Management of medication overuse (MO) and medication overuse headache (MOH) S1 guideline.

INTRODUCTION Chronic headache due to the overuse of medication for the treatment of migraine attacks has a prevalence of 0.5-2.0%. This guideline provides guidance for the management of medication overuse (MO) and medication overuse headache (MOH). RECOMMENDATIONS Treatment of headache due to overuse of analgesics or specific migraine medications involves several stages. Patients with medication overuse (MO) or medication overuse headache (MOH) should be educated about the relationship between frequent use of symptomatic headache medication and the transition from episodic to chronic migraine (chronification), with the aim of reducing and limiting the use of acute medication. In a second step, migraine prophylaxis should be initiated in patients with migraine and overuse of analgesics or specific migraine drugs. Topiramate, onabotulinumtoxinA and the monoclonal antibodies against CGRP or the CGRP-receptor are effective in patients with chronic migraine and medication overuse. In patients with tension-type headache, prophylaxis is performed with amitriptyline. Drug prophylaxis should be supplemented by non-drug interventions. For patients in whom education and prophylactic medication are not effective, pausing acute medication is recommended. This treatment can be performed in an outpatient, day hospital or inpatient setting. Patients with headache due to overuse of opioids should undergo inpatient withdrawal. The success rate of the stepped treatment approach is 50-70% after 6 to 12 months. A high relapse rate is observed in patients with opioid overuse. Tricyclic antidepressants, neuroleptics (antiemetics) and the administration of steroids are recommended for the treatment of withdrawal symptoms or headaches during the medication pause. Consistent patient education and further close monitoring reduce the risk of relapse

Efficacy and safety of fremanezumab in clinical trial participants aged ≥60 years with episodic or chronic migraine: pooled results from 3 randomized, double-blind, placebo-controlled phase 3 studies

Background: Although migraine is less common in older people, preventive treatment of migraine in these individuals may be more challenging due to the presence of multiple comorbidities and polypharmacy. Additionally, evidence for migraine treatment efficacy, safety, and tolerability is limited in this population. We evaluated efficacy, safety, and tolerability of fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), in clinical trial participants aged ≥60 years with episodic migraine (EM) or chronic migraine (CM). Methods: This analysis included data from 3 randomized, double-blind, placebo-controlled phase 3 studies: the HALO EM study, HALO CM study, and FOCUS study in participants with EM or CM and prior inadequate response to 2-4 migraine preventive medication classes. Participants in all studies were randomized 1:1:1 to receive 12 weeks of subcutaneous treatment with quarterly fremanezumab (Months 1/2/3: EM/CM, 675 mg/placebo/placebo), monthly fremanezumab (Months 1/2/3: EM, 225 mg/225 mg/225 mg; CM, 675 mg/225 mg/225 mg), or matched monthly placebo. Results: These pooled analyses included 246 participants aged ≥60 years. Reductions in monthly migraine days from baseline over 12 weeks were significantly greater with fremanezumab (least-squares mean change from baseline [standard error]: quarterly fremanezumab, - 4.3 [0.59]; monthly fremanezumab, - 4.6 [0.54]) versus placebo (placebo, - 2.3 [0.57]; both P \u3c 0.01 vs placebo). As early as Week 1, significant reductions from baseline in weekly migraine days were observed with fremanezumab versus placebo (both P \u3c 0.01). With fremanezumab treatment versus placebo, a significantly higher proportion of participants achieved ≥50% reduction in monthly migraine days, and significant improvements in disability and quality-of-life outcomes were observed (P \u3c 0.05). Proportions of participants experiencing serious adverse events and adverse events leading to discontinuation were low and similar in the fremanezumab and placebo groups. Efficacy and safety results were comparable to the overall pooled population (N = 2843). Conclusions: This pooled subgroup analysis demonstrates that fremanezumab treatment is efficacious and well-tolerated over 12 weeks in participants aged ≥60 years with EM or CM. These data may help healthcare providers with clinical decision making and preventive treatment selection for older patients with migraine. Trial registration: ClinicalTrials.gov identifiers: HALO CM: NCT02621931 ; HALO EM: NCT02629861 ; FOCUS: NCT03308968

Noninvasive vagus nerve stimulation in the management of cluster headache: clinical evidence and practical experience

The efficacy of invasive vagal nerve stimulation as well as other invasive neuromodulatory approaches such as deep brain stimulation, occipital nerve stimulation, and ganglion sphenopalatine stimulation has been shown in the treatment of headache disorders in several studies in the past. However, these invasive treatment options were quite costly and often associated with perioperative and postoperative side effects, some severe. As such, they were predominantly restricted to chronic and therapy refractory patients. Transcutaneous vagal nerve stimulation now offers a new, noninvasive neuromodulatory treatment approach. Recently published studies showed encouraging results of noninvasive vagus nerve stimulation (nVNS), especially with respect to cluster headache, with high tolerability and a low rate of side effects; however, randomized controlled trials are needed to prove its efficacy. Further data also indicate therapeutic benefits regarding treatment of migraine and medication overuse headache. This review summarizes current knowledge and personal experiences of nVNS in the treatment of cluster headache

Visual snow syndrome is probably not mediated by CGRP: A case series.

