Health care resource utilization and costs associated with diagnosed medication overuse headache and potential acute medication overuse in individuals with migraine.

OBJECTIVE: Estimate health care resource utilization and costs associated with medication overuse headache and potential acute medication overuse. METHODS: A retrospective analysis was conducted with Clinformatics Data Mart data (1 January 2019-31 December 2019) that included continuously enrolled commercially insured adults with migraine (International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] code G43.xxx). Medication overuse headache was defined as ≥1 inpatient or ≥2 outpatient claims with an ICD-10-CM code G44.41/40 (drug-induced headache). Potential acute medication overuse was defined as possessing sufficient medication for >10 mean treatment days/month for ergots, triptans, opioids, or combination analgesics or >15 mean cumulative days/month for simple prescription analgesics (e.g., acetaminophen, aspirin, other non-opioid analgesics) for >6 consecutive months. All-cause and migraine-related health care resource utilization and costs were compared after adjusting for demographic and clinical characteristics. RESULTS: Among 90,017 individuals with migraine, the frequency of medication overuse headache/potential acute medication overuse was 12.6% (diagnosed medication overuse headache: 0.6%; potential acute medication overuse: 12.1%). Adjusted all-cause total costs ($31,235 vs $21,486; difference: $9,749 [P < 0.001]) and adjusted migraine-related total costs ($9,770 vs $6,207; difference: $3,563 [P < 0.001]) were higher in the medication overuse headache/potential acute medication overuse group versus those without medication overuse headache/potential acute medication overuse. CONCLUSIONS: Individuals with diagnosed medication overuse headache/potential acute medication overuse had higher all-cause and migraine-related health care resource utilization and costs versus individuals without medication overuse headache/potential acute medication overuse, suggesting that improved migraine management is needed to reduce associated costs.

Internal stigmatization in patients with chronic migraine and medication overuse headache.

OBJECTIVES: Internalized stigma can have profound effects on how individuals with migraines and other primary headache disorders see themselves and their quality of life. We aimed to investigate internalized stigma in patients with chronic migraines and medication overuse headaches. METHODS: A total of 57 patients (52 women, 5 men) were included in the study, 26 of these patients were affected by chronic migraine, 31 of them were affected by medication overuse headache and chronic migraine. The Internalized Stigma Scale in Mental Illness (Ristsher's stigmatization scale) and General Health Questionnaire were applied to all patients. RESULTS: In Ristsher's stigmatization scale, which measures internalization of stigma, internalized stigmatization was more significant in patients with medication overuse headache than in patients with chronic migraine compared to groups (p:0.05). The subtitle of alienation was statistically significant when the groups were compared to all subscales in the form of alienation, confirmation of stereotypes, perceived discrimination, social withdrawal and resistance to stigma (p:0.05). DISCUSSION: Although internal stigmatize has been observed in chronic migraine patients, medication overuse headache is also a type of headache with intense stigma. In addition, this internal stigma perhaps plays an active role in the transformation of chronic migraine patients to medication overuse headaches patient.

Effect of prednisolone for the treatment of medication-overuse headache: A 3-month result from a multicenter REgistry for Load and management of mEdicAtion overuSE headache (RELEASE) study.

OBJECTIVE: To evaluate the efficacy of prednisolone in the treatment of medication-overuse headache (MOH) using data from a multicenter prospective registry (Registry for Load and Management of Medication Overuse Headache [RELEASE]). BACKGROUND: The treatment of MOH is challenging, especially when withdrawal headache manifests during the cessation of overused medication. Although systemic corticosteroids have been empirically used to reduce withdrawal headaches, their efficacy on the long-term outcomes of MOH has not been documented. METHODS: This was a post hoc analysis of the RELEASE study. The RELEASE is an ongoing multicenter observational cohort study in which patients with MOH have been recruited from seven hospitals in Korea since April 2020. Clinical characteristics, disease profiles, treatments, and outcomes were assessed at baseline and specific time points. We analyzed the effect of prednisolone on MOH reversal at 3 months. RESULTS: Among the 309 patients enrolled during the study period, prednisolone was prescribed to 59/309 (19.1%) patients at a dose ranging from 10 to 40 mg/day for 5-14 days; 228/309 patients (73.8%) completed the 3-month follow-up period. The MOH reversal rates at 3 months after baseline were 76% (31/41) in the prednisolone group and 57.8% (108/187) in the non-prednisolone group (p = 0.034). The effect of steroids remained significant (adjusted odds ratio 2.78, 95% confidence interval 1.27-6.1, p = 0.010) after adjusting for the number of monthly headache days at baseline, mode of discontinuation of overused medication, use of early preventive medications, and the number of preventive medications combined. CONCLUSIONS: Although our observational study could not draw a definitive conclusion, prednisolone may be effective in the treatment of MOH.

Long-term effectiveness of eptinezumab in the treatment of patients with chronic migraine and medication-overuse headache.

