Tolfenamic acid rapid release versus sumatriptan in the acute treatment of migraine: comparable effect in a double-blind, randomized, controlled, parallel-group study.

The efficacy and safety of tolfenamic acid and oral sumatriptan in the acute treatment of migraine was studied at five neurological centers in Finland. One hundred forty-one patients experiencing 289 migraine attacks, fulfilling the diagnostic criteria for migraine with or without aura as defined by the International Headache Society, were randomized. For first attacks, 77% of patients receiving tolfenamic acid experienced a reduction of the initial severe or moderate headache to mild or no headache after 2 hours, as compared to 79% in the sumatriptan group and 29% in the placebo group. No significant difference was found between active treatments (P = 0.85, 95% CI [-22%, 18%]), however, both active treatments were significantly better than placebo; P = 0.001, 95% CI (26%, 69%) for tolfenamic acid and P = 0.001, 95% CI (28%, 71%) for sumatriptan. For second attacks, results were similar with 70% of patients receiving tolfenamic acid experiencing relief, as compared to 64% in the sumatriptan group and 39% in the placebo group. No significant differences were observed in accompanying symptoms. Both drugs were well tolerated with the frequency of adverse events; 30% for tolfenamic acid and 41% for sumatriptan, a nonsignificant difference. In this study, tolfenamic acid and oral sumatriptan are comparably effective in the acute treatment of migraine. When comparably effective, factors like individual effect, tolerance, and cost of treatment should be considered when prescribing migraine medication.

The efficacy and safety of subcutaneous sumatriptan in the acute treatment of menstrual migraine. The Sumatriptan Menstrual Migraine Study Group.

OBJECTIVE: To compare the efficacy and safety of subcutaneous sumatriptan with placebo in the treatment of menstrual migraine. METHODS: A double-blind, placebo-controlled, parallel group study was conducted to assess the efficacy and safety of subcutaneous sumatriptan in the treatment of menstrual migraine over two attacks. A total of 179 subjects received sumatriptan or placebo to treat at least one menstrual migraine attack. RESULTS: The efficacy results were consistent for attacks one and two. Two hours after treatment in attacks one and two, 53 (73%) and 51 (81%) of the sumatriptan-treated subjects, respectively, reported headache relief (reduction of a severe or moderately severe headache to a mild or no headache), compared with 27 (31%) and 18 (29%) of the placebo-treated subjects (P < .001). Within 24 hours of treatment in attack one, 28 (53%) and 14 (52%) of the initial responders to sumatriptan and placebo, respectively, experienced headache recurrence. The incidence and nature of adverse events in this study were similar to that seen in previous studies. CONCLUSIONS: Subcutaneous sumatriptan is an effective and well-tolerated acute treatment for menstrual migraine.

Ketoprofen and ergotamine in acute migraine.

The objectives of this study were to evaluate and compare the efficacy and tolerability of ketoprofen and ergotamine in the treatment of acute migraine attacks without aura. The study design was a single-centre, double-blind, placebo-controlled, cross-over comparison of a single dose of ketoprofen (100 mg) and ergotamine (2 mg) suppositories in the treatment of acute migraine attacks. Fifty patients were included in the statistical evaluation. Ketoprofen was found to be more efficient than ergotamine and placebo in reducing the severity of pain. Ketoprofen was found to be more satisfactory than ergotamine and placebo with regard to influence on working ability, and better than placebo in global assessment. We conclude that ketoprofen (100 mg suppository) is superior to ergotamine (2 mg suppository) and placebo in the symptomatic treatment of acute migraine attacks, and has better tolerability.

Alpha rhythm in classical migraine (migraine with aura): abnormalities in the headache-free interval.

The alpha rhythm of 18 patients with classical migraine (migraine with aura) was studied by EEG spectrum analysis for evidence of neural abnormalities during the asymptomatic period. The temporal relationship of the findings to attacks was studied by serial records in 11 cases. Increased frequency dispersion and frequency asymmetries of the alpha rhythm were found. The records were, however, mostly normal when separated from attacks by at least 10 asymptomatic days. The abnormalities increased significantly before the onset of prodromal symptoms and clearly outlasted the headache phase. The results give evidence of a fluctuating asymmetric neural disorder in classical migraine.

Transient asymmetries of steady-state visual evoked potentials in classic migraine.

Unilateral abnormalities in the regional cerebral blood flow (rCBF) and visual evoked potentials (VEPs) during the visual aura of classic migraine have been reported. On the other hand, there are only few observations suggesting unilateral abnormality of neural function during the headache-free period. An experiment is described in which the symmetries of steady state VEPs (SVEPs) are compared in healthy subjects and classic migraineurs in the headache-free interval. In the patients an increased number of strong short-lasting interhemispheric asymmetries was found. In the serial recordings performed, pathologic recordings were obtained intermittently, usually with complete normalisation in the following session. The incidence of abnormalities was relatively independent of the interval between the recording and attack, except for the next few hours. The findings may be related to instability of occipital cortical function in classic migraine.

Difference of steady-state visual evoked potentials in classic and common migraine.

