Migraine patients in Germany - need for medical recognition and new preventive treatments: results from the PANORAMA survey.

BACKGROUND: Migraine is a primary headache disorder characterized by recurrent attacks that may have a significant impact on patients' daily life. Treatment options must often be re-evaluated in light of efficacy, tolerability and compliance issues. Few data on commonly applied treatment algorithms and treatment failures have existed in Germany in 2017/2018. The PANORAMA survey was designed to explore and characterize the migraine healthcare landscape and to demonstrate the medical treatment need at that time in Germany. METHODS: Three different questionnaires were used to assess the profile of the 119 participating centers, characterize migraine patients at centers and evaluate qualitative aspects of the current migraine healthcare situation from a physician´s professional perspective. Data were analyzed as observed and summarized by descriptive statistics. RESULTS: The results demonstrate that once referred to a migraine specialist, the majority of patients continue to be treated at a specialist. At specialized centers, 41.6 % of migraine patients receive prophylactic treatment. 45.4 % of prophylactic treatments are initiated with a beta-blocker and 28.1 % with an anti-epileptic. Pivotal factors to initiate prophylactic treatment are migraine attack frequency and intensity (58.0 %). Treatment decisions are largely based on prior / concomitant diseases and physical constitution of the patient (52.1 %). Following an inadequate treatment, most patients either switch substance class or discontinue prophylactic treatment. CONCLUSIONS: PANORAMA gives a comprehensive overview of the migraine healthcare landscape in Germany in 2017/2018, elucidates a lack of common treatment algorithms and reveals a high demand for defined therapy strategies and new prophylactic treatment going forwards.

[Treatment of chronic migraine with botulinum neurotoxin A : Expert recommendations of the German Migraine and Headache Society]. / Therapie der chronischen Migräne mit Botulinumneurotoxin A : Expertenempfehlung der Deutschen Migräne- und Kopfschmerzgesellschaft.

BACKGROUND: Injection of botulinum neurotoxin A (BoNT-A) according to the PREEMPT (Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy) paradigm has been approved for the treatment of refractory chronic migraine in Germany in 2011. OBJECTIVE: The practical application raises some questions, such as the choice of dose and injection intervals during the course of the treatment, and the appropriate time point for discontinuation of BoNT-A treatment. MATERIAL AND METHODS: Taking into account the existing literature, the German Migraine and Headache Society (Deutsche Migräne- und Kopfschmerzgesellschaft, DMKG) gives recommendations for the treatment of chronic migraine with BoNT-A. RESULTS: Treatment is usually started with a dose of 155 U BoNT-A. During the first year of treatment, 3­month injection intervals are recommended. Goal of the treatment is an improvement of migraine by ≥30%. If needed, dose escalation up to 195 U can be used to reach this goal. If improvement by ≥30% is not reached after the third injection cycle, the treatment is usually considered to be insufficiently efficient and discontinuation is recommended. If a stable success is reached during the first year of treatment, prolongation of injection intervals to 4 months can be considered. If success continues to be stable for at least two 4­month intervals, discontinuation of BoNT-A treatment can be tried. CONCLUSION: The literature on these points is insufficient for recommendations at the guideline level. The present recommendations are based on an expert consensus of the DMKG for the structured approach to the treatment of chronic migraine with BoNT-A.

Occipital nerve stimulation for chronic migraine: a randomized trial on subthreshold stimulation.

INTRODUCTION: Occipital nerve stimulation (ONS) may provide pain relief in migraine patients. In this double-blinded trial we investigated the significance of paresthesia and possible placebo effects. METHODS: Patients already treated with ONS reporting stable treatment effect were included. "Effective stimulation," "subthreshold stimulation" and "no stimulation" were compared. Patients cycled through all three treatment groups. Outcome was measured using the visual analog scale (VAS) for pain, McGill Pain Questionnaire and SF-36. RESULTS: Eight patients were included, mean preoperative VAS was 8.20 ± 1.22. A significant improvement in pain was observed in favor of suprathreshold stimulation compared to subthreshold stimulation (1.98 ± 1.56 vs 5.65 ± 2.11). Pain also significantly improved under subthreshold stimulation compared to no stimulation (5.65 ± 2.11 vs 8.45 ± 0.99). No changes in SF-36 were observed. CONCLUSIONS: Paresthesia is not required to achieve pain reduction but suprathreshold stimulation yields better results, underlining the significance of stimulation parameter customization.

Prevention of episodic migraine with topiramate: a prospective 24-week, open-label, flexible-dose clinical trial with optional 24 weeks follow-up in a community setting.