OBJECTIVE: This post hoc analysis of the PREVAIL study explored the effectiveness of eptinezumab for up to 2 years of open-label treatment in the subgroup of patients with chronic migraine who had a confirmed diagnosis of medication-overuse headache (MOH) at screening. BACKGROUND: MOH is a disabling and costly secondary headache disorder characterized by increased headache frequency and/or severity with increased acute headache medication use. Eptinezumab, an anti-calcitonin gene-related peptide monoclonal antibody, reduces headache frequency, severity, and associated disability and improves functioning and health-related quality of life as a preventive migraine therapy; short-term benefits in patients with concurrent MOH have also been reported. METHODS: Participants received up to eight quarterly intravenous infusions of eptinezumab 300 mg in the phase 3, single-arm, open-label PREVAIL study. Safety and patient-reported outcome measures (Migraine Disability Assessment [MIDAS], 6-item Headache Impact Test [HIT-6], patient-identified most bothersome symptom [PI-MBS], Patient Global Impression of Change [PGIC], and 36-item Short-Form Health Survey [SF-36]) were conducted at predefined intervals. Patients were observed up to 20 weeks after their last infusion (Week 104). RESULTS: A total of 49/128 (38.3%) patients enrolled in PREVAIL had an MOH diagnosis at screening. In the MOH subgroup, long-term eptinezumab treatment was associated with reductions in headache frequency (43/49 [87.8%] patients reported ≥50% reduction in MIDAS-derived headache days at ≥1 visit), severity (2.2-point reduction [on a 10-point scale]), disability (mean MIDAS total score reduction of 51.9 points), and impact (mean HIT-6 total score reduction of 9.7 points) at Week 104. Most patients described a "much improved" or "very much improved" status by Week 48 (PI-MBS, 31/46 [67.4%]) and Week 104 (PGIC, 31/36 [86.1%]). Health-related quality of life improvements in the SF-36 were also observed. CONCLUSION: Eptinezumab preventive therapy in patients with chronic migraine showed benefits that extended to the subset of patients with concomitant MOH.

Functional impairment of chronic migraine with medication overuse: Secondary analysis from the Medication Overuse Treatment Strategy (MOTS) trial.

BACKGROUND: Chronic migraine exerts substantial negative impacts on daily functioning. Efforts to manage impaired functioning may result in medication overuse, which contributes to the worsening profile and chronification of migraine. The Migraine Functional Impact Questionnaire (MFIQ) is a recently developed measure assessing the impact of migraine on physical, social, and emotional function. OBJECTIVE: The objective of this analysis was to assess changes in MFIQ scores following initiation or modification of migraine preventive medication and determine if changes in function are associated with changes in other aspects of migraine burden, such as headache frequency, headache intensity, and symptoms of anxiety and depression. METHODS: This is a secondary analysis of data from the Medication Overuse Treatment Strategy (MOTS) trial, a prospective pragmatic clinical trial that investigated two treatment strategies for those with chronic migraine and medication overuse. Data from both treatment arms were pooled and analyzed using a pre-post design. Prior to and 12 weeks following initiation or modification of migraine preventive medication, participants completed a series of questionnaires that captured migraine characteristics, medication use, migraine-related physical impairment (MFIQ), anxiety (Generalized Anxiety Disorder-7), and depression (Patient Health Questionnaire 9 [PHQ-9]) symptoms. Changes from baseline in all measures were assessed using the paired t-test. Relationships between changes in MFIQ scores and other measures were assessed using linear regression. Multivariable modeling was performed to determine which additional variables contributed to the change in MFIQ beyond that already explained by an individual variable. Model terms were selected by using elastic net regularization. Only those participants who completed the baseline and 12-week MFIQ were included in this analysis. RESULTS: Of the 537 patients, 88.2% were female, and the average age was 45 years (standard deviation 13). The mean frequency of days with moderate-to-severe headache improved 39.2% from 13.5 per 30 days at baseline to 8.1 per 30 days at week 12. The mean MFIQ Usual Activities Global score improved by 15.0 points (on a 100-point scale). All five domains (Usual Activities Global, Usual Activities, Social Function, Emotional Function, Physical Function) of the MFIQ improved by a mean of at least 13.0 points. Changes in PHQ-9 score, followed by changes in headache frequency, had the strongest associations with change in all domains of the MFIQ. CONCLUSIONS: The negative impact of chronic migraine with medication overuse on physical, social, and emotional functioning substantially lessened following initiation or modification of migraine preventive medication. Improved functioning, as measured by the MFIQ, was most strongly associated with reductions in depression scores and headache frequency, highlighting the importance of recognizing and monitoring changes in depressive symptoms, in addition to headache frequency and functional impairment, when evaluating response to preventive medications.

The transition of medication overuse status by acute medication categories in episodic or chronic migraine patients to non-overuse status after receiving anti-CGRP monoclonal antibodies: a systematic review and meta-analysis of phase 3 randomized control trial.

