One-Year and Five-Year Outcomes in Medication Overuse Headache: A Real-World Study.

BACKGROUND: Medication overuse headache (MOH) is one of the global health-related problems that imposes significant morbidity. Effective management requires the abrupt cessation of the overused medications, transition therapy in the initial days, and initiation of preventive treatment. The objective of this study is to provide one-year and five-year follow-ups of study participants diagnosed with chronic migraine and MOH. The study will examine the efficacy of withdrawal therapy, the use of conventional preventive medication, and the use of anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies. METHODOLOGY: We conducted a single-center, prospective, and descriptive study at a tertiary center in Brazil. The population was included by convenience sampling of consecutive subjects diagnosed with chronic migraine and MOH. Demographics and clinical data at baseline and one-year and five-year follow-ups were collected in the clinical records. RESULTS: Among 142 subjects, 116 were females and 26 were males, with a mean age of 42.1±14.3. They were followed for five years. The diagnosis was performed at the mean age of 24.9±14.7 years after the headache onset, and the time with headache ≥15 days per month was 6.3±7.6 years. On baseline, the average number of headache days per month (HDM) was 25.2±5.9. There was a reduction in HDM. At one-year and five-year follow-ups, a ≥75% reduction in HDM was observed, respectively, in 51.4% and 70.4% of the sample. CONCLUSIONS: The five-year follow-up of chronic migraine and MOH treated with the discontinuation of excessive medication, the use of preventative pharmacological agents, and the optional inclusion of anti-CGRP pathway monoclonal antibody led to a significant decrease in the initial occurrence of HDM.

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.

Medication Overuse Headache, Chronic Migraine and Monoclonal Antibodies Anti-CGRP: A Real-World Study.

OBJECTIVE: Medication overuse headache (MOH) in chronic migraineurs may be a cause or consequence of the overuse of symptomatic medications for headache attacks. It is highly prevalent in tertiary centers. We compared the efficacy of 3 anti-CGRP monoclonal antibodies with traditional pharmacological agents in patients with chronic migraine (CM) and MOH. METHODS: A randomized, cross-sectional, prospective, and open trial with real-world comparison groups was carried out. The sample consisted of 100 consecutive patients having CM and MOH. RESULTS: Eighty-eight patients (65 women and 23 men) were included in the study and divided into 4 groups: those having used erenumab (19.3%), galcanezumab (29.6%), fremanezumab (25%) and conventional medications, and the control group (26.1%). Ages ranged from 18 to 78 years (mean, 44.1 ± 13.6 years). In the 6 months of follow-up, there was a significant reduction in the number of headache days in the 3 groups when compared with the control ( P < 0.0001). CONCLUSIONS: The small number of patients included in each group and the open design do not allow definitive conclusions, but the use of anti-CGRP monoclonal antibodies in patients with CM and MOH may result in lessening the number of headache days when compared with conventional treatment with drugs.

"Growing pains" in children and adolescents as an early symptom of migraine: A prospective study.

BACKGROUND: Children and adolescents may experience pain in the lower limbs, predominantly at the end of the day or during the night, without any relation to organic disease. These pains are often called "growing pains" (GP) by pediatricians and orthopedists. They are commonly attributed to rapid growth. OBJECTIVE: The aim of this study was to review and characterize GP in children and adolescents as a precursor/comorbidity with migraine. METHODS: The study was of a cross-sectional, prospective, longitudinal cohort, with group comparison. A sample of 100 children/adolescents born to mothers with migraine seen at a headache clinic was recruited in a random order chosen by lot, maintaining the ratio of 1:1 for the group with GP and the controls. Both groups were followed for a period of 5 years. RESULTS: After 5 years of follow-up, 78 patients completed the study, of which 42 were from the GP group and 36 were from the control group. Headache fulfilling the International Classification of Headache Disorders, 3rd edition diagnostic criteria for migraine without aura or probable migraine occurred in 32/42 (76%) of patients with GP and in 8/36 (22%) of controls (p < 0.001). In the sample that initially had "growing pains," these pains persisted in 6/42 (14%) and appeared in 14/36 (39%) of those who were previously asymptomatic (p = 0.026). CONCLUSIONS: Pain in the lower limbs of children and adolescents, commonly referred to as GP by pediatricians and orthopedists, may reflect a precursor or comorbidity with migraine.

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.

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.

