2000 Wolfe Award. Sumatriptan for the range of headaches in migraine sufferers: results of the Spectrum Study

BACKGROUND: Migraineurs experience a spectrum of headaches: migraine, migrainous, and episodic tension-type as defined by the International Headache Society (IHS). OBJECTIVE: To evaluate the effectiveness of sumatriptan, 50-mg tablets, in treating the spectrum of headaches in IHS-diagnosed migraineurs. DESIGN/METHODS: Migraineurs with severe disability (Headache Impact Questionnaire score 250 or greater) were enrolled in a randomized, double-blind, placebo-controlled, crossover study. Patients treated up to 10 headaches with sumatriptan, 50 mg, or placebo (4:1). Headache features, recorded prior to treatment, were used to classify each headache using IHS criteria. Headache response (moderate or severe pain reduced to mild or no pain) and pain-free response were recorded at 2 and 4 hours postdose (primary endpoint). Because patients treated multiple attacks, statistical methods controlling for within-subject correlation were used. RESULTS: Two hundred forty-nine migraineurs treated 1576 moderate or severe headaches: migraine (n = 1110), migrainous (n = 103), and tension-type (n = 363). Sumatriptan was superior to placebo for headache response 4 hours postdose (primary endpoint) across all headache types (migraine, 66% versus 48%; P<.001; migrainous, 71% versus 39%; P<.01; tension-type, 78% versus 50%, P<.001). Sumatriptan was also superior to placebo for pain-free response 4 hours postdose for migraine (41% versus 24%, P<.001) and tension-type headaches (56% versus 36%, P =.001). Sumatriptan provided superior pain-free response 2 hours postdose for migraine (18% versus 7%, P<.0001) and tension-type headache (28% versus 14%, P =.0005) compared with placebo. CONCLUSION: Sumatriptan, 50-mg tablets, are effective for the full spectrum of headaches experienced by patients with disabling migraine due to a sumatriptan-responsive mechanism.     

Responsiveness of non-IHS migraine and tension-type headache to sumatriptan

In a long-term efficacy and satiety study, 424 patients were treated with sumatriptan (6 mg sc) for 1,904 migraine attacks. The patients were diagnosed with migraine based on IHS criteria but individual migraine attacks treated in the study were physician diagnosed; not necessarily required to meet IHS criteria. A re-analysis of the treatment response to open label sumatriptan (6 mg sc) indicated that 43 patients had treated at least one migraine that fulfilled IHS criteria for tension-type headache. Analysis of this population revealed they treated 232 headaches. Of these headaches, 114 were classified per IHS criteria as migraine; 76 as tension-type; and 42 as. non-IHS migraine (not classifiable as IHS migraine or IHS tension-type headache). Of the 114 migraines a positive response to sumatriptan occurred in 109 (96%) cases; of the 76 tension-types, 73 responded to sumatriptan (97%); of the 42 non-IHS migraine, 40 (95%) responded to sumatriptan. An equivalent response to sumatriptan among three diagnostic groups of headache supports the concept of a common biologic mechanism involving 5HT₁ receptors that spans a range of clinical presentations.     

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

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

Chronic daily headache. How should it be included in the IHS classification?

A number of patients attending specialty headache centers complain of very frequent, almost continuous or continuous headaches, which are usually grouped together under the term chronic daily headache , a category which does not appear in the International Headache Society (IHS) classification. On the basis of the IHS criteria, these patients can only be classified as having a chronic tension-type headache with the possible addition of migraine, if migrainous attacks are superimposed on the "background" headache. However, several studies have demonstrated that most patients with chronic daily headache originally suffered from migraine and that their migraine has transformed, in the course of time, into a chronic headache picture in which isolated migraine attacks may or may not persist. Despite some differences in the personal opinions of authors involved in the care of patients with chronic daily headache, some views seem to be generally accepted: (1) the great majority of chronic daily headaches are transformations of an original episodic migraine and cannot be included in the chronic tension-type headache category, (2) the current IHS classification does not allow many patients presenting with chronic daily headache to be classified correctly, (3) an important nosological category (transformed migraine) has emerged from all the studies on this subject, (4) it is impossible to diagnose transformed migraine merely by "photographing" the picture of single attacks. Although some theoretical problems remain unresolved, it seems to us that the next revision of the IHS classification can no longer ignore the existence of chronic daily headache.     