OBJECTIVE: The objective of this systematic review and meta-analysis was to determine whether patients with episodic (EM) or chronic migraine (CM), who were treated with anti-CGRP antibodies, showed a reversal from medication overuse (MO) or medication overuse headache (MOH) status at their baseline to non-overuse status. Furthermore, this study aimed to establish which acute headache medication (AHM) categories responded more effectively to anti-CGRP antibodies. METHODS: A systematic search was conducted in the PubMed database for relevant studies from January 2013 to September 2023. We included phase three randomized controlled trials to examine the role of anti-CGRP antibodies in patients with EM or CM and their MO status. A meta-analysis was conducted to find the association between anti-CGRP antibodies and the number of EM and CM patients with MO or MOH at baseline that reverted to non-MO status or below the MOH threshold. RESULTS: The initial search yielded a total of 345 studies. After removing duplicates and screening with inclusion criteria, 5 studies fulfilled our conditions. Each study reviewed the response to changes in the MO status of patients after receiving anti-CGRP antibodies, including eptinezumab, fremanezumab, galcanezumab, and erenumab, compared to placebo. Our study analyzed three AHM categories: triptans, simple analgesics, and multiple drugs. The overall relative risk (RR) was 1.44 (95% CI, 1.31 to 1.59; p < 0.001). The RRs for triptans, simple analgesics, and multi-drug groups were 1.71 (95% CI, 1.53 to 1.91; p < 0.001), 1.10 (95% CI, 0.83 to 1.47; p = 0.5), and 1.29 (95%CI 1.14 to 1.46; p < 0.001) respectively. CONCLUSION: The meta-analysis has shown that anti-CGRP antibodies were statistically significant in transitioning from MO or MOH status to non-MO status or below the MOH threshold (RR = 1.44) for all included studies and all AHM categories except for simple analgesics. Patients from the triptan group had the highest RR of 1.71 with a p-value < 0.001, while the simple analgesics group had an RR of 1.10, however, with a p-value > 0.05. Interestingly, this analysis can be interpreted as that anti-CGRP antibodies might not be effective in reducing simple analgesics use in EM or CM patients. Further studies are needed to investigate these matters.

Multimodal digital health treatments for Chronic Migraine associated with Medication Overuse Headache: a literature appraisal and results of a single-arm open trial (the BE-HOME program).

BACKGROUND: Mindfulness-based treatments gained popularity for migraine treatment. In this manuscript we report the results of a single-arm open pilot study that evaluated the impact of a multimodal web-based intervention combining home-based medication withdrawal, patients' education, and online mindfulness-based interventions. We aimed to address whether our program had the ability to show a change in the observed parameters and the study should therefore be intended as an early phase trial. METHODS: Consecutive patients with chronic migraine associated with medication overuse headache were enrolled, followed-up for 12 months, in a program that included home-based medication withdrawal, education on the correct use of drugs and lifestyle issues, prescription of tailored pharmacological prophylaxis, and attendance to six online mindfulness-based sessions. We tested the effect of the program on improving headache frequency, medication intake, quality of life (QoL), headache impact, depression, self-efficacy, and pain catastrophizing. RESULTS: A total of 37 patients completed the study (10 dropped out). We observed a large improvement in headache frequency, medication intake, headache impact, and QoL, a moderate improvement in pain catastrophizing and a mild improvement in depression symptoms; 70% to 76% of patients achieved 50% or more reduction in headache frequency from baseline to each follow-up (p < .01). CONCLUSIONS: The results of our multimodal program showed significant improvements in headache frequency, medication intake, and patient-reported outcomes. Future studies are needed to better identify patients who might benefit most from Digital Health Interventions and to demonstrate at least an equivalence in outcome with in-person programs carried out in hospital settings.

Somatic amplification and addiction profile as risk factors for medication overuse headache with chronic migraine.

INTRODUCTION: Overuse of analgesics can lead to medication-overuse headache (MOH) in chronic migraine (CM) patients, and is often linked to addiction. This study explores the addiction-related characteristics and somatic amplification in patients with, CM with medication overuse headache (CM+MOH), CM, and healthy controls. METHODS: 73 CM patients and 70 CM+MOH, along with 63 healthy controls, participated in the study. Assessments included a Sociodemographic Form, Migraine Disability Assessment Scale (MIDAS), Addiction Profile Index (API), Addiction Profile Index-Clinical Version (API-C), and the Somatosensory Amplification Scale (SSAS). RESULTS: Substance use characteristics, craving, motivation for use, and addiction severity scores were higher in the CM+MOH group than in both the CM and the control group. Specifically, the SSAS scores within the CM+MOH group surpassed those of both the CM and control groups. In the CM+MOH group, SSAS scores were a strong predictor of the amount of analgesic usage. Besides, craving and motivation for substance use scores significantly predicted the number of days analgesic taken per month in the CM+MOH group CONCLUSION: CM patients with MOH exhibit a pronounced association with addiction, and a heightened manifestation of somatic symptoms. Addressing addiction characteristics and psychosomatic amplification is important to ensure comprehensive management.

