Sumatriptan is used orally, by subcutaneous injection, or intranasally for the acute management of attacks of migraine with aura (also called classic migraine) or migraine without aura (also called common migraine) and by subcutaneous injection for the acute management of cluster headache episodes. Sumatriptan should be used only in patients in whom a clear diagnosis of migraine or cluster headache has been established. The manufacturers and some clinicians state that the drug is not to be used for the management of hemiplegic or basilar migraine or for prophylaxis of migraine or cluster headache. In patients with a history of migraine or cluster headache who present with atypical symptoms (e.g., ataxia, vertigo, tinnitus, mental status changes, visual field cuts/ blindness, paresthesia, hemiparesis), care should be taken to exclude other potentially serious neurologic conditions (e.g., cerebrovascular accident, subarachnoid hemorrhage) before initiation of sumatriptan therapy.
(See Cautions: Precautions and Contraindications.)
General Principles in Migraine Therapy
Drug therapy in the management of migraine headache must be individualized and adjusted based on the severity and frequency of attacks, response to therapy (single or multiple drugs), and tolerance to drug-induced adverse effects. Important considerations in the choice of drug therapy include the wide range in severity of the attacks, considerable interindividual variation in response and tolerance, toxic potentials of the drugs, presence of concomitant illness (e.g., cardiovascular disease, uncontrolled hypertension) or pregnancy, potential tolerance to the therapeutic effects of the drugs, the potential for abuse and misuse of the drugs, and cost. Decisions regarding drug therapy in the management of migraine headache should be weighed carefully (e.g., do the headaches threaten to disrupt the patient's normal functioning), particularly when potentially toxic, habituating, and/or potent drugs are considered. Although the benefit of therapy may principally be pain relief, the long-term goals of therapy are to prevent or reduce the frequency and severity of attacks, reduce the disability associated with migraine headaches, improve quality of life, avoid escalation of antimigraine drug therapy, and educate and enable patients to manage their illness. Management also should include appropriate nondrug therapy such as lifestyle modification, avoidance of precipitating factors, and behavioral and/or psychologic therapy. Although the pathogenesis of migraine headache has not been fully elucidated
(see Pharmacology), it is known that avoidance of certain triggering factors such as alcohol (e.g., red wine), certain foods or food additives (e.g., chocolate, certain cheeses, monosodium glutamate, nitrates), irregular eating habits, irregular sleep, and acute changes in stress level as well as proper management of other factors such as travel across time zones, high-altitude barometric pressure changes, and association with the menstrual cycle may be useful in the management of migraine attacks. The possible presence of other types of headaches (e.g., tension-type, cluster) should be evaluated.
Although migraine headache is common (about 15-18% of women and 6% of men in the general population suffer migraine attacks), the condition is underrecognized and undertreated probably because of the lack of biologic markers to confirm the diagnosis. About two-thirds of patients with migraine headache experience infrequent attacks (e.g., 1 or 2 per year), with the remainder experiencing one or more migraine attacks each month. Over 80% of migraine sufferers experience some degree of headache-associated disability. For a diagnosis of migraine without aura (also called common migraine) or with aura (also called classic migraine), the criteria established by the International Headache Society (IHS) usually are used. According to IHS, migraine without aura is an idiopathic, recurring headache disorder manifested by untreated or unsuccessfully treated attacks lasting 4-72 hours and characterized by unilateral, pulsating headache of moderate to severe intensity that may disrupt routine physical activity and is associated with nausea, vomiting, photophobia, and/or phonophobia and worsens with movement; some experts also consider osmophobia a diagnostic criterion. Migraine with aura is characterized by the same manifestations as migraine without aura, but it also is accompanied before or during the attack by neurologic manifestations (e.g., visual disturbance) indicating focal cerebral cortical and/or brain stem dysfunction.