Migraine treatment with biological therapies. The state of the art / Tratamento da enxaqueca com terapias biológicas. O Estado da arte

Migraine is a highly prevalent and debilitating neurological disorder. Most patients do not receive a correct diagnosis and effective treatments. Apart of the few specialists and tertiary centers worldwide, the treatment of migraine is usually symptomatic and prevention, as well as treatments of the underlying mechanisms, are not aimed. It results in frustration and substantial burden. The last few years witnessed the releasing of specific biological therapies, mostly addressing one of the peptides involved in migraine pathophysiology, the calcitonin gene-related peptide (CGRP). Either the small molecules as well as the monoclonal antibodies against CGRP or its canonical receptor have been launched in markets across the globe and represent interesting options for the treatment of migraine. Onabotulinumtoxin A has also been proposed for chronic migraine as well, but not for episodic migraine, based on its unique ability to inhibit the SNARE complex formation and the release of numerous potential mediators of migraine. However, despite the favorable figures on efficacy and tolerability of these compounds, the regulations, and particulars of different countries, regarding the structures and reimbursement of medical care, demonstrated different adhesion profiles of chosen populations to receive these emerging weapons against migraine-imposed suffering. This review addresses the use and characteristics of biological therapies used in migraine treatment.

A enxaqueca é um distúrbio neurológico altamente prevalente e debilitante. A maioria dos pacientes não recebe um diagnóstico correto e tratamentos eficazes. Com exceção dos poucos especialistas e centros terciários em todo o mundo, o tratamento da enxaqueca é geralmente sintomático e a prevenção, bem como o tratamento dos mecanismos subjacentes, não são direcionados. Isso resulta em frustração e fardo substancial. Os últimos anos testemunharam o lançamento de terapias biológicas específicas, abordando principalmente um dos peptídeos envolvidos na fisiopatologia da enxaqueca, o peptídeo relacionado ao gene da calcitonina (CGRP). Tanto as pequenas moléculas como os anticorpos monoclonais contra CGRP ou o seu receptor canônico foram lançados em mercados em todo o mundo e representam opções interessantes para o tratamento da enxaqueca. A onabotulinumtoxina A também foi proposta para enxaqueca crônica, mas não para enxaqueca episódica, com base em sua capacidade única de inibir a formação do complexo SNARE e a liberação de numerosos mediadores potenciais da enxaqueca. No entanto, apesar dos números favoráveis ​​sobre a eficácia e tolerabilidade destes compostos, os regulamentos e particularidades de diferentes países, no que diz respeito às estruturas e reembolso dos cuidados médicos, demonstraram diferentes perfis de adesão das populações escolhidas para receber estas armas emergentes contra o sofrimento imposto pela enxaqueca. Esta revisão aborda o uso e as características das terapias biológicas utilizadas no tratamento da enxaqueca.

Preventive and abortive treatment of migraine with traditional drugs. The state of the art / Tratamento preventivo e abortivo da enxaqueca com medicamentos tradicionais. O Estado da arte

Introduction: Migraine is a chronic neurological disease, with a prevalence of 15.2% in Brazil. It is 2.2 times more prevalent in women, predominantly in the 18-50 age group. Its pathophysiological mechanism is still not completely understood. Possibly headache attacks and symptoms are associated with cortical spreading depression, the trigeminovascular system, neurogenic inflammation, vasodilation and genetic vulnerability. Objective:This is a narrative review of preventive and abortive treatment of migraine. Comment: Migraine treatment is based on three pillars: patient education, treatment of the disease itself or prevention of attacks, and acute treatment of headache attacks. The therapeutic classes of traditional drugs used in migraine prevention are beta-blockers, tricyclic antidepressants, calcium channel antagonists or blockers, and anticonvulsant neuromodulators. Specific drugs used in the treatment of headache attacks are triptans or serotonergic 5-HT1B/1D receptor agonists, ditans or 5-HT1F receptor agonists, and gepants or CGRP receptor antagonists. Conclusion: Traditional drugs used in the preventive or abortive treatment of migraine are considered to be effective. Through modulation of the disease mechanisms, there is a reduction in the frequency, intensity and duration of headache attacks, and also in the disability caused by the headache. All this to improve the quality of life of patients. The therapeutic classes of traditional drugs used in migraine prevention are beta-blockers, tricyclic antidepressants, antagonists or blockers of calcium channels and anticonvulsant neuromodulators. Specific drugs used in the treatment of headache attacks are triptans or serotonergic 5-HT1B/1D receptor agonists,ditans or 5-HT1F receptor agonists, and gepants or CGRP receptor antagonists.

