Management of medication overuse headache.

Medication overuse headache (MOH) is a secondary headache characterized by frequent use of acute or symptomatic migraine medications at a sufficient frequency to transform patients from episodic to chronic migraine. MOH represents a significant medical problem, with a serious burden on patients' lives and on society as a whole. MOH patients often have additional comorbidities, and the clinical challenge of helping patients reduce acute medication use and revert to episodic headache can be marked. Treatment includes education and prevention; withdrawal programs; pharmacological prophylaxis; multidisciplinary therapies with behavioral and noninvasive neuromodulation options; and scheduled, frequent follow-up to prevent relapses. The advent of anti-CGRP therapy monoclonal antibodies may provide an alternative to more extensive programs for less complex patients. This review also provides guidance for which patients may benefit most from coordinated integrated programs.

A narrative review of the importance of pharmacokinetics and drug-drug interactions of preventive therapies in migraine management.

OBJECTIVE: To review the pharmacokinetics of major classes of migraine preventives and the clinical implications of drug-drug interactions (DDIs) with the use of these therapies in migraine management. BACKGROUND: Preventive treatments for migraine are recommended for a large proportion of patients with frequent migraine attacks. These patients often exhibit a number of comorbidities, which may lead to the introduction of multiple concomitant therapies. Potential DDIs must be considered when using polytherapy to avoid increased risk of adverse events (AEs) or inadequate treatment of comorbid conditions. METHODS: A literature search was performed to identify pharmacokinetic properties and potential DDIs of beta-blockers, antiepileptic drugs, antidepressants, calcium channel blockers, gepants, and monoclonal antibody therapies targeting the calcitonin gene-related peptide pathway with medications that may be used for comorbid conditions. RESULTS: Most DDIs occur through alterations in cytochrome P450 isoenzyme activity and may be complicated by genetic polymorphism for metabolic enzymes. Additionally, drug metabolism may be altered by grapefruit juice ingestion and smoking. The use of migraine preventive therapies may exacerbate symptoms of comorbid conditions or increase the risk of AEs associated with comorbid conditions as a result of DDIs. CONCLUSIONS: DDIs are important to consider in patients with migraine who use multiple medications. The development of migraine-specific evidence-based preventive treatments allows for tailored clinical management that reduces the risk of DDIs and associated AEs in patients with comorbidities.

Vascular safety of erenumab for migraine prevention.

OBJECTIVE: To examine the cardiovascular, cerebrovascular, and peripheral vascular safety of erenumab across migraine prevention studies. METHODS: Vascular adverse events (AEs) and blood pressure data were integrated across 4 double-blind, placebo-controlled studies of erenumab and their open-label extensions in patients with chronic or episodic migraine. Subgroup analyses were conducted by acute migraine-specific medication use and number of vascular risk factors at baseline. Standardized search terms were used to identify vascular AEs (cardiovascular, cerebrovascular, or peripheral). An independent committee adjudicated whether targeted events were vascular in origin. RESULTS: In placebo-controlled studies, 2,443 patients received placebo (n = 1,043), erenumab 70 mg (n = 893), or erenumab 140 mg (n = 507) subcutaneously once monthly. Regardless of acute migraine-specific medication use or vascular risk factors at baseline, AE incidence was similar across the placebo and erenumab treatment groups. Hypertension AEs were reported for 0.9% (placebo), 0.8% (erenumab 70 mg), and 0.2% (erenumab 140 mg) of patients. Vascular AEs, which were similar across double-blind and open-label treatment, generally were confounded, with plausible alternative etiologies. In 18 patients with events reviewed by the independent committee, 4 events were positively adjudicated as cardiovascular in origin: 2 deaths and 2 vascular events. All 4 positively adjudicated cardiovascular events occurred during open-label erenumab treatment. CONCLUSION: Selective blockade of the canonical calcitonin gene-related peptide receptor with erenumab for migraine prevention had a vascular safety profile comparable to that of placebo over 12 weeks, with no increased emergence of events over time. Further study of long-term safety of erenumab in patients with migraine is needed. CLINICALTRIALSGOV IDENTIFIERS: NCT02066415, NCT02456740, NCT01952574, NCT02483585, NCT02174861, and NCT01723514. CLASSIFICATION OF EVIDENCE: This analysis provides Class II evidence that for patients with migraine, erenumab does not increase the risk of vascular AEs.

