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Sumatriptan: pharmacological basis and clinical results.

Sumatriiptan was the first selective serotonin (5-HT)1B/1D agonist for the acute treatment of migraine attacks. Apart from the subcutaneous and oral formulation, it is also available as nasal spray and suppository. In placebo-controlled clinical trials, sumatriptan, administered subcutaneously, orally, intranasally or rectally was significantly more effective than placebo in relieving migraine headache and in producing relief or resolution of other symptoms associated with migraine, including nausea, photophobia and phonophobia. For patients who desire particularly rapid relief that cannot be provided by a tablet form, sumatriptan injection with a 10-minute onset of action may be an appropriate choice. Patients with very severe attacks and those with vomiting may also benefit from the injection. For patients with nausea who do not wish to take tablets or who fear injections, a sumatriptan nasal spray or a suppository may be appropriate options. New triptans, zolmitriptan, rizatriptan, and naratriptan began entering the market in 1997 but in clinical practice, in particular after dose adjustments have been made, all triptans appear to be very similar with respect to efficacy and tolerability as well as safety.

Administration, Inhalation↗

Sumatriptan blocks neurogenic inflammation in the peripheral nerve trunk.

We tested the action of intraperitoneal sumatriptan, a 5-HT1D receptor agonist that aborts migraine headaches, using a model of neurogenic inflammation induced by capsaicin applied to the rat sciatic epineurium. Sumatriptan prevented the development of capsaicin-induced hyperemia without inducing pretreatment vasoconstriction or altering AV shunt flow. The findings indicate that sumatriptan prevents "neurogenic" vasodilation by a mechanism other than vasoconstriction or changes in AV shunt flow.

Animals↗

Cardiac arrest following use of sumatriptan.

I report a 35-year-old woman with occult coronary artery disease who experienced cardiac arrest within minutes after receiving a first-time dose of subcutaneous sumatriptan for migraine. The patient was resuscitated, and subsequent serial cardiac enzymes indicated myocardial infarction. Because sumatriptan can cause coronary artery vasospasm, patients with significant risk factors for coronary artery disease should be carefully evaluated for cardiovascular disease prior to the use of sumatriptan.

Adult↗

The thigh may not be suitable as an injection site for patients self-injecting sumatriptan.

The objective of our study was to evaluate the differences between injection sites in the midthigh and the upper lateral quadrant of the gluteal area regarding the effect, depth of subcutaneous tissue, side effects, and patient preference in patients with cluster headache who self-inject 6 mg (0.5 ml) of sumatriptan. Our open, prospective clinical study was performed at the outpatient department of a Swedish university clinic. There were 19 male and one female subjects, 34 to 68 years old, suffering from cluster headache. We measured the subcutaneous tissue depth by ultrasound. Subjects performed four self-injections of sumatriptan, two in the thigh and two in the gluteal area. We evaluated the subcutaneous tissue depth from the skin surface to the muscle fascia, the effect on headache, side effects, and patient preference regarding the injection site. Subcutaneous tissue depth laterally in the thigh was 2 to 12 mm (median, 4 mm) and in the gluteal area was 34 to 68 mm (median, 45 mm). The needle of the self-injector protrudes 5 to 6 mm. Forty thigh and 39 gluteal injections were recorded. The effect on headache was equal. Following injection in thigh the patients experienced more bleeding (p < 0.001, chi 2); local pain (p < 0.05, chi 2); and a feeling of oppression in the head, neck, and chest area (p < 0.05, chi 2); compared with injections in the gluteal area. Fifteen patients preferred the gluteal area as the injection site after the study, two patients had no preference, and three preferred the thigh. When using the self-injector in the lateral aspect of the thigh, intramuscular injection is liable to occur frequently in male patients. This may explain the differences in local and general side effects observed in this study. The upper lateral quadrant of the gluteal area is a more suitable injection site for male, and some female, patients when using the sumatriptan self-injector.

Adult↗

Economic evaluation of oral sumatriptan compared with oral caffeine/ergotamine for migraine.