Medication-overuse headache: a narrative review.

Medication-overuse headache (MOH), which potentially involves 1-2% of the population, is defined as a headache, on ≥ 15 days a month affected, along with overuse of one or other acute attack medications. MOH presents with significant challenges in the headache community, particularly in clinical settings raising various questions about its pathophysiology. Through a review of the current literature and our clinical experience, we have explored the mechanisms through which MOH may occur, provide an understanding of the current state of treatment and detail some possible views on the understanding and treatment of this condition. We evaluate the variations in treatment methods offered globally and understanding of the disorder. Above all interventions, patient education is crucial, which is underscored by an analysis of the academic publications. Given the condition is preventable, early intervention is imperative and patient awareness is highlighted as key. Globally, there is no uniform treatment methodology, which may be advantageous as approaches need to take local circumstances into account.

[Medication overuse headache]. / Kopfschmerz bei Medikamentenübergebrauch.

Medication overuse headache (MOH) is a globally prevalent and debilitating condition that results from excessive use of acute therapies and can significantly affect quality of life, despite the fact that simple information about the causes and consequences of the condition can help prevent or stop MOH. In recent years, many new insights have been gained into headaches caused by medication overuse. In addition, the diagnostic criteria and guideline recommendations have changed considerably. This article provides a comprehensive overview of the clinic, definition/classification, epidemiology, risk factors, pathophysiology, controversies, prevention, and treatment of MOH.

Comparative efficacy and safety of different pharmacological therapies to medication overuse headache: a network meta-analysis.

BACKGROUND: Controversy exists whether prophylactic drugs are necessary in the treatment of medication overuse headache (MOH). OBJECTIVES: To determine comparative benefits and safety of available drugs for the treatment of MOH including elimination of medication overuse (MO). METHODS: We systematically reviewed randomized controlled trials though an extensive literature search comparing different drug effects on MOH. A random-effect network meta-analysis was conducted to rank comparative effects of interventions. Outcome improvements from baseline include responder rate defined as ≥ 50% reduction of headache frequency, proportion of patients who revert to no acute medication overuse (nMO), and reduction in monthly headache and acute medication intake frequency. Certainty of evidence was classified using the Grading of Recommendations, Assessment, Development & Evaluation (GRADE). RESULTS: Of 8,248 screened publications, 28 were eligible for analysis. Topiramate was found to be beneficial based on its responder rate (odds ratios [OR] 4.93), headache frequency (weighted mean difference [WMD] -5.53) and acute medication intake frequency (WMD - 6.95), with fewer safety issues (i.e., tolerability, or more adverse events) than placebo (OR 0.20). Fremanezumab, galcanezumab and botulinum toxin type A (BTA) were beneficial for increased responder rates (OR 3.46 to 3.07, 2.95, and 2.57, respectively). For reversion to nMO, eptinezumab, fremanezumab and BTA were superior to placebo (OR 2.75 to 2.64, 1.87 to1.57, and 1.55, respectively). Eptinezumab, fremanezumab, erenumab 140 mg, and BTA were more efficacious than erenumab 70 mg (OR 3.84 to 3.70, 2.60 to 2.49, 2.44 and 2.16, respectively) without differences in safety and tolerability. CONCLUSION: Despite lower safety and greater intolerability issues, topiramate has large beneficial effects probably on increasing responder rates, reducing headache frequency, and might reduce monthly medication intake frequency. Fremanezumab, galcanezumab, and eptinezumab are promising for increasing responder rates. For reversion to nMO, eptinezumab has large beneficial effects, fremanezumab has a smaller effect. BTA might have a moderate effect on responder rates and probably has a small effect on reversion to nMO. TRIAL REGISTRATION: PROSPERO, CRD42021193370.

Prediction models for identifying medication overuse or medication overuse headache in migraine patients: a systematic review.