BACKGROUND Visual snow syndrome is a phenomenon for which no effective treatment is known. It is highly comorbid with migraine, therefore we performed a retrospective chart review of patients with visual snow syndrome treated with a monoclonal antibody against calcitonin gene related peptide or its receptor. FINDINGS We enrolled 15 patients with visual snow syndrome who received at least once a monoclonal antibody against calcitonin gene related peptide or its receptor. None of the patients reported relief of visual snow syndrome whereas those patients with comorbid migraine reported a very good efficacy of the antibody against the migraine headache but not against the migraine aura. CONCLUSION The data suggest that visual snow syndrome is not mediated by calcitonin gene related peptide in a relevant way and that the calcitonin gene related peptide receptor is not involved in the network underlying the visual snow syndrome

Galcanezumab bei episodischem und chronischem Clusterkopfschmerz

Zusammenfassung Hintergrund Der Clusterkopfschmerz (CK) ist eine schwerwiegende Kopfschmerzerkrankung mit heftigen unilateralen Schmerzattacken, begleitet von ipsilateralen autonomen Symptomen. Pathophysiologisch wird u. a. dem „calcitonin gene-related peptide“ (CGRP) eine wichtige Rolle beigemessen. Fragestellung Prophylaktische Wirksamkeit und Verträglichkeit des Anti-CGRP-Antikörpers Galcanezumab bei episodischem (eCK) und chronischem CK (cCK), Diskussion der Studienergebnisse und der Herausforderungen bei der Entwicklung von Medikamenten für die prophylaktische Behandlung des Clusterkopfschmerzes. Material und Methoden In zwei Phase-III-Studien wurde Galcanezumab (300 mg subkutan alle 4 Wochen) mit Placebo verglichen. Der Doppelblindphase (8 Wochen bei eCK, 12 Wochen bei cCK) ging jeweils eine Baseline-Phase voraus. Primärer Endpunkt war der Rückgang der wöchentlichen Attackenhäufigkeit. Ergebnisse und Diskussion In der Studie bei eCK wurden 106 Patienten randomisiert (49 Galcanezumab, 57 Placebo). In der Galcanezumabgruppe ging im Durchschnitt der ersten 3 Wochen die Häufigkeit von Kopfschmerzattacken um 52 % zurück, in der Placebogruppe um 27 % (p = 0,036). In der Studie beim cCK wurden 237 Patienten randomisiert (117 Galcanezumab, 120 Placebo). Hier wurde der primäre Studienendpunkt verfehlt (Rückgang der mittleren wöchentlichen Attackenhäufigkeit um 5,4 mit Galcanezumab vs. 4,6 mit Placebo; p = 0,334). In beiden Studien war Galcanezumab gut verträglich. Schlussfolgerungen Galcanezumab hat beim eCK eine prophylaktische Wirkung, nicht aber beim cCK. Mögliche Gründe für diese Diskrepanz werden diskutiert. Abstract Background Cluster headache (CH) is a highly debilitating headache disorder characterized by frequent attacks of excruciating unilateral pain accompanied by cranial autonomic symptoms. Calcitonin gene-related peptide (CGRP) is implicated in the pathophysiology of CH. Objectives Preventive efficacy and tolerability of the anti-CGRP antibody galcanezumab in patients with episodic (eCH) and chronic CH (cCH). Review of the study results and the challenges in developing drugs for the preventive treatment of CH. Materials and methods In two international multicenter phase III trials galcanezumab 300 mg given subcutaneously every 4 weeks was compared with placebo. The double-blind study period (8 weeks in eCH, 12 weeks in cCK) was preceded by a baseline period in both trials. The primary endpoint was the reduction in weekly attack frequency. Results In the eCH trial, 106 patients were randomized to either galcanezumab (n = 49) or placebo (n = 57). The mean weekly attack frequency during the first 3 weeks decreased by 52% in the galcanezumab group compared with 27% in the placebo group (p = 0.036). In the cCH trial, 237 patients were randomized to galcanezumab (n = 117) or placebo (n = 120). The primary endpoint was not met in this study. The reduction in mean weekly attack rate was 5.4 with galcanezumab versus 4.6 with placebo (p = 0.334). Galcanezumab was well tolerated in both studies. Conclusions Galcanezumab had a significant effect in the prevention of eCH attacks but not in cCH. Possible reasons for this discrepancy are discussed

Migraine Prophylaxis Expectation

Migraine is one of the leading causes of years lived with disability and considered to be a major global health concern. Pharmacological preventive treatment often causes side effects that limit the adherence to longer-term treatment regimens. Both experimental and clinical evidence suggests that positive expectations can modulate pain and analgesic treatment effects. However, the role of expectations in migraine prophylactic treatment has not systematically been investigated. Here, we examined the influence of treatment expectation before commencing pharmacological preventive treatment on its efficacy and tolerability in N 5 134 episodic (30%) and chronic migraine (70%) patients in a prospective, longitudinal observational study over the course of 6 months. The migraine prophylaxis reduced the number of headache and migraine days with acceptable tolerability. Positive treatment expectation was associated with a generally lower number of headache and migraine days and a stronger reduction in headache days over the course of the treatment in chronic but not in episodic migraine patients. Moreover, patients with prior treatment showed a stronger reduction in headache days with higher expectation as compared to patients without prior experience. Our results underscore the relevance of further exploring the role of treatment expectation and its systematic modulation in patients with migraine and other pain conditions

Treatment of Migraine Attacks and Prevention of Migraine: Guidelines by the German Migraine and Headache Society and the German Society of Neurology

In collaboration with some of the leading headache centres in Germany, Switzerland and Austria, we have established new guidelines for the treatment of migraine attacks and the prevention of migraine. A thorough literature research of the last 10 years has been the basis of the current recommendations. At the beginning, we present therapeutic novelties, followed by a summary of all recommendations. After an introduction, we cover topics like drug therapy and practical experience, non-effective medication, migraine prevention, interventional methods, non-medicational and psychological methods for prevention and therapies without proof of efficacy