Because patients may experience a wide spectrum of severity in migraine attacks with variable effects on functioning, multiple appropriate therapies for attacks of differing severity generally are made available to the patient. The goals of acute migraine therapy are as follows: provide rapid and consistent relief of migraine attacks without recurrence; restore the patient's ability to function; minimize the use of back-up and rescue medications (i.e., drugs used at home when other therapies fail); optimize self-care and reduce subsequent use of medical resources; be cost-effective for overall management; and relieve the headache while minimizing or avoiding adverse effects of therapy. To meet these goals, some experts recommend use of selective 5-HT1 receptor agonists, dihydroergotamine, or ergotamine in patients with moderate or severe migraine or in those with mild to moderate headaches that respond poorly to nonsteroidal anti-inflammatory agents (NSAIAs) or fixed-combination analgesics such as those containing aspirin, acetaminophen, and caffeine. Failure to promptly use an effective treatment may increase pain, disability, and the impact of the headache. Patients should be advised, however, that excessive use of some of these drugs (e.g., ergotamine [but not dihydroergotamine], opiates, selective 5-HT1 analgesics [including fixed combinations containing butalbital, caffeine, or isometheptene]) may cause rebound headache. Medical attention (including hospitalization) may be necessary for detoxification from drug overuse or abuse. Because nausea is one of the most aversive and disabling symptoms of migraine attacks, selection of nonoral routes of administration and/or use of antiemetics is recommended in patients in whom nausea and/or vomiting are prominent early symptoms of migraine attacks. Antiemetics should not be restricted to patients who are vomiting or likely to vomit. In some patients, concomitant therapy with an antiemetic and an oral antimigraine drug may be appropriate. In addition, some experts state that IV metoclopramide may be considered as monotherapy for relief of migraine pain.
Some clinicians recommend that mild migraine headache (patient's normal activities are minimally disrupted; headache usually lasts for 4-8 hours and may be accompanied by nausea) be treated with an NSAIA (e.g., aspirin, ibuprofen, indomethacin, naproxen sodium) or combined acetaminophen, aspirin, and caffeine. In addition to these analgesics, an antiemetic (e.g., dimenhydrinate, metoclopramide, prochlorperazine), mild vasoconstrictor (e.g., isometheptene), or sedative-hypnotic may be beneficial.
For the management of moderate migraine headache (patient's normal activities are moderately disrupted; headache may last for more than 4 hours and up to about 24 hours and may be accompanied by nausea and vomiting), many clinicians recommend an oral NSAIA either given alone or in fixed combination with acetaminophen, an opiate analgesic (e.g., codeine), a barbiturate (e.g., butalbital), and/or caffeine. However, because of the risk of dependency and misuse or abuse, some clinicians recommend that use of opiate analgesics and barbiturates be reserved for patients with infrequent migraine headaches, for those who do not respond to other drugs, and when the sedative effects of the drugs will not put the patient at risk and the abuse potential has been addressed. In addition, many clinicians state that moderate migraine headache can be treated with a 5-HT1 selective (e.g., almotriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan [given orally, subcutaneously, or intranasally], zolmitriptan) or nonselective (e.g., dihydroergotamine [given parenterally or intranasally], or possibly ergotamine [given alone or in fixed combination with caffeine and/or a barbiturate]) receptor agonist. Parenteral dihydroergotamine or 5-HT1 selective receptor agonists are particularly useful in patients with rapid onset of migraine, and parenteral and intranasal preparations of these drugs may be particularly useful in those unable to take oral drugs because of severe nausea and/or vomiting. Many moderate headaches may respond to an NSAIA alone; combinations of an NSAIA or acetaminophen with an opiate or barbiturate may be useful for attacks not responding to initial therapy or if vasoconstrictors are not tolerated. Although the role of ergotamine has been questioned (e.g., because of toxicity profile [including severe nausea and vomiting], rebound effect), some patients continue to find the drug useful, particularly when combined with an antiemetic.