The present study was designed to find evidence for the neural hypothesis of migraine and to evaluate possible interictal differences in the two varieties of migraine by electrophysiological means. Steady-state visual evoked potentials (SVEPs) in response to sinusoidally modulated light were measured in 20 patients with classic migraine and compared with those of 30 common migraineurs and 49 reference subjects. SVEPs to stimuli at 10-24 Hz were recorded occipitally from a pair of midline electrodes and, in classic migraineurs and controls, additionally from left and right occipital areas. The response was processed by the Fast Fourier Transform and automatically analysed. The fundamental component of the midline response to medium frequency stimuli (16-22 Hz) appeared normal in patients with classic migraine, contrary to an augmented response in common migraineurs (ANOVA between groups, P = 0.006). In classic migraine the 2nd harmonic component was attenuated (P less than 0.01 at 18-20 Hz) and the amount of strong interhemispheric f1 asymmetries was increased in about half of the patients. The groups also diverged significantly in the SVEP dynamics during stimulation. The results support the hypothesis of a primary neural disorder in both types of migraine. Different sites and mechanisms of brain dysfunction in classic and common migraine are suggested. Hypothetical neuroanatomical correlates for the abnormalities are presented.

Symptoms of classic migraine attacks: modifications brought about by metoprolol.

There is little information available concerning whether, and to what extent, migraine-prophylactic agents interfere with the symptoms of migraine attacks. The present study is a placebo-controlled, double-blind study concerning metoprolol in classic migraine. The data refer to the symptoms of single migraine attacks. During metoprolol treatment more attacks were characterized as mild (p = 0.002), and mean global rating (an integrated estimate of headache intensity and of other discomfort) was lower (4.2 versus 5.2, p = 0.003). The mean headache intensity per attack (1.97 versus 2.15) and the mean duration (5.5 versus 6.8 h) were not significantly different. Consumption of analgesics per attack was lower during metoprolol treatment (0.6 versus 1.1; p = 0.02). Attacks with associated symptoms accompanying the headache were fewer during metoprolol treatment (p = 0.014). Total visual and non-visual aura symptoms occurred with similar frequency, but scintillations and paraesthesia were more frequent during metoprolol treatment, whereas speech disturbances were less frequent. In spite of lower consumption of analgesics, the symptoms appeared milder during metoprolol than during placebo. The pattern of changes indicates that metoprolol exerts its action via the sympathetic nervous system; peripheral vasoconstriction is hardly the underlying mechanism of action.

Classic migraine: effective prophylaxis with metoprolol.

Metoprolol slow-release tablets (Durules), 200 mg, given once daily in the morning were compared with placebo in the prophylaxis of classic migraine. The trial comprised eight Scandinavian neurologic centres and was designed as a double-blind cross-over study with 4 weeks' run-in, four weeks washout, and 8 weeks of either treatment. Seventy-seven patients with two to eight migraine attacks per month were entered in the trial, and 73 completed it. A total of 1119 attacks with aura symptoms and 374 without were recorded. Metoprolol was significantly better than placebo with regard to the total frequency of attacks (1.8 versus 2.5 attacks/4 weeks), mean duration of attacks (6.0 versus 8.0 h/attack), mean global rating, and consumption of analgesics per attack. Similar differences could be shown for attacks with aura symptoms alone, except for the duration of attacks. Metoprolol is the first drug for which a prophylactic effect in classic migraine has been convincingly demonstrated.

Response to occlusal treatment in headache patients previously treated by mock occlusal adjustment.

Headache patients who had received mock occlusal adjustment and who, after the placebo treatment, were judged to have moderate to severe mandibular dysfunction were offered further treatment. The present study reports the results of occlusal treatment in 19 patients who were willing to undergo further treatment. Statistically significant reduction after occlusal treatment (occlusal adjustment, aided in some cases by temporary use of occlusal splints) was observed in clinical signs (P less than 0.05) and subjective symptoms (P less than 0.01) of mandibular dysfunction and in the frequency of headache (P less than 0.05). The results are complementary to our earlier clinical studies and corroborate the conclusion that improvements after occlusal treatment exceed those after placebo treatment.

Effect of occlusal adjustment on mandibular dysfunction. A double-blind study.

A group of headache patients who also had many signs and symptoms of mandibular dysfunction were randomly assigned to treatment and placebo groups. All 48 patients in the treatment group received occlusal adjustment and 19 of them also splint therapy. In the placebo group all 43 patients received mock adjustment. The changes in symptoms and signs of mandibular dysfunction were evaluated after 8 months in the treatment group and after 4 months in the placebo group, in a double-blind design. Placebo treatment and real treatment were equally effective in relieving symptoms of mandibular dysfunction, but there was significantly more reduction in signs of dysfunction in the treatment group than in the placebo group. When tested statistically, this reduction appeared to be independent of the use of splints as an aid to treatment. It can be concluded that the elimination of occlusal disturbances was an effective treatment for mandibular dysfunction.

Changes in headache after treatment of mandibular dysfunction.