Diagnosis of headache in childhood and adolescence: a study in 437 patients

We investigated whether the criteria for idiopathic headache published by the International Headache Society (IHS) are useful in childhood and adolescence and compared the diagnoses according to this classification with those of Vahlquist. We used a semi-structured questionnaire to examine a total of 437 children and adolescents referred consecutively to a headache outpatient clinic. Twenty-eight of 437 patients were excluded because of symptomatic or unclassifiable headache. Of 409 patients with idiopathic headache, 70.4% had definite migraine or tension-type headache (IHS 1.1, 1.2, 2.1, 2.2), 20.5% had a migrainous disorder (IHS 1.7) and 9.1% had headache of the tension-type not fulfilling the criteria (IHS 2.3). In the differential diagnosis of migraine and tension-type headache the intensity of pain, aggravation of headache by physical activity, nausea and vomiting were the most important features. The quality of pain, photo- and phonophobia were less helpful and location least important. The duration of migraine attacks was less than 2 h in 19.0% of the migraine patients. In general, the diagnostic criteria of migraine were highly specific but less sensitive, and those of tension-type headache highly sensitive but less specific. The agreement between IHS criteria and those of Vahlquist was marked (kappa = 0.57). We conclude that the IHS criteria are useful for classifying headache in children and adolescents referred to a headache outpatient clinic. A forthcoming modification of the IHS criteria should consider a reduction of the minimum duration of migraine attacks from 2 h to I h and should try to increase the sensitivity of the criteria for migraine and the specificity of the criteria for tension-type headache.     

Variability of reported headache symptoms and diagnosis of migraine at 12 months

Assignment of a diagnosis of migraine has been formalized in diagnostic criteria proposed by the International Headache Society. The objective of the present study is to determine the reproductibility of the formal diagnosis of migraine in a cohort of headache sufferers over a one-year period. The study was performed in a community cohort taking part in a long-term prospective health survey, the GAZEL study. Two thousand five hundred individuals reporting headache in the GAZEL cohort were sent two postal questionnaires concerning headache symptoms and features at 12-monthly intervals. Replies to the questions allowed a migraine diagnosis to be attributed retrospectively using an algorithm based on the IHS classification scheme. The response rate was 82% for the first questionnaire and 69% for both questionnaires. Of the 1733 subjects providing information at both time-points, the agreement rate for the diagnosis of strict migraine (IHS categories 1.1 or 1.2) was 77.7% (kappa = 0.48), with 62.2% of the patients with this diagnosis (IHS categories 1.1 or 1.2) at Month 0 retaining the same diagnosis at Month 12. When diagnostic criteria were widened to include IHS category 1.7 (migrainous disorder), the agreement rate of the diagnosis was similar at 77.6% (kappa = 0.52), but 82% of the patients with this diagnosis (IHS categories 1.1 or 1.2 or 1.7) at Month 0 now retained the same diagnosis at Month 12. In conclusion, the one-year reproducibility of reporting of migraine headache symptoms is only moderate, varies between symptoms, and leads to instability in the formal assignment of a migraine headache diagnosis and to diagnostic drift between headache types. This finding is compatible with the continuum model of headache, where headache attacks can vary along a severity continuum from episodic tension-type headaches to full-blown migraine attacks.     

One-year tolerability and efficacy of sumatriptan nasal spray in adolescents with migraine: results of a multicenter, open-label study

