Medical Undergraduate Survey on Headache Education in Singapore: Knowledge, Perceptions, and Assessment of Unmet Needs.

Secondary headaches attributed to exposure to or the overuse of a substance are classified under chapter eight in the International Classification of Headache Disorders 3rd edition. Three distinct sub-chapters consider: 1. Headache attributed to exposure to a substance, 2. Medication overuse headache, and 3. Headache attributed to substance withdrawal. Headache attributed to exposure to a substance refers to a headache with onset immediately or within hours after the exposure, while medication overuse headache is a headache occurring on 15 or more days per month that has developed as a consequence of regular usage of acute headache medication(s) for more than three consecutive months in a patient with a pre-existing primary headache disorder. The withdrawal of caffeine, oestrogen, and opioids is most often associated with the development of headache. Despite the current headache classification, there is no certainty of a causal relationship between the use of any substance and the development of headache. Some substances are likely to provoke headache in patients that suffer from a primary headache disorder like migraine, tension-type headache or cluster headache, while others were described to cause headache even in people that generally do not get headaches. Toxic agents, such as carbon monoxide (CO) are difficult to investigate systematically, while other substances such as nitric oxide (NO) were specifically used to induce headache experimentally. If a patient with an underlying primary headache disorder develops a headache, in temporal relation to exposure to a substance, which is significantly worse than the usual headache it is considered secondary. This is even more the case if the headache phenotype is different from the usually experienced headache characteristics. Medication overuse headache is a well-described, distinct disease entity with only marginally understood pathophysiology and associated psychological factors. Managing medication overuse headache patients includes education, detoxification, prophylactic treatments and treating comorbidities, which is reflected in available guidelines. Viewing medication overuse headache as a separate entity helps clinicians and researchers better recognise, treat and study the disorder. Identification of substances that may cause or trigger secondary headache is important in order to educate patients and health care professionals about potential effects of these substances and prevent unnecessary suffering, as well as deterioration in quality of life. Treatment in case of medication overuse and other chronic headache should be decisive and effective.

Migraine

The frequent or regular intake of medication to treat acute headache episodes can lead to an increase in headache frequency and finally to a transition from episodic to chronic headache. Many patients with chronic headache take abortive medication on a daily basis. Medication overuse headache (MOH) is defined by the International Classification of Headache Disorders as a headache in patients with a pre-existing primary headache disorder (e.g., migraine or tension-type headache) occurring on ≥15 days per month for >3 months. Also, these primary headache disorders occur in association with overuse of medication for acute or symptomatic headache treatment. The prevalence of MOH in the general population is around 1%. MOH is more common in people with chronic migraine and chronic daily headache than in patients with episodic migraine. The phenotype of the headache in MOH depends on the initial primary headache and the type of overused acute medication. Treatment of MOH occurs in three stages. First, we educate patients about the relationship between frequent intake of acute headache medication and MOH to reduce intake of acute medication. In a second step migraine prevention should be initiated in chronic migraine (topiramate or onabotulinumtoxinA in migraine) or amitriptyline in chronic tension-type headache. In patients who fail to cease overuse of overused medication with preventive therapy, then detoxification occurs on an outpatient basis or in a day hospital or inpatient setting, depending on severity and comorbidities. The success rate of treatment is around 50–70%, with higher relapse rates in patients with opioid overuse. Patient education and continuity of care in the follow-up period reduce relapse rates.

