The effect of anesthetic blockade of greater occipital nerve during the withdrawal period of the medication overuse headache treatment.

Background and purpose:

Discontinua­tion of medication still remains a key element in the treatment of medication overuse headache (MOH), but there is no consensus on the withdrawal procedure. We aimed to share the promising results of anesthetic blockade of greater occipital nerve (GON), which can be an alternative to existing treatments during the early withdrawal period of MOH treatment.

This study was conducted using regular electronic medical records and headache diaries of patients diagnosed with MOH and treated with anesthetic GON blockade with 0.5% bupivacaine solution in a specia­lized headache outpatient clinic. A total of 86 patients who developed MOH while being followed up for chronic migraine were included in the study.

The treatment schemes for MOH are based on expert consensus and withdrawal strategies are the most challenging part of treatment. In our study, numerical rating scale for headache intensity, overused medication consumption per month, headache frequency (day/month) and the duration of each attack (hour/day) decreased significantly in the first month compared to pre-treatment (p < 0.01). 

Conclusion – Our study suggests that GON blockade can be used as a good alternative therapy in the treatment of MOH.

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.

Management of medication overuse headache.

Medication overuse headache (MOH) is a secondary headache characterized by frequent use of acute or symptomatic migraine medications at a sufficient frequency to transform patients from episodic to chronic migraine. MOH represents a significant medical problem, with a serious burden on patients' lives and on society as a whole. MOH patients often have additional comorbidities, and the clinical challenge of helping patients reduce acute medication use and revert to episodic headache can be marked. Treatment includes education and prevention; withdrawal programs; pharmacological prophylaxis; multidisciplinary therapies with behavioral and noninvasive neuromodulation options; and scheduled, frequent follow-up to prevent relapses. The advent of anti-CGRP therapy monoclonal antibodies may provide an alternative to more extensive programs for less complex patients. This review also provides guidance for which patients may benefit most from coordinated integrated programs.

Changes in the hippocampal volume in chronic migraine, episodic migraine, and medication overuse headache patients.

Background and purpose:

Hippocampi are the structures located in the medial depths of both temporal lobes, mainly responsible for memory, navigation and regulation of emotions, and activated during the processing of pain and the modification of nociceptive stimuli. Chronic pain is thought to have stress-like detrimental modulatory effects on the hippocampal neurogenesis, and adults with chronic pain have been showed to have lower hippocampal volumes. The present study aims to show the relationship between headaches and hippocampal volume by comparing the right, left and total hippocampal volumes of patients with Episodic Migraine (EM), Chronic Migraine (CM) and Medication Overuse Headache (MOH) to those of the healthy control group using the Magnetic Resonance Imaging (MRI) technique, also by looking into the correlation between the number of painful days and attacks and the current hippocampal volumes.

A total of 30 patients (10 EM, 10 CM, 10 MOH) from 18 to 45 years of age diagnosed with migraine and also followed up by the neurology outpatient clinic from February to May 2022 and 30 healthy volunteers of similar ages and sexes to the patient group were included in the study. In addition to the routine cranial MRI protocols of all the participants, further cranial images were taken with the addition of the T1W 3D FSPGR sequence adjusted to the hippocampal body in the coronal plane and covering the whole brain. Hippocampal volumes were measured manually.

There were 27 females and 3 males in the patient group versus 28 females and 2 males in the control group, and no statistically significant differences in age and sex were found between the groups. The control group had higher average right, left and total hippocampal volumes than the whole patient group, but only the total hippocampal volume was significantly different between the groups. There was a negative correlation between the number of painful days and the measured right hippocampal and total hippocampal volumes; however, the measured values were not statistically significant. 

It was concluded that the changes in the hippocampal volume in migraine might be associated with the pain characteristics of the disorder. 

Alterations in DNA methylation associate with reduced migraine and headache days after medication withdrawal treatment in chronic migraine patients: a longitudinal study.