We conducted an economic comparison of oral sumatriptan with oral caffeine/ergotamine in the treatment of patients with migraine. Cost-effectiveness, cost-utility and cost-benefit analyses were conducted from societal and health-departmental perspectives. A decision tree was used. Utilities were assigned to health states using the Quality of Well-Being Scale. Simple and probabilistic sensitivity analyses were also carried out. From a societal perspective, using sumatriptan instead of caffeine/ergotamine resulted in an incremental cost-effectiveness ratio of -25 Canadian dollars ($Can) per attack aborted, an incremental cost-utility ratio of -$Can7507 per quality-adjusted life-year (QALY), and a net economic benefit of $Can42 per patient per year (1995 values). From the perspective of the health department, the incremental cost-effectiveness ratio was $Can98 per attack aborted, the incremental cost-utility ratio was $Can29,366 per QALY; the grade of recommendation based on past decisions regarding health technology for adoption into health insurance plans was 'moderate'. Sensitivity analysis showed that the results were robust to relatively large changes in the input variables. The incremental health benefits obtained from using oral sumatriptan rather than oral caffeine/ergotamine were achieved at moderately acceptable incremental costs, if past decisions on the adoption of other health technologies are used as a guide.

Administration, Oral↗

The effectiveness of combined oral lysine acetylsalicylate and metoclopramide (Migpriv) in the treatment of migraine attacks. Comparison with placebo and oral sumatriptan.

In two, double-blind, randomised, clinical, trials (RCTs), oral lysine acetylsalicylate (1620 mg, equivalent to 900 mg aspirin) combined with metoclopramide (10 mg) (LAS + MTC) was compared with placebo, and with oral sumatriptan (100 mg) in one of these RCTs. In both RCTs the LAS + MTC combination was superior to placebo with therapeutic gains (percentage relief after active treatment minus percentage relief after placebo) of 30% and 31% for the first treated attack. These therapeutic gains are in the same range as those found for 100 mg oral sumatriptan, and in the comparative RCT the LAS + MTC combination was quite comparable to 100 mg sumatriptan, with success rates for the first attack of 57% and 53%, respectively.

Anti-Inflammatory Agents, Non-Steroidal↗

[Chest pain due to sumatriptan].

Since the registration of sumatriptan (Imigran) in May 1991, the Netherlands Centre for Monitoring of Adverse Reactions to Drugs received 13 reports of substernal chest tightness or pain attributed to its use. These concerned 11 women and two men with an average age of 41 years, who developed angina-like symptoms mostly within one hour after oral or subcutaneous administration. Electrocardiography (in three patients) and echocardiography (in one patient), performed after resolution of the symptoms, were normal. With the exception of one patient, none had experienced such symptoms before. Although sumatriptan is an effective anti-migrainous drug, cautious use is strongly advised. Sumatriptan is contraindicated in patients with coronary artery disease or variant angina pectoris.

Adult↗

The effect of i.v. sumatriptan, a selective 5-HT1-receptor agonist on central haemodynamics and the coronary circulation.

1. Sumatriptan (GR43175) is a selective 5-HT1-receptor agonist effective in the acute treatment of migraine. Vasoactive properties in other vascular beds have been suggested by recent in vitro studies. 2. Its effects on coronary artery dimensions and central haemodynamics were assessed in 10 patients undergoing diagnostic coronary arteriography using digital subtraction angiography and invasive haemodynamic monitoring. 3. Following a 10 min i.v. infusion of sumatriptan to a total dose of 48 micrograms kg-1 there was a significant increase (P < 0.05) in systemic and pulmonary arterial pressures. There was a significant reduction in coronary artery diameter from 4.3 +/- 1.6 mm to 3.6 +/- 1.6 mm 12.9 +/- 6.9% (P < 0.001). There was no significant change in heart rate or ECG morphology. 4. Sumatriptan, a 5-HT1-receptor agonist, causes a vasopressor response in the systemic and pulmonary arterial circulations and coronary artery vasoconstriction; in this study there were no clinical sequelae.

Adolescent↗

[Sumatriptan--future development, alternative features and potential new indications].

