The prevalence and demographic associations of headache in the adult population of Peru: a national cross-sectional population-based study.

BACKGROUND: The Global Campaign against Headache is conducting a series of population-based studies to fill the large geographical gaps in knowledge of headache prevalence and attributable burden. One major region not until now included is South America. Here we present a study from Peru, a country of 32.4 million inhabitants located at the west coast of South America, notable for its high Andes mountains. METHODS: The study was conducted in accordance with the standardized methodology used by the Global Campaign. It was a cross-sectional survey using cluster randomised sampling in five regions to derive a nationally representative sample, visiting households unannounced, and interviewing one randomly selected adult member (aged 18-65 years) of each using the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire translated into South American Spanish. The neutral screening question ("Have you had headache in the last year?") was followed by diagnostic questions based on ICHD-3 and demographic enquiry. RESULTS: The study included 2,149 participants from 2,385 eligible households (participating proportion 90.1%): 1,065 males and 1,084 females, mean age 42.0 ± 13.7 years. The observed 1-year prevalence of all headache was 64.6% [95% CI: 62.5-66.6], with age-, gender- and habitation-adjusted prevalences of 22.8% [21.0-24.6] for migraine (definite + probable), 38.9% [36.8-41.0] for tension-type headache (TTH: also definite + probable), 1.2% [0.8-1.8] for probable medication-overuse headache (pMOH) and 2.7% [2.1-3.5] for other headache on ≥ 15 days/month (H15+). One-day prevalence of headache (reported headache yesterday) was 12.1%. Migraine was almost twice as prevalent among females (28.2%) as males (16.4%; aOR = 2.1; p < 0.001), and strongly associated with living at very high altitude (aOR = 2.5 for > 3,500 versus < 350 m). CONCLUSION: The Global Campaign's first population-based study in South America found headache disorders to be common in Peru, with prevalence estimates for both migraine and TTH substantially exceeding global estimates. H15 + was also common, but with fewer than one third of cases diagnosed as pMOH. The association between migraine and altitude was confirmed, and found to be strengthened at very high altitude. This association demands further study.

Medication-overuse headache-a review of different treatment strategies.

Medication-overuse headache (MOH) can develop from primary headaches. MOH is usually the result of overuse of symptomatic medications. It is a noteworthy personal and societal burden. The identification and treatment of patients at risk for MOH is an essential component of MOH management. Medication overuse can be modifiable and can advance from episodic to chronic migraine. Treatment for MOH is complex, and experts in the field have varied views on the most appropriate strategy for MOH treatment. The objective of this review is to give a comprehensive synopsis of the literature for the management of MOH. Treatment strategies, such as detoxification and prevention, are the debatable issues. Medication withdrawal is the foundation for management. The available literature suggested abrupt withdrawal with preventive approaches for early management. Bridging therapy could be useful to get relief from withdrawal symptoms. Multidisciplinary choices proved beneficial in supporting withdrawal and preventing relapse. Worldwide, the termination of overused medications has been observed as a standard treatment strategy; however, patient-specific approaches should be taken.

Monoclonal antibodies for chronic migraine and medication overuse headache: A real-world study.

Background: Medication-overuse headache is highly prevalent in tertiary care centers. It may be a cause or consequence of the overuse of symptomatic medications for migraine attacks. Objective: We aimed to compare the efficacy of anti-CGRP monoclonal antibodies (mAbs) added to conventional pharmacological treatments in patients with chronic migraine (CM) and medication overuse headache (MOH). Methods: A cross-sectional, prospective, randomized, open study with real-world comparison groups of patients was carried out. The sample consisted of 200 patients with CM and MOH, who received the same approach to withdraw overused medications, started preventative treatment, and either did or did not receive mAbs. Results: A total of 172 patients (126 women and 46 men) were included in the study and divided into two groups: group one consisting of 58 patients (control) and group two of 114 patients who used mAbs added to conventional pharmacological agents. The mean age was 44.1 ± 13.6 years, ranging from 18 to 78 years. In the 3 months follow-up after starting the treatment, both groups presented headache frequency reduction, but those with monoclonal antibodies had a significantly higher reduction in the number of headache days and symptomatic medication intake when compared to the control (p < 0.0001). Conclusions: The addition of an anti-CGRP monoclonal antibody to the treatment for medication overuse headaches in chronic migraineurs may result in decreasing headache frequency and symptomatic medication use when compared to conventional treatments with drugs.