Introdução: A enxaqueca é uma doença neurológica crônica, com prevalência de 15,2% no Brasil. É 2,2 vezes mais prevalente em mulheres, predominantemente na faixa etária de 18 a 50 anos. Seu mecanismo fisiopatológico ainda não está completamente esclarecido. Possivelmente, os ataques e sintomas de dor de cabeça estão associados à depressão alastrante cortical, ao sistema trigeminovascular, à inflamação neurogênica, à vasodilatação e à vulnerabilidade genética. Objetivo: Esta é uma revisão narrativa do tratamento preventivo e abortivo da enxaqueca. Comente: O tratamento da enxaqueca baseia-se em três pilares: educação do paciente, tratamento da própria doença ou prevenção de crises e tratamento agudo das crises de cefaleia. As classes terapêuticas de medicamentos tradicionais utilizados na prevenção da enxaqueca são betabloqueadores, antidepressivos tricíclicos, antagonistas ou bloqueadores dos canais de cálcio e neuromoduladores anticonvulsivantes. Os medicamentos específicos utilizados no tratamento de crises de dor de cabeça são triptanos ou agonistas do receptor serotoninérgico 5-HT1B/1D, ditans ou agonistas do receptor 5-HT1F e gepants ou antagonistas do receptor CGRP. Conclusão: Os medicamentos tradicionais utilizados no tratamento preventivo ou abortivo da enxaqueca são considerados eficazes. Através da modulação dos mecanismos da doença, há redução na frequência, intensidade e duração das crises de cefaleia, e também na incapacidade causada pela cefaleia. Tudo isso para melhorar a qualidade de vida dos pacientes. As classes terapêuticas de medicamentos tradicionais utilizados na prevenção da enxaqueca são betabloqueadores, antidepressivos tricíclicos, antagonistas ou bloqueadores dos canais de cálcio e neuromoduladores anticonvulsivantes. Os medicamentos específicos utilizados no tratamento de crises de cefaleia são triptanos ou agonistas do receptor serotoninérgico 5-HT1B/1D, ditans ou agonistas do receptor 5-HT1F e gepants ou antagonistas do receptor CGRP.

Psychosis and Bilateral Peripheral Facial Palsy Associated With COVID-19.

Neuropsychiatric disorders associated with coronavirus infections emerged with the coronavirus disease 2019 (COVID-19) pandemic. We describe the clinical, laboratory and radiological features of a patient who presented, after recent COVID-19, two rare neuropsychiatric manifestations: a brief psychotic break followed by severe bilateral peripheral facial palsy.

Brazilian descriptive study of 104 consecutive real-world migraine patients treated with monoclonal antibodies.

BACKGROUND: Migraine is a highly disabling and prevalent neurological disorder. A peptide, calcitonin gene-related peptide, was identified as involved in migraine pathophysiology and monoclonal anti-CGRP antibodies have been developed. AIM: To describe the clinical characteristics and therapeutic response of migraine patients treated with monoclonal antibodies. METHOD: An observational, prospective, uncontrolled, and descriptive study was carried out with a sample of 112 consecutive patients with episodic or chronic migraine treated with monoclonal antibodies. Eight patients did not return for the following medical consultation. They were excluded from the study. RESULTS: A total of 104 patients were described. There was a predominance of episodic migraine. Before treatment, the average frequency of headache was 15.3 ± 8.5 days per month, during the previous three months. Monoclonal antibodies were prescribed at the following frequency: erenumab (49%), galcanezumab (45.2%), and fremanezumab (5.8%). After the third month, the reduction in headache attacks was greater than 50% in 57.7% of patients. Adverse events were referred by 18.3% of patients, in this order of frequency: constipation (7.7%), insomnia (2.9%), vertigo (1.9%), erythema at the injection site (1.9%), arthralgia (1%), nasopharyngitis (1%), facial and hand edema (1%), irritation at the injection site (1%), and paresthesia at the injection site (1%). CONCLUSIONS: This described analysis of migraine patients who used monoclonal antibodies presented one of the first Brazilian experiences with real-world patients. Our results may enlighten clinicians on the outcomes and ways of prescribing anti-CGRP antibodies.

Indomethacin for refractory COVID or post-COVID headache: a retrospective study.

