Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 28.720
Filtrar
1.
Cephalalgia ; 43(1): 3331024221128250, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36620892

RESUMO

BACKGROUND: Atogepant is a United States Food and Drug Administration-approved oral calcitonin gene-related peptide receptor antagonist for the preventive treatment of episodic migraine. The study objective was to evaluate the long-term safety and tolerability of atogepant in participants who completed the phase 3 ADVANCE trial (NCT03777059). METHODS: This 40-week, open-label extension trial (NCT03939312) monitored safety in participants receiving oral atogepant 60 mg once daily, followed by a four-week safety follow-up period. RESULTS: Of the 685 participants taking at least one dose of atogepant, the treatment period was completed by 74.6% of participants with a mean (standard deviation) treatment duration of 233.6 (89.3) days. Treatment-emergent adverse events occurred in 62.5% of participants, with upper respiratory tract infection (5.5%), urinary tract infection (5.3%), nasopharyngitis (4.8%), sinusitis (3.6%), constipation (3.4%), and nausea (3.4%) occurring at ≥3%. Serious adverse events were observed in 3.4% of participants (none were treatment-related), and there were no deaths. Adverse events leading to discontinuation occurring at >0.1% were nausea (0.4%) and abdominal pain, vomiting, weight decrease, dizziness, and migraine (0.3% each). CONCLUSION: These results are consistent with atogepant's known safety profile and support long-term use of atogepant 60 mg once daily dosing as safe and well tolerated.ClinicalTrials.gov Registration Number: NCT03939312.


Assuntos
Transtornos de Enxaqueca , Humanos , Resultado do Tratamento , Método Duplo-Cego , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/prevenção & controle , Náusea
2.
BMC Neurol ; 23(1): 8, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36609224

RESUMO

BACKGROUND: The Chronic Headache Education and Self-Management Study (CHESS) multicentre randomised trial evaluated the impact a group education and self-management support intervention with a best usual care plus relaxation control for people living with chronic headache disorders (tension type headaches or chronic migraine, with or without medication overuse headache). Here we report the process evaluation exploring potential explanations for the lack of positive effects from the CHESS intervention. METHODS: The CHESS trial included 736 (380 intervention: 356 control) people across the Midlands and London UK. We used a mixed methods approach. Our extensive process evaluation looked at context, reach, recruitment, dose delivered, dose received, fidelity and experiences of participating in the trial, and included participants and trial staff. We also looked for evidence in our qualitative data to investigate whether the original causal assumptions underpinning the intervention were realised. RESULTS: The CHESS trial reached out to a large diverse population and recruited a representative sample. Few people with chronic tension type headaches without migraine were identified and recruited. The expected 'dose'of the intervention was delivered to participants and intervention fidelity was high. Attendance ("dose received") fell below expectation, although 261/380 (69%) received at least at least the pre-identified minimum dose. Intervention participants generally enjoyed being in the groups but there was little evidence to support the causal assumptions underpinning the intervention were realised. CONCLUSIONS: From a process evaluation perspective despite our extensive data collection and analysis, we do not have a clear understanding of why the trial outcome was negative as the intervention was delivered as planned. However, the lack of evidence that the intervention causal assumptions brought about the planned behaviour change may provide some insight. Our data suggests only modest changes in managing headache behaviours and some disparity in how participants engaged with components of the intervention within the timeframe of the study. Moving forwards, we need a better understanding of how those who live with chronic headache can be helped to manage this disabling condition more effectively over time. TRIAL REGISTRATION: ISRCTN79708100 .


Assuntos
Transtornos da Cefaleia , Transtornos de Enxaqueca , Autogestão , Cefaleia do Tipo Tensional , Humanos , Autogestão/métodos , Transtornos da Cefaleia/terapia , Cefaleia/terapia , Transtornos de Enxaqueca/terapia
3.
Trials ; 24(1): 25, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635741