BACKGROUND: Migraine is a debilitating neurological disorder that presents significant management challenges, resulting in underdiagnosis and inappropriate treatments, leaving patients at risk of medication overuse (MO). MO contributes to disease progression and the development of medication overuse headache (MOH). Predicting which migraine patients are at risk of MO/MOH is crucial for effective management. Thus, this systematic review aims to review and critique available prediction models for MO/MOH in migraine patients. METHODS: A systematic search was conducted using Embase, Scopus, Medline/PubMed, ACM Digital Library, and IEEE databases from inception to April 22, 2024. The risk of bias was assessed using the prediction model risk of bias assessment tool. RESULTS: Out of 1,579 articles, six studies with nine models met the inclusion criteria. Three studies developed new prediction models, while the remaining validated existing scores. Most studies utilized cross-sectional and prospective data collection in specific headache settings and migraine types. The models included up to 53 predictors, with sample sizes from 17 to 1,419 participants. Traditional statistical models (logistic regression and least absolute shrinkage and selection operator regression) were used in two studies, while one utilized a machine learning (ML) technique (support vector machines). Receiver operating characteristic analysis was employed to validate existing scores. The area under the receiver operating characteristic (AUROC) for the ML model (0.83) outperformed the traditional statistical model (0.62) in internal validation. The AUROCs ranged from 0.84 to 0.85 for the validation of existing scores. Common predictors included age and gender; genetic data and questionnaire evaluations were also included. All studies demonstrated a high risk of bias in model construction and high concerns regarding applicability to participants. CONCLUSION: This review identified promising results for MO/MOH prediction models in migraine patients, although the field remains limited. Future research should incorporate important risk factors, assess discrimination and calibration, and perform external validation. Further studies with robust designs, appropriate settings, high-quality and quantity data, and rigorous methodologies are necessary to advance this field.

Longitudinal neurofunctional changes in medication overuse headache patients after mindfulness practice in a randomized controlled trial (the MIND-CM study).

BACKGROUND: Mindfulness practice has gained interest in the management of Chronic Migraine associated with Medication Overuse Headache (CM-MOH). Mindfulness is characterized by present-moment self-awareness and relies on attention control and emotion regulation, improving headache-related pain management. Mindfulness modulates the Default Mode Network (DMN), Salience Network (SN), and Fronto-Parietal Network (FPN) functional connectivity. However, the neural mechanisms underlying headache-related pain management with mindfulness are still unclear. In this study, we tested neurofunctional changes after mindfulness practice added to pharmacological treatment as usual in CM-MOH patients. METHODS: The present study is a longitudinal phase-III single-blind Randomized Controlled Trial (MIND-CM study; NCT03671681). Patients had a diagnosis of CM-MOH, no history of neurological and severe psychiatric comorbidities, and were attending our specialty headache centre. Patients were divided in Treatment as Usual (TaU) and mindfulness added to TaU (TaU + MIND) groups. Patients underwent a neuroimaging and clinical assessment before the treatment and after one year. Longitudinal comparisons of DMN, SN, and FPN connectivity were performed between groups and correlated with clinical changes. Vertex-wise analysis was performed to assess cortical thickness changes. RESULTS: 177 CM-MOH patients were randomized to either TaU group or TaU + MIND group. Thirty-four patients, divided in 17 TaU and 17 TaU + MIND, completed the neuroimaging follow-up. At the follow-up, both groups showed an improvement in most clinical variables, whereas only TaU + MIND patients showed a significant headache frequency reduction (p = 0.028). After one year, TaU + MIND patients showed greater SN functional connectivity with the left posterior insula (p-FWE = 0.007) and sensorimotor cortex (p-FWE = 0.026). In TaU + MIND patients only, greater SN-insular connectivity was associated with improved depression scores (r = -0.51, p = 0.038). A longitudinal increase in cortical thickness was observed in the insular cluster in these patients (p = 0.015). Increased anterior cingulate cortex thickness was also reported in TaU + MIND group (p-FWE = 0.02). CONCLUSIONS: Increased SN-insular connectivity might modulate chronic pain perception and the management of negative emotions. Enhanced SN-sensorimotor connectivity could reflect improved body-awareness of painful sensations. Expanded cingulate cortex thickness might sustain improved cognitive processing of nociceptive information. Our findings unveil the therapeutic potential of mindfulness and the underlying neural mechanisms in CM-MOH patients. TRIAL REGISTRATION: Name of Registry; MIND-CM study; Registration Number ClinicalTrials.gov identifier: NCT0367168; Registration Date: 14/09/2018.

Persistent effectiveness of CGRP antibody therapy in migraine and comorbid medication overuse or medication overuse headache - a retrospective real-world analysis.

