[Show abstract][Hide abstract] ABSTRACT: PurposeTo investigate the efficacy of prednisone for treatment of withdrawal headache in patients with medication overuse headache (MOH).Patients and methodsIn this prospective double-blind, placebo-controlled, parallel designed multicentre trial, 96 consecutive patients with MOH were randomized to withdrawal treatment with either 100 mg prednisone or placebo over 5 days. Patients were enrolled if they met the International Headache Society criteria for MOH and were diagnosed with migraine or episodic tension-type headache as primary headache. Exclusion criteria comprised significant neurological or psychiatric disorders. Withdrawal symptoms, including headache severity and intake of rescue medication, were documented for 14 days after randomization.ResultsPatients treated with prednisone did not experience fewer hours of moderate or severe headache than patients receiving placebo. However, patients requested less rescue medication within the first 5 days.Conclusions
During withdrawal in MOH, prednisone reduces rescue medication without decreasing the severity and duration of withdrawal headache.
[Show abstract][Hide abstract] ABSTRACT: Cluster headache is a rare primary neurovascular headache and a severe pain condition with unilateral headache over 15-180 minutes and concomitant unilateral autonomic symptoms. The detailed pathophysiology of the condition is still unclear. Only a few evidence-based therapeutic options for acute therapy and the preventive management of the disease are available. Triptans, in particular sumatriptan 6 mg subcutaneously, are highly effective for acute treatment. This review focuses on the potential use of oral triptans in the prophylaxis of cluster headache.
Current Pain and Headache Reports 03/2012; 16(2):180-4. DOI:10.1007/s11916-012-0251-5 · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine whether frovatriptan would show efficacy in short term prophylactic treatment of episodic cluster headache (ECH) in comparison to placebo.
The 5-hydroxytryptamine(1B/d) (5-HT(1B/d) )-agonists naratriptan, eletriptan, and frovatriptan have been shown to reduce the frequency of ECH. So far, no double-blind placebo-controlled trials have investigated the potential prophylactic effects of 5-HT(1B/d) -agonists in ECH.
The trial was conducted as a multi-center, placebo-controlled, randomized, double-blind, prospective phase III parallel-group trial with two independent treatment groups (5 mg frovatriptan vs placebo). It was planned to randomize about 96 patients (48 patients per group) into the trial to obtain 80 evaluable patients (40 patients per group).
The study was prematurely discontinued after 13 months and enrollment of 11, instead of the planned 80 patients, by the sponsor due to infeasibility. Recruitment was slow and each of the patients included conducted major protocol violations. The differences in the primary and secondary endpoints were not significant.
This study shows that particular therapeutic aims are impossible to be addressed in a double-blind, randomized, parallel group, study design with specific inclusion and exclusion criteria according to the International Headache Society (IHS) guidelines for controlled trials of drugs in cluster headache. Further studies are required to evaluate the potential efficacy of triptans in the prophylactic treatment of ECH. The outcome of the trial suggests that the recommendations of the Guidelines for controlled Trials of Drugs in Cluster Headache from the IHS should be revised.
Headache The Journal of Head and Face Pain 01/2011; 51(1):129-34. DOI:10.1111/j.1526-4610.2010.01772.x · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This analysis evaluates and ranks efficacy endpoints often used in headache trials concerning their clinical relevance in relation to the patient-related criterion "global assessment of overall efficacy" based on data gained in a large trial investigating different over-the-counter drugs in the treatment of headache.
The original study showed a significant superiority of the fixed combination of acetylsalicylic acid+paracetamol+caffeine over the combination without caffeine, the single preparations, and placebo in the treatment of headache.
For 1734 patients included in the efficacy analysis we investigated the correlation of patient's global efficacy assessment with the endpoints "time to 50% pain relief" (primary endpoint), "time to be pain-free," pain intensity difference, sum of pain intensity difference, and extent of impairment of daily activities. Patients recorded pain intensity on a visual analog scale. Efficacy, tolerability, and extent of impairment of daily activity were assessed on verbal rating scales.A logistic regression, proportional odds model was adapted to the time to event data.
The highest correlation with patient's global efficacy assessment was demonstrated for the primary endpoint time to 50% pain relief (r = 0.6727) and the sum of pain intensity difference (r = 0.7037). The frequency distribution of patient's global efficacy assessment depended primarily on the time to 50% pain relief and similarly, but to a somewhat lesser extent, on the reduction of pain intensity to 10 mm as assessed on the visual analog scale. More than 86% of the patients assessed efficacy as very good or good when their pain was reduced by 50% at least within 1 hour after drug intake. The patients accept a longer time span than 2 hours for reaching no pain to give a positive global evaluation of efficacy.
Headache The Journal of Head and Face Pain 06/2009; 49(5):646-54. DOI:10.1111/j.1526-4610.2008.01242.x · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare the superior efficacy of the fixed combination of acetylsalicylic acid, paracetamol, and caffeine over the single substances, which was observed in the randomized, double-blind phase of the clinical trial, with the efficacy of the respective usual nonprescription medication taken by the patients in the open-label pre-phase of the same study.