BACKGROUND: Chronic migraine, a highly disabling migraine subtype, affects nearly 2% of the general population. Understanding migraine chronification is vital for developing better treatment and prevention strategies. An important factor in the chronification of migraine is the overuse of acute headache medication. However, the mechanisms behind the transformation of episodic migraine to chronic migraine and vice versa have not yet been elucidated. We performed a longitudinal epigenome-wide association study to identify DNA methylation (DNAm) changes associated with treatment response in patients with chronic migraine and medication overuse as part of the Chronification and Reversibility of Migraine clinical trial. Blood was taken from patients with chronic migraine (n = 98) at baseline and after a 12-week medication withdrawal period. Treatment responders, patients with ≥ 50% reduction in monthly headache days (MHD), were compared with non-responders to identify DNAm changes associated with treatment response. Similarly, patients with ≥ 50% versus < 50% reduction in monthly migraine days (MMD) were compared. RESULTS: At the epigenome-wide significant level (p < 9.42 × 10-8), a longitudinal reduction in DNAm at an intronic CpG site (cg14377273) within the HDAC4 gene was associated with MHD response following the withdrawal of acute medication. HDAC4 is highly expressed in the brain, plays a major role in synaptic plasticity, and modulates the expression and release of several neuroinflammation markers which have been implicated in migraine pathophysiology. Investigating whether baseline DNAm associated with treatment response, we identified lower baseline DNAm at a CpG site (cg15205829) within MARK3 that was significantly associated with MMD response at 12 weeks. CONCLUSIONS: Our findings of a longitudinal reduction in HDAC4 DNAm status associated with treatment response and baseline MARK3 DNAm status as an early biomarker for treatment response, provide support for a role of pathways related to chromatin structure and synaptic plasticity in headache chronification and introduce HDAC4 and MARK3 as novel therapeutic targets.

Efficacy and safety of eptinezumab in patients with chronic migraine and medication-overuse headache: a randomized, double-blind, placebo-controlled study.

BACKGROUND: For some people with migraine, despite taking greater amounts of acute headache medication (AHM), they develop an increase in monthly headache days. This cycle of increasing headache days, and in turn AHM use, can lead to a secondary headache disorder called medication-overuse headache (MOH). Preventive medications can prevent migraine from occurring and reduce reliance on AHMs, thereby preventing the cycle of MOH. This study was performed to evaluate the efficacy and safety of eptinezumab to prevent migraine/headache in a mainly Asian patient population with a dual diagnosis of chronic migraine and MOH. METHODS: SUNLIGHT was a phase 3, multicenter, double-blind, parallel-group, placebo-controlled trial. Patients aged 18-75 years with ≥ 8 migraine days/month and a diagnosis of MOH were randomly allocated (1:1) to one of two treatment groups: eptinezumab 100 mg or placebo. Monthly migraine days (MMDs) were captured using a daily electronic diary; the change from baseline in the number of MMDs over Weeks 1-12 was the primary efficacy endpoint. RESULTS: Patients were randomized to eptinezumab 100 mg (n = 93) or placebo (n = 100). Over Weeks 1-12, eptinezumab reduced mean MMDs more than placebo (difference between treatments was -1.2; p = 0.1484). Differences between treatment groups with p-values below 0.05 favoring eptinezumab were observed in 3 out of the 6 key secondary endpoints. CONCLUSION: All endpoints numerically favored eptinezumab treatment when compared to placebo; however, this study did not meet its primary endpoint and is therefore negative. No new safety signals were identified in this study, like previous reports that confirmed the safety and tolerability of eptinezumab treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04772742 (26/02/2021).

Medication Overuse Headache, Chronic Migraine and Monoclonal Antibodies Anti-CGRP: A Real-World Study.

OBJECTIVE: Medication overuse headache (MOH) in chronic migraineurs may be a cause or consequence of the overuse of symptomatic medications for headache attacks. It is highly prevalent in tertiary centers. We compared the efficacy of 3 anti-CGRP monoclonal antibodies with traditional pharmacological agents in patients with chronic migraine (CM) and MOH. METHODS: A randomized, cross-sectional, prospective, and open trial with real-world comparison groups was carried out. The sample consisted of 100 consecutive patients having CM and MOH. RESULTS: Eighty-eight patients (65 women and 23 men) were included in the study and divided into 4 groups: those having used erenumab (19.3%), galcanezumab (29.6%), fremanezumab (25%) and conventional medications, and the control group (26.1%). Ages ranged from 18 to 78 years (mean, 44.1 ± 13.6 years). In the 6 months of follow-up, there was a significant reduction in the number of headache days in the 3 groups when compared with the control ( P < 0.0001). CONCLUSIONS: The small number of patients included in each group and the open design do not allow definitive conclusions, but the use of anti-CGRP monoclonal antibodies in patients with CM and MOH may result in lessening the number of headache days when compared with conventional treatment with drugs.

