Placebo-controlled comparison of effervescent acetylsalicylic acid, sumatriptan and ibuprofen in the treatment of migraine attacks.

Acetylsalicylic acid (ASA) in combination with metoclopramide has been frequently used in clinical trials in the acute treatment of migraine attacks. Recently the efficacy of a new high buffered formulation of 1000 mg effervescent ASA without metoclopramide compared to placebo has been shown. To further confirm the efficacy of this new formulation in comparison with a triptan and a nonsteroidal anti-inflammatory drug (ibuprofen) a three-fold crossover, double-blind, randomized trial with 312 patients was conducted in Germany, Italy and Spain. Effervescent ASA (1000 mg) was compared to encapsulated sumatriptan (50 mg), ibuprofen (400 mg) and placebo. The percentage of patients with reduction in headache severity from moderate or severe to mild or no pain (primary endpoint) was 52.5% for ASA, 60.2% for ibuprofen, 55.8% for sumatriptan and 30.6% for placebo. All active treatments were superior to placebo (P < 0.0001), whereas active treatments were not statistically different. The number of patients who were pain-free at 2 h was 27.1%, 33.2%, 37.1% and 12.6% for those treated with ASA, ibuprofen, sumatriptan or placebo, respectively. The difference between ASA and sumatriptan was statistically significant (P = 0.025). With respect to other secondary efficacy criteria and accompanying symptoms no statistically significant differences between ASA and ibuprofen or sumatriptan were found. Drug-related adverse events were reported in 4.1%, 5.7%, 6.6% and 4.5% of patients treated with ASA, ibuprofen sumatriptan or placebo. This study showed that 1000 mg effervescent ASA is as effective as 50 mg sumatriptan and 400 mg ibuprofen in the treatment of migraine attacks regarding headache relief from moderate/severe to mild/no pain at 2 h. Regarding pain-free at 2 h sumatriptan was most effective.

Efficacy of 1,000 mg effervescent acetylsalicylic acid and sumatriptan in treating associated migraine symptoms.

Recently a new effervescent acetylsalicylic acid (ASA) tablet with high buffering capacity has been developed. In this double-blind, 3-arm, multicenter, parallel-group study, 433 patients were treated either with 1,000 mg effervescent ASA or 50 mg encapsulated sumatriptan or placebo. The primary endpoint was the percentage of patients with complete remission of the 3 accompanying symptoms nausea, photophobia and phonophobia within 2 h after intake of the study drug. 43.8% of patients treated with ASA, 43.7% of patients treated with sumatriptan and 30.9% of patients treated with placebo showed complete remission of all 3 accompanying symptoms (p < 0.05 for ASA and sumatriptan vs. placebo). Both active treatments were superior to placebo regarding the individual symptoms photophobia and phonophobia, but not for nausea. The percentage of patients with reduction in headache severity from moderate or severe to mild or no pain (secondary objective) was 49.3% for ASA, 48.8% for sumatriptan and 32.9% for placebo. All active treatments were superior to placebo (p < 0.05). 25.3, 24.4 and 14.5% of patients treated with ASA, sumatriptan or placebo were pain free at 2 h. Drug-related adverse events were reported in 3.9, 4.7 and 6.7% of patients treated with placebo, ASA or sumatriptan. The study showed that administration of effervescent ASA leads to remission of the migraine symptoms nausea, photophobia and phonophobia, reduces migraine headache and is comparable to sumatriptan.

Impact of migraine on patients and their families: the Migraine And Zolmitriptan Evaluation (MAZE) survey--Phase III.

OBJECTIVE: To investigate the impact of migraine on migraineurs and their families and evaluate migraineurs' preference for different treatment formulations. This study also assessed the prevalence and impact of migraine with menstruation. METHODS: Participants (n = 1028) from around the world (USA [39%], Canada [20%], Europe [37%] and other countries [4%]) completed an online questionnaire. Of these, 866 were migraineurs and 162 were non-migraineurs living with/related to migraineurs. Migraineurs were identified based on responses to a modified Kiel questionnaire and/or diagnosis of migraine by a doctor. Disability was quantified using the Migraine Disability Assessment Scale (MIDAS). RESULTS: Migraineurs missed more days from family/leisure activities than from work/school (mean 4.2 vs 2.4 days) in the previous 3 months. On an additional 6.2 days within the 3-month period, productivity at work/school was reduced by at least half. Inability and reduced ability (by at least half) to perform household work were reported on 6.0 and 6.5 days, respectively. Of the women surveyed, 51% identified menstruation as a trigger for attacks and 6% reported attacks solely with menstruation (i. e. attacks occurred during menstruation on at least 9 out of 10 occasions), the latter associated with a higher pain score than other attacks. Living with or being related to a migraineur decreased nonmigraineurs' ability to participate in home/family life (moderate/great impact 49%) and social/leisure activities (moderate/great impact 47%). In a tradeoff analysis, 60% of treatment choice was driven by formulation type and 40% was driven by speed of onset. As migraine disability increased, speed of onset became more important. CONCLUSIONS: This study confirms the significant burden of migraine on patients and families/cohabitants, highlighting not only reduced productivity and absences from work/school, but also time missed from family/social occasions. Many women identify menstruation to be associated with more painful attacks. Overall, in terms of treatment choice, formulation type was a more important driver than speed of onset; however, as migrainerelated disability escalates, speed of onset becomes more important. To optimise migraine management, treatment choice should be based on individual patients' needs and preferences.