BACKGROUND: COVID-19, a disease caused by SARS-CoV-2, manifests with headache, both in the acute phase and as a post-infection symptom, which may be refractory to usual analgesics. OBJECTIVES: Investigate the therapeutic response of refractory COVID or post-COVID headache to indomethacin. METHODS: This was an observational, retrospective, open and uncontrolled. A sample of 37 patients diagnosed with COVID-19 presenting headache during the acute phase or after the resolution of the disease, with refractoriness to the usual symptomatic medication was treated with indomethacin. RESULTS: Of the 37 patients (24 women and 13 men), 29 were migraineurs and 8 had no previous history of headache. The average age was 40.4 ± 9.4 years, ranging from 19 to 65 years. In 26 (70.3%) patients, the onset of headache occurred within 72 h, and in 11 (29.7%), after 10 days of positivity for Sars-CoV-2. After treatment with indomethacin, 36 patients reported greater than 50% headache relief from the third day and 5 became asymptomatic on the fifth day. CONCLUSIONS: In patients with migraine or no prior history of headache who present with refractory COVID or post-COVID headache to common analgesics, anti-inflammatory drugs, and/or triptans, indomethacin should be considered a therapeutic option.

Cluster headache in children and adolescents: a systematic review of case reports.

AIM: To describe the clinical characteristics and therapeutic options available to paediatric patients with cluster headache. METHOD: Based on a literature search of the medical databases PubMed, LILACS, and Web of Science and using selected descriptors, we carried out a systematic review of case reports on cluster headache in paediatric patients published from 1990 to 2020. RESULTS: Fifty-one patients (29 males, 22 females) with a mean (SD) age of 9 years 7 months (3y 10mo; range 2-16y) were diagnosed with cluster headache. The mean (SD) diagnosis was made 27.8 months (26.2mo) after the onset of cluster headache. Pain occurred at night or on waking up (76.5%) and consisted of 1 to 3 attacks per day (62.7%) lasting 30 to 120 minutes (68.6%). Headaches were unilateral (90.2%), had a pulsatile character (64.7%), and severe intensity (100%). There were autonomic manifestations (90.2%) predominantly ipsilateral to pain, in this order: lacrimation; conjunctival injection; nasal congestion; ptosis; eyelid oedema; and rhinorrhoea. Sumatriptan and oxygen inhalation were the most effective treatments for acute manifestation. Prophylaxis, corticosteroids, verapamil, and gabapentin were the most effective drugs. INTERPRETATION: Due to the small number of published studies, this review could not provide reliable data; however, it appears that cluster headache in children and adolescents is similar to adults, both in clinical characteristics and treatment. What this paper adds Cluster headache in children and adolescents is poorly studied. Cluster headache is uncommon before 10 years of age and diagnosis is difficult in the first few years of life. Treatment of cluster headache in children and adolescents is similar to that used in adults. The notion of the effectiveness of prophylactic treatment is based only on authors' experience.

Cefaleia em Salvas em Crianças e Adolescentes: Uma revisão sistemática de relatos de casos.

OBJETIVO: Descrever as características clínicas e as melhores opções terapêuticas para cefaleia em salvas na idade pediátrica. MÉTODO: Com base em pesquisa bibliográfica nas bases de dados médicos PubMed, LiLacs e WoS e usando descritores selecionados, analisamos todos os relatos de casos de cefaleia em salvas em idade pediátrica publicados de 1990 a 2020. RESULTADOS: Cinquenta e um pacientes (29 meninos e 22 meninas) com idade média (DP) de 9 anos e 7 meses (3 anos e 10 meses), variando de 2 a 16 anos, foram diagnosticados com cefaleia em salvas. O diagnóstico médio (DP) foi feito 27,8 meses (26,2 meses) após o início da cefaleia em salvas. A dor ocorreu à noite ou ao despertar (76,5%), uma a três crises por dia (62,7%), com duração de 30-120 minutos (68,6%), localizada unilateralmente (90,2%), de caráter pulsátil (64,7%) e intensidade severa (100%). Houve manifestações autonômicas (90,2%), predominantemente ipsilaterais à dor, nesta ordem: lacrimejamento, injeção conjuntival, congestão nasal, ptose, edema palpebral e rinorreia. Sumatriptano e inalação de oxigênio foram os tratamentos agudos mais eficazes. Na profilaxia, corticosteroides, verapamil e gabapentina foram os medicamentos mais eficazes. INTERPRETAÇÃO: Devido ao pequeno número de estudos publicados, esta revisão não foi capaz de fornecer dados confiáveis, mas parece que a cefaleia em salvas em crianças e adolescentes é semelhante à do adulto, tanto nas características clínicas quanto no tratamento.