OBJECTIVE: The objective of this study was to determine the 1-year tolerability and efficacy of sumatriptan nasal spray (NS) at doses of 5, 10, and 20 mg for the treatment of acute migraine in adolescents. METHODS: This was a prospective, multicenter, open-label, 1-year, multiple-attack study. Adolescents (aged 12-17 years) with a > or =6-month history of migraine with or without aura, 2 to 8 moderate or severe migraines per month, and a typical migraine duration of > or =4 hours were eligible for participation. After initial treatment with sumatriptan 10 mg, the dose could be adjusted down to 5 mg or up to 20 mg at the investigator's discretion to optimize tolerability or efficacy. Patients could treat an unlimited number of moderate or severe migraine attacks, provided there was a 24-hour headache-free period between treated attacks and a 2-hour period between doses of sumatriptan NS. A second dose of sumatriptan NS was available for headache recurrence 2 to 24 hours after initial treatment; no more than 2 doses could be used within a 24-hour period. Adverse events, vital signs, electrocardiographic and physical findings, and laboratory variables were assessed. Headache response (reduction of moderate/severe predose pain to mild/no pain) and pain-free response (reduction of moderate/severe predose pain to no pain) were reported by patients 2 hours after dosing. RESULTS: A total of 437 patients treated > or =1 migraine; 3272 total attacks were treated, with 3675 drug exposures (mean, 1.1 dose/attack). Patients had a mean age of 14.1 years, 91% were white, and 53% were female. Seven patients used the 5-mg dose; meaningful conclusions concerning this dose could not be made. Drug-related adverse events were reported in 33% of attacks with the 10-mg dose and 31% with the 20-mg dose; most were related to taste disturbance. Adverse events did not increase with a second dose or over time. Four percent (16/437) of patients withdrew due to drug-related adverse events. One serious adverse event, a facial-nerve ischemic event (10-mg dose), was considered drug related. No drug-related changes in vital signs or electrocardiographic findings were observed. Headache response 2 hours after dosing was reported by 76% of patients taking the 10-mg dose and 72% of those taking the 20-mg dose. Pain-free response 2 hours after dosing was reported by 43% and 40% of patients in the 10- and 20-mg groups, respectively. Conclusions: Based on these results, sumatriptan NS at doses of 10 and 20 mg was well tolerated and effective in the 1-year treatment of multiple migraine attacks in adolescents.     

Long-term tolerability of sumatriptan nasal spray in adolescent patients with migraine

OBJECTIVE: This 1-year, open-label, multicenter study was designed to assess the long-term tolerability and efficacy of sumatriptan nasal spray 20 mg in adolescent patients with migraine. METHODS: A prospective, multicenter, open-label study was conducted in patients aged 12 to 17 years who were allowed to treat an unlimited number of migraines at severe, moderate, or mild pain intensity with sumatriptan nasal spray for up to 1 year. All patients started the study at the 20-mg dose of sumatriptan nasal spray. Dose could be adjusted downward to 5 mg at the discretion of the investigator to optimize therapy. RESULTS: A total of 484 adolescent migraineurs treated 4676 migraines with sumatriptan nasal spray 20 mg (3593 during the first 6 months and 1083 during the second 6 months). A total of 3940 migraines and 699 migraines were treated with one and two 20-mg doses of sumatriptan nasal spray, respectively. Only 10 patients (treating 42 migraines) took the 5-mg dose of sumatriptan nasal spray. The overall percentage of migraines treated with either one 20-mg dose or one, two, or three 20-mg doses with at least 1 drug-related adverse event was 19%. The most common specific drug-related adverse event was unpleasant taste, reported in 17% of migraines. No other single drug-related adverse event was reported in more than 1% of migraines over the 1-year treatment period. When unpleasant taste was excluded from the adverse-event tabulations, the percentages of migraines with at least 1 drug-related adverse event after one or one, two, or three 20-mg doses declined to 4% and 3%, respectively. No patient experienced any drug-related changes in 12-lead ECGs, vital signs, or nasal assessments; and no clinically meaningful changes in clinical laboratory values were observed. Across all migraines with evaluable efficacy data (n=4334), headache relief was reported in 43% of migraines at 1 hour and in 59% at 2 hours after dosing with sumatriptan nasal spray 20 mg. Of the 2561 migraines with headache relief 2 hours postdose, headache recurrence was reported within 24 hours of initial dosing in 7% of migraines. None of the efficacy or tolerability results varied as a function of time in the study (ie, first 6 months vs. second 6 months). CONCLUSION: Sumatriptan nasal spray 20 mg is generally well tolerated and may be beneficial during long-term use by adolescent migraineurs ages 12 to 17 years.     