The "Thomapyrin Study" showed significant superiority of the fixed combination containing acetylsalicylic acid, paracetamol, and caffeine over the combination without caffeine, the single preparations, and placebo in the treatment of headache.
Prior to the randomized treatment phase, a headache episode treated with the patient's usual nonprescription medication was recorded (open-label pre-phase). Patients assessed their pain intensity on a 100-mm visual analog scale. For the 1734 patients included in the efficacy analysis, we compared the time course of the pain intensity difference (PID) to baseline after the patients took their usual medication with the time course of the PID after intake of the randomized study medication.
Time course of PID after intake of the patient's usual medication was very similar to the time course of PID after intake of the randomized study medication. After 2 hours, pain reduction was on average 43.0, 38.2, 38.1, and 37.7 mm as assessed on the visual analog scale in the group of patients who took their usual triple combination containing acetylsalicylic acid, paracetamol, and caffeine, the single agents acetylsalicylic acid, paracetamol, and ibuprofen, respectively, in the open-label phase. The corresponding mean pain reduction was 44.7, 40.7, and 39.5 mm in patients allocated to the triple combination containing acetylsalicylic acid, paracetamol, and caffeine, the single agents acetylsalicylic acid, and paracetamol, respectively, in the randomized, double-blind phase.
Headache The Journal of Head and Face Pain 06/2009; 49(5):638-45. DOI:10.1111/j.1526-4610.2009.01402.x · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated the consistency between the headache diagnosis based on medical history and three treated headache episodes diagnosed based on a diary. In a randomized double-blind study including individuals with either migraine or tension-type headache (TTH) we showed significant superiority of the fixed combination of acetylsalicylic acid + paracetamol + caffeine over the combination without caffeine, the single preparations, and placebo in the treatment of headache. A neurologist performed a classification of the usual headache episodes and each of the three treated ones in a blinded fashion based on a structured questionnaire. This was done for the 1734 patients included in the efficacy analysis who usually treated their episodic TTH or migraine attacks with non-prescription analgesics. The overall percentage of patients with migraine and TTH remained relatively stable. The treated headache episodes were between 75 and 77% migraine, 18-20% were TTH and 5-7% could not be classified. We observed some shift in headache type within patients from prior history and in treated attacks. In 60% of patients all three treated episodes were of the type initially diagnosed by the neurologist by history (56% migraine and 4% episodic TTH). Of those with an initial diagnosis of migraine, 24% had at least one attack meeting criteria for TTH. Of patients with an initial diagnosis of TTH, 54% had at least one attack meeting the diagnostic criteria for migraine. Our results demonstrate that an initial headache diagnosis does not accurately predict the headache type treated in a randomized trial. Symptom features of treated headaches should be captured to ensure that the attack is of the type targeted by the clinical trial. The International Headache Society Guidelines for controlled clinical trials should be updated accordingly.
[Show abstract][Hide abstract] ABSTRACT: This proof-of-concept study evaluated the efficacy of prednisone for the treatment of withdrawal symptoms in patients with medication overuse headache (MOH) in a randomized, placebo-controlled, double-blind design. Twenty patients were randomized and underwent in-patient withdrawal therapy. The total number of hours with severe or moderate headache within the first 72 and 120 h was significantly lower in the prednisone group. The results show that prednisone might be effective in the treatment of medication withdrawal headache.
[Show abstract][Hide abstract] ABSTRACT: We present a series of seven migraine patients with typical features of a migraine attack without aura, but atypical pain localization in the face in one or both of the lower two distributions of the trigeminal nerve (V2 and V3). All of them responded well to triptans. Three patients responded to preventive treatment for migraine with beta-blockers (n = 2) or valproic acid (n = 1). These cases underline the heterogenic clinical presentation of migraine, which is sometimes difficult to diagnose even for headache specialists, and broaden the pathophysiological understanding of trigeminal nociceptive processing in migraine in the light of neuronal plasticity.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to identify predictors of hazardous alcohol consumption in patients with cluster headache (CH). We investigated 246 German CH patients with the Alcohol Use Disorders Identification Test (AUDIT). The average daily alcohol consumption was 6.5 g. Predictors for hazardous drinking (AUDIT>or=5 points; 21.5% of patients) were male gender [odds ratio (OR) 4.15, 95% confidence interval (CI) 1.35, 12.71], episodic as opposed to chronic CH (OR 4.8, 95% CI 1.38, 16.67) and a low demanding job as opposed to a high demanding job (OR 2.28, 95% CI 1.15, 4.51). Our data indicate that CH patients drink less alcohol compared with the German population and that CH seems to protect against hazardous alcohol consumption. Moreover, predictors for hazardous alcohol consumption in CH patients are not different from the general population.