For the initial management of severe migraine headache (patient's normal activities are severely disrupted; headache generally lasts for longer than 12 hours and usually is accompanied by nausea, and vomiting occasionally may occur), many clinicians recommend dihydroergotamine (given parenterally or intranasally) or a 5-HT1 selective receptor agonist, including almotriptan (given orally), frovatriptan (given orally), naratriptan (given orally), rizatriptan (given orally), zolmitriptan (given orally), or sumatriptan (given orally, subcutaneously, or intranasally). Alternatively, a phenothiazine (e.g., chlorpromazine given IM, IV, or rectally) may be used; if pain is not relieved, a parenteral NSAIA (e.g., ketorolac given IM) or a corticosteroid (e.g., dexamethasone given IV) may be considered.Self-administration of rescue medications (e.g., butorphanol nasal solution, parenteral opiates) in a home setting also should be considered for patients with severe migraine attacks that do not respond adequately to other treatments once the drugs' abuse potential has been addressed. Although rescue medications often do not completely eliminate pain and return patients to normal functioning, they permit the patient to achieve relief without the discomfort and expense of an office or emergency department visit.
For the management of ultra-severe migraine attacks, including status migrainosus (patient's normal activities are severely disrupted for more than 72 hours) that are accompanied by vomiting, it is recommended that patients be rehydrated initially, which should be followed by administration of dihydroergotamine (given IV every 8 hours for 24 hours), and each dose should be preceded by a dose of metoclopramide to prevent nausea. Some clinicians state, however, that IV dihydroergotamine should be reserved for patients who do not respond to any other drug therapy, including 5-HT1 selective receptor agonists. Alternatively, for ultra-severe migraine attacks, an IV phenothiazine (e.g., chlorpromazine, prochlorperazine) may be given alone or in combination with a parenteral corticosteroid (e.g., dexamethasone, methylprednisolone) and/or an opiate agonist (e.g., meperidine). Parenteral opiate-agonist therapy generally is considered a last resort because of the risks of dependence, tolerance, and associated adverse effects.
Prophylaxis of Chronic Attacks
Previously accepted recommendations for prophylaxis of chronic migraine attacks principally focused on patients who had 2 or more attacks per month. Such recommendations have been described by some experts as being arbitrary and as failing to account for individual patient needs or other migraine characteristics. Therefore, prophylactic therapy currently can be considered in patients with recurring migraine attacks when, in the opinion of the patient and despite acute therapy, the attacks substantially interfere with daily routines; in patients in whom the frequency of migraine attacks and resultant reliance on acute therapy would increase the potential for drug-induced (rebound) headache; in patients in whom acute therapy is ineffective, contraindicated, or not tolerated; in patients who prefer prophylactic therapy; and in those with uncommon migraine conditions, including hemiplegic migraine, basilar migraine, migraine with prolonged aura, or migrainous infarction (to prevent neurologic damage). The goals of prophylactic therapy are to decrease the frequency, severity, and duration of migraine attacks and the disability associated with such attacks; improve responsiveness of acute attacks to therapy; and improve patient functioning. For prevention of migraine headache, a β-adrenergic blocking agent (e.g., atenolol, metoprolol, nadolol, propranolol, timolol), calcium-channel blocking agent (e.g., verapamil), tricyclic antidepressant (e.g., amitriptyline), anticonvulsant (e.g., valproate sodium), high-dose riboflavin (e.g., 400 mg daily), or NSAIA (e.g., naproxen sodium) may be used. However, analysis of clinical studies in which these agents were used for prophylaxis of chronic migraine attacks has shown that efficacy and safety of individual agents, even within the same class of drugs, may exhibit substantial interpatient variation.