Comparison of chronic daily headache with and without medication overuse headache using ICHD II R and ICHD 3 beta criteria

Introduction: Medication-overuse headache (MOH) is a secondary chronic headache disorder that occurs in individuals with a pre-existing primary headache disorder, particularly migraine disorder. Obesity is often combined with chronic daily headaches and is considered a risk factor for the transformation of episodic headaches into chronic headaches. However, the association between obesity and MOH among individuals with migraine has rarely been studied. The present study explored the association between body mass index (BMI) and MOH in people living with migraine. Methods: This cross-sectional study is a secondary analysis of data from the Survey of Fibromyalgia Comorbidity with Headache study. Migraine and MOH were diagnosed using the criteria of the International Classification of Headache Disorders, 3rd Edition. BMI (kg/m2) is calculated by dividing the weight (kg) by the square of the height (m). Multivariable logistic regression analysis was used to evaluate the association between BMI and MOH. Results: A total of 2,251 individuals with migraine were included, of whom 8.7% (195/2,251) had a concomitant MOH. Multivariable logistic regression analysis, adjusted for age, sex, education level, headache duration, pain intensity, headache family history, chronic migraine, depression, anxiety, insomnia, and fibromyalgia, demonstrated there was an association between BMI (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01–1.11; p = 0.031) and MOH. The results remained when the BMI was transformed into a category. Compared to individuals with Q2 (18.5 kg/m2 ≤ BMI ≤23.9 kg/m2), those with Q4 (BMI ≥28 kg/m2) had an adjusted OR for MOH of 1.81 (95% CI, 1.04–3.17; p = 0.037). In the subgroup analyses, BMI was associated with MOH among aged more than 50 years (OR, 1.13; 95%, 1.03–1.24), less than high school (OR, 1.08; 95%, 1.01–1.15), without depression (OR, 1.06; 95%, 1.01–1.12), and without anxiety (OR, 1.06; 95%, 1.01–1.12). An association between BMI and MOH was found in a sensitivity analysis that BMI was classified into four categories according to the World Health Organization guidelines. Conclusion: In this cross-sectional study, BMI was associated with MOH in Chinese individuals with migraine.

Managing Migraine

Dependence scores predict prognosis of medication overuse headache: A prospective cohort from the Akershus study of chronic headache

Clinical trials on onabotulinumtoxinA for the treatment of chronic migraine

The International Classification of Headache Disorders, Third Edition (ICHD-3), significantly influences clinicians' understanding of headache disorders. In this study, we aim to elucidate how the hierarchical structure of ICHD-3 shapes the understanding of interconnectivity among headache disorders. A network comprises elements known as "nodes," with the connections between them referred to as "edges." In our study, a node represents a headache diagnosis that meets at least one ICHD-3 diagnostic criterion of the ICHD-3. We developed two network models for ICHD-3: a non-hierarchical model, where edges are only formed by cross-references found within the text of diagnoses, and a hierarchical model that incorporates the ICHD-3's structural organization by adding extra edges between sections and their subsections. We identified the top 10 disorders in terms of their centrality, which assesses their popularity, their role as bridges in the network, and their proximity to other disorders. These measurements are calculated using the network's degree, betweenness, and closeness centrality. Both our models contain 387 nodes. The choice between a non-hierarchical or hierarchical model affects which diagnoses occupy the top 10 centrality nodes. In both models, migraine and medication-overuse headaches consistently rank among the top 10 diagnoses according to all three centrality metrics. The hierarchical model includes a greater number of secondary headache diagnoses among its top 10 compared to the non-hierarchical model. Migraine and medication overuse headaches are the most interconnected nodes in ICHD-3. The addition of a diagnostic hierarchy facilitates the unification of secondary headaches, which would otherwise be considered isolated, miscellaneous diagnoses. When interconnected hierarchically, these secondary headache diagnoses become the majority of the most well-connected nodes in our field.

