Medication-Overuse Headache.

OBJECTIVE: Medication-overuse headache (MOH) has been described for almost 100 years and is characterized as a daily or near-daily headache that usually presents in patients with preexisting primary headache disorders who are overusing one or more acute or symptomatic headache medications. This article reviews the diagnosis and management of patients with MOH. LATEST DEVELOPMENTS: The International Classification of Headache Disorders criteria for MOH have changed over time. The worldwide prevalence appears to be between 1% and 2%. Together, headache disorders, including MOH, are currently ranked as the second leading cause of years lived with disability in the Global Burden of Disease world health survey. Significant neurophysiologic changes are seen in the brains of patients with MOH, including functional alterations in central pain processing and modulating systems and central sensitization. Research supports updates to the principles of management, including weaning off the overused medication, preventive therapy, biobehavioral therapy, and patient education. ESSENTIAL POINTS: MOH is a fairly common and treatable secondary headache disorder that produces significant disability and a substantial reduction in quality of life. The costs related to lost income and disability are substantial. MOH is intimately related to chronic migraine, which continues to be underrecognized and undertreated. Treatment focuses on both the institution of effective preventive migraine therapy and the reduction or removal of the overused medications. Educational efforts directed toward both providers and patients have been shown to be effective in reducing the effect of MOH.

Safety and tolerability of atogepant for the preventive treatment of migraine: a post hoc analysis of pooled data from four clinical trials.

BACKGROUND: Conventional, non-specific preventive migraine treatments often demonstrate low rates of treatment persistence due to poor efficacy or tolerability. Effective, well-tolerated preventive treatments are needed to reduce migraine symptoms, improve function, and enhance quality of life. Atogepant is a migraine-specific oral calcitonin gene-related peptide receptor antagonist that is indicated for the preventive treatment of migraine in adults. This analysis evaluated the safety and tolerability profile of atogepant for the preventive treatment of migraine, including adverse events (AEs) of interest, such as constipation, nausea, hepatic safety, weight changes, and cardiac disorders. METHODS: This post hoc analysis was performed using data pooled from 2 (12-week) randomized, double-blind, placebo-controlled trials (RCTs) and 2 (40- and 52-week) open-label long-term safety (LTS) trials of oral atogepant for episodic migraine (EM). RESULTS: The safety population included 1550 participants from the pooled RCTs (atogepant, n = 1142; placebo, n = 408) and 1424 participants from the pooled LTS trials (atogepant, n = 1228; standard care [SC], n = 196). In total, 643/1142 (56.3%) atogepant participants and 218/408 (53.4%) placebo participants experienced ≥ 1 treatment-emergent AEs (TEAEs) in the RCTs. In the LTS trials, 792/1228 (64.5%) of atogepant participants and 154/196 (78.6%) of SC participants experienced ≥ 1 TEAEs. The most commonly reported TEAEs (≥ 5%) in participants who received atogepant once daily were upper respiratory tract infection (5.3% in RCTs, 7.7% in LTS trials), constipation (6.1% in RCTs, 5.0% in LTS trials), nausea (6.6% in RCTs, 4.6% in LTS trials), and urinary tract infection (3.4% in RCTs, 5.2% in LTS trials). Additionally, weight loss appeared to be dose- and duration-dependent. Most TEAEs were considered unrelated to study drug and few led to discontinuation. CONCLUSIONS: Overall, atogepant is safe and well tolerated in pooled RCTs and LTS trials for the preventive treatment of EM in adults. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02848326 (MD-01), NCT03777059 (ADVANCE), NCT03700320 (study 302), NCT03939312 (study 309).

Chronic migraine and medication overuse.

Though clearly described as far back as the 17th century, chronic migraine has defied precise categorization and has continued to develop as an important diagnostic concept with significant societal impact. Worldwide prevalence is estimated to be between 1% and 3%, and these patients form a dynamic group cycling between chronic and episodic migraine. Theories of pathogenesis are developing supported by recent imaging and other findings. Of the many determinants of progression to chronic migraine, overuse of acute abortive headache medications may be one of the most important modifiable factors. Treatment strategies, in addition to educational measures, have included various preventive migraine medications such as topiramate, valproate, and onabotulinumtoxinA. CGRP monoclonal antibodies are efficacious for the management of chronic migraine both with and without medication overuse.

The Be-Home Kids Program: An Integrated Approach for Delivering Behavioral Therapies to Adolescents with Episodic and Chronic Migraine.