RESUMO

BACKGROUND: Migraine is a major pediatric health problem impacting 10-12% of youth. About 1 in 3 youth with migraine are diagnosed with insomnia. Sleep and migraine share a cyclical relationship, and data indicate that insomnia symptoms increase migraine severity. CBT for insomnia (CBT-I) has demonstrated efficacy for improving insomnia in adults with migraine and other pain conditions; however, effects in youth have not been evaluated. Moreover, in adults, there is some indication that CBT-I may lead to changes in pain after there are sustained improvements in sleep, but this has never been empirically tested. Cognitive-behavioral therapy for pain management (CBT-Pain) is an established treatment approach for youth with migraine, leading to reductions in headache frequency and disability. In the proposed study, we will address these gaps in knowledge by using an innovative two-phase trial design to (1) test the efficacy of Internet-delivered CBT-I intervention for youth with migraine and comorbid insomnia compared to Internet-delivered sleep education for modifying sleep and (2) investigate how changes in sleep may modify the response to Internet-delivered CBT-Pain intervention. METHODS: We will study a cohort of 180 adolescents, ages 11-17 years, with migraine (with or without aura, chronic migraine) and comorbid insomnia. In phase 1, youth will be randomly assigned to receive Internet-delivered CBT-I intervention or Internet sleep education control. In phase 2, all youth will receive Internet-delivered CBT-Pain intervention. Assessments will occur at baseline, immediately after phase 1 intervention, immediately after phase 2 intervention, and 6 months post-intervention. We will use a comprehensive multidimensional assessment of sleep and headache including self-report questionnaires, ambulatory actigraphy monitoring, and 14-day daily diaries. DISCUSSION: Given the high prevalence of insomnia in adolescents with migraine, an extension of CBT-I intervention to this population will address an important gap in clinical practice and in conceptual understanding of the relationship between sleep and migraine. By testing a separate CBT-I intervention, we will be able to apply this treatment in the future to other pediatric populations (e.g., cancer, arthritis) who commonly experience comorbid insomnia. TRIAL REGISTRATION: ClinicalTrials.gov NCT04936321. Registered on June 23, 2021.


Assuntos
Terapia Cognitivo-Comportamental , Transtornos de Enxaqueca , Distúrbios do Início e da Manutenção do Sono , Adolescente , Criança , Humanos , Terapia Cognitivo-Comportamental/métodos , Cefaleia , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/terapia , Dor , Manejo da Dor/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sono , Distúrbios do Início e da Manutenção do Sono/diagnóstico , Distúrbios do Início e da Manutenção do Sono/terapia , Resultado do Tratamento
5.
BMC Psychol ; 11(1): 17, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36691101

RESUMO

BACKGROUND: Migraine is a neurological disease that has several physical and psychological complications, which is characterized by disability and impaired quality of life. AIMS: The aim of this study was to explore the mediating role of pain self-efficacy in the relationship between meaning of life, perceived social support, spiritual well-being and pain catastrophizing with quality of life in migraine sufferers. The relationship between these factors with quality of life (QOL) was not fully explored in migraine patients. METHOD: This study was a correlational study of structural equations. Therefore, 300 patients with migraine who referred to one of the specialized neurological treatment centers in Zanjan in 2021 were recruited based on the inclusion criteria. Patients also completed the World Health Organization Quality of Life Scale (WHOQOL-BREF), Meaning in Life Questionnaire, Multidimensional Scale of Perceived Social Support, Spiritual Well-Being Scale, Pain Catastrophizing Scale, Pain Self-Efficacy Questionnaire. Finally, the hypotheses were then analyzed with correlation coefficient and path analysis method by using SPSS-26 and LISREL-10.2 programs. RESULTS: The results of the present study showed that pain self-efficacy has a mediating role in the relationship between meaning of life and quality of life (B = 0.015), perceived social support with quality of life (B = 0.022), spiritual well-being with quality of life (B = 0.021), as well as pain catastrophizing with quality of life (B = - 0.015). CONCLUSION: According to the results of this study, by considering the role of self-efficacy of pain, it is possible to develop the programs to strengthen and improve the meaning of life, perceived social support, spiritual well-being and also reduce pain catastrophizing, in order to improve the quality of life of patients with migraine.


Assuntos
Transtornos de Enxaqueca , Qualidade de Vida , Humanos , Qualidade de Vida/psicologia , Autoeficácia , Dor/psicologia , Catastrofização/psicologia , Apoio Social , Transtornos de Enxaqueca/psicologia , Inquéritos e Questionários
6.
PLoS One ; 18(1): e0279163, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36598881