BACKGROUND: Management of patients with migraine who have concomitant medication overuse (MO) or medication overuse headache (MOH) is a major problem in clinical practice. Detoxification of acute analgesics before or during initiation of prophylactic therapy has long been recommended although this concept has recently been questioned. Additionally, relapse after detoxification is a common problem. This real-world study analyses the initial and sustained effectiveness of prophylactic migraine therapy with CGRP (receptor) antibodies without prior detoxification in patients with comorbid MO or MOH for up to one year. METHODS: A retrospective real-world analysis was performed on 291 patients (episodic migraine (EM) with MO (EM-MO; n = 35), EM without MO (EM-noMO; n = 77), chronic migraine (CM) with MOH (CM-MOH; n = 109), CM without MOH (CM-noMOH; n = 70). All patients began treatment with either erenumab (n = 173), fremanezumab (n = 70) or galcanezumab (n = 48) without prior detoxification. Data were available for up to 12 months of treatment. Responder rates for monthly headache days (MHD), monthly migraine days (MMD) and monthly acute medication intake (AMD) were analysed. RESULTS: All groups showed a significant reduction in MHD, MMD and AMD at the last observed time point compared to baseline. In patients with CM and MOH, 60.6% (66/109) no longer fulfilled the definition of MO or MOH and a further 13.8% (15/109) had only EM-MO. In the EM cohort, 89% (31/35) of MO patients lost their MO during therapy. MHD and AMD 30% responder rates were comparable for CM-MOH and CM-noMOH (MHD: CM-MOH: 56.0% vs. CM-noMOH: 41.4%, p = 0.058, AMD: CM-MOH: 66.1% vs. CM-noMOH: 52.9%, p = 0.077). MMD responder rate did not differ significantly (after Bonferroni adjustment) (CM-MOH: 62.4% vs. CM-noMOH: 47.1%, p = 0.045, α = 0.017). After successful initiation of therapy, 15.4% of the initial CM-MOH patients relapsed and met the criterion for CM-MOH at the end of follow-up. There were no antibody specific differences in response to therapy. CONCLUSIONS: Our data confirms the effectiveness of CGRP antibody treatment in migraine patients with additional MOH or MO in a real-world setting. Low relapse rates after initial successful therapy support an early start of CGRP antibody treatment in patients with MOH or MO. TRIAL REGISTRATION: No registration, retrospective analysis.

Unsatisfactory response to acute medications does not affect the medication overuse headache development in pediatric chronic migraine.

BACKGROUND: Chronic migraine (CM) negatively impacts the quality of life of 2 to 4% of pediatric patients. In adults, CM is frequently linked to medication overuse headache (MOH), but there is a much lower prevalence of MOH in children. A suboptimal response to acute therapies may lead to their reduced use, thus preventing MOH development in children and adolescents. The frequency of patients with CM who do not respond to acute therapies was examined in the present study. We investigated whether the prevalence of MOH was different between responders and non-responders. We also examined whether patients receiving prophylactic therapy had an improved response to acute therapy. Finally, we investigated if there was a difference in the frequency of psychiatric comorbidities between responders and non-responders. METHODS: We retrospectively analysed clinical data of all chronic pediatric migraineurs under the age of 18 referred to the Headache Centre at Bambino Gesù Children Hospital in June 2021 and February 2023. ICHD3 criteria were used to diagnose CM and MOH. We collected demographic data, including the age at onset of migraine and the age of the CM course. At baseline and after 3 months of preventive treatment, we evaluated the response to acute medications. Neuropsychiatric comorbidities were referred by the children's parents during the first attendance evaluation. RESULTS: Seventy patients with CM were assessed during the chosen period. Paracetamol was tried by 41 patients (58.5%), NSAIDs by 56 patients (80.0%), and triptans by 1 patient (1.4%). Fifty-one participants (73%) were non-responder to the abortive treatment. The presence of MOH was detected in 27.1% of the whole populations. Regarding our primary aim, MOH was diagnosed in 29% of non-responder patients and 22% of responders (p > 0.05). All patients received preventative treatment. After 3 months of preventive pharmacological therapy, 65.4% of patients who did not respond to acute medications achieved a response, while 34.6% of patients who were non-responder remain non-responder (p < 0.05). Prophylactic therapy was also effective in 69% of patients who responded to acute medication (p < 0.05). Psychiatric comorbidities were detected in 68.6% of patients, with no difference between responders and non-responders (72.2% vs. 67.3%; p = 0.05). CONCLUSIONS: Despite the high prevalence of unresponsiveness to acute therapies in pediatric CM, it does not act as a protective factor for MOH. Moreover, responsiveness to acute drugs is improved by pharmacological preventive treatment and it is not affected by concomitant psychiatric comorbidities.

Lipopolysaccharide, VE-cadherin, HMGB1, and HIF-1α levels are elevated in the systemic circulation in chronic migraine patients with medication overuse headache: evidence of leaky gut and inflammation.

