Medication Overuse Withdrawal in Children and Adolescents Does Not Always Improve Headache:A Cross-Sectional Study

Background:MOH can be diagnosed in subjects with headache occurring 15 days/month in association with a regular medication overuse, but its existence is not universally accepted. ICHD-3 redefined criteria for MOH, removing the criterion associating drug suspension with headache course. The aim of our study was to compare the rate of patients diagnosed with medication overuse headache (MOH) according to ICHD-2 and ICHD-3 criteria, to verify the degree of concordance. The secondary aim was to verify if drug withdrawal was really associated with pain relief. Methods:In this cross-sectional study, we retrospectively analyzed a sample of 400 patients followed for primary chronic headache at the Headache Center of Bambino Gesu Children's Hospital. We then selected those presenting with a history of medication overuse, and we applied both ICHD-2 and ICHD-3 criteria to verify in which patients the criteria would identify a clinical diagnosis of MOH. Results:We identified 42 subjects (10.5%) with MOH; 23 of them (55%) presented a relief of headache withdrawing drug overuse. Regarding the applicability of the ICHD-2 criteria, 43% of patients (18/42) fulfilled all criteria, while all ICHD-3 diagnostic criteria were satisfied in 76% of patients (32/42). Eighteen patients (43%) satisfied both ICHD-2 and ICHD-3 criteria, while 10 patients (24%) did not satisfy either diagnostic criterion. Conclusions:Our study suggests that in children and adolescents, withdrawing medication overuse is not always associated with a clinical benefit. Therefore, though allowing a MOH diagnosis in a higher rate of patients as compared to ICHD-2, the application of ICHD-3 criteria does not guarantee a true a causal relationship between medication overuse and headache worsening

Alexithymia and psychopathological symptoms in adolescent outpatients and mothers suffering from migraines. A case control study

Background: Headache is a common disorder affecting a growing number of children and adolescents. In recent years, there has been an increase in scientific interest in exploring the relationship between migraine and emotional regulation, and in particular, the impact of emotional dysregulation on mental and physical health. The present study aims to explore the relationship between migraine and alexithymia among adolescents and their mothers as well as the impact of this association on mental health. An additional aim is to verify whether alexithymia may be a predictor of psychopathological symptoms in adolescents and mothers with migraines. Methods: A total of 212 subjects were involved in this study. The sample was divided into (a) Experimental Group (EG) consisting of 106 subjects (53 adolescents and 53 mothers) with a diagnosis of migraine according to International Classification of Headache Disorders (ICHD-3) and (b) Control Group (CG) including 106 subjects (53 adolescents and 53 mothers) without a diagnosis of migraine. All participants completed the Toronto Alexithymia Scale to assess alexithymia and the Symptom Checklist-90-R to assess psychopathological symptoms. Results: Higher rates of alexithymia were found in the adolescents and mothers of the EG in comparison to the adolescents and mothers of the CG. Furthermore, adolescents and mothers experiencing both migraine and alexithymia, demonstrated a higher risk of psychopathology. Conclusions: Findings from this study provide evidence that the co-occurrence of migraine and alexithymia increases the risk of psychopathology for both adolescents and their mother