RESUMO

OBJECTIVES: Understand the continuity and changes in headache not-otherwise-specified (NOS), migraine, and post-traumatic headache (PTH) diagnoses after the transition from ICD-9-CM to ICD-10-CM in the Veterans Health Administration (VHA). BACKGROUND: Headache is one of the most commonly diagnosed chronic conditions managed within primary and specialty care clinics. The VHA transitioned from ICD-9-CM to ICD-10-CM on October-1-2015. The effect transitioning on coding of specific headache diagnoses is unknown. Accuracy of headache diagnosis is important since different headache types respond to different treatments. METHODS: We mapped headache diagnoses from ICD-9-CM (FY 2014/2015) onto ICD-10-CM (FY 2016/2017) and computed coding proportions two years before/after the transition in VHA. We used queries to determine the change in transition pathways. We report the odds of ICD-10-CM coding associated with ICD-9-CM controlling for provider type, and patient age, sex, and race/ethnicity. RESULTS: Only 37%, 58% and 34% of patients with ICD-9-CM coding of NOS, migraine, and PTH respectively had an ICD-10-CM headache diagnosis. Of those with an ICD-10-CM diagnosis, 73-79% had a single headache diagnosis. The odds ratios for receiving the same code in both ICD-9-CM and ICD-10-CM after adjustment for ICD-9-CM and ICD-10-CM headache comorbidities and sociodemographic factors were high (range 6-26) and statistically significant. Specifically, 75% of patients with headache NOS had received one headache diagnoses (Adjusted headache NOS-ICD-9-CM OR for headache NOS-ICD-10-CM = 6.1, 95% CI 5.89-6.32. 79% of migraineurs had one headache diagnoses, mostly migraine (Adjusted migraine-ICD-9-CM OR for migraine-ICD-10-CM = 26.43, 95% CI 25.51-27.38). The same held true for PTH (Adjusted PTH-ICD-9-CM OR for PTH-ICD-10-CM = 22.92, 95% CI: 18.97-27.68). These strong associations remained after adjustment for specialist care in ICD-10-CM follow-up period. DISCUSSION: The majority of people with ICD-9-CM headache diagnoses did not have an ICD-10-CM headache diagnosis. However, a given diagnosis in ICD-9-CM by a primary care provider (PCP) was significantly predictive of its assignment in ICD-10-CM as was seeing either a neurologist or physiatrist (compared to a generalist) for an ICD-10-CM headache diagnosis. CONCLUSION: When a veteran had a specific diagnosis in ICD-9-CM, the odds of being coded with the same diagnosis in ICD-10-CM were significantly higher. Specialist visit during the ICD-10-CM period was independently associated with all three ICD-10-CM headaches.


Assuntos
Transtornos de Enxaqueca , Cefaleia Pós-Traumática , Veteranos , Humanos , Classificação Internacional de Doenças , Saúde dos Veteranos , Cefaleia/epidemiologia , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/epidemiologia , Comorbidade
7.
Cephalalgia ; 43(1): 3331024221132008, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36622876

RESUMO

BACKGROUND: It has been suggested that patients with migraine have a higher risk of stroke. Despite considerable research on this topic in younger populations, a clear answer is still lacking for older individuals. We studied the association between migraine and the risk of stroke in a middle-aged and elderly population. METHODS: Within the ongoing prospective population-based Rotterdam Study, the presence of migraine was assessed using a validated questionnaire in a structured interview between 2006 and 2011, which formed the baseline. The association between migraine and the risk of stroke was analyzed using Cox proportional-hazards models with adjustments for age, sex, and cardiometabolic risk factors. RESULTS: A total of 6925 (mean age 65.7 ± 11.3 years, 57.8% females) stroke-free participants were included. At baseline, 1030 (14.9%) participants had lifetime history of migraine. During a median follow-up of 6.2 years, 195 participants developed a stroke (163 ischemic stroke). Analyzing the association between migraine and stroke, we found a hazard ratio of 1.44 with a 95% confidence interval of 0.96-2.15. The results were similar for the ischemic stroke (HR 1.50, CI: 0.97-2.32). CONCLUSION: Our data suggested an association between migraine and the risk of stroke in a middle-aged and elderly population, but this was not statistically significant.


