-mg dose (n = 131); there was no significant difference between the 50-mg dose and placebo for this outcome (n = 127). For headache relief at 2 hours, NNTs were 3.4 (3.0 to 4.0), 3.2 (2.4 to 5.1), and 3.4 (2.3 to 6.6) for sumatriptan 100 mg (n = 2940), 50 mg (n = 420), and 25 mg (n = 226), respectively. Precise estimates of the efficacy of the 50- and 25-mg doses relative to the 100-mg dose could not be obtained.Adverse events were more common with sumatriptan 100 mg than with placebo (risk difference [RD] = 0.14 [0.09 to 0.20]; number-needed-to-harm [NNH] = 7.1 [5.0 to 11.1]; n = 3172). RDs for the 50- and 25-mg vs. placebo comparisons were not statistically significant. REVIEWER'S CONCLUSIONS: Oral sumatriptan has been shown to be an effective drug for the treatment of a single acute attack of migraine. It is well tolerated, though minor adverse events were not uncommon in the included trials. Other triptans were generally similar in efficacy and adverse events. Among non-triptan drugs, ergotamine + caffeine was significantly less effective than sumatriptan, and other drugs have been insufficiently studied to draw firm conclusions.

CNS Spectr. 2003 Jun;8(6):446-9.
The link between glutamate and migraine.
Ramadan NM.
Department of Neurology, Finch University of Health Sciences/The Chicago Medical School, Chicago, Illinois 60064-3095, USA.
Migraine pain-relay centers, including the trigeminal ganglion, trigeminal nucleus caudalis, and thalamus, contain glutamate-positive neurons, and glutamate activates the trigeminal nucleus caudalis. Glutamate is implicated in cortical spreading depression, trigeminovascular activation, and central sensitization. Glutamate receptor-subtype antagonists are effective in preclinical models of migraine, and in the clinic. These preclinical and clinical observations argue for a strong link between migraine and the glutamatergic system, a link that is important to further characterize in an effort to better understand migraine mechanisms and deliver effective therapies.

Drugs. 2003;63(16):1637-77.
Management of trigeminal autonomic cephalgias and hemicrania continua.
Matharu MS, Boes CJ, Goadsby PJ.
Headache Group, Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK.
The trigeminal autonomic cephalgias (TACs) are a group of primary headache disorders characterised by unilateral trigeminal distribution pain that occurs in association with ipsilateral cranial autonomic features. This group of headache disorders includes cluster headache, paroxysmal hemicrania and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT syndrome). Although hemicrania continua has previously been classified amongst the TACs, its nosological status remains unclear. Despite their similarities, these disorders differ in their clinical manifestations and response to therapy, thus underpinning the importance of recognising them. We have outlined the clinical manifestations, differential diagnoses, diagnostic workup and the treatment options for each of these syndromes.

Obstet Gynecol. 2003 Oct;102(4):835-42.
Nett R, Landy S, Shackelford S, Richardson MS, Ames M, Lener M.
Texas Headache Associates, San Antonio, Texas, USA.
Pain-free efficacy after treatment with sumatriptan in the mild pain phase of menstrually associated migraine.
To estimate the efficacy of sumatriptan 50-mg and 100-mg tablets in menstrually associated migraine when treatment is administered during the mild pain phase. A randomized, double-blind, placebo-controlled, single-attack study was conducted. Menstrually associated migraine was defined as any migraine beginning on or between day -2 and day 4, with day 1 = first day of flow. Patients had at least a 1-year history of migraine as defined by International Headache Society criteria and reported regularly occurring menstrually associated migraines typically having a mild pain phase. Patients treated attacks within 1 hour of the onset of pain but only if the pain was mild at onset and while the pain was still mild. RESULTS: In the 349 women with menstrually associated migraine, sumatriptan was significantly more effective than placebo: 61% and 51% of patients who used sumatriptan 100 mg and 50 mg, respectively, were pain-free 2 hours after treatment compared with 29% of patients who used placebo (P <.001 for both comparisons). At 2 hours, 51% and 45% of patients who used sumatriptan 100 mg and 50 mg were free of pain and associated symptoms (photophobia, phonophobia, nausea, vomiting) compared with 25% of placebo patients (P <.001 for both comparisons). Adverse events were low for sumatriptan 100 and 50 mg, and both doses were generally well tolerated. Sumatriptan 50-mg and 100-mg tablets are generally well tolerated and effective in providing pain-free relief and relief of the associated symptoms of menstrually associated migraine when administered in the mild pain phase.