Efficacy of mindfulness added to treatment as usual in patients with chronic migraine and medication overuse headache: a phase-III single-blind randomized-controlled trial (the MIND-CM study).

BACKGROUND: Mindfulness gained considerable attention for migraine management, but RCTs are lacking. We aimed to assess the efficacy of a six-sessions mindfulness-based treatment added to treatment as usual (TaU) in patients with Chronic Migraine (CM) and Medication Overuse Headache (MOH) on headache frequency, medication intake, quality of life, disability, depression and anxiety, cutaneous allodynia, awareness of inner states, work-related difficulties, and disease cost. METHODS: In this Phase-III single-blind RCT carried out in a specialty Italian headache center, 177 patients with CM and MOH were randomized 1:1 to either TaU (withdrawal from overused drugs, education on proper medication use and lifestyle issues, and tailored prophylaxis) or mindfulness-based intervention added to TaU (TaU + MIND). The mindfulness-based intervention consisted of six group session of mindfulness practice and 7-10 min daily self-practice. The primary endpoint was the achievement of ≥ 50% headache frequency reduction at 12 months compared to baseline, and was analyzed on an intention-to-treat principle using Pearson's Chi-Squared test. Secondary endpoints included medication intake, quality of life (QoL), disability, depression and anxiety, cutaneous allodynia, awareness of inner states, work-related difficulties, and disease cost. The secondary endpoints were analyzed using per-protocol linear mixed models. RESULTS: Out of the 177 participants 89 were randomized to TaU and 88 to TaU + MIND. Patients in the TaU + MIND group outperformed those in TaU for the primary endpoint (78.4% vs. 48.3%; p < 0.0001), and showed superior improvement in headache frequency, QoL and disability, headache impact, loss of productive time, medication intake, and in total, indirect and direct healthcare costs. CONCLUSIONS: A mindfulness-based treatment composed of six-week session and 7-10 min daily self-practice added on to TaU is superior to TaU alone for the treatment of patients with CM and MOH. TRIAL REGISTRATION: MIND-CM was registered on clinicaltrials.gov (NCT03671681) on14/09/2018.

[Headache in the general practice]. / Kopfschmerzen in der Hausarztpraxis.

Headaches are one of the most frequent causes of consultations in general practice. Of more than 350 known headache tendencies, tension-type headache and migraine are particularly common in general practice. Medication overuse headache (MOH) is also common but rarely diagnosed. The medical consultation with a targeted anamnesis is the cornerstone of the diagnosis and correct classification. A detailed neurological examination completes the basic diagnosis. Additional laboratory and instrumental diagnostics follow in cases of atypical headache or clinical suspicion of secondary headache. This article focuses on the diagnosis and treatment of Tension-type Headache, migraine and Medication Overuse Headache.

Galcanezumab for the treatment of chronic migraine and medication overuse headache: Real-world clinical evidence in a severely impaired patient population.

BACKGROUND: Galcanezumab is a monoclonal antibody acting against the calcitonin gene-related peptide approved for the preventive treatment of migraine. The aim of this article is to explore its effectiveness and safety of galcanezumab in chronic migraine (CM) with medication overuse-headache (MOH). METHODS: Seventy-eight patients were consecutively enrolled at the Modena headache center and followed up for 15 months. Visits were scheduled every 3 months, and the following variables were collected: the number of migraine days per month (MDM); the painkillers taken per month (PM); the number of days per month in which the patient took, at least, one painkiller; the six-item headache impact test; and the migraine disability assessment questionnaire (MIDAS) score. Demographic features of the analyzed sample were collected at the baseline and adverse events (AEs) were collected at every visit. RESULTS: After 12 months, galcanezumab significantly reduced the MDM, the PM, the number of days on medication, the HIT-6 as well as the MIDAS scores (all p < .0001). The greatest amelioration was obtained in the first trimester of treatment. A higher MDM, a higher NRS score at the baseline, and a higher number of failed preventive treatments negatively predict the CM relief at the year of treatment. No serious AEs were registered and only one drop-out was due to AE. CONCLUSIONS: Galcanezumab is effective and safe for the treatment of patients affected by CM and MOH. Patients with a higher impairment at the baseline may found less benefits with galcanezumab.