Sumatriptan is a highly selective 5 HT1 receptor subtype agonist. The efficacy and safety profiles of sumatriptan given by tablet or subcutaneous injection have been extensively investigated in the acute treatment of migraine attacks, where it has proved effective and well tolerated. A substantial proportion of patients with an acute attack of migraine suffer from once or more gastrointestinal symptom, including nausea, vomiting and occasionally diarrhoea. The presence of these symptoms may make the oral administration of acute treatments unsatisfactory. Subcutaneous administration is an alternative, but fear or dislike of injections or an inability to self inject makes subcutaneous treatment unacceptable to some patients. Alternative routes of administration are being investigated to overcome these difficulties including intranasal sprays and rectal suppositories. For those patients who experience difficulties swallowing whole tablets, an effervescent tablet is under development. Recent data have demonstrated that sumatriptan offers effective relief of cluster headache attacks, a condition where suffers experience repeated severe headache attacks, of short duration, during a cluster period. Further new indications are being investigated including the treatment of menstrual migraine, paediatric migraine and other headaches.

Administration, Oral↗

[Subcutaneous sumatriptan in the treatment of migraine attacks. An analysis of its long term efficaciousness and tolerance].

We present the results of treatment with subcutaneous sumatriptan in migraine attacks. The study comprised forty-two patients suffering from migraine both with and without aura, with migraine attacks not susceptible to analgesics, non-steroid anti-inflammatory drugs (NSAID), ergotics or else intolerance to the same. Two groups were independently analyzed, one consisting of ten patients who had menstrual migraine continually for twelve months, the other consisting of thirty-two patients suffering from migraine with and without aura for six months. We assessed the effectiveness of the drug (reduction in the intensity and duration of the attack, action, speed, recurrence) and tolerance (adverse effects). The effectiveness of sumatriptan in relieving headache was 75.9% (80% in the case of the menstrual migraine group and 71.8% in the case of the migraine with and without aura group). This effectiveness was maintained in a similar fashion by analyzing independently the first and last months of treatment. Adverse effects were noted in 38.7% of patients treated (40% for the menstrual migraine group, 37.5% for those with migraine with and without aura). The most frequent effects were pain at the point of injection, a feeling of general tiredness, nausea and a sensation of tension in the neck or chest. These effects were largely slight and short lived. No serious adverse effects were reported. A long term analysis carried out on the menstrual migraine group shows the efficacy of sumatriptan is kept up, with improved tolerance of the drug and a decrease in the number of negative side effects noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Is the unresponsiveness to sumatriptan in cluster headache related to an alteration in the 5-HT receptors?

It is well established that cluster headache shows impaired functions at the neuroimmunomodulatory system level. Defects in the expression of receptors for 5-HT, IL-1 and IL-2 have been found in these patients. Sumatriptan, an agonist activity for 5-HT1D receptor, truncates cluster headache attack in 74% of patients. Flow cytometric analysis of monocytes expressing 5-HT receptor in cluster headache patients showed different trends clearly correlated with the clinical response to sumatriptan. Our findings strongly support the concept that cluster headache patients which are non-responders to sumatriptan could present a block in their 5-HT receptor expression possibly due to specific autoantibodies for this receptor site.

Adult↗

Efficacy and tolerability of oral sumatriptan in the treatment of acute migraine.

An open prospective study of the efficacy and tolerability of oral sumatriptan in the treatment of acute migraine attacks at the Kenyatta National Hospital, Nairobi, Kenya, is presented. Thirty two patients were initially recruited and 24 completed the trial giving a drop-out rate of 25%. The age range was 17 to 55 years with a mean of 35 years. Sumatriptan was found to be effective in 22 (92%) out of 24 patients. Side effects occurred in 38% (9/24) patients. These were mild and transient and included nausea, vomiting, numbness of limbs, fever and a feeling of heat in the head. It is concluded that oral sumatriptan is an effective drug in the treatment of acute migraine headaches. It has few side effects and is well tolerated by majority of patients.

Acute Disease↗

[Coronary vasospasm secondary to subcutaneous administration of sumatriptan].