Preference comparison of rizatriptan ODT 10-mg and sumatriptan 50-mg tablet in migraine

OBJECTIVE: To compare the proportion of patients who prefer rizatriptan orally disintegrating tablet (ODT) 10-mg to sumatriptan 50-mg tablet. BACKGROUND: Migraineurs express treatment preference based on a variety of attributes including the speed of pain relief and medication formulation. Rizatriptan ODT is an orally disintegrating formulation of rizatriptan, a selective 5-HT1B/1D receptor agonist. This study was conducted to determine patient preference between rizatriptan ODT 10-mg and sumatriptan 50-mg tablet for the acute treatment of migraine. METHODS: This was a multicenter, randomized, open-label, two-period crossover study conducted in the United States with 524 enrolled patients. Patients treated a single moderate or severe headache in each treatment period. Patients treated one migraine with either rizatriptan ODT 10-mg or sumatriptan 50-mg tablet, then treated a second migraine with the alternate therapy. Patients completed diary assessments at baseline, and 30, 45, 60, 90, and 120 minutes postdose and rated headache severity on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). At the final study visit following treatment of their second migraine, patients expressed preference for one of the two study medications by completing an interviewer-administered Global Preference Question and then responded to a self-administered series of questions to capture their most important reason for preferring one study medication over the other. Safety measurements were recorded through standard adverse experience reporting. RESULTS: Three hundred eighty-six patients treated two migraine attacks. For those patients who expressed a preference for either rizatriptan ODT or sumatriptan (n = 374), the percentage of patients who preferred rizatriptan ODT 10-mg (57%, n = 213) was significantly greater than those who preferred sumatriptan 50-mg tablet (43%, n = 161) (P<.01). For those patients who treated two migraine attacks and had drug severity measures for both attacks (n = 384), a significantly greater percentage of patients reported pain relief after taking rizatriptan ODT than sumatriptan at the 45- and 60-minute time points (38% versus 29% and 58% versus 49%, respectively) (P<.01). In addition, a significantly greater percentage of patients taking rizatriptan ODT reported a pain-free status at the 60- and 120-minute time points (23% versus 17% [P<.05] and 60% versus 52% [P<.01], respectively). Both rizatriptan ODT and sumatriptan were well tolerated. CONCLUSIONS: A significantly greater proportion of patients preferred rizatriptan ODT 10-mg to sumatriptan 50-mg tablet for the acute treatment of migraine. Efficacy and safety data are consistent with the preference findings.     

Cephalic venous congestion aggravates only migraine-type headaches

We performed the Queckenstedt's (Q)-test (compression over bilateral internal jugular veins) and a sham test on 33 patients with migraine attacks (coded as 1.1 based on headache classification proposed by International Headache Society (IHS)), 15 with migrainous attacks (IHS code 1.7), and 15 with tension-type headache (IHS code 2.1) in both supine and sitting positions. 'Migrainous headache' (code 1.7) was defined if the headache characteristics fulfilled all but one criteria for 'migraine without aura'. Migraine sufferers reported a marked increase in headache intensity after a 30-second Q-test in both supine and sitting positions. Aggravation was greater in the supine position. The intensity increase was not demonstrated in the sham test, or in patients with migrainous attacks or tension-type headaches after the Q-test. Patients with acute migraine thus appear more sensitive to increased cerebral venous pressure or intracranial pressure. The discrepancy of intensity changes between supine and sitting positions may reflect different amount of venous return through the internal jugular veins.     