Background and PurposeChronic daily headache (CDH) is defined as a headache disorder in which headaches occur on a daily or near-daily basis (at least 15 days/month) for more than 3 months. Chronic migraine (CM) and medication overuse headache (MOH) are very disabling headaches that remain underdiagnosed. The aim of this study was to establish the frequency of CDH and its various subtypes, and examine the associations with MOH among first-visit headache patients presenting at neurology outpatient clinics in Korea.MethodsEleven neurologists enrolled first-visit patients with complaints of headaches into outpatient clinics for further assessment. Headache disorders were classified according to the International Classification of Headache Disorder (third edition beta version) by each investigator.ResultsPrimary CDH was present in 248 (15.2%) of the 1,627 included patients, comprising CM (143, 8.8%), chronic tension-type headache (CTTH) (98, 6%), and definite new daily persistent headache (NDPH) (7, 0.4%). MOH was associated with headache in 81 patients (5%). The association with MOH was stronger among CM patients (34.5%) than patients with CTTH (13.3%) or NDPH (14.3%) (p=0.001). The frequency of CDH did not differ between secondary and tertiary referral hospitals.ConclusionsThe frequencies of CDH and MOH diagnoses were 15.2% and 5%, respectively in first-visit headache patients presented at secondary or tertiary referral hospitals in Korea. CM was the most common subtype of CDH and was most frequently associated with MOH.

PACAP-PAC1 receptor inhibition is effective in opioid induced hyperalgesia and medication overuse headache models

Medication-overuse headache: a worldwide problem

We studied secondary chronic headaches (> or = 15 days/month for at least 3 months) in a random sample of 30 000 persons aged 30-44 years. They received a mailed questionnaire. Those with self-reported chronic headache within the last month and/or year were invited to an interview and examination by a neurological resident. The criteria of the International Classification of Headache Disorders (ICHD-II) were applied. The questionnaire response rate was 71%, and the participation rate of the interview was 74%. Of the 633 participants, 298 had a secondary chronic headache. The 1-year prevalence of secondary chronic headache was 2.14%, i.e. chronic posttraumatic headache 0.21%, chronic headache attributed to whiplash injury 0.17%, post-craniotomy headache 0.02%, medication-overuse headache (MOH) 1.72%, cervicogenic headache 0.17%, headache attributed to chronic rhinosinusitis 0.33% and miscellaneous headaches 0.04%. The majority of those with ICHD-II-defined secondary chronic headache had MOH, while about one-third had other secondary headaches often in combination with MOH.

Although secondary headaches due to e.g. temporal arteritis or a brain tumor are common among the elderly, primary headache disorders also occur in this age group, albeit less frequently than in younger individuals. A different presentation in the older age groups often makes a diagnosis difficult. Some headache syndromes, such as hypnic headache, are typical for the elderly. Furthermore, age-related physiologic changes, co-morbidities and contra indications require appropriate and targeted treatment in the elderly. Although treatments for the most common primary headaches are available, many limitations hamper their use in this group. For many headaches syndromes randomized controlled treatment trials in elderly are not available. In this article we review the clinical aspects of common primary headaches and medication overuse headache in the elderly and their treatments, with emphasis on age-specific problems.Relevance for patients: Primary headache syndromes in older patients ask for specific treatment considerations due to comorbidity, polypharmacy and an increased risk of side effects. Clinically, the headaches can be different and atypical. Results from clinical trials cannot be generalized to the elderly because these groups usually are not included in studies. In migraine, non-pharmacologic treatment should be considered, with depression and cerebrovascular disease as major comorbidities. Tension type headache, being the most common headache presentation in elderly, also includes a relatively large proportion of patients with a secondary headache warranting further testing. Trigeminal autonomous cephalalgias are rare, and can present with pseudo dementia. Medication overuse and medication-induced headaches are relatively common, for which patient education, ceasing drugs and withdrawal from caffeine containing substances are pivotal. Furthermore, hypnic headache, exploding head syndrome and benign thunderclap headache are specific for this patient group and require specific treatment.