Although most studies of drugs used for prophylaxis of migraine attacks are limited by poor study design and/or interpretation of study findings, analysis of these studies by the US Headache Consortium suggests that drugs with medium to high efficacy, good strength of evidence, and mild to moderate adverse effects include amitriptyline, divalproex sodium, propranolol, and timolol. Comparative studies have demonstrated few clinically important differences in efficacy among these agents. Agents with lower efficacy or limited strength of clinical evidence, and mild to moderate adverse effects include aspirin (alone), atenolol, fenoprofen, flurbiprofen, fluoxetine, gabapentin, guanfacine, ketoprofen, magnesium, mefenamic acid, metoprolol, nadolol, naproxen/naproxen sodium, nimodipine, riboflavin, and verapamil. While clinical efficacy has not been established in controlled studies for bupropion, cyproheptadine, diltiazem, doxepin, fluvoxamine, ibuprofen, imipramine, mirtazepine, nortriptyline, paroxetine, protriptyline, sertraline, tiagabine, topiramate, trazodone, or venlafaxine, experts consider these agents efficacious based on consensus and clinical experience. Experts consider phenelzine to be efficacious based on consensus and clinical experience, but the drug has adverse effects that are of concern to some experts. Similarly, methysergide (no longer commercially available in the US) has medium to high efficacy for prophylaxis of migraine attacks, but its usefulness is limited by reports of retroperitoneal and retropleural fibrosis associated with long-term (principally uninterrupted) therapy. Evidence from clinical studies indicate that efficacy of agents such as acebutolol, carbamazepine, clomipramine, clonazepam, clonidine, indomethacin, lamotrigine, nabumetone, nicardipine, nifedipine, and pindolol is comparable to that of placebo for prophylaxis of migraine attacks in patients with chronic migraine.
Experts from the US Headache Consortium currently recommend that the choice of an initial agent for prophylaxis of migraine attacks be individualized, taking into account concomitant illness (e.g., stroke, myocardial infarction, Raynaud's syndrome, seizure disorder, affective or anxiety disorders). Such experts recommend use of drugs that are effective for both the concomitant illness and migraine prophylaxis whenever possible.
Some clinicians recommend that drug therapy for migraine prophylaxis be initiated as monotherapy at a low dosage and then titrated upward as tolerated to a maximum effective dosage; such therapy should be given for several months and then withdrawn slowly to prevent rebound headaches. If initial drug therapy is not effective, a combination of drugs may be used.
Selection of an agent for prophylaxis of migraine attacks in women who are or may become pregnant should take into account the teratogenic potential of such agents. If drug therapy for migraine prophylaxis is absolutely necessary, some experts state that the prophylactic agent with the lowest risk of adverse effects to the fetus should be used.
Use of Sumatriptan in Migraine
Sumatriptan provides rapid relief of migraine headache and generally is well tolerated when appropriate precautions regarding patient selection are employed.
(See Cautions: Precautions and Contraindications.)The drug also relieves manifestations of migraine other than headache (including nausea, vomiting, photophobia, and phonophobia), decreases the need for supplemental analgesic therapy, and improves functional ability. Few comparative studies evaluating the efficacy and safety of sumatriptan relative to other antimigraine therapies have been performed to date. However, available evidence suggests that sumatriptan is at least as effective as current therapies for migraine (e.g., ergot alkaloids, oral analgesics) and generally provides more rapid headache relief and return to normal functioning than these therapies but may be associated more frequently with headache recurrence. Although cost considerations and concerns about the potential for headache recurrence may favor the use of other antimigraine agents (e.g., dihydroergotamine) over subcutaneous sumatriptan, effective self-management of migraine through patient self-administration of sumatriptan may be cost-effective if associated with a reduced need for hospital visits. While clinical studies directly comparing subcutaneous versus oral therapy with sumatriptan in patients with migraine have not been performed, response to oral sumatriptan therapy occurs later and generally is somewhat less than that with subcutaneous therapy. Therefore, subcutaneous therapy with the drug may be particularly advantageous in patients with severe migraine headache in whom the most rapid onset of action is desirable and/or in those who have appreciable nausea and vomiting associated with migraine; oral sumatriptan therapy should be less costly and may be useful in patients who are unable to tolerate subcutaneous sumatriptan, unwilling or unable to self-administer the injection, or who have relatively less severe migraine symptoms.