Impulsivity in migraine and in medication overuse headache: A literature review / Impulsividade na enxaqueca e na cefaleia por uso excessivo de medicamentos: uma revisão da literatura

Introduction: Psychiatric symptoms and analgesic overuse may contribute to migraine chronification. Impulsivity is a common symptom in several psychiatric disorders that can potentiate substance overuse, including analgesics. Dopamine has been associated with migraine pathophysiology and impulsivity. Objective: This review aims to assess the current knowledge about the potential association between migraine and impulsivity. Methods: PubMed and LILACS were queried using relevant descriptors related to migraine and impulsivity. Results: Five articles were selected; however, none revealed a significant correlation between migraine and impulsivity. This lack of correlation was verified in different migraine subtypes (with or without aura, chronic, or episodic). Conclusion: The heterogeneity in patient grouping and diverse impulsivity assessment tools of the studies precluded definitive conclusions. The Barratt Impulsivity Scale (BIS-11) was the most frequently used tool. Given the paucity of data and the potential impact on migraine management, further studies are crucial to elucidate the potential association between migraine and impulsivity.

Introdução: Sintomas psiquiátricos e uso excessivo de analgésicos podem contribuir para a cronificação da enxaqueca. A impulsividade é um sintoma comum em vários transtornos psiquiátricos que pode potencializar o uso excessivo de substâncias, incluindo analgésicos. A dopamina tem sido associada à fisiopatologia e impulsividade da enxaqueca. Objetivo: Esta revisão tem como objetivo avaliar o conhecimento atual sobre a potencial associação entre enxaqueca e impulsividade. Métodos: PubMed e LILACS foram consultados utilizando descritores relevantes relacionados à enxaqueca e impulsividade. Resultados: Foram selecionados cinco artigos; no entanto, nenhum revelou uma correlação significativa entre enxaqueca e impulsividade. Essa falta de correlação foi verificada em diferentes subtipos de enxaqueca (com ou sem aura, crônica ou episódica). Conclusão: A heterogeneidade no agrupamento de pacientes e as diversas ferramentas de avaliação da impulsividade dos estudos impediram conclusões definitivas. A Escala de Impulsividade Barratt (BIS-11) foi o instrumento mais utilizado. Dada a escassez de dados e o potencial impacto no tratamento da enxaqueca, mais estudos são cruciais para elucidar a potencial associação entre enxaqueca e impulsividade.

The state of the art in treating patients with a dual diagnosis of chronic migraine and medication-overuse headache / O estado da arte no tratamento de pacientes com diagnóstico duplo de enxaqueca crônica e cefaléia por uso excessivo de medicamentos

Migraine is a common, highly prevalent genetic neurological disorder. Its most burdensome form is the chronic migraine, which is clinically defined by the presence of headache on ≥15 days/month for longer than three months, with eight or more typical migraine days. Medication-overuse headache (MOH) is a secondary headache disorder associated with the overuse of symptomatic headache medications on ≥10 days/month for longer than 3 months. Chronic migraine and medication-overuse headache often coexist and most chronic migraineurs have medication overuse headache. Despite that, general practitioners and health professionals do not know about MOH. This review aims at presenting insights, recent knowledge, and guidance regarding the approach and treatments for patients with a dual diagnosis of chronic migraine and medication-overuse headache.

A enxaqueca é um distúrbio neurológico genético comum e altamente prevalente. Sua forma mais grave é a enxaqueca crônica, que é clinicamente definida pela presença de cefaleia ≥15 dias/mês por mais de três meses, com oito ou mais dias típicos de enxaqueca. A cefaleia por uso excessivo de medicamentos (MOH) é uma cefaleia secundária associada ao uso excessivo de medicamentos sintomáticos para cefaleia em ≥10 dias/mês por mais de 3 meses. A enxaqueca crônica e a cefaleia por uso excessivo de medicamentos geralmente coexistem e a maioria dos pacientes com enxaqueca crônica apresenta cefaleia por uso excessivo de medicamentos. Apesar disso, os clínicos gerais e os profissionais de saúde não conhecem o MS. Esta revisão tem como objetivo apresentar insights, conhecimentos recentes e orientações sobre a abordagem e tratamentos para pacientes com diagnóstico duplo de enxaqueca crônica e cefaleia por uso excessivo de medicamentos.