<h3>Objective:</h3> To analyze the migraine-preventive efficacy of eptinezumab in patients with a dual diagnosis of chronic migraine (CM) and medication-overuse headache (MOH). <h3>Background:</h3> Eptinezumab, a humanized anti-calcitonin gene-related peptide monoclonal antibody, is approved for the preventive treatment of migraine and has demonstrated effectiveness in patients with CM. <h3>Design/Methods:</h3> PROMISE-2 (NCT02974153), a double-blind, placebo-controlled, phase 3 study, randomized adults with CM to intravenous eptinezumab 100mg, 300mg, or placebo at day 0 and week 12 (wk12), for 24 weeks total treatment. Endpoints included changes in monthly migraine days (MMDs), monthly days of acute headache medication (AHM) use, percentage of patients below International Classification of Headache Disorders (ICHD) thresholds for CM and MOH, and assessments of patient-reported outcomes (PROs): 6-item Headache Impact Test (HIT-6), Patient Global Impression of Change (PGIC), and patient-identified most bothersome symptom (PI-MBS). <h3>Results:</h3> At baseline, 431/1072 (40.2%) patients with CM (eptinezumab 100mg [n=139]; 300mg [n=147]; placebo [n=145]) were diagnosed with MOH and averaged 16.7 MMDs. At wk12, mean MMDs decreased 8.4 (100mg) and 8.6 (300mg) from baseline, versus 5.4 placebo (P&lt;0.0001 for both doses). At 24wks, 29.0% of eptinezumab-treated patients were below CM and MOH diagnostic thresholds versus 6.3% with placebo. Total monthly AHM use decreased 9.8 days [BR1] (100mg) and 8.4 days [BR2] (300mg) during wks 1–12 vs 5 days [BR3] with placebo. HIT-6 total scores improved 7.0 (100mg) and 7.8 (300mg) vs 4.1 points (placebo) at wk12. At wk12, 58.5% (100mg) and 67.4% (300mg) of patients indicated PGIC was "much" or "very much" improved vs 35.8% placebo. PI-MBS improvement with eptinezumab treatment over placebo was similar to PGIC. <h3>Conclusions:</h3> This post hoc analysis of patients with dual diagnoses of CM and MOH suggests that eptinezumab treatment resulted in greater reductions in MMDs and AHM use compared with placebo and is associated with sustained, clinically meaningful improvements in PROs. <b>Disclosure:</b> Dr. Marmura has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Marmura has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Supernus. Dr. Marmura has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Axsome. Dr. Marmura has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Marmura has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Upsher-Smith. Dr. Marmura has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Marmura has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Theranica. Dr. Marmura has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Amgen/Novartis. Dr. Marmura has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Lilly. Dr. Marmura has stock in Curelator. The institution of Dr. Marmura has received research support from Teva. The institution of Dr. Marmura has received research support from AbbVie. Dr. Marmura has received publishing royalties from a publication relating to health care. Dr. Marmura has received publishing royalties from a publication relating to health care. Dr. Marmura has received publishing royalties from a publication relating to health care. Dr. Diener has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Diener has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for TEVA. Dr. Diener has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Lundbeck. Dr. Diener has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer. Dr. Diener has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Thieme. The institution of Dr. Diener has received research support from German Research Council. Dr. Cowan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Cowan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva. Dr. Cowan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbvie. Dr. Cowan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. Dr. Cowan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Cowan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for lundbeck. Dr. Cowan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for biohavenn. Dr. Cowan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbviie. Dr. Cowan has stock in Percept. Dr. Cowan has received intellectual property interests from a discovery or technology relating to health care. Dr. Cowan has received intellectual property interests from a discovery or technology relating to health care. Dr. Cowan has received publishing royalties from a publication relating to health care. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Axsome Therapeutics. Dr. Starling has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Starling has received personal compensation in the range of $0-$499 for serving as a Consultant for Med-IQ. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medscape. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurolief. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Everyday Health. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Allergan. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for WebMD. Joe Hirman, PhD has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck . Joe Hirman, PhD has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Impel NeuroPharma. Thomas Brevig has received personal compensation for serving as an employee of H. Lundbeck A/S. Thomas Brevig has received personal compensation for serving as an employee of Gedeon Richter Plc.. Thomas Brevig has stock in H. Lundbeck A/S. Dr. Cady has received personal compensation for serving as an employee of Lundbeck. Dr. Cady has stock in Alder Biopharmaceutical.