Assuntos
AVC Isquêmico , Transtornos de Enxaqueca , Acidente Vascular Cerebral , Pessoa de Meia-Idade , Feminino , Idoso , Humanos , Masculino , Estudos Prospectivos , Acidente Vascular Cerebral/epidemiologia , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/complicações , Estudos Longitudinais , Fatores de Risco
9.
Cephalalgia ; 43(1): 3331024221131337, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36606562

RESUMO

OBJECTIVE: The objective is to summarize the knowledge on the epidemiology, pathophysiology and management of secondary headache attributed to SARS-CoV-2 infection and vaccination; as well as to delineate their impact on primary headache disorders. METHODS: This is a narrative review of the literature regarding primary and secondary headache disorders in the setting of COVID-19 pandemic. We conducted a literature search in 2022 on PubMed, with the keywords "COVID 19" or "vaccine" and "headache" to assess the appropriateness of all published articles for their inclusion in the review. RESULTS: Headache is a common and sometimes difficult-to-treat symptom of both the acute and post-acute phase of SARS-CoV-2 infection. Different pathophysiological mechanisms may be involved, with the trigeminovascular system as a plausible target. Specific evidence-based effective therapeutic options are lacking at present. Headache attributed to SARS-CoV-2 vaccinations is also common, its pathophysiology being unclear. People with primary headache disorders experience headache in the acute phase of COVID-19 and after vaccination more commonly than the general population. Pandemic measures, forcing lifestyle changes, seemed to have had a positive impact on migraine, and changes in headache care (telemedicine) have been effectively introduced. CONCLUSIONS: The ongoing COVID-19 pandemic is a global challenge, having an impact on the development of secondary headaches, both in people with or without primary headaches. This has created opportunities to better understand and treat headache and to potentiate strategies to manage patients and ensure care.


Assuntos
COVID-19 , Transtornos de Enxaqueca , Humanos , COVID-19/epidemiologia , COVID-19/complicações , Pandemias , SARS-CoV-2 , Cefaleia/epidemiologia , Cefaleia/etiologia , Cefaleia/diagnóstico , Transtornos de Enxaqueca/complicações
10.
Cephalalgia ; 43(1): 3331024221128265, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36606574

RESUMO

BACKGROUND: In this manuscript, we aim to systematically estimate the pooled prevalence and incidence of primary headaches and its subtypes (migraine, tension-type headache, and chronic headaches) in Latin America and the Caribbean, describing its epidemiological profile and associated factors. METHODS: We systematically searched PubMed/MEDLINE, Scopus, and LILACS (From conception to March 2021), for populational studies reporting the epidemiology of primary headaches and their associated factors in Latin America and the Caribbean. The data extraction was conducted independently. We performed random-effect model meta-analysis of prevalence (overall primary headaches and by subtypes) and associated factors, assessed potential sources of heterogeneity, the risk of bias, publication bias, and the evidence certainty (GRADE methodology). RESULTS: We included 32 populational studies (38 subpopulations, n = 63,813). The prevalence of primary headaches was 41.4% (95% CI 31.1-52.2%; n = 54,357), 15% for migraine (95% CI 12.0-18.3; n = 53,658 individuals), 20.6% for tension-type headache (95% CI 12.4-30.2; n = 25,840), and 6% for chronic headaches (95% CI 3.3-9.6; n = 21,720), with high between-study heterogeneity. No incidence data was found. Female sex, white ethnicity, high BMI, comorbid mental health disorders, and low-back pain were associated with higher prevalence of primary headaches. The prevalence was less in rural areas. CONCLUSION: In Latin America and the Caribbean, primary headaches are highly prevalent affecting young females disproportionally. The prevalence of chronic headaches is higher than in other systematic global and regional estimations. The presence of comorbidities as modifiable risk factors should encourage their integration as targets for community-based preventive and therapeutic interventions. PROTOCOL REGISTRATION NUMBER: CRD42018105116.


Assuntos
Transtornos de Enxaqueca , Cefaleia do Tipo Tensional , Humanos , Feminino , Cefaleia do Tipo Tensional/epidemiologia , América Latina/epidemiologia , Etnicidade , Cefaleia/epidemiologia , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/prevenção & controle , Região do Caribe/epidemiologia , Prevalência
11.
J Headache Pain ; 24(1): 1, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36597043