Migraine disorders are common in populations of children and adolescents. There are different pharmacological treatments for migraine in young patients, but none have specific indications, and doubts about their efficacy exist. The feasibility and effectiveness of behavioral approaches have already been documented in clinical experiences, and they are generally associated with fewer or no unpleasant effects. Among them, mindfulness practice offers a suitable alternative to other adolescent treatments. We present the results of a pilot study, the Be-Home Kids program, performed during the COVID-19 emergency. It was delivered by web and included education on drug use, lifestyle issues, and six sessions of mindfulness-based behavioral practice. We assessed headache frequency, medication intake, and other psychological variables and followed twenty-one adolescents with chronic or high-frequency episodic migraine without aura for 12 months. Results indicated an overall clinical improvement, particularly a 64% reduction in headache frequency over 12 months. In conclusion, our results indicate that a combined treatment which includes patients' education and six sessions of mindfulness-based practice delivered over the web, can be of great support in reducing headache frequency, medication intake, and the associated psychological burden disability in adolescent migraine patients.

A Single-Group Study on the Effect of OnabotulinumtoxinA in Patients with Chronic Migraine Associated with Medication Overuse Headache: Pain Catastrophizing Plays a Role.

Pain catastrophizing and cutaneous allodynia are commonly altered in patients with chronic migraine associated with medication overuse headache (CM-MOH) and tend to improve in parallel with clinical improvement. The relation between pain catastrophizing and cutaneous allodynia is poorly understood in patients with CM-MOH receiving OnabotulinumtoxinA therapy. In this single-arm open-label longitudinal observational study, patients with CM-MOH were assigned to structured withdrawal and then administered OnabotulinumtoxinA (5 sessions on a three-month basis, 195 UI per 31 sites). Headache frequency, medication intake, disability, impact, cutaneous allodynia and pain catastrophizing were evaluated with specific questionnaires. In total, 96 patients were enrolled and 79 completed the 12-month follow-up. With the exclusion of cutaneous allodynia and the magnification subscale of the pain catastrophizing questionnaire, all variables showed significant improvement by the sixth month, which was maintained at 12 months. Reduction of pain catastrophizing, and particularly of its helplessness subscale, was a significant predictor of reduction in headache frequency and medication intake. Pain catastrophizing is often implicated in the clinical improvement in patients with CM-MOH receiving behavioral treatments, but, in this study, also showed a role in patients receiving OnabotulinumtoxinA; combining OnabotulinumtoxinA and behavioral treatments specifically addressing pain catastrophizing might further enhance patients' clinical outcome.

Refractory Headaches.

Medication overuse headache (MOH), new daily persistent headache (NDPH), and persistent refractory headache attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection represent a significant burden in terms of disability and quality of life, and a challenge in terms of definition, pathophysiology, and treatment. Regarding MOH, prevention without withdrawal is not inferior to prevention with withdrawal. Preventive medications like topiramate, onabotulinumtoxinA, and calcitonin gene-related peptide (CGRP) monoclonal antibodies improve chronic migraine with MOH regardless of withdrawal. The differential diagnosis of NDPH is broad and should be carefully examined. There are no guidelines for the treatment of NDPH, but options include a short course of steroids, nerve blocks, topiramate, nortriptyline, gabapentin, CGRP monoclonal antibodies, and onabotulinumtoxinA. The persistence of headache 3 months after SARS-CoV2 infection is a predictor of poor prognosis.

Feasibility and effect of mindfulness approach by web for chronic migraine and high-frequency episodic migraine without aura at in adolescents during and after COVID emergency: preliminary findings.

BACKGROUND: Migraine disorders are common among adolescents: however, the efficacy of medical prophylaxis is limited in this population. This study reports preliminary findings on the feasibility and effect of a mindfulness-based intervention delivered via web for adolescents with chronic migraine (CM) and high-frequency episodic migraine (HFEM) without aura. METHODS: Patients with CM or HFEM received six session of a mindfulness-based treatment and were followed-up for 6 months as part of a larger study. Repeated measure analyses were carried out to test the effect of this behavioral intervention. RESULTS: A total of 12 patients were included in this analysis. A significant improvement was observed up to 6 months for headache frequency, symptoms of depression, and catastrophizing, and up to 3 months for patients' disability. No change was detected for patients' anxiety level. CONCLUSIONS: The results of our study provides initial support to the hypothesis that patients' education and mindfulness-based programs can be very useful in populations of adolescents with CM or HFEM.