Cefalea por abuso de medicamentos y sus marcadores clínicos / Medication overuse headache and its specific clinical markers

Resumen Introducción: Los marcadores clínicos de la cefalea por uso excesivo de medicación (CMA) se basan en la clasificación de las cefaleas desarrollada por la Sociedad Internacional de Cefaleas (IHS). Esta clasificación incluye sólo dos criterios: la frecuencia de los días de cefalea debe ser de 15 o más días al mes durante al menos tres o más meses; - y el número de días de uso excesivo de la medicación debe ser de 10 o 15 días al mes dependiendo del tipo de medicación. Sin embargo, los pacientes suelen tener otros marcadores clínicos asociados distintos, que la mayoría de los médicos pasan por alto durante la evaluación inicial. Metodología: Este estudio es un estudio prospectivo, longitudinal y observacional de 76 pacientes ingresados en la Unidad de Cefaleas del hospital DIPRECA. Todos ellos fueron diagnosticados de HMO según los criterios establecidos por su ICHD III beta.(1) Los pacientes recibieron un tratamiento estándar que incluía desintoxicación y medicación preventiva y fueron seguidos durante 6 meses. Se registraron los síntomas de interés en cada visita de seguimiento clínico y se administraron escalas de evaluación como Zung, MIDAS, HIT-6. Resultados: Los medicamentos sobreutilizados incluyeron antiinflamatorios no esteroideos (AINE), triptanes y cornezuelos. Los síntomas clínicos más significativos asociados fueron: despertar por la mañana con dolor de cabeza, despertar al paciente al amanecer por dolor de cabeza, dificultades de atención, depresión, dolor cervical y síndrome de dolor miofascial. Todos los síntomas mejoraron significativamente al iniciar el tratamiento, al igual que la calidad de vida medida por las escalas MIDAS y HIT-6. Discusión: Al evaluar a los pacientes con HMO, hay que tener en cuenta tanto los criterios diagnósticos de la ICHD III beta como los síntomas comunes y específicos que se observan en la mayoría de los casos de HMO.

Introduction: Clinical markers of medication overuse headache (MOH) are based on headache classification developed by the International Headache Society (IHS). This classification include only two criteria: frequency of headache days must be 15 or more days per month for at least three or more months; - and the number of days of overuse medication must be either 10 or 15 days per month depending on the type of medication. However, patients often have others distinct associated clinical markers, which are overlooked by most physicians during the initial evaluation. Methodology: This study is a prospective, longitudinal and observational study of 76 patients admitted to DIPRECA´s hospital Headache Unit. They were all diagnosed with, MOH according to the criteria established by the his ICHD III beta.(1) Patients were given standard treatment including detoxification and preventive medications and followed for 6 months. Symptoms of interest were recorded in at each clinical monitoring visit and assessment scales such as Zung, MIDAS, HIT-6 were administered. Results: Overused medications included nonsteroidal anti-inflammatory drugs (NSAIDs), triptans and ergots. The most significant clinical symptoms associated were: awaking in the morning with headache, awaking the patient at dawn by headache, attention difficulties, depression, cervical pain and myofascial pain syndrome. All symptoms significantly improved when treatment began, as did quality of life as measured by MIDAS and HIT-6 scales. Discussion: In evaluating patients with MOH consider both the ICHD III beta diagnostic criteria and the common and specific symptoms seen in most cases of MOH.

High rates of (treated) hypothyroidism among chronic migraine patients consulting a specialized headache clinic: are we missing something?

BACKGROUND: Roughly three percent of episodic migraine patients evolve into the most burdensome chronic form of this condition every year. While some of the determinants behind this transformation are well established, others are still ill defined. Hypothyroidism is a prevalent endocrinological disorder that can both produce a secondary headache or aggravate a pre-existing primary headache disorder such as migraine. OBJECTIVE: We aimed to re-assess the association between hypothyroidism and chronic migraine controlling for factors such as hormone replacement treatment status and bodyweight. METHODS: We retrospectively analyzed the medical records of episodic and chronic migraine patients who consecutively consulted our headache clinic in order to determine the prevalence of adequately treated hypothyroidism in each group. Only patients receiving a stable dose regimen were included. The body mass index and other possibly confounding covariates were also collected. RESULTS: Data from 111 migraine patients was included for analysis. Most (88.6%) of chronic migraine sufferers were overusing acute medication. Treated hypothyroidism was significantly more prevalent in chronic migraine patients (29.55%) compared to episodic migraine patients (8.96%). This association was independent of the patients' body mass index or other variables. CONCLUSION: Alterations of neuronal metabolism, deficient calcitonin release, or focal inflammation causing local hormonal deactivation might explain why hypothyroidism, in spite of levothyroxine replacement therapy, is associated with migraine chronification. Further studies evaluating these factors are warranted.

FRAMES protocol versus simple advice for medication-overuse headache: a prospective, randomized, controlled clinical trial.