We present the case of a 38-year-old woman with no previous history of coronary heart diseases, who suffered from cluster headaches and had undergone a subcutaneous sumatriptan treatment for two years. With no previous history of underlying ischaemic heart diseases or Prinzmetal's angina or any other significant coronary diseases supported by an angiographic exam, the patient suffered from an episode of coronary vasospasm following a subcutaneous administration of sumatriptan. Therefore particular care should be placed when subcutaneous sumatriptan is administered to patients who experienced chest pain or other related symptoms after the use of the drug.

Adult↗

[Use of sumatriptan (Imigran) in a female patient with coronary spasm].

Sumatriptan (Imigran), an effective drug against symptoms of migraine may cause a sensation of thoracic oppression. In some patients, this is accompanied by ECG alterations. In such cases, the underlying mechanism is probably coronary spasm, although this has never been demonstrated angiographically. The case is described of a young woman who was hospitalized after resuscitation because of ventricular fibrillation. One week previously, after subcutaneous administration of sumatriptan, she had had chest pains for half an hour. A spasm provocation test during coronary angiography gave a positive result. The patient was treated with a calcium antagonist following which she remained free of symptoms. In patients with chest pain after administration of sumatriptan, it is necessary to use this drug cautiously; spasm of the coronary arteries as a cause should be excluded.

Adult↗

[Sumatriptan in the treatment of migraine in general practice].

Approximately 5% of the adult Norwegian population suffer from migraine. Sumatriptan is a new anti-migraine drug which has been shown in clinical studies to be efficacious in up to 80% of attacks treated. These early clinical studies have all been carried out at specialist centres and the present study was planned to see if migraine patients treated by general practitioners would also benefit from this new therapy. This placebo controlled, randomized, double blind study was carried out by 50 general practitioners and two neurologists, and included 294 patients. A total of 1,485 migraine attacks were treated. The results show that Sumatriptan is equally efficacious and well tolerated when used to treat patients in general practice as at specialist clinics. Sumatriptan was efficacious in relieving pain and other migraine symptoms in 76% of the migraine attacks treated, while placebo had the desired effect in 29% of attacks.

Adolescent↗

[Therapy of migraine with special reference to sumatriptan].

A migraine attack results from an inflammatory process of intracranial blood vessels with secondly vasodilation. Sumatriptan activates vascular 5-HT1-receptors to constrict the affected vessels (12, 14) and clinical studies have shown, that it is highly effective in the treatment of migraine and cluster headache. Results from controlled, double-blind studies are discussed, comparing sumatriptan with placebo or standard treatment. Over all it produced faster and greater relief of migraine or cluster headache and was well-tolerated. Advising patients of the risk of side-effects is necessary; it is a safe treatment. Sumatriptan 100 mg tablets or 6 mg in pre-filled syringes for use with autoinjector are available, intranasal administration still needs testing.

Cluster Headache↗

[Treatment of migraine attacks with sumatriptan].

The serotonin agonist, sumatriptan, is a new, highly promising alternative treatment for migraine that has a vasoconstricting effect on the blood vessels dilated during an attack. In addition, sumatriptan inhibits the neurogen-mediated sterile inflammation associated with migraine. Its effects, pharmacological properties and side effects are discussed and considered in relation to its high price. The subcutaneous form of sumatriptan is indicated for use in attacks accompanied by initial violent vomiting, and the oral form for attacks in which standardised medication elicits either no response or side effects, as also to treat migraine that regularly renders the sufferer unable to work. When attacks are a frequent occurrence, migraine prophylaxis should first be initiated. The significance of cardiovascular side effects is interpreted, and hints provided on instructing the patient in the use of this drug.

Administration, Oral↗

The use of sumatriptan in the treatment of migraine.

Sumatriptan is a selective agonist of 5-hydroxytryptamine receptors, recommended for the acute treatment of migraine. The 5-HT1 receptor subtype is found in the cranial vasculature of many species including humans, and causes vasoconstriction of these vessels. Sumatriptan as a highly potent 5-HT1 agonist selectively constricts large intracranial blood vessels and also blocks neurogenic inflammation. Those treating patients with severe or inconveniently timed attacks will find sumatriptan the drug of choice.

Humans↗