Management of chronic migraine with medication overuse by web-based behavioral program during the COVID-19 emergency: results at 12 months.

BACKGROUND: The study had been initiated because of restrictions put in place to control the spread of coronavirus in Milan in March 2020 that impacted clinical activities at our tertiary headache center in Milan (Foundation IRCSS Carlo Besta Neurological Institute). Treatment efforts were modified to make use of telephonic and internet communication to maintain care of our patients. METHODS: Nineteen patients had undergone our withdrawal protocol for medication overuse headache and were scheduled for follow-up that included pharmacological prophylaxis combined with behavioral therapy and mindfulness, generally performed in small group face-to-face sessions. A behavioral program was organized for them by technology modality (smartphone) due to the pandemic restrictions. RESULTS: The results concern 12-month follow-up. The clinical indexes showed migraine days per month 20.6 (± 6) pre vs 11.2 (± 3.1 at 12 months); medications intake per month 19.4 (± 5.8) pre vs 9.0 (± 4.6) at 12 months; MIDAS 67.7 (± 52.6) pre vs 71.1 (± 60) at 12 months; HIT-6 66.2 (± 5.3) pre vs 62.2 (± 5.9). CONCLUSION: The present study confirmed literature data, supporting the behavioral approach combined to traditional therapies as a novel method to follow patients and guarantee their benefit, also when applied using technology by telemedicine or smartphone.

Effect of a Mindfulness-Based Intervention for Chronic Migraine and High Frequency Episodic Migraine in Adolescents: A Pilot Single-Arm Open-Label Study.

In this single-arm pilot open-label study we examined the effect of a mindfulness-based intervention on reduction of headache frequency after 12 months in adolescents aged 12-18 with chronic or high-frequency migraine without aura. Adolescents were recruited at the headache center of the C. Besta Neurological Institute and followed-up for 12 months. The mindfulness-based intervention was delivered in small groups and consisted of six weekly group sessions of guided meditation, and one booster session 15 days after. Patients filled in questionnaires assessing headache frequency (primary endpoint), medication intake, disability, anxiety, depression, catastrophizing, and caregivers' burden. Within-person ANOVA was used to address variation of endpoints over time. Thirty-five out of 37 patients completed the study for primary endpoints, and 33 for secondary endpoints. Headache frequency dropped from 21.3 (95% CI 18.5; 24.1) to 9.6 (95% CI 6.1; 13.1) days per month at 12 months (F = 30.5, p < 0.001); 23 patients out of 35 (65.7%) achieved a headache frequency reduction greater than or equal to 50%. Significant improvements were also reported for medication intake (F = 18.7, p < 0.001), disability (F = 3.8, p = 0.027), trait anxiety (F = 5.1, p = 0.009), symptoms of depression (F = 9.5, p < 0.001), and catastrophizing (F = 23.6, p < 0.001). In conclusions, our study shows a reduction of headache attacks in adolescents who follow a mindfulness-based program, suggesting benefit of this nonpharmacological approach.

Efficacy of Erenumab in the Treatment of Trigeminal Neuralgia: A Retrospective Case Series.

OBJECTIVE: Trigeminal neuralgia (TN) is a chronic, often refractory, pain condition, which adversely affects the lives of patients. Current treatments are only mildly effective. Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies have been successfully studied in the treatment of migraines. CGRP plays a role in both TN and migraine. It is prudent to attempt CGRP monoclonal antibody therapy in TN. Erenumab, a human anti-CGRP monoclonal antibody medication, modulates CGRP, which is elevated in patients with TN. The primary objective of this study was to evaluate the efficacy of erenumab for patients with TN. METHODS: Retrospective analysis was performed on data collected from 10 patients diagnosed with TN and treated with erenumab for 6 months. Pain was tracked using a numeric pain rating scale (NPRS) from 0 to 10. The effect of erenumab on NPRS after 6 months' time was the primary end point. Secondary end points included side effects to therapy, improvement in headache frequency in those with comorbid migraine, evaluating mood following therapy, and global mood improvement using scale (worse, no change, improved). RESULTS: Nine of 10 patients (90.0%) reported improvement in pain severity and in global mood improvement. Three patients reported resolution of anxiety and/or depression. Side effects were minimal, with 3 patients reporting constipation, injection site reactions, or both. CONCLUSIONS: Based on these results, erenumab appears to be an efficacious treatment option for patients with refractory TN. Patients experienced improvement in pain, reduced frequency of headache, and improvement in mood. Treatment was well tolerated with only mild side effects reported. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that erenumab increases the probability of improved pain control in patients with medication-resistant TN.