It is central to the management of patients with Medication-overuse headache that they reverse their behavior regarding the frequent use of pain medication. The objective of this study was to compare two counseling techniques for treating patients with Medication-overuse headache (MOH). This was a randomized, blind, controlled clinical trial that compared a structured (FRAMES) and unstructured counseling, for the treatment of MOH. Patients were assessed before the counseling and then again four and eight weeks after it. Semi-structured interview, headache diary, the Headache Impact Test (HIT-6) and the Hospital Anxiety and Depression Scale were used. Primary endpoints were the following: number of patients who stopped medication overuse; days with acute medication use; HIT-6; the number of patients who returned for consultations. Secondary endpoints were as follows: days per month of headache; 50% reduction in monthly days with acute medication use; the number of patients with less than 15 days of headache. Thirty-seven patients were allocated to the "FRAMES Group" and 33 to the "Control Group". There was no difference regarding primary or secondary outcomes between the two groups. There was a significant reduction in the frequency of headache and the number of days using pain medication in the first and second months of follow-up compared to baseline in both groups. There was a significant reduction in the HIT-6 in the first and second months of follow-up compared to baseline in the FRAMES Group, but not in the control group. Patients in both counseling groups significantly decreased the use of pain medications and the frequency of their headaches.

Evaluation of structural changes in orbitofrontal cortex in relation to medication overuse in migraine patients: a diffusion tensor imaging study / Avaliação das mudanças estruturais no córtex orbitofrontal em relação ao uso excessivo de medicamentos em pacientes com migrânea: um estudo de imagem por tensor de difusão

Abstract Background: Migraine is a prevalent neurological disease that leads to severe headaches. Moreover, it is the commonest among the primary headaches that cause medication overuse headache (MOH). The orbitofrontal cortex (OFC) is one of the structures most associated with medication overuse. Objective: To determine microstructural changes in the OFC among migraine patients who developed MOH, through the diffusion tensor imaging (DTI) technique. Methods: Fifty-eight patients who had been diagnosed with migraine based on the Classification of Headache Disorders (ICHD-III-B) were included in the study. Patients were sub-classified into two groups, with and without MOH, based on the MOH criteria of ICHD-III-B. DTI was applied to each patient. The OFC fractional anisotropy (FA), and apparent diffusion coefficient (ADC) values of the two groups were compared. Results: The mean age of all the patients was 35.98±7.92 years (range: 18-65), and 84.5% (n=49) of them were female. The two groups, with MOH (n=25) and without (n=33), were alike in terms of age, gender, family history, migraine with or without aura and duration of illness. It was found that there was a significant difference in FA values of the left OFC between the two groups (0.32±0.01 versus 0.29±0.01; p=0.04). Conclusions: An association was found between MOH and changes to OFC microstructure. Determination of neuropathology and factors associated with medication overuse among migraine patients is crucial in terms of identifying the at-risk patient population and improving proper treatment strategies specific to these patients.

RESUMO Introdução: A migrânea é uma doença neurológica prevalente que causa fortes dores de cabeça. Além disso, é a mais comum entre as cefaleias primárias que causam cefaleia por uso excessivo de medicamentos (CUEM). O córtex orbitofrontal (OF) é uma das estruturas mais associadas ao uso excessivo de medicamentos. Objetivo: Determinar alterações microestruturais no córtex OF em pacientes com migrânea que desenvolveram CUEM, por meio da técnica de imagem por tensor de difusão (ITD). Métodos: Cinquenta e oito pacientes com diagnóstico de migrânea, com base na Classificação das Cefaleias (ICHD-III-B), foram incluídos no estudo. Os pacientes foram subclassificados em dois grupos, com e sem CUEM, com base nos critérios de CUEM da ICHD-III-B. A ITD foi aplicada a cada paciente. Os valores de anisotropia fracionada OFC (AF) e coeficiente de difusão aparente (CDA) dos dois grupos foram comparados. Resultados: A média de idade de todos os pacientes foi de 35,98±7,92 anos (variação: 18‒65), sendo 84,5% (n=49) do sexo feminino. Os dois grupos, com CUEM (n=25) e sem (n=33), são semelhantes em termos de idade, sexo, história familiar, migrânea com ou sem aura e duração da doença. Verificou-se que houve diferença significativa nos valores de AF do córtex OF esquerdo entre os dois grupos (0,32±0,01 versus 0,29±0,01; p=0,04). Conclusões: Foi encontrada associação entre o CUEM e as alterações na microestrutura do córtex OF. A determinação da neuropatologia e dos fatores associados ao uso excessivo de medicamentos entre pacientes com migrânea é crucial para identificar a população de pacientes em risco e melhorar as estratégias de tratamento adequadas específicas para esses pacientes.

The prevalence of migraine in Argentina: A reappraisal.