[Show abstract][Hide abstract] ABSTRACT: Medication-overuse headache (MOH) can be caused by almost all anti-headache drugs including analgesics, ergots, triptans, and combined preparations The prevalence of chronic daily headache (CDH) appears to be between 2% and 4% in the general population. Current epidemiologic studies suggest that MOH accounts for approximately 50% of these cases. The pathophysiology of MOH remains unclear. The only therapy is withdrawal from the overused substances. Prednisone decreases the duration of headache in the first days of withdrawal therapy. The only strategy to reduce the prevalence of MOH is to prevent the development of MOH in the first place by restriction of anti-headache drugs and constant education of patients.
Current Pain and Headache Reports 01/2006; 9(6):430-5. DOI:10.1007/s11916-005-0023-6 · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated efficacy, safety, and tolerability of two tablets of the fixed combination of 250 mg acetylsalicylic acid (ASA) + 200 mg paracetamol + 50 mg caffeine (Thomapyrin) in comparison with two tablets of 250 mg ASA + 200 mg paracetamol, two tablets of 500 mg ASA, two tablets of 500 mg paracetamol, two tablets of 50 mg caffeine, and placebo in patients who were used to treating their episodic tension-type headache or migraine attacks with non-prescription analgesics. For the primary endpoint "time to 50% pain relief" in the intention-to-treat dataset (n = 1743 patients), the fixed combination of ASA, paracetamol and caffeine was statistically significantly superior to the combination without caffeine (P = 0.0181), the mono-substances ASA (P = 0.0398), paracetamol (P = 0.0016), caffeine (P < 0.0001) and placebo (P < 0.0001). All active treatments except caffeine differed significantly (P < 0.0001) from placebo. The superior efficacy of the triple combination could also be shown for all secondary endpoints such as time until reduction of pain intensity to 10 mm, weighted sum of pain intensity difference (%SPIDweighted), extent of impairment of daily activities, global assessment of efficacy. All treatments were well tolerated. The incidence of adverse events observed was low.
[Show abstract][Hide abstract] ABSTRACT: The study compared efficacy and tolerability of intravenous valproate (iVPA) with intravenous lysine-acetylsalicylic acid (iLAS) in acute migraine attacks. Background.-iLAS has been proven to be a highly effective treatment in acute migraine attacks, but it is not available in many countries and contraindicated in patients with asthma or peptic ulcers. Current data suggest that iVPA may be effective in the treatment of acute migraine attacks.
In this randomized, double-blind, parallel-group phase-II study, 40 patients with acute migraine attacks (onset <5 hours, severe or moderate headache on a four-point IHS scale) alternately received iVPA 800 mg or iLAS 1000 mg. Primary outcome criteria were the percentage of patients reporting pain relief after 1 hour and patients who remained sustained pain free for 24 hours following drug administration. Secondary outcome criteria were relief of pain and associated migrainous symptoms (nausea, photophobia, and phonophobia) at 1, 2, 24, and 48 hours following drug administration.
There were no significant differences in demographic and clinical features between both treatment groups. Percentage of pain relief after 1 hour in the iVPA and iLAS groups were 25% and 30%, respectively, and of sustained pain free for 24 hours were 20% and 30%, respectively, without significant differences (P = 1 and P= .72, respectively). Both drugs improved associated migrainous symptoms without significant differences at the different time points, but again with a trend in favor of iLAS. No adverse events were observed.
Both drugs were effective in acute migraine attacks with a trend in favor of iLAS. As both drugs were well tolerated, further studies with higher doses of iVPA for the treatment of acute migraine attacks are recommended.
Headache The Journal of Head and Face Pain 02/2005; 45(1):42-6. DOI:10.1111/j.1526-4610.2005.05009.x · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated efficacy, safety, and tolerability of two tablets of the fixed combination of 250 mg acetylsalicylic acid (ASA) plus 200 mg paracetamol plus 50 mg caffeine (Thomapyrin®) in comparison to two tablets of 250 mg ASA plus 200 mg paracetamol, two tablets of 500 mg ASA, two tablets of 500 mg paracetamol, two tablets of 50 mg caffeine, and placebo in patients who are used to treat their episodic tension-type headache or migraine attacks with non-prescription analgesics. For the primary endpoint "time to 50% pain relief" in the ITT data set (n = 1 743 patients), the fixed combination of acetylsalicylic acid, paracetamol and caffeine was statistically significantly superior to the combination without caffeine (p = 0,0181), the mono substances ASA (p = 0,0398), paracetamol (p = 0,0016), caffeine (p < 0,0001) and placebo (p < 0,0001). All active treatments except caffeine differed significantly (p < 0,0001) from placebo. The superior efficacy of the triple combination could also be shown for all secondary endpoints like time until reduction of pain intensity to 10 mm, weighted Sum of Pain Intensity Difference (% SPID weighted), extent of impairment of daily activities, global assessment of efficacy. All treatments were well tolerated. The incidence of adverse events observed was low.