Intracranial hemorrhages associated with sumatriptan.
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Biomedical subjects
Publications and source records attributed to E L Spierings.
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BACKGROUND: Almotriptan malate is a novel, selective serotonin(1B/D) agonist, or triptan, developed for the abortive treatment of migraine. In double-blind, placebo-controlled studies, it has been shown to be effective, well tolerated, and safe. OBJECTIVE: To compare the efficacy, tolerability, and safety of almotriptan with that of the "standard triptan," sumatriptan succinate. The power calculation of the study was based on 24-hour headache recurrence, an efficacy measure in the abortive treatment of migraine, and on the occurrence of adverse events. SUBJECTS AND METHODS: Subjects, aged between18 and 65 years, with migraine with or without aura but otherwise healthy, were randomized to take orally either almotriptan malate, 12.5 mg, or sumatriptan succinate, 50 mg. The medications were provided in identical-looking capsules to ensure blinding and were taken for the treatment of moderate or severe headache. Efficacy was determined in terms of (1) headache relief-a decrease in pain intensity to mild or no pain; (2) headache freedom-a decrease to no pain; (3) use of rescue medications, allowed after 2 hours; and (4) headache recurrence-moderate or severe pain returning within 24 hours after headache relief at 2 hours. Adverse events were collected for 96 hours after treatment and for safety evaluation, vital signs, blood tests, and electrocardiograms were performed at the screening and exit visits. RESULTS: Seventy-five investigators enrolled 1255 subjects of whom 1173 were treated (591 with almotriptan and 582 with sumatriptan). At 2 hours, almotriptan treatment provided headache relief in 58.0% of the subjects and sumatriptan treatment in 57.3%; headache freedom was provided by the medications in 17.9% and 24.6%, respectively (P =.005). Rescue medications were taken by 36.7% of the subjects in the almotriptan-treated group and by 33.2% in the sumatriptan-treated group; headaches returned to moderate or severe intensity in 27.4% and 24.0%, respectively. Treatment-emergent adverse events occurred in 15.2% of the subjects in the almotriptan-treated group and in 19.4% in the sumatriptan-treated group (P =.06); treatment-related adverse events occurred in 9.1% and 15.5% of the subjects, respectively (P =.001), including chest pain, which occurred in 0.3% and 2.2%, respectively (P =.004). CONCLUSIONS: Almotriptan and sumatriptan are similarly effective in the abortive treatment of moderate or severe migraine headache; they are also similarly well tolerated and safe.
Dilation and inflammation of cephalic arteries and intracranial extra cerebral arteries cause the migraine headache. The migraine-associated symptoms result from the activation of the sympathetic nervous system caused by the pain. The migraine aura is caused by the neurophysiological phenomenon of spreading excitation/depression. The various mechanisms are tied together in the so-called "parallel theory" of the pathogenesis of the migraine attack. The abortive antimigraine medications act by constricting the dilated arteries through stimulation of the serotonin 1B receptor. The preventive antimigraine medications act by increasing the tone of the extacranial arteries, inhibiting the mechanism of neurogenic inflammation, or inhibiting pain transmission within the central nervous system.
In this randomized, double-blind, placebo-controlled, parallel-group study, patients received a single 50-mg oral dose of a 5-HT(1D) agonist, PNU-142633 (n = 34), or matching placebo (n = 35) during an acute migraine attack. No statistically significant treatment effects were observed at 1 and 2 h after dosing, even after stratifying by baseline headache intensity. At 1 and 2 h post-dose, 8.8% and 29.4% of the PNU-142633 group, respectively, and 8.6% and 40.0% of the placebo group, respectively, experienced headache relief; 2.9% and 8.8% of the PNU-142633 group and 0% and 5.7% of the placebo group were free of headache pain. Adverse events associated with PNU-142633 treatment included chest pain (two patients) and QTc prolongation (three patients). Results from this study suggest that anti-migraine efficacy is not mediated solely through the 5-HT(1D) receptor subtype, although this receptor may contribute, at least in part, to the adverse cardiovascular effects observed with 5-HT agonist medications.