BACKGROUND: Argentina has one of the largest territories in the world, which spreads over a lengthy latitudinal span. Its population is mainly composed of a mixture of South American natives and the descendants of numerous waves of European immigrants. Results from a previous study suggested that the prevalence of migraine in Argentina is the lowest in the region. Here we aimed to reassess the prevalence of migraine in Argentina applying a more sensitive and specific screening tool. METHODS: We conducted a random computer assisted telephonic interview (n= 2500) using the Migraine Screen Questionnaire to evaluate the prevalence of migraine and some of its features among Argentinian adults. RESULTS: The overall prevalence of migraine was 9.5% (14% in females and 5% in males). Estimated migraine prevalence rates ranged between 6.3% and 12% across different regions. The approximated prevalence of high frequency and chronic migraine were 1.9% and 1.5% of the total population respectively. Consumption of analgesics on 10 or more days per month was reported by 18% of migraine sufferers (≈1.7% of the population). CONCLUSIONS: The prevalence of migraine in Argentina is higher than previously reported. Prevalence rates vary extensively across the territory. Specifically evaluating the determinants of these variations might be a promising avenue of research.

Intravenous Chlorpromazine as Potentially Useful Treatment for Chronic Headache Disorders.

OBJECTIVE: The aim of this study was to describe a group of patients with chronic headache disorders (CH) and medication overuse headache (MOH) treated with intravenous chlorpromazine (IVC). We hypothesized that IVC is an effective and safe addition to well-known treatment strategies for CH and MOH management. INTRODUCTION: Up to 4% of the general population could experience CH. Most cases occur in women, in association with MOH. To date, evidence to support different treatment strategies is lacking. Although IVC is frequently used in the emergency room (ER), documentation on its use as supportive treatment for CH and for withdrawal management of MOH is poor. METHODS: A retrospective cohort of patients hospitalized to receive treatment for CH in a specialized neurological center in Argentina was analyzed. RESULTS: A total of 35 CH patients were included. Of the 35 patients, 33 (94%) patients also presented MOH. Patients reported only minor side effects to IVC administration (mainly drowsiness and symptomatic hypotension). Three months after inpatient treatment, the number of ER visits made by these patients decreased from an average of 2.8 in the 3 months prior to hospitalization to 0.7 after it (72%, P = .009). Headache frequency decreased in 20/34 (59%) patients during the same time period. Pain levels had dropped from a mean of 8 points at admission (in the scale of 1-10) to 2 points at discharge. In the first 3 months of follow-up, the average number of days per month in which patients experienced headache decreased from 28.9 to 15.4 days (53.3%, P < .0001). CONCLUSION: In this particular group of inpatients, there were no significant safety issues with IVC administration and the study might suggest that the efficacy of IVC as an add-on treatment for CH and MOH.

Medication overuse headache: an overview of clinical aspects, mechanisms, and treatments.

INTRODUCTION: Medication-overuse headache (MOH) is a common debilitating neurological disorder, with a prevalence of 1% to 7% in general population. It affects more than 60 million people worldwide and provokes substantial burden. Despite that, most practitioners don't know MOH. This review aims at presenting MOH clinical features, pathophysiology insights, and recent knowledge and guidance regarding treatments. AREAS COVERED: A literature search in the major medical databases including the terms 'medication overuse headache,' 'chronic daily headache,' 'chronic migraine,' 'symptomatic medication overuse' and others, published between 1990 and 2020, was carried out. EXPERT COMMENTARY: Primary headache sufferers such as migraineurs and tension-type headache patients may increase the headache frequency and induce the transition from episodic to chronic forms, as well as develop MOH, in the presence of medication overuse. There is evidence of structural and functional changes in some areas of the brain, which may identify those likely to respond or not to treatments. Despite the geographical differences and lack of consensus regarding approaches, to educate the patients about reducing medication intake, to withdraw overused medications and to start prophylaxis in some sufferers are crucial steps. Emerging treatments as monoclonal antibodies to migraine may result in better adherence and tolerability profiles as well as outcomes.

Medication-Overuse Headache: Protocols and Outcomes in 149 Consecutive Patients in a Tertiary Brazilian Headache Center.