OBJECTIVE: Medication overuse headache (MOH) was recently shown to be associated with leaky gut in rodents. We aimed to investigate whether chronic migraine (CM) patients with MOH have elevated lipopolysaccharide levels and inflammatory molecules in blood circulation. MATERIALS AND METHODS: The study included women participants (40 CM patients with NSAID overuse headache, 35 episodic migraine (EM) patients, and 20 healthy non-headache sufferers). Migraine duration, monthly migraine headache days, MigSCog, HADS-D, HADS-A, and HIT-6 scores were recorded. Serum samples were collected to measure circulating LPS, LPS binding protein (LBP), tight junction protein occludin, adherens junction protein vascular endothelial cadherin (VE-cadherin), CGRP, HMGB1, HIF-1α, IL-6, and IL-17 levels. RESULTS: Serum LPS, VE-Cadherin, CGRP, HIF-1α, and IL-6 levels were significantly higher in the CM + MOH group compared to the EM group and healthy controls while serum LBP and HMGB1 were higher in the CM + MOH group compared to healthy controls. IL-17 and occludin levels were comparable between the three groups. Serum HMGB1 levels in EM patients were higher compared to the control group. Mig-SCog and HIT-6 scores were higher in the CM + MOH group compared to EM patients. HADS-A and HADS-D scores were significantly higher in the CM + MOH group compared to EM patients and healthy controls, and they were also higher in EM patients compared to healthy subjects. LPS levels were correlated with VE-cadherin and occludin levels. The number of monthly migraine headache days was positively correlated with serum LPS, HIF-1α, VE-cadherin, and IL-6 levels, HADS-A, HADS-D, HIT-6, and MigSCog scores. CONCLUSION: We have evidence for the first time that CM + MOH is associated with elevated serum LPS and LBP levels suggestive of LPS leak into the systemic circulation. Higher levels of nociceptive and/or pro-inflammatory molecules such as HMGB1, HIF-1α, IL-6, and CGRP may play a role in trigeminal sensitization and neurobiology of MOH. Intestinal hyperpermeability and consequent inflammatory response should be considered as a potential contributory factor in patients with MOH.

The prevalence of headache in the adult population of Morocco: a cross-sectional population-based study.

BACKGROUND: The series of population-based studies conducted by the Global Campaign against Headache has, so far, included Pakistan and Saudi Arabia from the Eastern Mediterranean Region. The Maghreb countries of North Africa, also part of this Region, are geographically apart and culturally very different from these countries. Here we report a study in Morocco. METHODS: We applied the standardised methodology of Global Campaign studies, with cluster-randomized sampling in regions of Morocco selected to be representative of its diversities. In three of these regions, in accordance with this methodology, we made unannounced visits to randomly selected households and, from each, interviewed one randomly selected adult member (aged 18-65 years) using the HARDSHIP structured questionnaire translated into Moroccan Arabic and French. In a fourth region (Fès), because permission for such sampling was not given by the administrative authority, people were randomly stopped in streets and markets and, when willing, interviewed using the same questionnaire. This was a major protocol violation. RESULTS: We included 3,474 participants, 1,074 (41.7%) from Agadir, 1,079 (41.9%) from Marrakech, 422 (16.4%) from Tétouan and 899 from Fès. In a second protocol violation, interviewers failed to record the non-participating proportion. In the main analysis, excluding Fès, observed 1-year prevalence of any headache was 80.1% among females, 68.2% among males. Observed 1-day prevalence (headache yesterday) was 17.8%. After adjustment for age and gender, migraine prevalence was 30.8% (higher among females [aOR = 1.6]) and TTH prevalence 32.1% (lower among females [aOR = 0.8]). Headache on ≥ 15 days/month (H15+) was very common (10.5%), and in more than half of cases (5.9%) associated with acute medication overuse (on ≥ 15 days/month) and accordingly diagnosed as probable medication-overuse headache (pMOH). Both pMOH (aOR = 2.6) and other H15+ (aOR = 1.9) were more common among females. In the Fès sample, adjusted prevalences were similar, numerically but not significantly higher except for other H15+. CONCLUSIONS: While the 1-year prevalence of headache among adults in Morocco is similar to that of many other countries, migraine on the evidence here is at the upper end of the global range, but not outside it. H15 + and pMOH are very prevalent, contributing to the high one-day prevalence of headache.

Headache in the adult population of Cameroon: prevalence estimates and demographic associations from a cross-sectional nationwide population-based study.

BACKGROUND: Knowledge of headache prevalence, and the burdens attributable to headache disorders, remains incomplete in sub-Saharan Africa (SSA): reliable studies have been conducted only in Zambia (southern SSA) and Ethiopia (eastern SSA). As part of the Global Campaign against Headache, we investigated the prevalence of headache in Cameroon, in Central SSA. METHODS: We used the same methodology as the studies in Zambia and Ethiopia, employing cluster-randomized sampling in four regions of Cameroon, selected to reflect the country's geographic, ethnic and cultural diversities. We visited, unannounced, randomly selected households in each region, and randomly selected one adult member (aged 18-65 years) of each. Trained interviewers administered the Headache-Attributed Restriction, Disability and Impaired Participation (HARDSHIP) structured questionnaire, developed by an international expert consensus group and translated into Central African French. Demographic enquiry was followed by diagnostic questions based on ICHD-3 criteria. RESULTS: Headache was a near-universal experience in Cameroon (lifetime prevalence: 94.8%). Observed 1-year prevalence of headache was 77.1%. Age- and gender-adjusted estimates were 76.4% (95% confidence interval: 74.9-77.9) for any headache, 17.9% (16.6-19.3) for migraine (definite + probable), 44.4% (42.6-46.2) for tension-type headache (TTH; also definite + probable), 6.5% (5.7-7.4) for probable medication-overuse headache (pMOH) and 6.6% (5.8-7.6) for other headache on ≥ 15 days/month (H15 +). One-day prevalence ("headache yesterday") was 15.3%. Gender differentials were as expected (more migraine and pMOH among females, and rather more TTH among males). pMOH increased in prevalence until age 55 years, then declined somewhat. Migraine and TTH were both associated with urban dwelling, pMOH, in contrast, with rural dwelling. CONCLUSIONS: Headache disorders are prevalent in Cameroon. As in Zambia and Ethiopia, estimates for both migraine and TTH exceed global mean estimates. Attributable burden is yet to be reported, but these findings must lead to further research, and measures to develop and implement headache services in Cameroon, with appropriate management and preventative strategies.

