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The Role of Melatonin in the Treatment of Primary Headache Disorders.

ABSTRACT: 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.

SUBMITTER: Gelfand AA

PROVIDER: S-EPMC5012937 | biostudies-other | 2016 Sep

REPOSITORIES: biostudies-other

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The Role of Melatonin in the Treatment of Primary Headache Disorders.

Gelfand Amy A AA Goadsby Peter J PJ

Headache 20160617 8

<h4>Objective</h4>To provide a summary of knowledge about the use of melatonin in the treatment of primary headache disorders.<h4>Background</h4>Melatonin is secreted by the pineal gland; its production is regulated by the hypothalamus and increases during periods of darkness.<h4>Methods</h4>We undertook a narrative review of the literature on the role of melatonin in the treatment of primary headache disorders.<h4>Results</h4>There are randomized placebo-controlled trials examining melatonin fo ...[more]

PMID: 27316772

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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.

Project description:BackgroundPrimary headache disorders are common and burdensome conditions. They are associated to several comorbidities, such as cardiovascular or psychiatric ones, which, in turn, contribute to the global burden of headache. The aim of this study is to provide a comprehensive description of the pooled prevalence of comorbidities of primary headache disorders using a meta-analytical approach based on studies published between 2000 and 2020.MethodsScopus was searched for primary research (clinical and population studies) in which medical comorbidities were described in adults with primary headache disorders. Comorbidities were extracted using a taxonomy derived from the Global Burden of Disease (GBD) study. We compared prevalence of comorbidities among headache sufferers against general population using GBD-2019 estimates, and compared comorbidities' proportions in clinical vs. population studies, and by age and gender.ResultsA total of 139 studies reporting information on 4.19 million subjects with primary headaches were included: in total 2.75 million comorbidities were reported (median per subject 0.64, interquartile range 0.32-1.07). The most frequently addressed comorbidities were: depressive disorders, addressed in 51 studies (pooled proportion 23 %, 95 % CI 20-26 %); hypertension, addressed in 48 studies (pooled proportion 24 %, 95 % CI 22-26 %); anxiety disorders addressed in 40 studies (pooled proportion 25 %, 95 % CI 22-28 %). For conditions such as anxiety, depression and back pain, prevalence among headache sufferers was higher than in GBD-2109 estimates. Associations with average age and female prevalence within studies showed that hypertension was more frequent in studies with higher age and less females, whereas fibromyalgia, restless leg syndrome, and depressive disorders were more frequent in studies with younger age and more female.ConclusionsSome of the most relevant comorbidities of primary headache disorders - back pain, anxiety and depression, diabetes, ischemic heart disease and stroke - are among the most burdensome conditions, together with headache themselves, according to the GBD study. A joint treatment of headaches and of these comorbidities may positively impact on headache sufferers' health status and contribute to reduce the impact of a group of highly burdensome diseases.

Project description:BackgroundNon-invasive stimulation of the vagus nerve has been proposed as a new neuromodulation therapy to treat primary headache disorders, as the vagus nerve is hypothesized to modulate the headache pain pathways in the brain. Vagus nerve stimulation can be performed by placing an electrode on the ear to stimulate the tragus nerve, which contains about 1% of the vagus fibers. Non-invasive vagus nerve stimulation (nVNS) conventionally refers to stimulation of the cervical branch of the vagus nerve, which is made up entirely of vagal nerve fibers. While used interchangeably, most of the research to date has been performed with nVNS or an implanted vagus nerve stimulation device. However, the exact mechanism of action of nVNS remains hypothetical and no clear overview of the effectiveness of nVNS in primary headache disorders is available.MethodsIn the present study, the clinical trials that investigated the effectiveness, tolerability and safety of nVNS in primary headache disorders were systematically reviewed. The second part of this study reviewed the central connections of the vagus nerve. Papers on the clinical use of nVNS and the anatomical investigations were included based on predefined criteria, evaluated, and results were reported in a narrative way.ResultsThe first part of this review shows that nVNS in primary headache disorders is moderately effective, safe and well-tolerated. Regarding the anatomical review, it was reported that fibers from the vagus nerve intertwine with fibers from the trigeminal, facial, glossopharyngeal and hypoglossal nerves, mostly in the trigeminal spinal tract. Second, the four nuclei of the vagus nerve (nuclei of the solitary tract, nucleus ambiguus, spinal nucleus of the trigeminal nerve and dorsal motor nucleus (DMX)) show extensive interconnections. Third, the efferents from the vagal nuclei that receive sensory and visceral input (i.e. nuclei of the solitary tract and spinal nucleus of the trigeminal nerve) mainly course towards the main parts of the neural pain matrix directly or indirectly via other vagal nuclei.ConclusionThe moderate effectiveness of nVNS in treating primary headache disorders can possibly be linked to the connections between the trigeminal and vagal systems as described in animals.

Dataset Information

The Role of Melatonin in the Treatment of Primary Headache Disorders.

Publications

The Role of Melatonin in the Treatment of Primary Headache Disorders.

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