Telehealth as a new care delivery model: The headache provider experience.

OBJECTIVE: To assess telehealth practice for headache visits in the United States. BACKGROUND: The rapid roll out of telehealth during the COVID-19 pandemic impacted headache specialists. METHODS: American Headache Society (AHS) members were emailed an anonymous survey (9/9/20-10/12/20) to complete if they had logged ≥2 months or 50+ headache visits via telehealth. RESULTS: Out of 1348 members, 225 (16.7%) responded. Most were female (59.8%; 113/189). Median age was 47 (interquartile range [IQR] 37-57) (N = 154). The majority were MD/DOs (83.7%; 159/190) or NP/PAs (14.7%; 28/190), and most (65.1%; 123/189) were in academia. Years in practice were 0-3: 28; 4-10: 58; 11-20: 42; 20+: 61. Median number of telehealth visits was 120 (IQR 77.5-250) in the prior 3 months. Respondents were "comfortable/very comfortable" treating via telehealth (a) new patient with a chief complaint of headache (median, IQR 4 [3-5]); (b) follow-up for migraine (median, IQR 5 [5-5]); (c) follow-up for secondary headache (median, IQR 4 [3-4]). About half (51.1%; 97/190) offer urgent telehealth. Beyond being unable to perform procedures, top barriers were conducting parts of the neurologic exam (157/189), absence of vital signs (117/189), and socioeconomic/technologic barriers (91/189). Top positive attributes were patient convenience (185/190), reducing patient travel stress (172/190), patient cost reduction (151/190), flexibility with personal matters (128/190), patient comfort at home (114/190), and patient medications nearby (103/190). Only 21.3% (33/155) of providers said telehealth visit length differed from in-person visits, and 55.3% (105/190) believe that the no-show rate improved. On a 1-5 Likert scale, providers were "interested"/"very interested" in digitally prescribing headache apps (median 4, IQR 3-5) and "interested"/"very interested" in remotely monitoring patient symptoms (median 4, IQR 3-5). CONCLUSIONS: Respondents were comfortable treating patients with migraine via telehealth. They note positive attributes for patients and how access may be improved. Technology innovations (remote vital signs, digitally prescribing headache apps) and remote symptom monitoring are areas of interest and warrant future research.

Acceptance and commitment therapy for high frequency episodic migraine without aura: Findings from a randomized pilot investigation.

OBJECTIVE: We compared the incremental effects of adding acceptance and commitment therapy (ACT) to pharmacological treatment as usual (TAU) in a sample of patients with high frequency episodic migraine without aura (HFEM), assessing impact on a spectrum of measures across multiple domains. BACKGROUND: Patients with HFEM are at risk of developing chronic migraine and medication overuse headache. ACT has been shown to be effective for the treatment of various chronic pain conditions, but little attention has been given to its therapeutic value in the management of recurring headaches. METHODS: In this single-blind (masking for outcome assessor), open-label, randomized clinical trial, 35 patients with HFEM, with a monthly headache frequency ranging from 9 to 14 days, were recruited at the headache center of C. Besta Neurological Institute and randomized to either TAU (patient education and pharmacological prophylaxis; n = 17) or TAU + ACT (n = 18). Patients assigned to the combined treatment arm additionally received six 90-min weekly group sessions of ACT therapy and two supplementary "booster" sessions. All patients were on a stable course of prophylactic medication in the 3 months prior to initiating either treatment. Monthly headache frequency served as the primary outcome measure, with all other data collected being considered as secondary measures (medication intake, disability, headache impact, anxiety and depression, catastrophizing, allodynia, cognitive inflexibility, pain acceptance, mindful attention and awareness). RESULTS: A total of 35 patients were enrolled: 17 randomized to TAU, of whom three dropped out, and 18 to TAU + ACT (no dropouts in this group). Headache frequency and medication intake decreased in both groups over 12 months, with patients in the TAU + ACT group showing statistically significant reduction earlier, that is, by month 3. Headache frequency was reduced by 3.3 days (95% CI: 1.4 to 5.2) among those randomized to ACT + TAU, whereas it increased by 0.7 days (95% CI: -2.7 to 1.3) among those randomized to TAU only (p = 0.007, partial η2  = 0.21), the difference being 4 days (95% CI: 1.2 to 6.8). Medication intake was reduced by 4.1 intakes (95% CI: 2.0 to 6.3) among those randomized to ACT + TAU and by 0.4 intakes (95% CI: -1.8 to 2.5) among those randomized to TAU only (p = 0.016; partial η2  = 0.17), the difference being 3.8 intakes (95% CI: 0.7 to 6.8). At 6 and 12 months, the variations were not different between the two groups for headache frequency and medication intake. The opposite was found for measures of headache impact and pain acceptance, where the differences over time favored patients allocated to TAU. Both groups improved with regard to measures of disability, anxiety and depression, catastrophizing, and cognitive inflexibility, whereas measures of allodynia and pain acceptance were stable over time. CONCLUSIONS: Our preliminary findings indicate that supplementing TAU with ACT can enhance the main clinical outcomes, namely headache frequency and medication intake of patients with HFEM.