OBJECTIVE: To explore efficacy and safety outcomes of topiramate for episodic migraine prevention in community practice. RESEARCH DESIGN AND METHODS: Open-label, multicenter, flexible-dose clinical trial consisting of a 4-week baseline phase, 24-week core phase and an optional 24-week follow-up phase in patients (18-80 years) with episodic migraine treated in community practices outside tertiary care centers. MAIN OUTCOME MEASURES: The primary efficacy endpoint was the change in the number of migraine days/28 days (baseline vs. the last 4 weeks of core treatment) Secondary efficacy parameters included aspects of quality of life (QoL) and subjective patient ratings. RESULTS: A total of 360 patients entered the core phase (ITT population); 37.6% (97 patients) discontinued prematurely, mainly due to adverse events (AEs; 23.6%). Mean topiramate dosage was 90 mg/day. Migraine days decreased from 8.30/28 days to 5.65/28 days and QoL (HIT-6 and MIDAS) was improved. Efficacy, tolerability and satisfaction were rated as 'good' or better by 56, 61 and 63% of patients, respectively. A total of 321 of 364 patients (88.2%) reported at least one treatment emergent AE, and the most common during the core phase were paraesthesia (46.4% of 364 patients), fatigue (17.0%), nausea (15.4%), dizziness (12.9%), viral infection (12.9%), weight decrease (12.6%) and impaired concentration (10.2%). Of 227 patients completing the core phase, 199 (88%) participated in the follow-up phase. A total of 187 patients received topiramate and 38 (20.3%) of these stopped treatment prematurely due to insufficient efficacy (6.4%), AEs (4.8%) or other reasons (10.2%). Reduction in migraine days and improvements in QoL (HIT-6) were maintained or improved (MIDAS) during follow-up, and 84% rated their satisfaction with topiramate therapy as 'good to very good'. CONCLUSIONS: This community practice study showed that long-term treatment with topiramate in the prevention of episodic migraine was effective and well-tolerated, and it was associated with clinically relevant improvements in several aspects of QoL.

Migraines with and without aura and their response to preventive therapy with topiramate.

Data from the Prolonged Migraine Prevention (PROMPT) with Topiramate trial were evaluated post hoc to determine whether topiramate could prevent migraine auras, and whether its efficacy in preventing migraine headaches was similar in patients with (MA; n = 269) and without (MoA; n = 542) aura. Migraines and auras were recorded during prospective baseline, 6-month open-label (OL) topiramate and 6-month double-blind (DB), placebo-controlled phases. In the last 28 OL days, migraines without aura and migraine auras decreased by 43.1% and 54.1%, respectively, in MA patients. MoA patients experienced a 44.3% reduction in migraines. In the DB phase, increases in migraines with placebo vs. topiramate were similar to the full study, but were generally not statistically significant, probably due to lack of power in the subgroup analysis. Similarly, there were no statistically significant changes in number of auras between groups. Thus, topiramate appears to reduce migraine auras in parallel with headache reductions, which are similar in patients with and without aura.

[Diagnosis and treatment of head and facial pain]. / Diagnose und Therapie von Kopf- und Gesichtsschmerzen.

The symptom headache is very frequent. Most frequently headache is the leading symptom of a primary headache syndrome such as migraine or tension-type headache. Sometimes it is caused by another disease. In everyday clinical practice it is important to diagnose and treat primary headaches properly. It is even more important not to miss a secondary headache, which is rare, but if misdiagnosed could conceal life-threatening conditions. This review provides an overview of the clinical picture, diagnostic procedures and treatment strategies of frequent headache syndromes such as migraine, tension-type headache, medication overuse headache, trigeminal autonomic cephalgias and trigeminal neuralgia. This is followed by a brief summary on symptomatic headache caused by non-neurological diseases as well as on diagnostic procedures and management of headache in the emergency situation.

Telmisartan in migraine prophylaxis: a randomized, placebo-controlled trial.

We evaluated telmisartan 80 mg for migraine prophylaxis. Migraine patients (n = 95) with three to seven migraine attacks in 3 months were randomized, double-blind to telmisartan or placebo. The primary end-point was the reduction in the number of migraine days (i.e. a day with > or = 1 h of symptoms) between the 4-week baseline period and the last 4 weeks of the 12-week treatment period. A responder was recorded when there was a symptom reduction of > or = 50% in these 4-week baseline and treatment periods. The reduction in migraine days was 1.65 with telmisartan and 1.14 with placebo (P > 0.05). Post hoc analyses adjusting for baseline and centre showed a 38% reduction in migraine days with telmisartan vs. 15% with placebo (P = 0.03), and a borderline significant difference in responders (40% vs. 25%, P = 0.07). The incidence of adverse events was similar between treatments. This study indicates that telmisartan might be effective in migraine prophylaxis.

Validity and reliability of the Migraine-Treatment Optimization Questionnaire.