OBJECTIVE: We conducted the present study to determine whether there are headache precipitating and aggravating factors that differentiate migraine from tension-type headache and headache precipitating and aggravating factors that differentiate tension-type headache from migraine. METHODS: We interviewed 38 patients with migraine and 17 patients with tension-type headache (diagnosed using International Headache Society criteria) by telephone, using a questionnaire. The questionnaire inquired about the following precipitating and aggravating headache factors: (1) physical activity, (2) straining, (3) bending over, (4) stress/tension, (5) coughing/sneezing, (6) fatigue, (7) reading, (8) driving, (9) lack of sleep, (10) specific foods/drinks, (11) alcohol, (12) not eating on time, (13) smoke, (14) smell, (15) light, (16) noise, (17) menstruation, and (18) weather. RESULTS: The most common precipitating factors acknowledged by both groups of patients were stress/tension, not eating on time, fatigue, and lack of sleep. Weather, smell, smoke, and light were the precipitating factors that differentiated migraine from tension-type headache. Excluding those factors that are part of the International Headache Society migraine diagnosis, the aggravating factors were straining, bending over, and smell. We found no precipitating or aggravating factors differentiating tension-type headache from migraine. CONCLUSION: Apparently there are precipitating and aggravating factors differentiating migraine from tension-type headache but not vice versa. It is interesting that three of the migraine-specific precipitating factors (ie, weather, smell, and smoke) involve the nose/sinus system, suggesting a greater significance of this system in headache than is generally considered.
A 51-year-old woman with daily attacks of migraine with visual aura is described. The aura always occurred on the right and the headache always on the left side of the head, suggesting a structural lesion in the left occipital lobe. The lesion appeared to be an arteriovenous malformation of which almost full obliteration resulted in a decrease in frequency of the aura and in intensity of the headache. Subsequent treatment of borderline hypothyroidism with levothyroxine brought about a dramatic improvement in frequency of both the aura and the headache. The case is discussed in the light of our present understanding of the pathogenesis of the migraine attack.
A headache continuum on the basis of the dynamic nature of headache is presented, with episodic headaches developing into daily headaches and vice versa. The concept is supported by evidence from recent study of (gradual-onset) chronic daily headache.
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OBJECTIVE: This randomized, double-blind, parallel group multicenter study compared response rates and tolerability of zolmitriptan with sumatriptan in the acute treatment of migraine. METHODS: A sample consisting of 1445 outpatients with an established diagnosis of migraine was randomized to zolmitriptan, 2.5 mg or 5 mg, or sumatriptan, 25 mg or 50 mg. Patients took 1 tablet for moderate/severe migraine and a second identical tablet, if necessary, for recurrent headache of moderate/severe intensity 4 to 24 hours after the initial dose. Up to six attacks were treated during a 6-month period. The primary outcome measure was headache response 2 hours after the initial dose. Secondary end points included 1-hour and 4-hour headache response and pain relief over 24 hours. RESULTS: A headache response at 2 hours was noted in 67.1% of patients taking zolmitriptan, 2.5 mg, and 64.8% of those taking zolmitriptan, 5 mg, versus 59.6% of patients taking sumatriptan, 25 mg, and 63.8% of those taking sumatriptan, 50 mg. At 2 and 4 hours, the differences between zolmitriptan, 2.5 mg, and sumatriptan, 25 mg, were statistically significant (odds ratio=1.49 and 1.67, respectively; both P<.001). Statistically significant differences between zolmitriptan, 2.5 mg, and sumatriptan, 50 mg, were seen at 2 and 4 hours post dose (odds ratio=1.21 and 1.23, respectively; both P<.05). At 1 hour post dose, the headache response rate for zolmitriptan, 2. 5 mg, was numerically higher than response rates for sumatriptan, 25 mg and 50mg (odds ratio=1.16, odds ratio=1.06, though they failed to reach statistical significance; P=.061, P=.461 respectively). Differences between zolmitriptan, 5 mg, and sumatriptan, 25 mg, were statistically significant at 1, 2, and 4 hours (odds ratio=1.43, 1. 46, and 1.78, respectively; all P<.001) and at 1 and 4 hours versus sumatriptan, 50 mg (odds ratio=1.28, P=.002; odds ratio=1.29, P=.012, respectively). Although not statistically significant at 2 hours, more patients responded to zolmitriptan, 5 mg, than to sumatriptan, 50 mg (odds ratio=1.16, P=.064). Patients receiving zolmitriptan, 2. 5 mg or 5 mg, achieved more pain relief over 24 hours than patients receiving sumatriptan, 25 mg (odds ratio=1.47, and 1.54 respectively, both P<.001) or sumatriptan, 50 mg (odds ratio=1.17, P=.021; odds ratio=1.22, P=.005, respectively). All treatments were well tolerated. CONCLUSIONS: Zolmitriptan, 2.5 mg and 5 mg, was at least as effective as sumatriptan, 25 mg or 50 mg, for all parameters studied. Zolmitriptan, 2.5 mg, was significantly more effective than sumatriptan, 50 mg, in terms of headache response at 2 and 4 hours. Patients taking zolmitriptan were significantly more likely to have pain relief over 24 hours than those taking sumatriptan.