Migraine Treatment in Emergency Departments of Brazil: A Retrospective Study of 2 Regions.

OBJECTIVE: This study describes the approaches, medications used, and time of care for migraineurs, who have been in emergency departments (ED) from 2 different regions of Brazil. METHODS: Retrospective, cross-sectional, observational, non-randomized study of migraine patients seen at 2 headache centers in Brazil. RESULTS: Eighty-four migraine patients (15 men and 69 women) were divided into 2 groups: chronic (19%, n = 16) and episodic migraineurs (81%, n = 68). In the ED, medications were used in the following order of frequency: dipyrone or metamizole (89.3%, 75/84), nonsteroidal anti-inflammatory drugs (57.1%; 48/84) opioids (51.1%; 43/84), metoclopramide (29.8%; 25/84), dexamethasone (28.6%; 24/84), chlorpromazine (13.1%; 11/84), and subcutaneous sumatriptan (7.1%; 6/84). The average time in the care center was 8.2 hours, but only 23 patients (27.4%) left the hospital with greater than 50% relief in headache severity. CONCLUSIONS: Dipyrone and nonsteroidal anti-inflammatories were the most used drugs, but nearly half received opioids. More efficient drugs were poorly used. Considering the number of patients leaving the hospital with headache relief, a changing treatment paradigm should be carried out in Brazil.

Prevalence of Headache Attributed to Airplane Travel Among Medical Students in Brazil.

BACKGROUND: Headache attributed to airplane travel is a rare form of headache that develops exclusively during airplane travel. It is characterized by occurring during takeoff, landing, or both, and improves spontaneously within 30 minutes after the ascent or descent of the airplane is completed. OBJECTIVES: Our objectives were to determine the prevalence of headache attributed to airplane travel among medical students who traveled by plane, the time of flight when it occurred, and the emotional state of passengers on new trips. METHODS: The study was prospective, cross-sectional, using a non-random sample of medical students who traveled by plane. In total, 155 passengers who traveled by plane on at least 3 flights, regardless of duration were interviewed. RESULTS: Headache during flight occurred 3 or more times in 7.5% (80/1070) of the trips and 14.2% (22/155) of the passengers, especially during takeoff or landing (17/22; 77.3%), having a stabbing character and lasting less than 30 minutes. The headache improved spontaneously at the end of the landing phase (17/22; 77.3%). When traveling again, 68.2% (15/22) of passengers traveled normally, despite previous painful experience. CONCLUSIONS: This study demonstrated that headache attributed to airplane travel is not as rare as previously thought, being predominant during takeoff or landing. In addition, despite the bothersome feeling, most passengers who experienced this headache traveled normally, despite previous painful experience.

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.

Sodium Divalproate in Low Alternating Daily Doses for Migraine Prevention: A Retrospective Study.

BACKGROUND AND OBJECTIVE: Sodium divalproate is an effective neuromodulator for migraine prevention. Recommended doses vary from 1,000 to 1,500 mg/day, which may provoke unpleasant side effects as weight gain, tremor, and hair loss. Some patients do respond to lower doses even used once daily in ER presentations, but alternating low daily doses was never studied so far. The aim of this study was to evaluate the adherence, the tolerability, and the efficacy of sodium divalproate (SD) in low alternating daily doses for migraine prevention in patients of a tertiary center. METHODS: Consecutive migraineurs from a tertiary center to whom SD was prescribed as monotherapy from January 2017 until September 2018 were studied retrospectively. The doses were 250 mg alternated with 500 mg and were used based on the treating physician expertise and previous experience with tolerability issues when using higher doses. Headache frequency compared to baseline, adherence expressed by returning to a visit after 2 and 4 months and side effects reported by the patients, were evaluated. RESULTS: Sixty-eight patients (53 women and 15 men, aged 18-58) were included. The average headache frequency (HF) during baseline was decreased from 8.2 to 5.1 headache days/month among the 50 out of 68 patients returning at 2 months (adherence rate 73.5%). Weight gain was reported by 15 patients (30%, mean 2.1 kg). At 4 months, HF was reduced to 4.2 days/month (adherence rate 61.8%, n = 42) and weight gain reported by 18 patients (42.8%, mean 2.3 kg). CONCLUSIONS: Despite the retrospective open design, which cannot allow definitive conclusions, SD in low alternating daily doses seems to be effective as with higher doses, but still induce modest weight gain. Controlled studies are necessary to confirm these observations.