RESUMO

Migraine is a major health burden worldwide with complex pathophysiology and multifarious underlying mechanisms. One poorly understood issue concerns the early steps in the generation of migraine pain. To elucidate the basic process of migraine pain further, it seems useful to consider key molecular players that may operate synergistically to evoke headache. While the neuropeptide CGRP is an important contributor, we propose that extracellular ATP (that generally plays a powerful nociceptive role) is also a major component of migraine headache, acting in concert with CGRP to stimulate trigeminal nociceptive neurons. The aim of the present focused review is to highlight the role of ATP activating its P2X3 membrane receptors selectively expressed by sensory neurons including their nerve fiber terminals in the meninges. Specifically, we present data on the homeostasis of ATP and related purines in the trigeminovascular system and in the CNS; the basic properties of ATP signalling at peripheral and central nerve terminals; the characteristics of P2X3 and related receptors in trigeminal neurons; the critical speed and persistence of P2X3 receptor activity; their cohabitation at the so-called meningeal neuro-immune synapse; the identity of certain endogenous agents cooperating with ATP to induce neuronal sensitization in the trigeminal sensory system; the role of P2X3 receptors in familial type migraine; the current state of P2X3 receptor antagonists and their pharmacological perspectives in migraine. It is proposed that the unique kinetic properties of P2X3 receptors activated by ATP offer an interesting translational value to stimulate future studies for innovative treatments of migraine pain.


Assuntos
Transtornos de Enxaqueca , Receptores Purinérgicos P2X3 , Humanos , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Células Receptoras Sensoriais/metabolismo , Dor , Trifosfato de Adenosina/farmacologia , Gânglio Trigeminal/metabolismo
12.
Cephalalgia ; 43(1): 3331024221131331, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36587297

RESUMO

OBJECTIVE: To compare clinical features in youth with continuous headache from migraine, persistent post-traumatic headache, and new daily persistent headache to determine if they are similar, contrary to their distinction in the International Classification of Headache Disorders. METHODS: We pursued a single center age- and sex-matched observational study comparing the clinical characteristics of 150 youth (11 - 17 years old) with continuous headache from migraine, persistent post-traumatic headache, and new daily persistent headache. A diagnostic algorithm based on international classification of headache disorders criteria was used to identify those with migraine (headache features of migraine with gradual onset), and persistent post-traumatic headache and new daily persistent headache (based on the circumstances of headache onset regardless of headache features). Fifty participants each with migraine, persistent post-traumatic headache, and new daily persistent headache were matched by age and sex. Participant survey responses on headache characteristics were compared. RESULTS: Median usual headache severity was 6.0 [95%CI 6.0, 6.0] and was not different across diagnostic groups (H statistic = 1.2, p = 0.55). Headache exacerbation frequency, disability, associated symptoms, and most triggers were not significantly different across groups. The majority of persistent post-traumatic headache and new daily persistent headache had headache features consistent with a diagnose of migraine (72% and 62%, respectively). CONCLUSION: Our findings suggest that most persistent post-traumatic headache and new daily persistent headache may represent abrupt onset of migraine.


Assuntos
Transtornos da Cefaleia , Transtornos de Enxaqueca , Cefaleia Pós-Traumática , Cefaleia do Tipo Tensional , Humanos , Adolescente , Criança , Cefaleia Pós-Traumática/epidemiologia , Cefaleia Pós-Traumática/etiologia , Cefaleia , Transtornos de Enxaqueca/epidemiologia , Transtornos da Cefaleia/diagnóstico
13.
Rev Med Liege ; 78(1): 46-54, 2023 Jan.
Artigo em Francês | MEDLINE | ID: mdl-36634067

RESUMO

Although migraine is one of the most common chronic diseases and is the subject of numerous studies, there is still a considerable proportion of patients who are not satisfied with their acute treatment. Left without any real new therapeutic option to offer patients since sumatriptan was introduced on the Belgian market 30 years ago, neurologists have recently seen a change in the therapeutic landscape with the advent of new specific acute treatments for migraine: gepants and ditans. Being the only ones currently available in Belgium, gepants (including the newly marketed rimegepant) bring added value to traditional treatments such as non-steroidal anti-inflammatory drugs and triptans. This is why it seemed useful to review the different therapeutic options available in Belgium today by including these new treatments and to propose a rational pharmacological approach to relieve acute migraine attack.


Bien que la migraine soit une des maladies chroniques les plus fréquentes et fasse l'objet de nombreuses recherches, il existe malheureusement encore une proportion importante de patients insatisfaits de leur traitement anti-douleur. Sans nouvelle vraie option thérapeutique à proposer aux patients depuis la mise sur le marché belge du sumatriptan voici 30 ans, le neurologue a vu récemment le paysage thérapeutique se modifier avec l'arrivée de nouveaux traitements spécifiques de la crise de migraine : les gépants et les ditans. Seuls disponibles pour le moment en Belgique, les gépants (avec notamment le rimégépant nouvellement commercialisé) apportent une plus-value aux traitements traditionnels que sont les anti-inflammatoires non stéroïdiens et les triptans. C'est la raison pour laquelle il nous a semblé utile de refaire le point sur les différentes options thérapeutiques disponibles aujourd'hui en Belgique en intégrant ces nouveaux traitements et de proposer une approche pharmacologique rationnelle pour soulager la douleur de la crise de migraine.