The efficacy of sumatriptan in alleviating established migraine attacks does not appear to be influenced by type of migraine (i.e., with or without aura), duration of the attack, timing of the attack (e.g., early morning, menstruation-associated), concomitant use of non-ergot-alkaloid drugs for migraine prophylaxis (e.g., β-blockers, calcium-channel blockers, tricyclic antidepressants), or by patient gender or age. Unlike other antimigraine drugs (e.g., ergotamine), sumatriptan has been effective even when given late in the attack. However, subsequent doses of sumatriptan in patients not responding adequately to an initial dose generally have not provided additional benefit.
Most controlled clinical studies of sumatriptan therapy involved patients who had migraine with aura or migraine without aura as defined by criteria established by the Headache Classification Committee of the International Headache Society (IHS). However, while a clear diagnosis of migraine is recommended before initiation of sumatriptan therapy, some evidence suggests that response to sumatriptan may be similar in patients not meeting strict IHS criteria for migraine. The efficacy of therapy for migraine in controlled studies generally was evaluated in terms of a reduction in headache severity as rated by the patient (i.e., a reduction in pain from severe or moderately severe to mild or absent using a 4-point scale). In placebo-controlled clinical studies, approximately 70-88% of patients receiving a single 6-mg subcutaneous dose of sumatriptan attained relief of migraine headache within 1-2 hours compared with 18-39% of placebo recipients; at 2 hours, 48-65% of sumatriptan-treated patients were pain free. Relief of migraine headache generally begins as early as 10 minutes following subcutaneous administration of sumatriptan and is maximal at 2 hours. Smaller doses (less than 6 mg) of sumatriptan also may be effective in relieving migraine, although the proportion of patients obtaining adequate relief is reduced and the time to obtain relief is greater. Subcutaneous doses exceeding 6 mg (e.g., 8 mg) do not appear to provide additional therapeutic benefit and are associated with a greater incidence of adverse effects.
Onset of relief of migraine symptoms with oral sumatriptan therapy is slower than that with subcutaneous administration of the drug, generally occurring 0.5-3 hours after single oral doses of 25-100 mg; maximum pain relief is attained within 3-6 hours. In clinical trials, 50-73% of patients receiving sumatriptan in single oral doses of 25-300 mg obtained relief of headache pain (defined as no pain or only mild pain) within 2 hours compared with 10-33% of patients receiving placebo; 65-78% of patients receiving sumatriptan reported relief of pain at 4 hours. The proportion of patients obtaining relief from single oral doses of sumatriptan appears to be greater with doses of 50 or 100 mg than with 25 mg; however, doses of 100 mg do not appear to provide greater benefit than doses of 50 mg.
In 2 controlled clinical studies in adults with moderate to severe migraine headache, efficacy of a single oral dose of sumatriptan 85 mg given in fixed combination with naproxen sodium 500 mg was compared with that of placebo and of each drug given in the same dosage as monotherapy. In these studies, a greater proportion of patients receiving combined therapy with sumatriptan and naproxen (57-65%) obtained relief of headache pain (defined as mild or no pain) within 2 hours of treatment compared with those receiving sumatriptan alone (50-55%) or placebo (28-29%). In addition, a greater proportion of patients receiving sumatriptan and naproxen (23-25%) remained free of headache pain without the use of rescue therapy through 24 hours after treatment compared with those receiving sumatriptan or naproxen monotherapy (14-16 or 10%, respectively) or placebo (7-8%). Combined therapy with sumatriptan and naproxen also relieved manifestations of migraine other than headache (including nausea, photophobia, and phonophobia).
Since migraine is a chronic, recurrent condition, successful therapy may require long-term, intermittent use of sumatriptan. In several controlled studies of 6-24 months' duration in patients with migraine, intermittent sumatriptan has remained effective throughout subsequent attacks. Among patients receiving oral sumatriptan during 9 migraine attacks, approximately 14% of patients responded during all 9 migraine episodes, 24% responded during 8 of 9 attacks, and 62% responded during 7 of 9 attacks. Among patients in a controlled study who were treated for 4 migraine attacks (3 with subcutaneous sumatriptan and one with placebo), 73% of patients responded to therapy during all 3 sumatriptan-treated attacks, 89% responded in at least 2 of 3 such attacks, and 93% responded in at least 1 of 3 such attacks; only 7% of patients receiving sumatriptan therapy did not respond at all. Data from long-term (1 year) uncontrolled studies suggest that oral sumatriptan was effective in 82-86% of patients and in 55% of all attacks treated. Patients who received subcutaneous or oral sumatriptan treated a median of 18 and 22 attacks per year, respectively, and used a mean of 1.4 injections or 1.9 tablets per attack. The mean number of doses used was similar in patients with frequent (more than 30) and infrequent (less than 10) attacks.