Determinants of pain interference and headache impact in patients who have chronic migraine with medication overuse: Results from the MOTS trial.

OBJECTIVE: "Pain interference" and "headache impact" refer to negative consequences that pain and headache have on one's life. This study investigated determinants of these negative impacts in a large patient cohort who have chronic migraine with medication overuse. METHODS: Six hundred and eleven adults were enrolled from 34 headache, neurology, and primary care clinics. Negative consequences of chronic migraine with medication overuse were determined using the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference 6b questionnaire and the Headache Impact Test 6. Relationships between PROMIS-6b and Headache Impact Test 6 scores with demographics, headache characteristics, medication use, anxiety symptoms, and depression symptoms were assessed with linear regression. Elastic Net regression was used to develop a multiple regression model. RESULTS: PROMIS-6b T-Scores averaged 65.2 (SD 5.4) and Headache Impact Test 6 scores averaged 65.0 (SD 5.3), indicating severe negative consequences of chronic migraine with medication overuse. Chronic migraine with medication overuse interfered with enjoyment of life, concentration, daily activities, doing tasks away from home, and socializing. Depression symptom severity had the strongest relationship with pain interference and headache impact. Moderate-to-severe headache frequency, headache intensity, and anxiety symptoms were also associated with pain interference and headache impact. CONCLUSIONS: Chronic migraine with medication overuse is associated with substantial negative consequences, the extent of which is most strongly related to depression symptoms.

The prevalence and impact of migraine and severe headache in the United States: Updated age, sex, and socioeconomic-specific estimates from government health surveys.

BACKGROUND AND OBJECTIVES: Accurate, up-to-date estimates of the burden of migraine and severe headache are important for evidence-based decision-making about workforce needs and the distribution of health resources. We used data from US government health surveys to report the prevalence, trends, and impact of this condition by age, sex, and poverty status. METHODS: We identified the most recent, publicly available summary statistics from the National Hospital Ambulatory Medical Care Survey, the National Ambulatory Medical Care Survey, and the National Health Interview Survey. We extracted and compiled relevant information from each study, with an emphasis on sex, age, and economic-related statistics. RESULTS: The age-adjusted prevalence of migraine and severe headache in the United States has remained stable over many years. In 2018, the age-adjusted prevalence was 15.9% across all adults. The sex ratio also remains stable, with 21% of women and 10.7% of men affected. Migraine continues to be an important public health problem, accounting for roughly 4 million emergency department (ED) visits in 2016, when headache was the fifth most common reason for an ED visit overall and the third most common reason for ED visits in females 15-64. Migraine also accounted for over 4.3 million office visits. Many adults with migraine or severe headaches are disadvantaged. In 2018, for example, roughly 40% of US adults with migraine were unemployed, and a similar proportion were classified as poor or "near poor." Roughly one in five had no health insurance and about a third had a high school education or less. CONCLUSIONS: Migraine and severe headaches are a serious public health issue in the United States, with the highest impact in women of childbearing age and those of lower socioeconomic status. Socioeconomic disadvantages also are highly prevalent among those with headaches. The economic consequences of the current coronavirus pandemic are likely to exacerbate all of these inequities. Increased attention to this high impact chronic pain condition, and improved funding for treatment provision and research, are warranted to reduce the future burden of disease.

Effectiveness of mindfulness by smartphone, for patients with chronic migraine and medication overuse during the Covid-19 emergency.

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