Treatment patterns and characteristics of patients with migraine: results from a retrospective database study in Japan.

BACKGROUND: Clinical characteristics and treatment practice of patients with migraine in Japan in real-world setting have not been fully investigated. We conducted a retrospective cohort study using claims database to understand the clinical practice of migraine in recent years and to characterize patients potentially not managed well by current treatment options. METHODS: Our study used data from the large claims database maintained by JMDC Inc. Patients with diagnosis of headache or migraine between January 1, 2018, and July 31, 2022, were defined as the headache cohort, and those with migraine diagnosis and prescription of migraine treatments among the headache cohort were included in the migraine cohort. In the headache cohort, characteristics of medical facilities and status of imaging tests to distinguish secondary headache were examined. Treatment patterns and characteristics of patients potentially not managed well by acute/preventive treatment were described in migraine cohort. RESULTS: In the headache cohort, 989,514 patients were included with 57.0% females and mean age of 40.3 years; 77.0% patients visited clinics (with ≤ 19 bed capacities) for their primary diagnosis, and 30.3% patients underwent imaging tests (computed tomography and/or magnetic resonance imaging). In the migraine cohort, 165,339 patients were included with 65.0% females and mean age of 38.8 years. In the migraine cohort, 95.6% received acute treatment while 20.8% received preventive treatment. Acetaminophen/non-steroidal anti-inflammatory drugs were most common (54.8%) as the initial prescription for migraine treatment followed by triptan (51.4%). First treatment prescription included preventive treatment in 15.6%, while the proportion increased to 82.2% in the fourth treatment prescription. Among patients with more than 12 months of follow-up, 3.7% had prescription patterns suggestive of risk of medication-overuse headache, and these patients were characterized by a higher percentage of females and a higher prevalence of comorbidities. CONCLUSIONS: This study revealed that approximately one-fifth of the patients with migraine visiting medical facilities use preventive drugs. The presence of potential patients at risk of medication-overuse headache and the role of clinics in migraine treatment were also described.

The prevalence and demographic associations of headache in the adult population of Peru: a national cross-sectional population-based study.

BACKGROUND: The Global Campaign against Headache is conducting a series of population-based studies to fill the large geographical gaps in knowledge of headache prevalence and attributable burden. One major region not until now included is South America. Here we present a study from Peru, a country of 32.4 million inhabitants located at the west coast of South America, notable for its high Andes mountains. METHODS: The study was conducted in accordance with the standardized methodology used by the Global Campaign. It was a cross-sectional survey using cluster randomised sampling in five regions to derive a nationally representative sample, visiting households unannounced, and interviewing one randomly selected adult member (aged 18-65 years) of each using the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire translated into South American Spanish. The neutral screening question ("Have you had headache in the last year?") was followed by diagnostic questions based on ICHD-3 and demographic enquiry. RESULTS: The study included 2,149 participants from 2,385 eligible households (participating proportion 90.1%): 1,065 males and 1,084 females, mean age 42.0 ± 13.7 years. The observed 1-year prevalence of all headache was 64.6% [95% CI: 62.5-66.6], with age-, gender- and habitation-adjusted prevalences of 22.8% [21.0-24.6] for migraine (definite + probable), 38.9% [36.8-41.0] for tension-type headache (TTH: also definite + probable), 1.2% [0.8-1.8] for probable medication-overuse headache (pMOH) and 2.7% [2.1-3.5] for other headache on ≥ 15 days/month (H15+). One-day prevalence of headache (reported headache yesterday) was 12.1%. Migraine was almost twice as prevalent among females (28.2%) as males (16.4%; aOR = 2.1; p < 0.001), and strongly associated with living at very high altitude (aOR = 2.5 for > 3,500 versus < 350 m). CONCLUSION: The Global Campaign's first population-based study in South America found headache disorders to be common in Peru, with prevalence estimates for both migraine and TTH substantially exceeding global estimates. H15 + was also common, but with fewer than one third of cases diagnosed as pMOH. The association between migraine and altitude was confirmed, and found to be strengthened at very high altitude. This association demands further study.