OBJECTIVE: To determine the development and outcome of chronic daily headache in 258 headache practice patients, consisting of 50 men and 208 women. Chronic daily headache was defined as headaches occurring on at least 5 days per week for at least 1 year. METHODS: Two hundred fifty-eight patients with headache were interviewed and evaluated. Ninety-one patients were contacted by telephone for follow-up. RESULTS: Twenty-two percent of the patients had daily headaches from the onset, and 78% initially experienced intermittent headaches. Of the patients with initially intermittent headaches, 19% experienced an abrupt transition into daily headaches and 81%, a gradual one. In the patients with gradual transition, the transition of the initial, intermittent headaches into daily headaches took an average of 10.7 years. The initial headaches were mild in 33% of the patients and severe in 67%. The severe headaches were associated with nausea and vomiting significantly more often than the mild ones. However, the daily headaches that these patients ultimately developed were the same, regardless of whether the initial headaches were mild or severe. The patients who gradually developed daily headaches from initially intermittent headaches were contacted to determine the outcome of their headaches. Of these patients, 33% continued to have daily headaches and 67% again experienced intermittent headaches. Of the latter group, 88% of the patients who now had migraine also had migraine initially.
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Fifty-six adult female patients with the clinical diagnosis of MwoA kept a diary 6 times per day for 10 consecutive weeks to record the occurrence, pain characteristics, and accompanying symptoms of headache. In order to avoid bias due to retrospection or expectancy the diary was programmed into palmtop computers which signaled the patients with a beep to enter the diary with a random-fixed time schedule: two signals occurred in, respectively, the morning, the afternoon, and the evening, but at different times for each day. The palmtop computers also warranted flawless data storage and automatic computations of response delay and missing values. Of the 339 attacks, 75% had a duration of 4-72 h and 94% confirmed the International Headache Society classification criteria for MwoA concerning pain characteristics and accompanying symptoms. Our results obtained for attacks in treated patients are highly comparable with the results of Rasmussen, Jensen, and Olesen (1991) obtained in the general population with unknown treatment of headache. Together, both studies support the IHS classification criteria for MwoA. The electronic Experience Sampling Method also allowed for an unbiased description of the course of treated MwoA attacks: 67% subsided in the first day. In the 16 attacks the characteristics and accompanying symptoms were present in 60-80% of the attacks at the first assessment (9.30 a.m.) with the exception of moderate to severe pain intensity (37%) and nausea or vomiting (31%). A waxing and waning of characteristics and symptoms over the day remained in about 30-40% of the attacks with a tendency towards increases in the evening (7.30 p.m. and 10 p.m.). The method is there for a replication of this study in untreated MwoA patients.
In a data base of 1013 patients with chronic headache, 44.1% reported the onset of headaches before the age of 20 (preadult-onset headache) and 55.9% at or after that age (adult-onset headache). Circumstances of headache onset were mentioned significantly more frequently in the latter than in the former group (8.5% versus 38.2%, P < .001). The 10 most common circumstances of headache onset in adult-onset chronic headache, accounting for 87.9% of all circumstances mentioned, are further discussed. The 3 most common factors, accounting for 58.4% of all circumstances, were head, neck, or back injury; stress; and pregnancy. Illnesses, influenzalike and otherwise, and estrogen administration for birth control or hormone replacement shared the fourth place. It is concluded that in the etiology of chronic headache, other than genetic factors should be considered as well.