Shared genetic factors underlie migraine and depression

Free to read\ud \ud Migraine frequently co-occurs with depression. Using a large sample of Australian twin pairs, we aimed to characterize the extent to which shared genetic factors underlie these two disorders. Migraine was classified using three diagnostic measures, including self-reported migraine, the ID migraine screening tool, or migraine without aura (MO) and migraine with aura (MA) based on International Headache Society (IHS) diagnostic criteria. Major depressive disorder (MDD) and minor depressive disorder (MiDD) were classified using the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria. Univariate and bivariate twin models, with and without sex-limitation, were constructed to estimate the univariate and bivariate variance components and genetic correlation for migraine and depression. The univariate heritability of broad migraine (self-reported, ID migraine, or IHS MO/MA) and broad depression (MiDD or MDD) was estimated at 56% (95% confidence interval [CI]: 53-60%) and 42% (95% CI: 37-46%), respectively. A significant additive genetic correlation (r G = 0.36, 95% CI: 0.29-0.43) and bivariate heritability (h 2 = 5.5%, 95% CI: 3.6-7.8%) was observed between broad migraine and depression using the bivariate Cholesky model. Notably, both the bivariate h 2 (13.3%, 95% CI: 7.0-24.5%) and r G (0.51, 95% CI: 0.37-0.69) estimates significantly increased when analyzing the more narrow clinically accepted diagnoses of IHS MO/MA and MDD. Our results indicate that for both broad and narrow definitions, the observed comorbidity between migraine and depression can be explained almost entirely by shared underlying genetically determined disease mechanisms

Comorbidities of psychiatric and headache disorders in Nepal: implications from a nationwide population-based study

Background Headache disorders, anxiety and depression – the major disorders of the brain – are highly comorbid in the western world. Whether this is so in South Asia has not been investigated, but the question is of public-health importance to countries in the region. We aimed to investigate associations, and their direction(s), between headache disorders (migraine, tension-type headache [TTH] and headache on ≥15 days/month) and psychiatric manifestations (anxiety, depression and neuroticism), and how these might affect quality of life (QoL). Methods In a nationwide, cross-sectional survey of the adult Nepalese population (N = 2100), trained interviewers applied: 1) a culturally-adapted version of the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire to diagnose headache disorders; 2) a validated Nepali version of the Hospital Anxiety and Depression Scale (HADS) to detect anxiety (HADS-A), depression (HADS-D) and comorbid anxiety and depression (HADS-cAD); 3) a validated Nepali version of the Eysenck Personality Questionnaire Revised Short Form-Neuroticism (EPQRS-N); and 4) the World Health Organization Quality of Life 8-question scale (WHOQOL-8). Associations with headache types were analysed using logistic regression for psychiatric caseness and linear regression for neuroticism. Adjustments were made for age, gender, household consumption, habitat, altitude and use of alcohol and marijuana. Results HADS-A was associated with any headache (p = 0.024), most strongly headache on ≥15 days/month (AOR = 3.2) followed by migraine (AOR = 1.7). HADS-cAD was also associated with any headache (p = 0.050, more strongly among females than males [p = 0.047]) and again most strongly with headache on ≥15 days/month (AOR = 2.7), then migraine (AOR = 2.3). Likewise, neuroticism was associated with any headache (p < 0.001), most strongly with headache on ≥15 days/month (B = 1.6), followed by migraine (B = 1.3). No associations were found between HADS-D and any headache type, or between TTH and any psychiatric manifestation. Psychiatric caseness of any sort, when comorbid with migraine or TTH, aggravated the negative impact on QoL (p < 0.001). Conclusion Headache disorders are highly comorbid with anxiety and show associations with neuroticism in Nepal, with negative consequences for QoL. These findings call for reciprocal awareness, and a holistic coordinated approach to management and in the health service. Care for common headache and common psychiatric disorders should be integrated in primary care.publishedVersion© 2016 Risal et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/

Validation of an algorithm for automated classification of migraine and tension-type headache attacks in an electronic headache diary