Data from comparative trials suggest that sumatriptan is at least as effective as current antimigraine therapies (e.g., ergot alkaloids, oral analgesics) and generally provides more rapid headache relief than these therapies. In a double-blind, controlled study in patients with migraine, subcutaneous therapy with sumatriptan was associated with headache relief and improvement in functional ability in a greater proportion of patients than was dihydroergotamine at 1 hour (78 versus 57%, respectively) and 2 hours (85 versus 73%, respectively) following the dose; headache relief and functional ability at 3 and 4 hours were similar with both drugs. However, the rate of headache recurrence within 24 hours after treatment was approximately 2.5 times as great with sumatriptan as with dihydroergotamine (45 versus 18%, respectively). In another placebo-controlled, comparative study, 66% of patients receiving oral sumatriptan (100 mg) obtained pain relief (reduction in headache intensity from severe or moderate to mild or none) at 2 hours compared with 48% of patients receiving the combination of ergotamine tartrate 2 mg and caffeine 200 mg (Cafergot). The onset of headache relief was more rapid with sumatriptan therapy, although more patients reported recurrence of migraine within 48 hours with sumatriptan; the incidence of adverse effects with both therapies was similar. In another controlled study in patients who treated up to 3 migraine attacks during a 3-month period either with oral sumatriptan (100 mg) or with oral aspirin (900 mg) and metoclopramide hydrochloride (10 mg), the proportion of patients who had pain relief at 2 hours during the initial attack (the primary end point) with sumatriptan versus aspirin and metoclopramide was similar (56 versus 45%, respectively), although sumatriptan was more effective than aspirin and metoclopramide during attack 2 (58 versus 36%, respectively, of patients with pain relief) and attack 3 (65 versus 34%, respectively, of patients with pain relief). In addition, sumatriptan therapy was associated with a reduced need for supplemental analgesics and greater incidence of improvement in functional ability than aspirin and metoclopramide therapy. Relief of nausea, vomiting, photophobia, and phonophobia was similar for both therapies, while the incidence of adverse effects, which usually were mild to moderate in intensity and transient, was higher with sumatriptan.
Recurrence of migraine within 24 hours after successful treatment of the initial migraine attack occurs in up to about 60% or up to about 40% of patients receiving initial therapy with subcutaneous or oral sumatriptan, respectively. The high rate of recurrent migraine with sumatriptan may be related to the short half-life of sumatriptan or the reversibility of the drug's binding to 5-HT receptors; however, in some cases, apparent repeat attacks of migraine may have been the result of breakthrough of the suppressed but ongoing original attack. Recurrent migraine has been characterized as resolution followed by return of headache within the typical 4-72 hours of a migraine attack without recurrence of aura or other premigraine symptoms. Recurrence of migraine appears to be more common with sumatriptan therapy than with ergotamine, dihydroergotamine, combined therapy with aspirin and metoclopramide, or placebo. The median time to headache recurrence has been reported to be approximately 9-13 hours in patients receiving sumatriptan subcutaneously and 14-24 hours in patients receiving the oral drug. Data from a limited number of controlled studies and clinical experience in patients treated for 3-12 episodes of migraine with oral or subcutaneous sumatriptan indicate that the incidence of migraine recurrence decreases as the number of successfully treated migraine attacks increases. An additional dose of oral sumatriptan appears to be more effective than placebo in treating recurrent migraine after successful treatment of the initial attack; 65-81% of patients receiving oral sumatriptan (100 mg) for the treatment of a recurrent headache following initial use of oral or subcutaneous sumatriptan experience relief of headache pain. However, the benefit or safety of administering a second dose of subcutaneous or oral sumatriptan in patients who have not responded to an initial dose has not been demonstrated conclusively in controlled studies.
