New management strategies for primary headache disorders: Insights from P4 medicine
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PROVIDER: S-EPMC10694333 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
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Project description:Neurostimulation has emerged as a potential treatment option for patients with chronic, disabling, intractable primary headache disorders. Although safety and efficacy data are limited in quantity, there is accumulating experience with the use of peripheral nerve stimulation for the treatment of intractable occipital neuralgia, cluster headache, migraine, and less common headache disorders. Deep brain stimulation has been used to treat intractable chronic cluster headache and short-lasting unilateral neuralgiform headache with conjunctival injection and tearing. This article discusses the theorized mechanisms of action of these novel treatment modalities and summarizes current knowledge regarding safety and efficacy of neurostimulation for the treatment of headache.
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Project description:Primary headache disorders, such as migraine, tension-type headache (TTH), and cluster headache, belong to the most common neurological disorders affecting a high percentage of people worldwide. Headache induces a high burden for the affected individuals on the personal level, with a strong impact on life quality, daily life management, and causes immense costs for the healthcare systems. Although a relatively broad spectrum of different pharmacological classes for the treatment of headache disorders are available, treatment effectiveness is often limited by high variances in therapy responses. Genetic variants can influence the individual treatment success by influencing pharmacokinetics or pharmacodynamics of the therapeutic as investigated in the research field of pharmacogenetics. This review summarizes the current knowledge on important primary headache disorders, including migraine, TTH, and cluster headache. We also summarize current acute and preventive treatment options for the three headache disorders based on drug classes and compounds taking important therapy guidelines into consideration. Importantly, the work summarizes and discusses the role of genetic polymorphisms regarding their impact on metabolism safety and the effect of therapeutics that are used to treat migraine, cluster headache, and TTH exploring drug classes such as nonsteroidal anti-inflammatory drugs, triptans, antidepressants, anticonvulsants, calcium channel blockers, drugs with effect on the renin-angiotensin system, and novel headache therapeutics such as ditans, anti-calcitonin-gene-related peptide antibodies, and gepants. Genetic variants in important phase I-, II-, and III-associated genes such as cytochrome P450 genes, UGT genes, and different transporter genes are scrutinized as well as variants in genes important for pharmacodynamics and several functions outside the pharmacokinetic and pharmacodynamic spectrum. Finally, the article evaluates the potential and limitations of pharmacogenetic approaches for individual therapy adjustments in headache disorders.
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Project description:The Aids to Management are a product of the Global Campaign against Headache, a worldwide programme of action conducted in official relations with the World Health Organization. Developed in partnership with the European Headache Federation, they update the first edition published 11 years ago.The common headache disorders (migraine, tension-type headache and medication-overuse headache) are major causes of ill health. They should be managed in primary care, firstly because their management is generally not difficult, and secondly because they are so common. These Aids to Management, with the European principles of management of headache disorders in primary care as the core of their content, combine educational materials with practical management aids. They are supplemented by translation protocols, to ensure that translations are unchanged in meaning from the English-language originals.The Aids to Management may be individually downloaded and, as is the case for all products of the Global Campaign against Headache, are available without restriction for non-commercial use.
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Project description:BackgroundTo support better headache management in primary care, the Global Campaign against Headache developed an 8-question outcome measure, the Headache Under-Response to Treatment (HURT) questionnaire. HURT was designed by an expert consensus group with patient-input. It assesses the need for and response to treatment, and provides guidance on actions to optimize therapy. It has proven content validity.We aim to evaluate the Arabic version of HURT for clinical utility in primary care in Saudi Arabia.MethodsHURT was translated according to the Global Campaign's translation protocol. We assessed test-retest reliability in consecutive patients of four primary-care centres, who completed HURT at two visits 4-6 weeks apart while receiving usual care. We then provided training in headache management to the GPs practising in these centres, which were randomized in pairs to control (standard care) or intervention (care guided by implementation of HURT). We assessed responsiveness of HURT to clinical change by comparing base-line responses to HURT questions 1-6 with those at follow up. We assessed clinical utility by comparing outcomes between control and intervention pairs after 3 months, using locally-developed 5-point verbal-rating scales: the patient-satisfaction scale (PSS) and doctor-satisfaction scale (DSS).ResultsFor test-retest reliability in 40 patients, intra-class correlation coefficients were 0.66-0.78 for questions 1-4 and 0.90-0.93 for questions 5-7 (all P ? 0.001). For the dichotomous response to question 8, Kappa coefficient=1 (P<0.0001). Internal consistency was good (Cronbach's alpha=0.74). In 342 patients, HURT signalled clinical improvement over 3 months through statistically significant changes in responses to questions 1-6. PSS scores were higher among those in whom HURT recorded improvement, and also higher among those with less severe headache at baseline. Patients treated with guidance from HURT (n=207) were more satisfied than controls (n=135), but this did not quite reach statistical significance (P=0.06).ConclusionThe Arabic HURT Questionnaire is reliable and responsive to clinical change in Arabic-speaking headache patients in primary care. HURT showed clinical utility in this first assessment, conducted in parallel with studies elsewhere in other languages, but this needs further study. Other Arabic instruments are not available as standards for comparison.