AIM: Medication-overuse headache (MOH) is a challenging clinical disorder often resulting in frustration for patients and physicians. Adherence issues are common and limited treatment evidence is an obstacle to effective care. Individual bias usually directs the treatment. The aim of this study was to evaluate outcome and treatment strategies in consecutive MOH patients from a tertiary center. METHODS: Every consecutive patient seen between January and December 2014 with the diagnosis of MOH was included. Psychiatric comorbidities, inability to report baseline headache frequency, current or previous 2-month use of preventive medications, and refusal to sign informed consent were exclusion criteria. The patients were evaluated by the same specialist (AVK) in thorough initial consultations. The diagnosis and treatment strategies were clearly explained, and a detailed headache diary was given to all patients. Endpoints were headache frequency and adherence after 2, 4, and 8 months. RESULTS: One hundred sixty-eight patients (31 M, 137 F) met the inclusion criteria. Nineteen patients (11.3%) were excluded. All patients had migraine or chronic migraine as primary headache. Mean baseline frequency was 24.8 headache days/month, average headache history was 20.6 years (1-37), and mean time with > 15 headache days/month was 4.8 years (.5-32). All patients were overusing acute symptomatic medications (SM), and 59 (39.5%) were using more than one pharmacological class. Outpatient withdrawal from overused medications was carried out with all patients, who received different preventive treatment choices and triptan plus NSAID for the acute attacks (maximum of 2 days/week). One hundred and one patients (67.8%) received prednisone during the first 5-7 days. After 2 months, 30 (20.1%) were lost to follow-up, and in those who followed up, the mean headache frequency decreased to 10.7 headache days/month (ITT 13.1). After 4 and 8 months, 109 and 105 patients, respectively, were under treatment, with a mean headache frequency of 7.9 and 8.2 headache days/month. Patients who received prednisone did not perform better than those who did not (P = .3032, 5 d vs no prednisone; P = .639, 7 d vs no prednisone). CONCLUSIONS: Withdrawing overused medications, starting prevention, and motivating patients may have helped the high adherence rates and decreasing headache frequency. Additionally, real-world patient studies are scarce and may be useful to guide clinicians struggling to help their daily headache patients. Open studies do not allow definitive conclusions and controlled studies with this subset of patients are necessary.

Prevention of stress- or nitric oxide donor-induced medication overuse headache by a calcitonin gene-related peptide antibody in rodents.

Objective The objective of this study was the determination of the role of calcitonin gene-related peptide (CGRP) in the induction of medication overuse headache (MOH)-related migraine in an injury-free preclinical model. Methods Rats were primed by a 7-day period of exposure to acute migraine therapies including sumatriptan and morphine. After an additional 14-day drug-free period, rats were exposed to putative migraine triggers including bright light stress (BLS) or nitric oxide (NO) donor in the presence or absence of TEV48125, a fully humanized CGRP antibody. Cutaneous allodynia (CA) was used as an outcome measure and CGRP blood and cerebrospinal fluid (CSF) levels were measured. Results BLS and NO donor challenge evoked delayed, long-lasting CA selectively in rats that were previously treated with sumatriptan or morphine. BLS produced a significant increase in CGRP in the plasma, but not CSF, in animals that were previously exposed to sumatriptan compared to saline controls. TEV48125 did not modify baseline tactile thresholds or produce behavioral side effects, but significantly inhibited both BLS- and NO donor-induced CA in animals that were previously primed with sumatriptan or morphine; an isotype control protein that does not bind CGRP had no effect. Interpretation These data suggest that acute migraine medications may promote MOH in susceptible individuals through CGRP-dependent mechanisms and that anti-CGRP antibodies may be a useful clinical strategy for the treatment of MOH.

Medication-Overuse Headache: Differences between Daily and Near-Daily Headache Patients.

UNLABELLED: Medication-overuse headache (MOH) is a challenging neurological disease, which brings frustration for sufferers and treating physicians. The patient's lack of adherence and limited treatment evidence are frequent. The aim of this study was to compare the outcome and treatment strategies between consecutive MOH patients with daily and near-daily headache from a tertiary center. METHODS: Every consecutive patient seen between January and December 2014 with the diagnosis of MOH was included. Psychiatric comorbidities, inability to inform baseline headache frequency, current or previous two-month use of preventive medications, and refusal to sign informed consent were exclusion criteria. The patients were evaluated in thorough initial consultations and divided in two groups based on their baseline headache frequency. The diagnosis and treatment strategies were clearly explained. The filling out of a detailed headache diary was requested from all patients. Endpoints compared headache frequency and adherence after two, four, and eight months between the two study groups. RESULTS: One-hundred sixty-eight patients (31 male, 137 female) met the inclusion criteria. Nineteen patients (11.3%) were excluded. All patients had migraine or chronic migraine as primary headaches. Eighty had daily (DH), and 69 near-daily headache (NDH), at baseline consultation. Mean baseline frequency was 24.8 headache days/month (18.9 days/month for the near-daily group), average headache history was 20.6 years and mean time with >15 headache days/month was 4.8 years. Outpatient withdrawal, starting prevention, and enforcing the correct use of rescue therapy was carried out with all patients. After two months, 88% of the DH and 71% of the NDH groups adhered to treatment (p = 0.0002). The HF decreased to 12 and 9 headache days/month, respectively in DH and NDH groups (p > 0.05, non-significant) (Intention-to-treat (ITT) 14 DH; 12 NDH; p > 0.05). After four and eight months, 86.3% and 83.7% of the DH patients, and 59.4% and 55% of the NDH patients were still under treatment (p = 0.0003 and p = 0.0001). The HF decreased, respectively, to nine and nine headache days/month in the DH patients compared to 6 and 7 headache days/month in the NDH group (p > 0.05) (ITT, 12; 12; DH; 10; 11; NDH; p > 0.05). CONCLUSIONS: Although open studies provide limited conclusions, withdrawing overused medications and starting prevention may have helped the favorable outcomes. However, daily headache patients had a significantly higher adherence and lower relapse rates than near-daily headache patients, despite a considerable reduced headache frequency in both groups. Additionally, real-world patient studies are scarce and the comparison between these two subsets of patients may be useful to guide clinicians in approaching their patients. Controlled studies are necessary to confirm these observations.