While most patients with migraine respond to initial subcutaneous or oral doses of sumatriptan, some patients do not experience relief; exacerbation of migraine has been reported in a few patients. Although administration of a second subcutaneous dose of sumatriptan generally does not provide relief of ongoing migraine headache in patients not responding to an initial subcutaneous dose for that attack, data from several studies in which multiple doses of subcutaneous or oral sumatriptan were administered over several episodes of migraine indicate that patients who fail to respond to therapy for one episode may respond to sumatriptan during subsequent episodes; only 5-7% of patients are consistent nonresponders.
Data from several long-term (1-2 year) studies suggest that subcutaneous or oral therapy with sumatriptan does not alter the frequency of migraine attacks. However, some case reports and data from uncontrolled and/or postmarketing surveillance studies indicate an increased frequency of initial or recurrent migraine attacks in some patients taking sumatriptan. In some patients with a history of frequent migraines or dependence on other antimigraine drugs, such as analgesics or ergot-alkaloid-containing compounds, this increased frequency of migraine attacks has been associated with inappropriate use/misuse of the drug.
(See Cautions: Precautions and Contraindications.)The contribution of sumatriptan to the increased frequency of migraine headaches in such patients has not been established.
Intranasal administration of sumatriptan is more effective than placebo in relieving migraine headache. In double-blind, controlled studies in patients with migraine, headache relief (defined as reduction in pain from moderate or severe to mild or none) at 2 hours following the dose occurred in approximately 55-75% of patients receiving intranasal sumatriptan (20 mg) versus about 25-36% of those receiving placebo; associated nausea, vomiting, photophobia, and functional disability also were improved in sumatriptan-treated patients. Smaller doses (5 or 10 mg) also may be effective, although in several studies the proportion of patients obtaining relief was reduced. Although sumatriptan has been given IV in patients with acute migraine attacks, this route of administration has been associated with a high incidence of adverse effects (probably because of the rapid increase in plasma drug concentrations associated with such administration); the manufacturers and most clinicians state that the drug should not be given IV.
(See Cautions: Precautions and Contraindications.)
The manufacturers state that sumatriptan is not to be used for prophylaxis of migraine headache, and prophylactic use of the drug following successful treatment of an initial attack has produced equivocal results. In one study, routine addition of a second oral dose of sumatriptan (100 mg) 2 hours after successful treatment of the initial migraine episode did not influence the frequency or time to recurrence of subsequent attacks. However, in another study, routine administration of a single oral dose of sumatriptan (100 mg) 4 hours after successful treatment with a subcutaneous dose of the drug (6 mg) delayed recurrence of the migraine attack.
Sumatriptan also is used subcutaneously for the acute management of cluster headache episodes; oral therapy with sumatriptan is unlikely to be beneficial because of its slower onset of action and is not indicated in the management of cluster headache. Cluster headache occurs principally in older men and is characterized by brief, unilateral, extremely intense headaches occurring up to 8 times daily and generally accompanied by ipsilateral manifestations of autonomic dysfunction, such as lacrimation, conjunctival injection, and rhinorrhea. Management of cluster headaches is difficult since the onset of action of many therapies often is delayed beyond the duration of the attack. Inhalation of 100% oxygen, rectal or sublingual ergotamine, or parenteral dihydroergotamine typically has been used effectively to treat cluster headache; intranasal administration of lidocaine, cocaine, or capsaicin also has been used with some success in treating acute attacks. Oral agents (e.g., ergot alkaloids, analgesics, oral sumatriptan) generally have not been effective in treating these brief headaches, as the onset of action of these drugs is too slow.