Our aim was to establish the validity and reliability of a patient-rated Migraine Treatment Optimization Questionnaire (M-TOQ) in primary care. Patients who met International Classification of Headache Disorders, 2nd edn criteria for migraine completed a 19-item questionnaire containing candidate items for the M-TOQ, and three questionnaires designed to test convergent/construct validity [Migraine Disability Assessment Scale (MIDAS), Headache Impact Test (HIT)-6 and Migraine-Specific Quality of Life Scale (MSQoL)]. A 15-item (M-TOQ-15) and a five-item (M-TOQ-5) questionnaire were derived. Two hundred and fifty-three adult patients were recruited. Five treatment optimization domains were identified: functioning, rapid relief, consistency of relief, risk of recurrence and tolerability; with Cronbach alphas of 0.70-0.84. The Cronbach alpha for M-TOQ-15 was 0.85, and it correlated well with MIDAS, HIT-6 and MSQoL (r = 0.33-0.44). The Cronbach alpha for M-TOQ-5 was 0.66, and it also correlated well with the three questionnaires (r = 0.33-0.41). The utility of the M-TOQ for assessing treatment benefit in research (M-TOQ-15) and primary care (M-TOQ-5) should be further validated.

[Diagnosis and treatment of head and facial pain]. / Diagnose und Therapie von Kopf- und Gesichtsschmerzen.

The symptom headache is very frequent. Most frequently headache is the leading symptom of a primary headache syndrome such as migraine or tension-type headache. Sometimes it is caused by another disease. In everyday clinical practice it is important to diagnose and treat primary headaches properly. It is even more important not to miss a secondary headache, which is rare, but if misdiagnosed could conceal life-threatening conditions. This review provides an overview of the clinical picture, diagnostic procedures and treatment strategies of frequent headache syndromes such as migraine, tension-type headache, medication overuse headache, trigeminal autonomic cephalgias and trigeminal neuralgia. This is followed by a brief summary on symptomatic headache caused by non-neurological diseases as well as on diagnostic procedures and management of headache in the emergency situation.

Early treatment in migraine: how strong is the current evidence?

Over the last 10 years, triptans (serotonin 5-HT(1B/1D) receptor agonists) have proved to be efficacious in treating migraine pain. However, recent evidence suggests that patients are still not receiving optimal pain management, particularly in clinical trials, where triptan treatment is generally not initiated until pain has reached moderate intensity. Pathophysiological evidence indicates that if treatment is initiated at an early stage, while pain is still mild and before the onset of central sensitization, outcomes for patients may be improved. In addition, a small number of clinical trials have been reported in which triptans were taken early (within 1 h of pain onset) or while pain was still mild; although constraints of trial design and data analysis limit definite conclusions, overall the results suggest that this early/mild approach results in more rapid and sustained pain relief. New studies are therefore needed to clarify the clinical benefits of early treatment, whilst taking into account potential risks, such as medication overuse. Ultimately, migraine treatment strategies require optimization in order to meet patient expectations and to reduce the current burden of migraine-associated disability.

[Development of a screening tool for migraine prophylaxis]. / Entwicklung eines Migräneprophylaxe-Screeninginstruments (MPS).

The aim of the present study was to develop a screening tool to aid non-headache specialists, like general practitioners, in deciding whether migraine prophylaxis in the individual migraine patient is useful or not. The first step was the development of a questionnaire, consisting of 10 items, which was filled in by 132 migraineurs who called on neurologists or headache experts. Independently, the physicians filled in another questionnaire to answer the question of whether they decided to prescribe migraine prophylaxis and if they had, to give their reasons for doing so. Using logistic regression analysis, we identified the three questions which had the most influence on the decision regarding prophylaxis in the data set. As results, we identified the following three questions: 1. Do you suffer from migraine on more than 3 days/month? 2. Do you have to rest in bed while experiencing a migraine attack? 3. Do you have to take medication against migraine on more than 5 days/month? Validation of this reduced questionnaire is currently ongoing and involves 150 migraine patients of general practitioners.

Clinical profile and practice experience of almotriptan.

Patients expect their acute migraine treatment to have a rapid onset of action, achieve complete pain relief that is sustained for 24 h, and to have a good tolerability profile. Almotriptan has a favourable pharmacokinetic profile that translates clinically to a rapid onset of action and consistent absorption regardless of age, sex, food intake and status of the acute migraine attack. In addition, almotriptan is not associated with any clinically relevant drug-drug interactions. Pain-free status at 2 h postdose is achieved by approximately 39% of patients receiving almotriptan in clinical trials. Recurrence of headaches within 24 h is low with almotriptan (<22%). Almotriptan has a sustained pain-free rate of 25-27%, which in a meta-analysis of triptans was superior to sumatriptan 100 mg. Almotriptan therapy is associated with a low incidence of adverse events, including those affecting the central nervous system and chest.

[Treatment and prophylaxis of an acute migraine attack]. / Wie scharf müssen Sie gegen die Migräne schiessen? Eisbeutel und ASS, oder Triptan und eine Prophylaxe.