Assuntos
Transtornos de Enxaqueca , Humanos , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/induzido quimicamente , Sumatriptana/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Triptaminas/uso terapêutico , Bélgica
14.
Sci Rep ; 13(1): 626, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635330

RESUMO

Emerging evidence reveals a close association between gut microbiota and human neurological disorders. The present study aimed to assess whether the composition of gut microbiota in participants with episodic migraine (EM) and chronic migraine (CM) was altered in comparison to that of the controls. This study was a cross-sectional, case-control study. The gut microbiota were evaluated by the partial, targeted sequencing of the 16S rRNA V3-V4 region. This study enrolled 42 and 45 participants with EM and CM, respectively, and 43 controls. Alpha and beta diversities revealed no significant difference among the three groups; however, the microbiota composition at the class, order, family, and genus levels differed significantly between EM and the control, CM and the control, and the EM and CM groups. Moreover, higher composition of PAC000195_g was significantly associated with a lower headache frequency among the five genera that exhibited significantly different microbiota composition in EM and CM. Agathobacter revealed a significant negative association with severe headache intensity. The findings of the present study provide evidence of altered gut microbiota in EM and CM. These findings will help in understanding the course and treatment of migraine.


Assuntos
Microbioma Gastrointestinal , Transtornos de Enxaqueca , Humanos , Estudos Transversais , RNA Ribossômico 16S/genética , Estudos de Casos e Controles , Cefaleia
15.
AAPS PharmSciTech ; 24(1): 32, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627414

RESUMO

Migraine headaches are usually intolerable, and a quick-relief treatment remains an unmet medical need. Almotriptan malate is a serotonin (5-HT1B/1D) receptor agonist approved for the treatment of acute migraine in adults. It is currently available in an oral tablet dosage form and has a Tmax of 1-3 h, and therefore, there is a medical need to develop a non-invasive rapidly acting formulation. We have developed an intranasal formulation of almotriptan malate using the quality-by-design (QbD) approach. A 2-factor 3-level full factorial design was selected to build up the experimental setting. The developed formulation was characterized for pH, viscosity, in vitro permeation, ex vivo permeation, and histopathological tolerance. To assess the potential of the developed formulation to produce a rapid onset of action following intranasal delivery, a pharmacokinetic study was performed in the Sprague-Dawley rat model and compared to the currently available marketed oral tablet formulation. For this, the LC-MS/MS bioanalytical method was developed and used for the determination of plasma almotriptan malate concentrations. Results of a pharmacokinetic study revealed that intranasal administration of optimized almotriptan malate formulation enabled an almost five-fold reduction in Tmax and about seven-fold increase in bioavailability in comparison to the currently available oral tablet formulation, suggesting the potential of developed almotriptan malate intranasal formulation in producing a rapid onset of action as well as enhanced bioavailability.


Assuntos
Transtornos de Enxaqueca , Agonistas do Receptor de Serotonina , Animais , Ratos , Administração Intranasal , Cromatografia Líquida , Agonistas do Receptor de Serotonina/farmacocinética , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Triptaminas/farmacocinética , Transtornos de Enxaqueca/tratamento farmacológico , Serotonina/uso terapêutico , Comprimidos
16.
Ann Intern Med ; 176(1): ITC1-ITC16, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36623287

RESUMO

Migraine affects about 1 billion people worldwide, and up to 15% of adults in the United States have migraine attacks in any given year. Migraine is associated with substantial adverse socioeconomic and personal effects. It is the second leading cause of years lived with disability worldwide for all ages and the leading cause in women aged 15 to 49 years. Diagnostic uncertainty increases the likelihood of unnecessary investigations and suboptimal management. This article advises clinicians about diagnosing migraine, ruling out secondary headache disorders, developing acute and preventive treatment plans, and deciding when to refer the patient to a specialist.