Early Effect of Calcitonin Gene-related Peptide Monoclonal Antibodies in Migraine with Medication Overuse: A Single-center Retrospective Study.

Objective Calcitonin gene-related peptide (CGRP)-(receptor) monoclonal antibody (mAb) has been reported to reduce the frequency of medication overuse in patients with migraine. The present study investigated whether or not CGRP-mAb treatment shows early effectiveness for medication overuse headache (MOH) in Japan. Methods We retrospectively reviewed 34 patients with MOH who received preventive treatment with CGRP-mAb from June 2021 to October 2022. The International Classification of Headache Disorders, 3rd edition was used to diagnose MOH. This study was conducted at the Department of Neurology, Saitama Medical University. Patients were recruited from this specialized headache outpatient center. Results In total, 69 patients with migraine had newly introduced CGRP-mAb, and 34 patients had MOH (49.3%). The mean±standard deviation patient age was 44±15.5 years old. The study population included 24 women (70.6%). The types of CGRP-mAb used were galcanezumab in 16 patients (47.0%), fremanezumab in 10 (29.4%), and erenumab in 8 (23.5%). The mean disease duration was 19.6±13.1 years. The types of migraine diagnosis were chronic migraine in 28 patients (82.4%) and migraine with aura in 11 patients (32.4%). The mean number of headache days in the month before administration of CGRP-mAb was 22±7.7 days; 1 month after administration, the MHD was 16.9±9.1 days. The change in MHD was -5.7 days (22.7%), indicating significant improvement (p<0.05). Conclusion CGRP-mAb has been suggested as a preventive treatment for patients with MOH. Further investigation of the long-term efficacy of CGRP-mAb for MOH is needed.

Randomized controlled studies evaluating Topiramate, Botulinum toxin type A, and mABs targeting CGRP in patients with chronic migraine and medication overuse headache: A systematic review and meta-analysis.

BACKGROUND: This systematic review focuses on chronic migraine patients with medication overuse headache using, respectively, topiramate, botulinum toxin type A, and human monoclonal antibodies targeting calcitonin gene-related peptide or its receptor. METHODS: A systematic search was conducted in the databases CENTRAL, MEDLINE, Embase and Web of Science until May 2022. We included randomized controlled trials reporting the outcomes of change in monthly headache/migraine days, ≥50% response rates and change in medication overuse status. Studies were excluded if response rates were not reported. Risk of bias assessment was performed using the Cochrane RoB2 tool. The quality of evidence for outcomes across included studies was evaluated according to the five factors outlined in Cochrane GRADE approach. FINDINGS: The initial search resulted in 1599 records. Following screening, 10 studies met our inclusion criteria, while seven studies with sufficient data were included in the meta-analysis. Studies assessing Botulinum toxin type A included 1139 patients and showed a mean reduction in headache frequency by 1.92 days per month compared to placebo (-1.92; 95% CI -2.68 to -1.16). Studies assessing human monoclonal antibodies included 1982 patients, and showed significant positive effect compared to placebo for all measured outcomes. The overall odds ratio for the ≥50% response rate was 2.90 (95% CI, 2.23 to 3.78). No significant difference was observed in the frequency of adverse effect for both Botulinum toxin type A and low dose of human monoclonal antibodies compared to placebo. There is currently insufficient evidence to determine the impact of topiramate in chronic migraine patients with medication overuse headache. INTERPRETATION: Botulinum toxin type A and human monoclonal antibodies targeting calcitonin gene-related peptide receptor were beneficial in reducing monthly migraine days and ≥50% response rate, but uncertainties remained for Botulinum toxin type A regarding response rate. The effect size for human monoclonal antibodies was greater with relatively lower drop-out rate. High-quality randomized trials are required to evaluate the effect of topiramate in chronic migraine patients with medication overuse headache.

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.