Clinical and Demographical Characteristics of Patients with Medication Overuse Headache in Argentina and Chile: Analysis of the Latin American Section of COMOESTAS Project.

BACKGROUND: Data on the characteristics of Medication Overuse Headache (MOH) in Latin American (LA) are scarce. Here we report the demographic and clinical features of the MOH patients from Argentina and Chile enrolled in the multinational COMOESTAS project in the period 2008-2010. METHODS: The LA population was formed by 240 MOH subjects, 110 from Chile and 130 from Argentina, consecutively attending the local headache centres. In each centre, specifically trained neurologist interviewed and confirmed the diagnosis according to the ICHD-II criteria. A detailed history was collected on an electronic patient record form. RESULTS: The mean patient age was 38.6 years, with a female/male ratio of 8:2. The mean time since onset of the primary headache was 21 years, whereas duration of MOH was 3.9 years. The primary headache was migraine without aura in 77.5 % and migraine with aura in 18.8 %. Forty two % of the patients self-reported emotional stress associated with the chronification of headache; 43.8 % reported insomnia. The most overused medications were acute drug combinations containing ergotamine (70 %), NSAIDs (33.8 %) and triptans (5.4 %). CONCLUSION: Though little described, MOH is present also in LA, where it affects mostly women, in the most active decades of life. Some differences emerge as regards the demographic and clinical characteristics of MOH in this population as compared to Europe or Northern America. What seems more worrying about MOH in Argentina and Chile is that most patients overuse ergotamine, a drug that may cause serious adverse events when used chronically. These findings once more underscore the importance of properly diagnose and treat MOH.

Study of the use of analgesics by patients with headache at a specialized outpatient clinic (ACEF) / Estudo do uso de analgésicos em pacientes com cefaleia em um ambulatório especializado (ACEF)

Objective : To evaluate the use of analgesics in headache diagnosed in Outpatients Headache Clinic (ACEF), as well as his involvement in the activities of the patients. Method : 145 patients with headache seen at ACEF during the period August/July 2009/2010 underwent a questionnaire and interview with neurologist responsible for the final diagnosis according to ICHD-II. Results : Relationship Women:Men 7:1. 1) Prevalence: Migraine without aura (52.4%), migraine with aura (12.4%), chronic migraine (15.2%) and medication overuse headache (MOH) (20%). 2) Analgesic drugs used: Compounds with Dipyrone (37%), Dipyrone (23%), Paracetamol (16%) compound with Paracetamol (6%), triptans (6%) and non steroidal anti-inflammatory drugs (12%). There was a significant decrease in the duration of pain and less interference in the activities of the headache patients after the use of analgesics. Conclusion : Prevalence of MOH has been increasing in population level and specialized services. New studies emphasizing the MOH are needed to assist in the improvement of their diagnostic and therapeutic approach. .

Objetivo : Avaliar a utilização de analgésicos nas cefaleias diagnosticadas no Ambulatório de Cefaleias (ACEF), bem como a sua intervenção nas atividades dos pacientes. Método : 145 pacientes com cefaleia atendidos no ACEF durante o período entre Agosto/2009 a Julho/2010 foram submetidos a um questionário e à entrevista com médico neurologista responsável pelo diagnóstico final, segundo a ICHD-II. Resultados : Relação Mulheres:Homens de 7:1. 1) Prevalência: Migrânea sem aura (52,4%), migrânea com aura (12,4%), migrânea crônica (15,2%) e CEM (20%). 2) Analgésicos utilizados: Compostos com Dipirona (37%), Dipirona (23%), Paracetamol (16%), compostos com Paracetamol (6%), triptanos (6%) e drogas antiinflamatórias esteroidais (12%). Houve uma diminuição significativa da duração da dor e menor interferência da cefaleia nas atividades dos pacientes após o uso dos analgésicos. Conclusão : Prevalência da cefaleia por uso excessivo de medicamento (CEM) vem aumentando em nível populacional e em serviços especializados. Novos estudos enfatizando a CEM são necessários para auxiliar na melhora da sua abordagem diagnóstica e terapêutica. .