Background: This study evaluates the accuracy of an automated classification tool of single attacks of the two major primary headache disorders migraine and tension-type headache used in an electronic headache diary. Methods: One hundred two randomly selected reported headache attacks from an electronic headache-diary of patients using the medical app M-sense were classified by both a neurologist with specialisation in headache medicine and an algorithm, constructed based on the ICHD-3 criteria for migraine and tension-type headache. The level of agreement between the headache specialist and the algorithm was compared by using a kappa statistic. Cases of disagreement were analysed in a disagreement validity assessment. Result: The neurologist and the algorithm classified migraines with aura (MA), migraines without aura (MO), tension-type headaches (TTH) and non-migraine or non-TTH events. Of the 102 headache reports, 86 cases were fully agreed on, and 16 cases not, making the level of agreement unweighted kappa 0.74 and representing a substantial level of agreement. Most cases of disagreement (12 out of 16) were due to inadvertent mistakes of the neurologist identified in the disagreement validity assessment. The second most common reason (3 out of 16) was insufficient information for classification by the neurologist. Conclusions: The substantial level of agreement indicates that the classification tool is a valuable instrument for automated evaluation of electronic headache diaries, which can thereby support the diagnostic and therapeutic clinical processes. Based on this study’s results, additional diagnostic functionalities of primary headache management apps can be implemented. Finally, future research can use this classification algorithm for large scale database analysis for epidemiological studies

A multicenter, open-label, long-term safety and tolerability study of DFN-02, an intranasal spray of sumatriptan 10 mg plus permeation enhancer DDM, for the acute treatment of episodic migraine.

BackgroundDFN-02 is a novel intranasal spray formulation composed of sumatriptan 10 mg and a permeation-enhancing excipient comprised of 0.2% 1-O-n-Dodecyl-β-D-Maltopyranoside (DDM). This composition of DFN-02 allows sumatriptan to be rapidly absorbed into the systemic circulation and exhibit pharmacokinetics comparable to subcutaneously administered sumatriptan. Rapid rate of absorption is suggested to be important for optimal efficacy. The objective of this study was to evaluate the safety and tolerability of DFN-02 (10 mg) in the acute treatment of episodic migraine with and without aura over a 6-month period based on the incidence of treatment-emergent adverse events and the evaluation of results of clinical laboratory tests, vital signs, physical examination, and electrocardiograms.MethodsThis was a multi-center, open-label, repeat-dose safety study in adults with episodic migraine with and without aura. Subjects diagnosed with migraine with or without aura according to the criteria set forth in the International Classification of Headache Disorders, 2nd edition, who experienced 2 to 6 attacks per month with fewer than 15 headache days per month and at least 48 headache-free hours between attacks, used DFN-02 to treat their migraine attacks acutely over the course of 6 months.ResultsA total of 173 subjects was enrolled, 167 (96.5%) subjects used at least 1 dose of study medication and were evaluable for safety, and 134 (77.5%) subjects completed the 6-month study. A total of 2211 migraine attacks was reported, and 3292 doses of DFN-02 were administered; mean per subject monthly use of DFN-02 was 3.6 doses. Adverse events were those expected for triptans, as well as for nasally administered compounds. No new safety signals emerged. Dysgeusia and application site pain were the most commonly reported treatment-emergent adverse events over 6 months (21% and 30.5%, respectively). Most of the treatment-emergent adverse events were mild. There were 5 serious adverse events, all considered unrelated to the study medication; the early discontinuation rate was 22.5% over the 6-month treatment period.ConclusionDFN-02 was shown to be well tolerated when used over 6 months to treat episodic migraine acutely

A REVIEW ON CLASSIFICATION, PATHOPHYSIOLOGY, DIAGNOSIS, AND PHARMACOTHERAPY OF HEADACHE

Headache disorders, characterized by recurrent headache, are among the most common disorders of the nervous system. Headache disorder is classified mainly into two major types, primary headache and secondary headache by the International Classification of Headache Disorders. Most types of headache are diagnosed by the clinical history and from headache classification committee of the International Headache Society (IHS). A number of intrinsic or extrinsic factors can trigger headache attack which release neurotransmitters and activate trigeminal vascular system. The grading of headache intensity is done by headache severity scale of IHS. Headache management includes pharmacological and non-pharmacological treatment

Validation of a guideline-based decision support system for the diagnosis of primary headache disorders based on ICHD-3 beta