Frequency of Migraine Headaches in Patients With Fibromyalgia.

OBJECTIVE: The purpose of this study was to evaluate the frequency of migraine headache in a large cohort of patients with fibromyalgia using a brief migraine headache-screening tool. BACKGROUND: Several studies report a high prevalence of fibromyalgia among patients with migraine headaches, but there is a dearth of research evaluating the frequency of migraine headaches in patients with fibromyalgia, despite clinical observations suggesting that migraine headaches are common in patients with fibromyalgia. DESIGN AND METHODS: This was a cross-sectional survey study. Patients (N = 3717) with a previous diagnosis of fibromyalgia who were members of the Mayo Clinic Fibromyalgia Registry were contacted by electronic survey and asked to complete a brief demographic and medical history questionnaire and the validated ID-Migraine screener. RESULTS: A total of 1730 patients (46.5%) completed the electronic survey. The majority of participants were white (97.2%), female (92.5%), with a mean age of 56.2 (±13.1) years. Of the respondents, 966 (55.8%) met criteria for migraine headaches. Hypertension (309 [32.3%] vs. 294 [40.1%], P = .004), asthma (312 [32.5%] vs. 189 [25.9%], P = .011), irritable bowel syndrome (520 [54.6%] vs. 348 [47.6], P = .017), chronic fatigue syndrome (486 [50.7%] vs. 271 [37.1], P < .0001), depression (634 [66.5%] vs. 413 [56.7%], P = .0002), anxiety (415 [43.5%] vs. 252 [34.7%], P = .0011), and post-traumatic stress disorder (172 [18.0%] vs. 96 [13.2%], P = .006) were all significantly more common in those who met criteria for migraine headaches than those who did not. CONCLUSION: The results of this study suggest that migraine headaches are common in patients with fibromyalgia. Clinicians who care for either population must be aware that these conditions commonly overlap and can significantly increase a patient's cumulative disease burden.

Headache following intracranial neuroendovascular procedures.

AIMS: Predicting who will develop post-procedure headache (PPH) following intracranial endovascular procedures (IEPs) would be clinically useful and potentially could assist in reducing the excessive diagnostic testing so often obtained in these patients. Although limited safety data exist, the use of triptans or dihydroergotamine (DHE) often raise concern when used with pre/post-coiled aneurysms. We sought to determine risk factors for PPH following IEP, to evaluate the utility of diagnostic testing in patients with post-coil acute headache (HA), and to record whether triptans and DHE have been used safely in this clinical setting. METHODS: We conducted a retrospective chart review of adult patients undergoing IEPs. Bivariate analyses were conducted to compare patients who did and did not develop PPH. RESULTS: We reviewed records pertaining to 372 patients, of whom 263 underwent intracranial coil embolizations, 21 acrylic glue embolizations, and 88 stent placements. PPH occurred in 72% of coil patients, 33% of glue patients, and 14% of stent patients. Significant risk factors for post-coil HA were female gender, any pre-coil HA history, smoking, and anxiety/depression. A pre-stent history of HA exceeding 1 year's duration, and smoking were risk factors for post-stent HA. A pre-glue history of HA exceeding 1 year was the only risk factor for post-glue HA. In the small subgroup available for study, treatment with triptans or DHE was not associated with adverse events in pre/post-coiled aneurysms. Diagnostic testing was low yield. CONCLUSIONS: Occurrence of PPH was common after IEPs and especially so with coiling and in women, smokers, and those with anxiety/depression, and was often of longer duration than allowed by current International Classification of Headache Disorders-II criteria. The yield of diagnostic testing was low, and in a small subgroup treatment with triptans or DHE did not cause adverse events in pre/post-coiled aneurysms. Prospective studies are needed to confirm these findings.

Iron deposition in pain-regulatory nuclei in episodic migraine and chronic daily headache by MRI.