To analyse the effect of treatment of mandibular dysfunction on headache, 35 patients with migraine, 20 patients with combination headache and 36 patients with muscle contraction headache were studied in a clinical double-blind trial. Patients in the treatment group received occlusal adjustment and those in the placebo group mock occlusal adjustment. After eight months and four months, respectively, the neurologist evaluated the treatment outcome. The frequency of headache was reduced in 79% and the intensity in 53% of patients suffering from muscle contraction headache or combination headache in whom the adjustment of the dental occlusion had been successfully accomplished. The difference from the placebo group was statistically significant. The decrease in headache frequency as calculated from the headache diaries correlated with the decrease in the index of clinical signs of mandibular dysfunction.

Tolfenamic acid, metoclopramide, caffeine and their combinations in the treatment of migraine attacks.

Tolfenamic acid is a fenamate which inhibits prostaglandin (PG) biosynthesis and may act as a PG antagonist as well. Caffeine and metoclopramide are used in combination with analgesics and ergotamine in the treatment of migraine attacks, but controlled clinical studies on fixed combinations with analgesics are rare. The effects of orally given tolfenamic acid (200 mg), caffeine (100 mg), metoclopramide (10 mg), tolfenamic acid + caffeine (200 mg + 100 mg), tolfenamic acid + metoclopramide (200 mg + 10 mg) and placebo were studied in 49 migraine patients (3 men, 46 women) in a double-blind randomized cross-over study comprising 482 migraine attacks. The patients were allowed to take either one or two capsules of each preparation for an attack. Additional drugs were allowed after 3 h. Parameters characterizing the effects and side-effects of the drugs were registered. Tolfenamic acid and its combinations were found to be effective in the treatment of acute migraine, but caffeine and metoclopramide alone did not differ from placebo. Combination with metoclopramide was better than tolfenamic acid alone as judged by the smaller dose needed and the intensity of attack. Between tolfenamic acid alone and its caffeine combination there were no statistically significant differences.

Metoprolol and propranolol in the prophylactic treatment of classical and common migraine. A double-blind study.

In a double-blind, cross-over study the effect and tolerance of the non-selective beta-blocker propranolol in a dosage of 80 mg twice daily was compared to that of the beta 1-selective beta-blocker metoprolol 200 mg once daily in Durules (a controlled-release formulation). The attack frequency, migraine days, severity score, consumption of acute medication and subjective evaluation were the main parameters used for evaluation. Thirty-six patients with classical or common migraine were included. Thirty-three completed the investigation. It is concluded from the results that there are no differences in efficacy between metoprolol and propranolol regarding the studied parameters. Both drugs reduced the migraine symptoms compared to the run-in period and were generally well tolerated.

Steady-state visual evoked potentials during migraine prophylaxis by propranolol and femoxetine.

The amplitude of visual evoked potentials (VEPs) for flickering light has been reported to be increased in migraine. In the present study, we have examined whether the VEPs are attenuated when the clinical state of the patient improves during a double-blind experiment with propranolol and femoxetine. VEPs for sinusoidally-modulated light were measured by spectral analysis, and an index depicting the visual reaction type was calculated. The group mean VEP index closely followed the group mean attack frequency, but individual variance was considerable. The changes were most evident in VEPs elicited by stimuli of about 20 Hz. During the treatments, the VEP and headache were also significantly correlated among subjects. The results suggest a close relationship between the enlarged VEPs and the headache mechanisms.

Femoxetine - a new 5-HT uptake inhibitor - and propranolol in the prophylactic treatment of migraine.

The prophylactic effect of a 5-HT uptake inhibitor, femoxetine, was compared with that of propranolol in a double-blind crossover study of 6-months duration. 29 patients commenced the experiment. 3 subjects withdrew because of side effects and 2 because the program was inconvenient for them. In the 24 patients who continued the study to the end, the periods of propranolol (administered 160 mg daily) and of femoxetine (given 400 mg daily) differed significantly from each other with respect to the attack frequency and headache index. A significant reduction in the use of medication relieving attacks was observed during the propranolol treatment as compared with the pre-treatment period. The study showed that partial depletion of thrombocyte 5-HT uptake inhibitor did not lead to a marked improvement in headache, contrary to what might be expected on the grounds of the 5-HT hypothesis of migraine.

Value of high contrast medium dose in brain CT.

Fifty-five patients with brain lesions were examined by computed tomography (CT) after two doses of contrast medium: a bolus injection of 65% meglumine diatrizoate, 1 ml/kg, and a bolus injection of 65% meglumine diatrizoate, 1.5 ml/kg, in combination with an infusion of 250 ml meglumine iodamide containing 110 mg I/ml. The studies were usually performed 2 days apart and were analyzed by three radiologists. In 25 patients, one or more of the radiologists changed the diagnosis or the number or size of the lesions when the two scans were observed separately. In three patients, the primary tumor or metastases were seen in the study performed after the higher dose only, and, in two other patients having cerebral metastases, a greater number of metastases were detected in the high dose study. The lower dose containing 15 to 31 g iodine (306 mg iodine/kg) seems to be inadequate in CT of the brain.