Comparison of naratriptan and sumatriptan in recurrence-prone migraine patients. Naratriptan International Recurrence Study Group

OBJECTIVE: This randomized, double-blind, crossover study was undertaken to compare the incidence of headache recurrence after treatment with naratriptan or sumatriptan in migraine patients with a history of frequent headache recurrence (recurrence in > or =50% of successfully treated attacks). BACKGROUND: Although the selective 5-hydroxytryptamine, (5-HT1) agonist sumatriptan is effective and well tolerated for acute treatment of migraine in most patients, headache recurrence within 24 hours of initial successful treatment with sumatriptan and other medications has been reported in approximately 35% of patients. The novel 5-HT1 agonist naratriptan possesses pharmacologic and pharmacokinetic characteristics that may address the issue of headache recurrence. METHODS: Men and women aged 18 to 65 years with a > or =1-year history of migraine with or without aura were randomly assigned to treat 1 moderate or severe migraine attack in a nonclinical setting with one 2.5-mg naratriptan tablet and 1 attack with one 100-mg sumatriptan tablet. A pain-free interval of > or =24 hours was required between attacks. At 4 hours, patients not using rescue medication and experiencing headache recurrence could take a second, identical dose of study medication to treat recurrence. No more than 2 tablets of study medication were permitted in any 24-hour period. RESULTS: A total of 253 patients treated > or =1 migrane attack and were included in the safety analysis; the 225 patients who treated both attacks were included in the efficacy analysis. Of the 164 naratriptan-treated and 181 sumatriptan-treated patients experiencing headache relief after > or =1 attack, headache recurrence 4 to 24 hours after treatment was reported by 74 naratriptan-treated patients (45%) and 101 sumatriptan-treated patients (57%; not statistically significant). (One naratriptan- and 3 sumatriptan-treated patients who experienced headache relief did not record recurrence status and were not included in the denominator for the percentage calculation.) In a subset of patients experiencing headache relief after 2 attacks, headache recurrence 4 to 24 hours after initial dosing was reported by 55 naratriptan- and 77 sumatriptan-treated patients (41% and 57%, respectively; P = 0.005). The overall incidence of adverse events was 22% after treatment with naratriptan and 33% after treatment with sumatriptan. This incidence did not increase after use of a second dose of naratriptan (20%) or sumatriptan (31%). CONCLUSION: These data suggest that naratriptan is a long-acting and well-tolerated addition to currently available medications for the treatment of acute migraine.     

Assessment of International Headache Society diagnostic criteria: a reliability study

In 1988 the International Headache Society (IHS) introduced new diagnostic criteria for headaches and craniofacial pain. Since headaches can be diagnosed solely on the basis of information provided by the patient, it is essential that the criteria are reproducible and consistent. Two neurologists evaluated the clinical records of 100 consecutive outpatients and transferred the data on headache and associated phenomena to a form designed to reflect the IHS criteria. Interobserver concordance (kappa statistics) in the application of the diagnostic criteria of primary headaches was: (i) "perfect" to "substantial" for the first IHS digit, being kappa = 1.0 for cluster headache and paroxysmal hemicrania; kappa = 0.88 for migraine; kappa = 0.75 for tension-type headache; (ii) "almost perfect" to "substantial" for the second digit (kappa = 0.94 for cluster headache; kappa = 0.90 for migraine with aura; kappa = 0.81 for episodic tension-type headache; kappa = 0.78 for migraine without aura; kappa = 0.71 for chronic tension-type headache; kappa = 0.66 for cluster headache-like disorder not fulfilling the criteria; (iii) "moderate" for migrainous disorder (kappa = 0.48) and headache of the tension-type (kappa = 0.43) not fulfilling the criteria. These results show that the IHS diagnostic criteria are satisfactorily applicable to high quality medical records abstracted by experienced neurologists.     

Migrainous disorder and headache of the tension-type not fulfilling the criteria: a follow-up study in children and adolescents

In this follow-up study in children and adolescents with recurrent headaches classified as migrainous disorder (IHS 1.7) and headache of the tension-type not fulfilling the criteria (IHS 2.3), 28.6% were headache-free and 71.4% still had headaches 2-5 years after the first examination. The majority remained in the same one-digit IHS diagnosis, whereas 20% changed from migraine to tension-type headache or vice versa. The number of IHS criteria fulfilled increased significantly from the first to the second examination. The reason for diagnosing IHS 1.7 and IHS 2.3 most often was a short headache duration or headache characteristics not meeting the criteria. By reducing the minimum headache duration to 1 h, 11 of 58 patients could be diagnosed as migraine without aura. There was a remarkable overlap in the diagnostic criteria for migraine without aura and tension-type headache. In IHS 1.7 and IHS 2.3 this overlap exceeded 80%, with a trend to decrease at the second examination.     