[Therapeutic concepts in the treatment of headache]. / Der Kopfschmerztyp weist den Weg für die Therapie.

One of the most common forms of primary headache is tension headache with a dull pressure-like pain on both sides of the head. In addition to treatment with acetylsalicylic acid, paracetamol or ibuprofen, the application of cold and relaxation techniques have proven to be of use. Chronic forms are treated with tricyclic antidepressants such as amitriptyline. Unilateral cluster headache responds to inhalation of oxygen and subcutaneous and intranasal treatment with tryptan. By way of prophylaxis, prednisone, verapamil, lithium carbonate and topiramate are applied. For persistent drug-induced headache, withdrawal is the first-line treatment. The more rare forms of nonsymptomatic headache include paroxysmal hemicrania and trigeminal neuralgia, in the prevention of which carbamazepine, phenytoin or oxcarbazepine have proven of value.

Incidence and predictors for chronicity of headache in patients with episodic migraine.

The authors followed 532 consecutive patients with episodic migraine (<15 days/month) for 1 year. Sixty-four patients (14%) developed chronic headache (>/=15 days/month). The odds ratios for developing CH were 20.1 (95% CI 5.7 to 71.5) comparing patients with a "critical" (10 to 14 days/month) vs "low" (0 to 4 days/month) and 6.2 (95% CI 1.7 to 26.6) in patients with an "intermediate" (6 to 9 days/month) vs "low" headache frequency and 19.4 (95% CI 8.7 to 43.2) comparing patients with and without medication overuse.

Headache associated with sexual activity: demography, clinical features, and comorbidity.

OBJECTIVE: S: To provide data on the demography, clinical features, and comorbidity of headache associated with sexual activity (HSA). METHODS: Between 1996 and 2001, 51 patients with the diagnosis of HSA were questioned using a structured interview. RESULTS: The mean age at onset was 39.2 (+/-11.1) years. There was a clear male preponderance (2.9:1). The age at onset had two peaks, with a first peak between the 20th and 24th (n = 13) years of life and a second peak between the 35th and 44th (n = 20) years of life. Eleven patients had HSA type 1 (dull subtype), which gradually increased with increasing sexual excitement. The remaining (n = 40) had HSA type 2 (explosive subtype). The pain was predominantly bilateral (67%), and diffuse or occipital (76%). The quality was nearly equally distributed among dull, throbbing, and stabbing. HSA was not dependent on specific sexual habits and most often occurred during sexual activity with the usual partner (94%) and during masturbation (35%). There was a high comorbidity with migraine (25%), benign exertional headache (29%), and tension-type headache (45%). HSA types 1 and 2 did not significantly differ in demography, clinical features, or comorbidity, except for a higher probability of stopping the attack by breaking off sexual activity in HSA type 1. There were no cases with HSA type 3 (postural subtype). CONCLUSION: Mean age at onset, a male preponderance, a predominantly bilateral and occipital pain, and a high comorbidity with other primary headaches are in concordance with case reports in the literature. The authors found two peaks for the age at onset, however. There was no clinical evidence proving subtypes 1 and 2 to be distinct disorders. HSA types 1 and 2 may be different manifestations of the same disease rather than distinct entities.

Effect of active treatment is lower when using placebo control in clinical trials on acute therapy of migraine.

Methodological aspects of study design affect therapeutic outcome. We tested the hypothesis that treatment effect of an active drug in studies on acute therapy of migraine is lower in placebo-controlled studies than in those not using a placebo-controlled design. From 522 eligible studies on acute therapy of migraine cited in Pubmed database which were published between 1964 and 1997 we randomly selected 100 studies for evaluation. We excluded five studies because they did not include a quantitative measurement of pain intensity. Of the 95 studies included in the analysis, 61 used placebo control. Response to active drug was significantly lower (P < 0.05) in placebo-controlled studies (61% [lower and upper quartiles 44% and 75%] vs. 71% [56% and 75%]). We did not find any significant effect of quality of study design on net effect of verum. This observation should be taken into account for future planning of controlled clinical studies in acute migraine.

A comparative study of oral acetylsalicyclic acid and metoprolol for the prophylactic treatment of migraine. A randomized, controlled, double-blind, parallel group phase III study.

This study was a multinational, multicentre, double-blind, active controlled phase III trial designed to investigate efficacy and safety of 300 mg acetylsalicyclic acid (ASA) (n = 135) vs. 200 mg metoprolol (n = 135) in the prophylaxis of migraine. In total 270 (51 male and 219 female) patients, aged 18-65 years, suffering between two and six migraine attacks per month were recruited. The main objective was to show equivalence with respect to efficacy, defined as a 50% reduction in the rate of migraine attacks. A run-in phase was carried out with placebo for 4 weeks, followed by a 16-week drug phase. In both treatment groups the median frequency of migraine attacks improved during the study period, from three to two in the ASA group and from three to one in the metoprolol group; 45.2% of all metoprolol patients were responders compared with 29.6% with ASA. Medication-related adverse events were less frequent in the ASA group (37) than in the metoprolol group (73). The findings from this trial show that metoprolol is superior to ASA for migraine prophylaxis but has more side-effects. Acetylsalicylic acid is better tolerated than metoprolol. Using a strict responder criterion ASA showed a responder rate comparable with the placebo rate in the literature.