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Project description:Objective To quantitatively synthesize extant literature on perceived triggers of primary headache disorders. Methods A meta-analytic review of headache trigger survey studies was conducted. Endorsement rates, assessment method, and headache and sample characteristics were extracted from included articles. Separate random-effects models were used to assess trigger endorsement rates and post-hoc meta-regressions examined potential moderator variables. Results 85 articles from 1958 to 2015 were included, involving 27,122 participants and querying 420 unique triggers (collapsed into 15 categories). Four-fifths (0.81; 95% CI .75 to .86) of individuals with migraine or tension-type headache endorsed at least one trigger. Rates increased with the number of categories queried (OR: 1.18, 1.08-1.30) and year of publication (OR: 1.04, 1.00-1.08). The triggers most commonly endorsed were stress (.58, .53-.63) and sleep (.41, .36-.47). Conclusions Extreme heterogeneity characterizes the headache trigger literature. Most individuals with a primary headache disorder perceive their attacks to be triggered by one or more precipitants, the most common of which are stress and sleep. However, trigger endorsement is influenced by method of assessment. Enhancing methodological consistency and prioritizing experimental studies would improve our understanding of headache triggers.
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Project description:Primary immunodeficiency disorders (PIDs) represent a range of genetically determined diseases that typically have increased susceptibility to infections and in many cases also have evidence of immune dysregulation that often presents as autoimmunity. Most recently, the concept of gain-of-function mutations associated with PIDs has become well recognized and adds a new dimension to the understanding of this group of disorders, moving beyond the more commonly seen loss-of-function mutations. The rapidly expanding genetic defects that have been identified in patients with previously uncharacterized PIDs has opened up the potential for targeted therapy directed at the specific disease-causing abnormality. This has been driven by linking PID-specific genetic defects to the associated unique abnormalities in cellular signaling pathways amenable to directed therapies. These include agents that either block overactive or enhance underresponsive cellular pathways. Selected primary immunodeficiencies were chosen, the genetic defects of which have been recently characterized and are amenable to targeted therapy, as a reflection of the power of precision medicine.
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Project description:OBJECTIVES:To define the characteristics of post-traumatic headache with cluster headache phenotype (PTH-CH) and to compare these characteristics with primary CH. METHODS:A retrospective study was conducted of patients seen between 2007 and 2017 in a headache centre and diagnosed with PTH-CH that developed within 7 days of head trauma. A control cohort included 553 patients with primary CH without any history of trauma who attended the headache clinic during the same period. Data including demographics, attack characteristics and response to treatments were recorded. RESULTS:Twenty-six patients with PTH-CH were identified. Multivariate analysis revealed significant associations between PTH-CH and family history of CH (OR 3.32, 95%?CI 1.31 to 8.63), chronic form (OR 3.29, 95%?CI 1.70 to 6.49), parietal (OR 14.82, 95%?CI 6.32 to 37.39) or temporal (OR 2.04, 95%?CI 1.10 to 3.84) location of pain, and presence of prominent cranial autonomic features during attacks (miosis OR 11.24, 95%?CI 3.21 to 41.34; eyelid oedema OR 5.79, 95%?CI 2.57 to 13.82; rhinorrhoea OR 2.65, 95%?CI 1.26 to 5.86; facial sweating OR 2.53, 95%?CI 1.33 to 4.93). Patients with PTH-CH were at a higher risk of being intractable to acute (OR 12.34, 95%?CI 2.51 to 64.73) and preventive (OR 16.98, 95%?CI 6.88 to 45.52) treatments and of suffering from associated chronic migraine (OR 10.35, 95%?CI 3.96 to 28.82). CONCLUSION:This largest series of PTH-CH defines it as a unique entity with specific evolutive profile. Patients with PTH-CH are more likely to suffer from the chronic variant, have marked autonomic features, be intractable to treatment and have associated chronic migraine compared with primary CH.
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Project description:To provide a summary of knowledge about the use of melatonin in the treatment of primary headache disorders.Melatonin is secreted by the pineal gland; its production is regulated by the hypothalamus and increases during periods of darkness.We undertook a narrative review of the literature on the role of melatonin in the treatment of primary headache disorders.There are randomized placebo-controlled trials examining melatonin for preventive treatment of migraine and cluster headache. For cluster headache, melatonin 10 mg was superior to placebo. For migraine, a randomized placebo-controlled trial of melatonin 3 mg (immediate release) was positive, though an underpowered trial of melatonin 2 mg (sustained release) was negative. Uncontrolled studies, case series, and case reports cover melatonin's role in treating tension-type headache, hypnic headache, hemicrania continua, SUNCT/SUNA and primary stabbing headache.Melatonin may be effective in treating several primary headache disorders, particularly cluster headache and migraine. Future research should focus on elucidating the underlying mechanisms of benefit of melatonin in different headache disorders, as well as clarifying optimal dosing and formulation.
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