Efficacy of sumatriptan tablets in migraineurs self-described or physician-diagnosed as having sinus headache: a randomized, double-blind, placebo-controlled study

BACKGROUND: Many patients and physicians interpret episodic headache in the presence or absence of nasal symptoms as "sinus' headache, while ignoring the possible diagnosis of migraine. OBJECTIVE: The purpose of this study was to assess the efficacy and tolerability of sumatriptan succinate 50-mg tablets in patients with migraine presenting with "sinus" headache. METHODS: A randomized, double-blind, placebo-controlled, multicenter study was conducted in adult (aged 18-65 years) migraine patients presenting with self-described or physician-diagnosed "sinus" headache. From November 2001 to March 2002, patients meeting International Headache Society criteria for migraine (with > or =2 of the following: unilateral location, pulsating quality, moderate or severe intensity, aggravation by moderate physical activity; and > or =1 of: phonophobia and phonophobia, nausea and/or vomiting) and with no evidence of bacterial rhinosinusitis were enrolled and randomized in a 1:1 ratio via computer-generated randomization schedule to receive either 1 sumatriptan 50-mg tablet or matching placebo tablet. The primary efficacy end point was headache response (moderate or severe headache pain reduced to mild or no headache pain) at 2 hours after administration. The presence or absence of migraine-associated symptoms and sinus and nasal symptoms was also measured. Tolerability was assessed through patient-reported adverse events (AEs). RESULTS: Two hundred sixteen patients with self-described or physician-diagnosed "sinus" headache received a migraine diagnosis and treated 1 migraine attack with sumatriptan 50 mg. The efficacy (intent-to-treat) analysis included 215 patients treated with sumatriptan 50 mg (n = 108; mean [SD] age, 39.6 [12.3] years; mean [SD] weight, 77.7 [17.7] kg; sex, 71% female; race, 69% white) or placebo (n = 107; mean [SD] age, 41.0 [11.3] years; mean [SD] weight 80.7 [20.9] kg; sex, 69% female; race, 64% white). Significantly more patients treated with sumatriptan 50 mg achieved a positive headache response at 2 and 4 hours after administration compared with those treated with placebo (69% vs 43% at 2 hours and 76% vs 49% at 4 hours, respectively; both, P < 0.001). Significantly more sumatriptan-treated patients were free from sinus pain compared with placebo recipients at 2 hours (63% vs 49% placebo, P = 0.049) and 4 hours (77% vs 55%, P = 0.001). All treatments were generally well tolerated. The most common drug-related AEs reported in the sumatriptan and placebo groups, respectively, were dizziness (5% vs < 1%), nausea (3% vs 2%), other pressure/tightness (defined as sense of heaviness; heaviness of upper body, upper extremities; jaw tension; neck tension) (4% vs 0%), and temperature sensations (defined as warm feeling of back of neck, or flushing) (2% vs 0%). No patients experienced any serious AEs. CONCLUSIONS: Sumatriptan 50-mg tablets were effective and generally well tolerated in the treatment of these patients presenting with migraine headaches that were self-described or physician-diagnosed as sinus headaches.     

Chronic daily headache in children and adolescents presenting to tertiary headache clinics