BACKGROUND: Progression of migraine toward a more disabling chronic form of at least 15 days/month is linked with frequency of attacks. Magnetic resonance imaging (MRI) findings of iron accumulation in the brain, especially in periaqueductal gray and red nucleus, have been correlated with both duration of illness and frequency of attacks. METHODS: This study therefore evaluated iron deposition as measured with MRI in basal ganglia and pain regulatory nuclei in neurologically healthy control volunteers and in patients with various migraine subtypes: episodic migraine (n = 10) with (n = 4) or without aura (n = 6), and chronic daily headache (n = 11), including medication overuse headache (MOH, n = 8), chronic tension-type headache (n = 1), and primary chronic migraine (n = 2). The goal was to assess differences in iron deposition among migraine subtypes and controls in the hopes of linking the by-products of frequent attacks or long duration of illness with these changes. RESULTS: The study sought to evaluate the tradeoff between sensitivity and specificity in T2 imaging of patients with migraine, and found that only T2 imaging in the globus pallidus was able to distinguish between episodic and chronic migraine, suggesting that this technique may be the most appropriate to assess migraine frequency. Patients with MOH did not demonstrate T2' shortening. CONCLUSIONS: Because iron accumulation should cause shortening of both T2 and T2', although the lack of significance in observed T2' difference could be due to increased variance in T2' the measurement, these results suggest that a mechanism other than increased iron deposition may play a role in the genesis or pathophysiology of MOH.

Unusual headaches in the elderly.

Prevalence of headache lowers with age, and headaches of elderly adults tend to be different than those of the younger population. Secondary headaches, such as headaches associated with vascular disease, head trauma, and neoplasm, are more common. Also, certain headache types tend to be geriatric disorders, such as primary cough headache, hypnic headache, typical aura without headache, exploding head syndrome, and giant cell arteritis. This review provides an overview of some of the major and unusual geriatric headaches, both primary and secondary.

Development of a simple menstrual migraine screening tool for obstetric and gynecology clinics: the menstrual migraine assessment tool.

OBJECTIVE: To develop and validate a brief questionnaire to screen for menstrual migraine (MM), and to estimate MM prevalence in an obstetrics and gynecology (OB/GYN) setting in a pilot study. METHODS: Patients with unknown MM status from a headache clinic completed a 9-item questionnaire. The attributes of each question were compared with a validated headache calendar to develop a 3-item MM questionnaire. The headache calendar and questionnaire were then administered to nonpregnant/nonmenopausal OB/GYN patients. A diagnosis was assigned by a blinded specialist using the headache calendar, and MM prevalence was determined. RESULTS: The analysis yielded 3 relevant questions administered to 250 women for our tool, called the Menstrual Migraine Assessment Tool (MMAT): (1) "Do you have headaches that are related to your period (ie, occur between 2 days before the onset of your period, until the third day of your period) most months?" (2) "When my headaches are related to my period, they eventually become severe"; (3) "When my headaches are related to my period, light bothers me more than when I don't have a headache." If question 1 was positive, questions 2 and 3 were answered. Among women responding positively to question 1 and > or =1 other question, the sensitivity and specificity were 0.94 and 0.74, respectively. Of 610 randomly chosen OB/GYN patients, 12.1% had pure MM (ie, migraine exclusively between days +2 and -3 of menses), 10.1% had menstrually related migraine (ie, MM and attacks at other times), and 14.1% had migraine without relation to their menses. CONCLUSION: The MM screener MMAT exhibits sufficient sensitivity and specificity to assess this frequently disabling condition presenting at the OB/GYN office.

Burden of migraine in Brazil: estimate of cost of migraine to the public health system and an analytical study of the cost-effectiveness of a stratified model of care.