Migraine treatment: the doors for the future are open, but with caution and prudence.

Migraine is a burdensome disorder. Current treatments are far from ideal. Recent knowledge has been indicating targets whose antagonism may improve efficacy. It is particularly true with the calcitonin gene-related peptide (CGRP) and the monoclonal antibodies anti-CGRP can interfere with this pathway and decrease the frequency of migraine attacks. Erenumab, fremanezumab and galcanezumab have recently been approved and eptinezumab is likely to be, soon. Although efficacy figures were not spectacular, tolerability and potential higher adherence were noteworthy. However, caution must be exercised. The time frame after the studies was limited to three years and dose administration was restricted to three-monthly doses. The CGRP is present throughout the human body and migraine is a life-long disease, often requiring treatment for decades. It is not known whether this favorable profile can be maintained or will be safe in pregnant women or adolescents. In addition, there were deaths during the studies, which may have happened without a clear relationship. New treatments are welcome, but caution is warranted.

Migraine treatment: the doors for the future are open, but with caution and prudence / Tratamento da migrânea: as portas para o futuro estão abertas, mas com cuidado e parcimônia

ABSTRACT Migraine is a burdensome disorder. Current treatments are far from ideal. Recent knowledge has been indicating targets whose antagonism may improve efficacy. It is particularly true with the calcitonin gene-related peptide (CGRP) and the monoclonal antibodies anti-CGRP can interfere with this pathway and decrease the frequency of migraine attacks. Erenumab, fremanezumab and galcanezumab have recently been approved and eptinezumab is likely to be, soon. Although efficacy figures were not spectacular, tolerability and potential higher adherence were noteworthy. However, caution must be exercised. The time frame after the studies was limited to three years and dose administration was restricted to three-monthly doses. The CGRP is present throughout the human body and migraine is a life-long disease, often requiring treatment for decades. It is not known whether this favorable profile can be maintained or will be safe in pregnant women or adolescents. In addition, there were deaths during the studies, which may have happened without a clear relationship. New treatments are welcome, but caution is warranted.

RESUMO A migrânea é incapacitante. Os tratamentos atuais apresentam resultados abaixo do desejado. O conhecimento atual indica alvos nos quais o bloqueio pode melhorar a eficácia do tratamento. Isso é mais claro com o peptídeo relacionado ao gene da calcitonina (CGRP) e anticorpos monoclonais contra este peptídeo ou seu receptor interferem com a fisiopatologia migranosa e reduzem a frequência da cefaleia. Erenumab, fremanezumab e galcanezumab já foram aprovados. Eptinezumab o será em breve. Embora a eficácia não tenho sido espetacular, a boa tolerabilidade e melhor adesão foram notáveis. No entanto, cautela deve ser empregada. Os estudos se limitaram a observar os pacientes por até três anos e com três doses mensais seguidas. Existe CGRP em todo o organismo e a migrânea é uma doença crônica, não raro requerendo tratamento por décadas. Não se sabe se a tolerabilidade favorável manter-se-á por anos ou em grávidas e adolescentes. Também houve mortes durante os estudos, mesmo sem ligação comprovada. Novos tratamentos são bem-vindos, mas cautela é necessária neste momento.

Medication-overuse headache. Retrospective comparison of preventive treatments.

OBJECTIVE: Medication-overuse headache is commonly seen in tertiary centers. Limited evidence is available regarding treatment. We compared the use of one or two drugs, three drugs, or four pharmacological agents for the prevention of headache. METHODS: This was a retrospective analysis of 149 consecutive patients. Sudden withdrawal and pharmacological prevention with one or more drugs were carried out. Adherence and the decrease of headache frequency of more than 50% were compared after four months between the one or two, three, and four drug groups. RESULTS: There was no difference in adherence (p > 0.6). Headache frequency reduction was shown in 23 (54.8%, one or two drugs), 33 (70%, three drugs) and 11 (55%, four drugs); p = 0.13 and p = 0.98, not significant. There was a tendency towards significance between the one or two drug takers versus the three drug and four drug takers together (p = 0.09). CONCLUSIONS: The use of more drugs was not better at improving headache. However, there is the possibility that acting simultaneously on different sites may promote broader modulation and better outcome.