While comparative studies with oxygen and/or oral analgesic therapy have not been performed, subcutaneous sumatriptan may be particularly useful in patients with cluster headache because of its ease of administration compared with oxygen and its rapid onset of action compared with oral analgesics. In 2 placebo-controlled studies in which patients were treated for up to 3 consecutive cluster headache attacks, headache improvement (as indicated by a reduction in headache pain to mild or no pain) occurred within 15 minutes in about 75% of patients receiving subcutaneous sumatriptan (6 mg) compared with 26-35% of patients receiving placebo. Amelioration of autonomic manifestations associated with cluster headache, such as nasal congestion, rhinorrhea, lacrimation, miosis, ptosis, photophobia, and periorbital edema, also has been reported with subcutaneous sumatriptan therapy. In the 2 placebo-controlled studies, conjunctival injection persisted in 36-38 or 60-74% of patients 15 minutes after receiving subcutaneous sumatriptan or placebo, respectively. Approximately 14% of patients receiving subcutaneous sumatriptan and 38-49% of patients receiving placebo in these studies required supplemental therapy with oxygen 15 minutes after administration of the study drug. Use of higher subcutaneous doses of sumatriptan (12 mg) does not appear to increase the response rate in patients with cluster headache; in fact, lower subcutaneous doses (e.g., 3 mg) reportedly may be effective in the management of acute cluster headache episodes.
Although an increased frequency of cluster headache attacks has been reported in some patients receiving sumatriptan in uncontrolled studies, such increases in attack frequency generally have been transient (lasting up to a few weeks) and may have been related in part to withdrawal of prophylactic antimigraine medication prior to initiation of sumatriptan therapy. Limited data based on long-term (e.g., up to 3 months) experience with the drug in patients with cluster headache suggest that tolerance to the effects of sumatriptan does not develop with such use; at least one patient used a total of 480 injections (6 mg each) of the drug over an 11-month period with reportedly consistent efficacy. Sumatriptan therapy is not associated with an increase in early recurrence of cluster headache and has little effect on the incidence of subsequent episodes (i.e., those occurring from 2-24 hours after the first cluster headache). In a controlled study, prophylactic administration of oral sumatriptan (100 mg 3 times daily for 7 days) did not reduce the number, severity, or duration of subsequent cluster headache attacks in patients who responded successfully to a single 6-mg subcutaneous dose of the drug for the first cluster attack of a series. Patients with a history of more than 2 cluster headaches per day may require prophylactic therapy in addition to the use of sumatriptan for the management of acute breakthrough cluster attacks, as 12 mg (two 6-mg injections) is the maximum recommended daily subcutaneous dose of sumatriptan.
Sumatriptan has been used with some success in a limited number of patients with chronic paroxysmal hemicrania, a rare, variant form of cluster headache. Sumatriptan also has been used in at least one patient with short-lasting, unilateral, neuralgiform headache with conjunctival injection and tearing (SUNCT), a possible variant of cluster headache characterized by brief (30-60 seconds), recurrent episodes of intense pain. In this patient, sumatriptan therapy was associated with relief of pain and limited relief of accompanying manifestations (e.g., conjunctival injection, Horner's syndrome, lacrimation).
Other Types of Headache
Sumatriptan has been used subcutaneously or orally in a limited number of patients with chronic tension-type headache, acute post-traumatic (e.g., post-dural puncture) headache, drug-induced headache (e.g., in combination with amitriptyline and dexamethasone), or high-altitude headache. In a limited number of patients receiving sumatriptan subcutaneously for the treatment of postdural puncture headache, a complication of spinal anesthesia and unintentional dural puncture during attempted epidural anesthesia, the onset of pain relief and the potential for headache recurrence was similar to that reported in patients with migraine. Additional study and experience are required to elucidate the safety and efficacy of sumatriptan therapy in these conditions.
Sumatriptan has been used in a few patients with intractable cyclic vomiting, which appears to share some common pathogenesis to migraine, and in the management of adverse events (e.g., perioperative migraine, severe anesthesia-associated vomiting) associated with general anesthesia in patients with a history of migraine. The safety and efficacy of sumatriptan therapy in these conditions require further evaluation.