BACKGROUND: Adults with chronic daily headache often describe a transformation from episodic migraine and partial retention of migrainous features. Although chronic daily headache has not been investigated as carefully in the pediatric population, one study showed a predominance of coexisting daily headache and episodic migraine, without a clear history of transformation. OBJECTIVE: To identify the clinical features of chronic daily headache in children and adolescents, to evaluate the efficacy of current headache classification criteria, and to compare the features of coexistent daily and episodic headaches so as to determine whether they represent separate syndromes or different stages in the "transformation" process. DESIGN: We surveyed 189 consecutive patients, 18 years of age or younger, who presented for initial evaluation of daily or near daily headache at one of 9 tertiary headache clinics. Data were collected in semistructured interviews employing a standard questionnaire and analyzed using Statistical Analysis Systems and Stata statistical software computer programs. RESULTS: Of the patients enrolled, 70% were female and 87% were white. Mean age was 13.0 +/- 3.1 years. Male gender was associated with a higher degree of reported disability. A family history of headache (typically migraine) was described in 79%. Use of nonsteroidal anti-inflammatory drugs 5 days per week or more was reported by 44% of patients. The International Headache Society (IHS) criteria failed to classify 64% of patients and criteria proposed by Silberstein et al failed to classify 31% of patients. Participating physicians misclassified patients according to criteria of the IHS and Silberstein et al in one third of cases. Nearly one quarter of patients reported two separate headache types with distinguishing characteristics. "Baseline" headache was present 27.3 +/- 4.1 days per month with a mean pain intensity of 5.9 +/- 2.1 on a 10-point scale. Superimposed episodic headache occurred 4.7 +/- 3.8 days per month with a mean pain intensity of 8.4 +/- 1.4, and was more often accompanied by other migrainous symptoms. After logistic regression to control for pain intensity, the only statistically significant difference between the two headache types was a lower prevalence of tension-type head pain with the superimposed headache. CONCLUSIONS: Our data suggest that rather than having two coexistent headache types, children and adolescents with chronic daily headache have a single syndrome that, in many cases, will paroxysmally worsen and gather migrainous features.     

Efficacy and Safety of Sumatriptan Tablets (25 mg, 50 mg, and 100 mg) in the Acute Treatment of Migraine: Defining the Optimum Doses of Oral Sumatriptan

That sumatriptan tablets are effective and well tolerated in the acute treatment of migraine has been established, but the relationship between dose and efficacy has not been adequately defined to date in clinical trials. This multinational double-blind trial (N=1003) in which patients treated up to three migraine attacks with sumatriptan 25 mg, 50 mg, 100 mg, or placebo, with a second independently randomized dose for headache recurrence, evaluated the efficacy and tolerability of three doses of sumatriptan. The results demonstrate that all doses of sumatriptan were superior ( P <0.05) to placebo in reducing moderate or severe predose headache to mild or no headache 4 hours postdose for each of the three treated attacks; sumatriptan 50 mg and 100 mg were each superior ( P <0.05) to sumatiptan 25 mg 4 hours postdose for two of three attacks. Sumatriptan (all doses) was similarly effective at relieving nausea and photophobia or phonophobia or both and at reducing clinical disability. Headache recurrence was experienced by similar proportions of patients across treatment groups (35% to 48% after placebo; 26% to 39% after sumatriptan). Relief of recurrent headache 2 hours after the second dose of study medication occurred in greater percentages of patients using any dose of sumatriptan compared with patients using placebo to treat recurrence. The incidence of adverse events with 25-mg and 50-mg sumatriptan tablets was similar to the incidence with placebo and lower than the incidence with 100-mg sumatriptan tablets. These data provide the first demonstration from a large well-controlled clinical trial that both the 50- and 100-mg doses are more effective than the 25-mg dose and that the 50-mg dose is associated with a lower incidence of adverse events than the 100-mg dose.     

Effect of age on the fulfilment of the IHS criteria for migraine in children at a headache clinic

In a headache clinic, 247 children suffering from severe recurrent headaches were studied in relation to the IHS criteria for migraine. Of the 247, 163 had migrainous headache, with 110 (67.5%) of these having migraine in accordance with the IHS criteria. The remaining 53 (32.5%) had headache attacks fulfilling all but one of the IHS criteria. Coverage of the IHS criteria for migraine was 93%. Symptoms of unilateral headache, aggravation by physical activity, and nausea showed the greatest differences in frequency between those with migraine and those with probable migraine. All children with aura fulfilled criteria for migraine. Children with migraine with aura (11.8, 95% CI: 11.0–12.6 years) were older than those without aura (10.1, 9.4–10.8 years; p = 0.001). Children with pulsating headache were slightly older than children without pulsating headache. No differences in age were detected for the other IHS criteria.     