The paradoxical effects of analgesics and the development of chronic migraine / Migrânea crônica e os efeitos paradoxais dos analgésicos

In a subgroup of individuals episodic migraine evolves into a stage where individuals have headaches on more days than not. Among the risk factors for chronification, excessive use of analgesic medications figure prominently and reviewing this topic is the scope of this article. The issue of causality is discussed and evidence suggesting that specific medications, at critical doses, are risk factors for chronic migraine (CM) is reviewed. The concept of critical dose of exposure for different classes is presented and biological plausibility and putative mechanisms are reviewed.

Fração não desprezível de pacientes com migrânea episodica evolve para um estágio em que cefaléias acontecem na maior parte dos dias. Dentre os fatores de risco para esse processo de cronificação, o uso excessivo de analgésicos tem importância particular e é o tema desse artigo. A causalidade da associação é discutida, assim como a especificidade da associação. Evidência sugerindo que doses críticas de exposição podem ser inferidas também é revisada, assim como a plausibilidade da associação e mecanismos da mesma.

Cefalea por uso excesivo de medicamentos y adicción a sustancias / Medications overuse headache and substance abuse disorders

Tanto en los trastornos de dependencia a sustancias (TDS), como en la migraña y cefalea por uso excesivo de medicaciones (CUEM), se implican mecanismos dopaminérgicos y opioides, así como alteraciones en el metabolismo de la corteza orbitofrontal. Si la CUEM y los TDS comparten una fisiopatología común, es de esperar que exista una asociación clínica entre estas entidades nosológicas. Objetivo. Determinar la asociación entre la CUEM y los TDS en una muestra de pacientes que consultaron a neurología general por cefalea diaria crónica. Materiales y métodos. Se realizó un estudio de corte observacional analítico transversal. Se tomó una muestra no probabilística, por conveniencia, que incluyó a todos los pacientes mayores de 18 años consecutivos que consultaron por cefalea diaria crónica (CDC) a un consultorio de neurología general entre octubre de 2007 y enero de 2009, a quienes luego de haber dado respuesta a un cuestionario se les hizo una entrevista clínica que indagó datos demográficos, consumo de analgésicos en los últimos tres meses, consumo de cafeína en forma de bebida caliente, dependencia a la nicotina y al alcohol, y antecedente familiar de consumo de alcohol. Los diagnósticos de CUEMy CDC se efectuaron atendiendo criterios de la IHS, y el de TDS según el DSM-IV.

In substance related disorders (SRD) like in migraine and Medication Overuse Headache (MOH) are implied dopaminergic and opioids mechanisms, as well as alterations in the metabolism of the orbitofrontal cortex. If the MOH and the SRD share a common physiopathology, it is of hoping exists a clinical association among these entities. Objective. To determine the association between the MOH and the SRD in a sample of patients that consulted with general neurologist for Chronic Daily Headache (CDH). Materials y methods. It was carried out an analytic observational cross sectional study. Was took a for convenience non probabilistic sample, that included all the serial patients 18 years old that consulted for CDH, to a consulting room of general neurology between October of 2007 and January of 2009. The patients responded a self-administrated questionnaire and a clinical interview was carried out that investigated demographic data, analgesic use in the last 3 months, consumption of caffeine in form of hot drink, nicotine dependence, alcohol dependence and family antecedent of consumption of alcohol.The diagnoses of MOH and CDH were carried out according to IHS criteria and that of SRD according to the DSM-IV. Results. A total of 129 patients presented MOH and other 103 patients were diagnosed with CDH without medication overuse. The groups were similar in age, gender, education level, socioeconomic status and the body mass index. There were not differences in the prevalence of: consumption of caffeine (49,6% vs. 47,5%; OR=1,1; IC95% 0,67-1,9); nicotine dependence (3,1% vs. 1,0%; OR=3,3 IC95% 0,36-29,4); alcohol dependence (0% vs. 1,9%; OR=0,98; IC95% 0,95-1,0); and family antecedent of consumption of alcohol (45,7% Vs. 43,7%; OR=1,1; IC95% 0,65-1,8) among patient with MOH and CDH without medication overuse. Conclusions: There is not association among consumption of caffeine, nicotine dependence, alcohol dependence and family history of consumption...