BACKGROUND: The search for rationality in health expenses in developing countries collides with the lack of effectively conducted epidemiologic studies. PURPOSE: To present an estimate of the impact and costs of migraine in the Brazilian public health system and to estimate the impact on these costs and the effectiveness of a model of stratified care in the management of migraine. METHODS: An analytical model of utilization of the Brazilian public health system was constructed. Data refer to 1999 and were obtained in accordance with the following steps: (1) Brazilian demographic characteristics; (2) characteristics of the public health system related to its 3 hierarchical levels-primary, secondary, and tertiary care, the last being subdivided into emergency department and hospital care; and (3) estimation of the number of migraine consultations at each complexity level. In Brazil, migraineurs seen in the public health system are most often discharged with an acute treatment, usually a nonspecific medication. We compared this treatment with a proposed stratified care model that uses a triptan as an acute care medication. We have made the following assumptions: (1) 15% of the patients would fall into the Migraine Disability Assessment (MIDAS) grade I category, 25% would fall into the MIDAS grade II category, 30% into the grade III category, and 30% into the MIDAS grade IV category; (2) the mean number of migraine attacks per year are: MIDAS I, 7.49; MIDAS II, 8.02; MIDAS III, 12.22; and MIDAS IV, 27.01. The annual costs of the treatment were calculated according to the following equation: AC = P x N x C + P x Cp + P x Cat x AMA, where P is the number of patients; N, the number of consultations per patient; C, the cost of consultation per level; Cp, the cost of preventive drugs; Cat, the cost of acute therapy drugs; and AMA is the number of migraine attacks per year. Results.-The public health system resources included 55 735 ambulatory units (primary and secondary) and 6453 emergency department and public hospital units, with a corresponding budget of US $2 820 899 621.26. The estimated cost of a consultation on the primary care level was US $11.53; on the secondary care level, US $22.18; in the emergency department, $34.82; and for hospitalization, US $217.93. The total estimated public health system expenses for migraine were US $140 388 469.60. The proposed model would imply a cost reduction of 6.2% (US $7 514 604.40) with an improvement in the quality of the public health system from the actual 18.2% to an estimated 84.5%. CONCLUSION: Migraine seems to pose a huge burden on the Brazilian public health system. The implementation of a stratified care model of treatment that would include specific acute migraine therapies could result in a dramatic increase in the quality of migraine care and a significant reduction in cost.

New migraine preventive options: an update with pathophysiological considerations

BACKGROUND: The pharmacological treatment of migraine may be acute or preventive. Frequent, severe and long-lasting migraine attacks require prophylaxis. Multiple threads of research over the last 15 years have led to the concept that migraine is generated from a hyperexcitable brain. A variety of causes for hyperexcitability of the brain in migraine have been suggested. These causes include low cerebral magnesium levels, mitochondrial abnormalities, dysfunctions related to increased nitric oxide or the existence of a P/Q type calcium channelopathy. The better knowledge about migraine pathophisiology led us to discuss new treatment options. OBJECTIVES: The aim of the present study is to present an evidence-based review of some new drugs or some agents that even though available for a long time, are not frequently used. METHODS/RESULTS: We present a review of anticonvulsants with various mechanisms of action such as lamotrigine, gabapentin, topiramate, tiagabine, levetiracetam and zonisamide. We also review natural products, like riboflavin and magnesium, botulinum toxin A, a specific CGRP antagonist and the anti-asthma medication montelukast, with pathophysiological discussion. CONCLUSIONS: We aimed to present an update of newer or less frequently used preventive migraine therapies, drugs that might reduce the burden and the costs of a disease that should be considered as a public health problem all around the world

Hemicrania continua: a report of ten new cases

Hemicrania continua (HC) is an uncommon primary headache first described as a syndrome in 1984. Being quite unusual, its clinical characterization still demands better description. The aim of this study is to present the main clinical characteristics of 10 patients with the diagnosis of HC seen in a tertiary center, critically discussing their main features. All subjects had strictly unilateral headache without side shift and absolute response to indomethacin. Seven patients (70 percent) presented autonomic features during pain exacerbations. Four (40 percent) had migrainous symptoms during the exacerbations and one presented partial relief with dihydroergotamine. One patient had pain excruciatingly severe during the exacerbations. Although the cardinal features of HC - continuous, unilateral, indomethacin responsive, remain strongly reliable, a refinement on the clinical characterization is needful and desired