Headache. 2003 Apr;43(4):400-3.
Barbanti P, Fabbrini G, Vanacore N, Pesare M, Buzzi MG.
Department of Neurosciences, University La Sapienza, Viale dell'Universita 30, 00185 Rome, Italy.
Sumatriptan in migraine with unilateral cranial autonomic symptoms: an open study.
To investigate the response to sumatriptan in migraineurs with unilateral cranial autonomic symptoms such as lacrimation, eye redness, eyelid edema, nasal congestion, and rhinorrhea. Given the potential large-scale recruitment of peripheral neurovascular 5-HT1B/1D receptors consequent to the activation of the trigeminal autonomic reflex in such patients, the presence of unilateral cranial autonomic symptoms may predict a positive response to sumatriptan. Seventy-two consecutive migraineurs with unilateral cranial autonomic symptoms were given sumatriptan 50-mg tablets to treat 1 migraine attack and were asked to record their clinical response to the drug at different time points. End points were pain-relief and pain-free response at 1 and 2 hours. Pain relief was reported by 47 patients (65.3%) at 1 hour and by 59 (81.9%) at 2 hours. Pain-free response was reported by 22 patients (30.6%) at 1 hour and by 44 (61.1%) at 2 hours. Responsiveness to sumatriptan did not correlate with the type or number of unilateral cranial autonomic symptoms, demographic characteristics, prophylactic treatments, use of contraceptives, or concomitant tension-type headache. Migraineurs with unilateral cranial autonomic symptoms seem to respond to sumatriptan better than other migraineurs. The presence of unilateral cranial autonomic symptoms may predict a positive response to the triptans.

Headache. 2003 Apr;43(4):395-9.
Carpay JA, Linssen WH, Koehler PJ, Arends LR, Tiedink HG.
Department of Neurology, Gooi-Noord Hospital, Blaricum, The Netherlands.
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.

Headache. 2003 Feb;43(2):109-16.
Rahimtoola H, Buurma H, Tijssen CC, Leufkens HG, Egberts AC.
Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, The Netherlands.
Single use of sumatriptan: a patient interview study.
To investigate the possible reasons associated with the use of a single prescription of sumatriptan. A few population-based studies concerning the usage patterns of sumatriptan have revealed a relatively high incidence (approximately 40%) of sumatriptan users who utilize only a single prescription of the drug. Using automated prescription data from 11 community pharmacies, we identified single and multiple sumatriptan prescription recipients. The data were collected from May 1, 1998, to April 30, 2000. Several patient- and medication-related variables possibly associated with single recipiency of sumatriptan were analyzed. In addition, single recipients of sumatriptan were invited for an interview and asked a number of questions related to their clinical status and their experience with the medication. Four hundred ninety-five, first-time users of sumatriptan were identified during the patient selection period, of whom 38% were single recipients of sumatriptan. Of the latter, 102 patients were considered eligible for interview. Reasons for terminating treatment after only 1 prescription included: inefficacy and/or occurrence of side effects, 78% (n=79); uncertain diagnosis of migraine, 39.2% (n=40); and reduction in headache frequency, 33.3% (n=34). Almost half of the population had terminated treatment without having consulted their physician. More than half relied upon the use of over-the-counter (OTC) analgesics after having tried sumatriptan. Compared to multiple users of sumatriptan, single recipients were far less likely to have used another form of migraine treatment prior to (odds ratio, 0.35; [95% confidence interval, 019 to 0.67]) and after (odds ratio, 0.34 [95% confidence interval, 0.19 to 0.63]) initiating sumatriptan. Furthermore, single recipients had demonstrated an increased tendency towards benzodiazepine use prior to receiving sumatriptan (odds ratio, 1.80 [95% confidence interval, 1.00 to 3.28]). Single use of a sumatriptan prescription reveals some issues that may impact negatively the provision of effective migraine management. These include: rapidly developing dissatisfaction with the treatment provided and a lower tendency to seek out medical care. Our results also suggest that the drug may be used (inappropriately) as a diagnostic tool.

J Intern Med. 2003 Feb;253(2):181-8.
Melchart D, Thormaehlen J, Hager S, Liao J, Linde K, Weidenhammer W.
Department of Internal Medicine II, Center for Complementary Medicine Research, Technical University, Munich, Germany.
Acupuncture versus placebo versus sumatriptan for early treatment of migraine attacks: a randomized controlled trial.
To investigate whether acupuncture is superior to placebo and equivalent to sumatriptan for the early treatment of an acute migraine attack. DESIGN: Randomized, partly double-blind (sumatriptan versus placebo) trial. Two hospitals in Germany (one specialized in traditional Chinese medicine and one in the treatment of headache). A total of 179 migraineurs experiencing the first symptoms of a developing migraine attack. Traditional Chinese acupuncture, sumatriptan (6 mg subcutaneously) or placebo injection. Number of patients in whom a full migraine attack (defined as severe migraine headache) within 48 h was prevented. In patients who developed a migraine attack in spite of early treatment, acupuncture and sumatriptan were applied a second time, whilst patients initially randomized to placebo received sumatriptan. A full migraine attack was prevented in 21 of 60 (35%) patients receiving acupuncture, 21 of 58 (36%) patients receiving sumatriptan and 11 of 61 (18%) patients receiving placebo (relative risk of having a full attack 0.79 (95% CI, 0.64-0.99) for acupuncture versus placebo, and 0.78 (95% CI, 0.62-0.98) for sumatriptan versus placebo). Response to the second intervention in patients who developed a full attack was better with sumatriptan (17/31 patients who received sumatriptan twice and 37/46 patients who had had placebo first) than with acupuncture (4/31). The number of patients reporting side-effects was 14 in the acupuncture group, 23 in the sumatriptan group and 10 in the placebo group. In this trial acupuncture and sumatriptan were more effective than a placebo injection in the early treatment of an acute migraine attack. When an attack could not be prevented, sumatriptan was more effective than acupuncture at relieving headache.