The treatment of migraine takes into consideration the intensity of the headache and the accompanying symptoms. The goal is to reduce the headache intensity, to relieve nausea and vomiting and to restore the ability to function in the daily routine. For drug treatment, there are now highly effective serotonin agonists available in addition to the older ergotamine preparations. A problem with all migraine analgesics is that in long lasting migraine attacks, the headache can recur as the pharmacological effect of the medication wears off. Through nonmedicinal and medicinal prophylactic measures, the frequency and intensity of the migraine attacks can be reduced. Keeping a headache diary for documentation is essential.

The therapeutic profile of zolmitriptan in clinical practice.

The efficacy and tolerability of the 5-HT1B/1D-receptor agonist zolmitriptan was evaluated in an open post-marketing surveillance study in 12,919 patients, treating 36,510 migraine attacks. Mean visual analogue scale scores for pain decreased (6.9-2.2; 68% improvement) and scores for impairment of normal activities decreased (6.6-2.2; 67% improvement) at 2 h after dose. Non-headache symptoms of migraine resolved in 73-86% of attacks. Improvement was achieved within 2 h in >80% of attacks and within 1 h in 37% of attacks. This high level of efficacy was achieved with a single 2.5 mg dose in 95% of attacks. Compared with previous migraine treatments, 85% of patients preferred zolmitriptan for efficacy and 56% for better tolerability. Corresponding preference rates were 87 and 63% when compared with ergot alkaloids. Adverse events occurred in 2% of patients and were either typical class effects or known symptoms and complications of migraine. These results provide evidence for the high efficacy and good tolerability of the 2.5 mg dose of zolmitriptan in clinical practice in migraine. Zolmitriptan was very well tolerated, with patients expressing a distinct preference for zolmitriptan over previous treatments.

[Difficult decisions: headache treatment in pregnancy and childhood]. / Schwierige Entscheidungen. Kopfschmerztherapie in der Schwangerschaft und bei Kindern.

In pregnancy and in childhood, headache and migraine are challenging therapeutic problems.However, this review aims to give treatment recommendations for drug and non-drug therapy in both patient groups which are based on scientific evidence. Pregnant women often lose their migraine attacks which reappear during lactation. During pregnancy acute headache can be treated with paracetamol, in the middle trimenon also ASA and ibuprofen are allowed. Triptans for the acute treatment of migraine are contraindicated. As prophylactic agents, only metoprolol, fluoxetine, and magnesium are possible. In childhood, drug of first choice for acute headache treatment is ibuprofen. Migraine can also be treated by sumatriptan nasal spray. In migraine prophylaxis, flunarizine is drug of first choice, no prophylactic drugs are evaluated for tension-type headache in childhood. The problems of specific contraindications and of the off-label use of drugs in this particular life periods are discussed.

[Migraine costs and success of non-medicamentous therapy procedures. Relation of diagnostic measures]. / Migräne--Kosten und Erfolg nicht-medikamentöser Therapieverfahren. Häufigkeit diagnostischer Massnahmen.

BACKGROUND: Migraine is a common neurological disorder (16% women, 6% men) associated with high direct and indirect costs. We evaluated the diagnostic and paramedical therapeutic measures by estimating the expenditure per patient and the effect of treatment. METHODS: A questionnaire was sent to 1000 patients attending the Essen outpatient headache centre in 1995. A total of 293 patients responded, of whom 165 were eligible and could be evaluated. Patients were asked to report diagnostic tests, paramedical treatments applied, average duration of success (defined as meaningful reduction in migraine frequency) and costs of paramedical therapy. RESULTS: Paramedical methods of therapy most frequently used were acupuncture, special pads, relaxation methods and herbal therapy. A total of 579 (3.5 on average) diagnostic procedures such as brain or cervical spine CT and MRI or EEG was performed. The average cost for acupuncture was 465 US dollars, while the success was maintained for 3.2 months. 1510 US dollars was spent on psychotherapy, which was successful for 1.7 months. Patients spent 93 US dollars for relaxation methods, achieving migraine relief for 7.4 months. CONCLUSION: Paramedical treatments lack scientific proof, while both acute and prophylactic treatment strategies have been successfully tested in many clinical trials. Paramedical treatment shows a good temporally effect in individual patients.

Emerging treatments in headache.

Recent PET studies performed in humans during migraine attacks revealed a 'spreading depression-like' oligemia in the occipital cortex during the aura phase and a region of increased blood flow in the brainstem during the headache phase. Animal models were established to test new migraine drugs. A number of 5-HT agonists, the so-called 'triptans', will be available in future besides sumatriptan to treat acute migraine attacks. Migraine prophylaxis is still hampered by the fact that we do not understand the action of drugs used for this purpose and do not have an animal model. Nevertheless, new substances were introduced recently into the prophylaxis of migraine.