BACKGROUND: China may have the largest population of headache sufferers and therefore the most serious burden of disease worldwide. However, the rate of diagnosis for headache disorders is extremely low, possibly due to the relative complexity of headache subtypes and diagnostic criteria. The use of computerized clinical decision support systems (CDSS) seems to be a better choice to solve this problem. METHODS: We developed a headache CDSS based on ICHD-3 beta and validated it in a prospective study that included 543 headache patients from the International Headache Center at the Chinese PLA General hospital, Beijing, China. RESULTS: We found that the CDSS correctly recognized 159/160 (99.4%) of migraine without aura, 36/36 (100%) of migraine with aura, 20/21 (95.2%) of chronic migraine, and 37/59 (62.7%) of probable migraine. This system also correctly identified 157/180 (87.2%) of patients with tension-type headache (TTH), of which infrequent episodic TTH was diagnosed in 12/13 (92.3%), frequent episodic TTH was diagnosed in 99/101 (98.0%), chronic TTH in 18/20 (90.0%), and probable TTH in 28/46 (60.9%). The correct diagnostic rates of cluster headache and new daily persistent headache (NDPH) were 90.0% and 100%, respectively. In addition, the system recognized 32/32 (100%) of patients with medication overuse headache. CONCLUSIONS: With high diagnostic accuracy for most of the primary and some types of secondary headaches, this system can be expected to help general practitioners at primary hospitals improve diagnostic accuracy and thereby reduce the burden of headache in China

Galcanezumab in episodic migraine: subgroup analyses of efficacy by high versus low frequency of migraine headaches in phase 3 studies (EVOLVE-1 & EVOLVE-2).

BACKGROUND: Patients with high-frequency episodic migraine (HFEM) have a greater disease burden than those with low-frequency episodic migraine (LFEM). Acute treatment overuse increases the risk of migraine chronification in patients with HFEM. Galcanezumab, a humanized monoclonal antibody binding calcitonin gene-related peptide (CGRP), is effective for migraine prevention with a favorable safety profile. Here, we investigate whether there are differences in galcanezumab efficacy in patients with LFEM or with HFEM. METHODS: Data were pooled from two double-blind, placebo-controlled phase 3 trials; EVOLVE-1 and EVOLVE-2. Patients were 18-65 years old, experienced 4-14 monthly migraine headache days (MHDs) for ≥1 year prior, with onset at \u3c 50 years of age. Migraine headaches were tracked via electronic patient-reported outcome system and randomization was stratified by low (LFEM; 4-7 monthly MHDs) or high (HFEM; 8-14 monthly MHDs) frequency. Subgroup analysis compared the HFEM and LFEM subgroups with a linear or generalized linear mixed model repeated measures approach. RESULTS: The intent-to-treat patients (N = 1773) had a mean age of 41.3 years, were mostly white (75%), female (85%), and 66% of patients had HFEM. In both the LFEM and HFEM subgroups, the overall (Months 1-6) and monthly changes from baseline in monthly MHDs and monthly MHDs with acute medication use compared with placebo were statistically significantly reduced for galcanezumab 120-mg and 240-mg. Galcanezumab (120-mg and 240-mg) significantly decreased the overall and monthly MHDs with nausea and/or vomiting, and with photophobia and phonophobia versus placebo in patients with LFEM or HFEM. In both subgroups, the mean overall (Months 1-6) and monthly percentages of patients with ≥50%, ≥75%, and 100% reduction in monthly MHDs from baseline were statistically significantly greater in patients receiving either dose of galcanezumab versus placebo. Galcanezumab (120-mg and 240-mg) significantly improved the Migraine-Specific Quality of Life Questionnaire role function-restrictive domain score as well as the Migraine Disability Assessment total score versus placebo for patients with LFEM or HFEM. There were no significant subgroup-by-treatment interactions. CONCLUSIONS: Galcanezumab was as effective in patients with HFEM as in those with LFEM. Associated symptoms, quality of life, and disability were similarly improved in patients with HFEM or LFEM. TRIAL REGISTRATION: NCT02614183 , NCT02614196