Sumatriptan in the Acute Treatment of Migraine Without Aura: Efficacy of 50-mg Dose

We conducted an open study on the efficacy of 50 mg of sumatriptan as an acute treatment for migraine without aura. We recruited 200 consecutive patients, with an established history of migraine without aura, presenting at a headache center. The patients were instructed to take half a 100-mg sumatriptan tablet for their next migraine attack, and to record details of their headache in a diary. The primary outcome of the study was headache relief from one migraine attack. Attacks were moderately intense (46%), moderate to severe (7%), or severe (47%). Total or partial benefit at 2 hours from the 50-mg dose was reported by 140 of 200 patients (70%). Thirty-six patients received no benefit from half a tablet, and 24 did not take sumatriptan, preferring their habitual medication. Side effects were few, mild, and short lasting. We conclude that the 50-mg oral dose is generally effective for migraine without aura attacks of both moderate and severe intensity and recommend this dose for all such patients. If, however, sumatriptan is ineffective at that dose it can be increased to a maximum of 100 mg.     

Characteristics of headache in migraine without aura and episodic tension-type headache in the Turkish population according to the IHS classification

We evaluated the characteristics of headache in migraine without aura and episodic tension-type headache diagnosed according to the International Headache Society (IHS) Classification. Fifty migraine without aura and 50 tension-type headache patients were selected prospectively. Fifty-eight percent of migraineurs had pain of a pulsating quality; 88% had severe pain and 74% had unilateral pain; aggravation by routine physical activity was reported by 96%. Episodic tension-type headache was of a pressing quality in 52%, moderate in 40%, bilateral in 82% and aggravated by routine physical activity in 16%. Nausea and/or vomiting, photophobia and phonophobia were reported significantly more commonly in migraineurs than tension-type headache patients.     

Outcome of juvenile headache in outpatients attending 23 Italian headache clinics. Italian Collaborative Study Group on Juvenile Headache (Società Italiana Neuropsichiatria Infantile [SINPI])

A multicenter 3-year follow-up study was carried out on young patients with headache referred to tertiary headache centers or pediatric clinics. Three years after the first examination in 1993, 442 (of an original sample of 719) young outpatients with headache (226 females and 216 males) were re-examined. The diagnostic criteria of the International Headache Society (IHS) and those modified for migraine without aura by Winner et al were applied at both the baseline evaluation and the 3-year re-examination. At the follow-up, 290 children still had headache, 101 were in clinical remission, and 51 had dropped out. Using the current diagnostic criteria, only 46.2% of patients having migraine without aura, 50% of those having migraine with aura, and 35.3% of those suffering from migraine disorders which do not fulfill IHS criteria for migraine received the same diagnosis at the time of follow-up. The percentage of patients receiving a diagnosis of migraine without aura rose significantly when new modified criteria were used (60.5%), whereas a drop in the frequency of migraine disorders not fulfilling IHS criteria was observed at follow-up, both in patients with the diagnosis of migraine without aura at the first examination (4.6%) and in patients with migraine not always fulfilling IHS criteria at the first examination (6.2%). Among all patients who received this latter diagnosis at the first examination, it was possible to make a diagnosis of migraine with aura at the follow-up in 8.8% of cases and that of migraine without aura in 26.5%. No significant variations in the frequency of either episodic tension-type headache or chronic tension-type headache were found, with the exception of a slight decrease in the percentage of tension-type headache which did not fulfill IHS criteria, but the difference between the first examination and the follow-up values does not reach the level of statistical significance (5% versus 12%). As far as the evolution of migraine is concerned, 17.4% of patients with migraine were headache-free at the 3-year follow-up. In tension-type headache, the percentage of patients who were headache-free was particularly high in those with the episodic form (32.9%) and in those suffering from tension-type headache not fulfilling IHS criteria (29.1%). The majority of patients who had been diagnosed as having unclassifiable headache at the first examination received a correct diagnosis at the follow-up with the exception of one patient. As observed in adult patients, variations in the headache characteristics were also observed in children and adolescents (that is, migraine with aura can change to migraine without aura, or the latter can transform into episodic tension-type headache or chronic tension-type headache can change into the episodic form). This follow-up study was aimed at reaching a better understanding of headache disturbances in children and adolescents, examining, in particular, variations of headache with time in this stage of life.