Assuntos
Pessoas com Deficiência , Transtornos de Enxaqueca , Adulto , Humanos , Feminino , Estados Unidos , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/prevenção & controle , Probabilidade
17.
J Headache Pain ; 24(1): 5, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36647006

RESUMO

BACKGROUND: Many migraine patients do not respond adequately to conventional preventive treatments and are therefore described as treatment/medically resistant or difficult to treat cases. Calcitonin gene-related peptide monoclonal antibodies are a relatively novel molecular treatment for episodic and chronic migraine that have been shown to be effective in short duration clinical trials in approximately 40-50% of all chronic migraine patients. Patient Related Outcome Measures (PROM) or Quality of Life (QoL) questionnaires are used to help measure response to treatment in migraine. Although some open label extension studies have become available for erenumab, there is a lack of real-world data pertaining to quality of life in the medium to long-term for chronic and treatment resistant migraine patients. METHODS: A total of 177 treatment resistant CM patients were started on erenumab (70 mg or 140 mg subcutaneous injection every 4 weeks) in our three specialist Headache Clinics. Of these, 174 had their first injection between December 2018 and October 2019. All patients were evaluated with the following PROM: the Headache Impact Test- 6, Migraine Associated Disability Assessment test and Migraine-Specific QoL Questionnaire, before starting treatment with erenumab and at intervals of 3-12 months after starting treatment. The decision to continue treatment was based on subjective clinical improvement of at least 30% (as reported by the patient), supported with diaries and QoL questionnaires. We present here the QoL measurements for this group of 177 patients. Prior preventive migraine treatments included conventional oral prophylactic medications (such as topiramate, candesartan, propranolol, or amitriptyline), at least two cycles of PREEMPT protocol onabotulinumtoxin A or (in a small number of cases) neuromodulation with single pulse Transcranial Magnetic Stimulation. RESULTS: Of the 177 patients who started treatment with erenumab, 68/177 (38.4%) stopped during the first year, either due to lack of efficacy (no significant benefit or only minimal improvement) and/or possible side effects. 109/177 (61.6%) patients reported clinically significant improvement after 6-12 months and wished to stay on treatment. Twelve of these 109 patients subsequently stopped treatment in the period between 1 year and up to June 2021 (mainly due to a worsening of their migraine). Therefore, a total of 97/177 patients (54.8%) remained on treatment as of June 2021 (duration of treatment 17-30 months, median of 25 months). CONCLUSION: Approximately 55% of treatment resistant or difficult to treat CM patients who trialled erenumab in our clinics reported a subjective benefit and were still on treatment after 17-30 months.


Assuntos
Transtornos de Enxaqueca , Qualidade de Vida , Humanos , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/farmacologia , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/uso terapêutico , Método Duplo-Cego , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/prevenção & controle , Medidas de Resultados Relatados pelo Paciente , Cefaleia/tratamento farmacológico , Resultado do Tratamento
18.
J Pharm Pharm Sci ; 25: 402-417, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36623477

RESUMO

PURPOSE: To describe patient characteristics, treatment patterns, and the burden of illness among adult migraine patients in Canada prescribed migraine prophylactics. Little is known about the relative persistence of treatments in the real-world setting and the impact of migraine prophylactic therapy on patients. As a result, migraine care in Canada continues to inadequately serve patients suffering from frequent headache days, reflecting a large unmet need. METHODS: This retrospective study used Reformulary Group's longitudinal prescription claims database. Private payer data were analyzed to identify 2007 migraine prophylactic naïve patients, with a prior history of acute therapy, for tracking over 24 months to determine treatment patterns and costs. Patient flow is summarized in a Sankey diagram visualizing persistence and switching across different timepoints. RESULTS: Patient persistence to migraine prophylactic medications was low at 24.9% (n=500); Switching from index medications to another prophylactic medication was common (27%), however 50% of patients discontinued without switching. It was observed that acute treatment and opioid use were much lower when patients established and maintained therapy on migraine prophylactics. Overall, angiotensin receptor blockers and CGRP antagonists had high persistence but were underutilized therapies while the inverse was true for antidepressants and anticonvulsants. CONCLUSION: In a real-word setting, recognizing that many patients may discontinue preventative treatment completely after their first therapy, there is a need to employ migraine-specific prophylactics and/or tolerable medications early. Treatment guidelines aligned to costs savings and/or requiring step therapy may be inadvertently failing patients. Further, the impact of migraine on the day-to-day lives of patients and high societal costs such as its impact on productivity should be weighed in considering migraine's burden of illness and the benefits of treatment.


Assuntos
Substituição de Medicamentos , Transtornos de Enxaqueca , Adulto , Humanos , Analgésicos , Efeitos Psicossociais da Doença , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/prevenção & controle , Estudos Retrospectivos , Canadá
19.
J Headache Pain ; 24(1): 3, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627561

RESUMO

BACKGROUND: Despite the pervasiveness of migraine, the underlying pathophysiological mechanisms initiating migraine attacks are far from well understood and are matter of scientific debate. OBJECTIVE: In this narrative review, we discuss key evidence for that suggest a peripheral origin or central origin and provide directions for future studies that may provide further clarification. DISCUSSION: Migraine pathogenesis is considered to involve the trigeminovascular system, a term that encompasses the trigeminal nerve and its axonal projections to the intracranial blood vessels. Beyond any doubt both peripheral and central mechanisms are involved in migraine pathogenesis, but an unresolved question is the how the initial activation occurs in a migraine attack. Evidence favoring a peripheral origin of migraine attacks, i.e., initial events occur outside of the blood-brain barrier, include the importance of sensitization of perivascular sensory afferents early on in a migraine attack. Evidence favoring a central origin include the occurrence of prodromal symptoms, migraine aura, and activation of structures within the central nervous system early in and during a migraine attack. CONCLUSIONS: Both peripheral and central mechanisms are likely involved in a migraine attack, e.g., peripheral nociceptive input is necessary for pain transmission and cortical activity is necessary for pain perception. Yet, the debate of whether migraine attacks are initiated a peripheral or central site remains unresolved. The increased focus on prodromal symptoms and on the development of a human model of migraine aura will possibly provide key arguments needed to answer this question in the near future. Until then, we cannot draw firm conclusions and the debate goes on. VIDEO LINK: Video recording of the debate held at the 1st International Conference on Advances in Migraine Sciences (ICAMS 2022, Copenhagen, Denmark) is available at: https://www.youtube.com/watch?v=NC0nlcKohz0 .


Assuntos
Epilepsia , Transtornos de Enxaqueca , Enxaqueca com Aura , Humanos , Sintomas Prodrômicos , Nervo Trigêmeo , Epilepsia/complicações
20.
Mol Pain ; 19: 17448069231152104, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36604774

RESUMO

Migraine is a neurological disease characterized by severe headache attacks. Combinations of different genetic variations such as copy number variation (CNV) in a gene and microRNA (miRNA) expression can provide a holistic approach to the disease as a pathophysiological, diagnostic, and therapeutic target. CNVs, the Cholinergic Receptor Nicotinic Alpha 7 Subunit (CHRNA7) gene, and expression of gene-targeting miRNAs (hsa-miR-548e-5p and hsa-miR-3158-5p) in migraineurs (n = 102; with aura, n = 43; without aura, n = 59) and non-migraines (n = 120) aged 15-60 years, comparative, case-control study was conducted. Genetic markers were compared with biochemical parameters (BMI, WBC, Urea, GFR, ESR, CRP, HBG). All analyzes were performed by quantitative Real-Time PCR (q-PCR) and fold change was calculated with the 2-ΔΔCT method. The diagnostic power of the CHRNA7 gene, CNV, and miRNAs were analyzed with the receiver operating curve (ROC). CHRNA7 gene and hsa-miR-3158-5p are down-regulated in migraineurs and the gene is controlled by this miRNA via CNVs (p < .05). Both deletion and duplication were detected in patients with migraine for CVN numbers (p = .05). The number of CNV deletions was higher than duplications. When CHRNA7-CNV-hsa-miR-3158-5p was modeled together in the ROC analysis, the area under the curve (AUC) was 0.805, and the diagnostic power was "good". In migraineurs, the CHRNA7 gene can be controlled by hsa-miR-3158-5p via CNVs to modulate the mechanism of pain. These three genetic markers have diagnostic potential and may be used in antimigraine treatments.


Assuntos
Variações do Número de Cópias de DNA , MicroRNAs , Transtornos de Enxaqueca , Receptor Nicotínico de Acetilcolina alfa7 , Humanos , Receptor Nicotínico de Acetilcolina alfa7/genética , Estudos de Casos e Controles , Marcadores Genéticos , MicroRNAs/genética , Transtornos de Enxaqueca/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...