Reduced frequency of migraine attacks following coronavirus disease 2019: a case report.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 is a virus affecting different organs and causing a wide variety and severity of symptoms. Headache as well as loss of smell and taste are the most frequently reported neurological manifestations of coronavirus disease 2019 induced by severe acute respiratory syndrome coronavirus 2. Here we report on a patient with chronic migraine and medication overuse headache, who experienced remarkable mitigation of migraine following coronavirus disease 2019. CASE PRESENTATION: For many years prior to the severe acute respiratory syndrome coronavirus 2 infection, a 57-year-old Caucasian male suffered from very frequent migraine attacks and for control of headaches he had been taking triptans almost daily. In the 16-month period before the outbreak of coronavirus disease 2019, triptan was taken 98% of the days with only a 21-day prednisolone-supported triptan holiday, which, however, had no longer-lasting consequences on migraine frequency. Upon severe acute respiratory syndrome coronavirus 2 infection, the patient developed only mild symptoms including fever, fatigue, and headache. Directly following recovery from coronavirus disease 2019, the patient surprisingly experienced a period with largely reduced frequency and severity of migraine attacks. Indeed, during 80 days following coronavirus disease 2019, migraine as well as triptan usage were restricted to only 25% of the days, no longer fulfilling criteria of a chronic migraine and medication overuse headache. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection might be capable of triggering mitigation of migraine.

Eptinezumab improved patient-reported outcomes in patients with migraine and medication-overuse headache: Subgroup analysis of the randomized PROMISE-2 trial.

OBJECTIVE: To evaluate the effect of eptinezumab on patient-reported outcomes in patients with chronic migraine (CM) and medication-overuse headache (MOH). BACKGROUND: MOH is a secondary headache disorder commonly occurring in patients with CM and associated with functional and psychological impairments. Medication overuse and monthly headache and migraine days were reduced with eptinezumab compared with placebo as published previously; however, these outcomes do not fully capture the burden of migraine and treatment effect. METHODS: PROMISE-2 was a phase 3, randomized, double-blind, placebo-controlled trial in adults with CM. Patients were randomized (1:1:1) to receive eptinezumab 100 mg, eptinezumab 300 mg, or placebo (up to 2 doses, 12 weeks apart). Patients completed the following patient-reported outcomes: 6-item Headache Impact Test (HIT-6), Patient Global Impression of Change (PGIC), patient-identified most bothersome symptom (PI-MBS), and 36-item Short-Form Health Survey (SF-36). RESULTS: A total of 431 CM patients (139, 147, and 145 patients in the eptinezumab 100 mg, eptinezumab 300 mg, and placebo groups, respectively) had MOH diagnosed at screening (40.2% of the total PROMISE-2 population [n = 1072]). In CM with MOH patients, both doses of eptinezumab were associated with clinically meaningful improvements in mean HIT-6 total scores by week 4 and remained improved throughout the 24-week study. Responder rates for individual HIT-6 items were greater with eptinezumab than with placebo at all time points. At week 12, almost twice as many eptinezumab-treated patients indicated the PGIC was "much" or "very much" improved (58.5% [79/135, 100 mg] and 67.4% [95/147, 300 mg] vs. 35.8% [48/134, placebo]). Patients in the eptinezumab groups showed numerically greater improvements over placebo in the PI-MBS and SF-36 scores. CONCLUSIONS: This subgroup analysis in patients with CM/MOH at baseline suggests that eptinezumab treatment is associated with early, sustained, and clinically meaningful improvements in patient-reported outcomes.

A Preliminary Analysis on the Feasibility and Short-Term Efficacy of a Phase-III RCT on Mindfulness Added to Treatment as Usual for Patients with Chronic Migraine and Medication Overuse Headache.

This preliminary analysis of a single-blind phase-III RCT aims to compare the feasibility and short-term efficacy of mindfulness as an add-on to treatment as usual (TaU) in the management of patients with chronic migraine (CM) and medication overuse headache (MOH). Patients were randomized to either TaU (structured withdrawal of overused drugs, patient education and pharmacological prophylaxis) or TaU + MIND, wherein patients additionally received six 90 min weekly group sessions of mindfulness-based therapy. Repeated measures analyses were used to test whether patients in the two arms showed different course with regard to headache frequency and medication intake over a three-month period. Drop-out rates were not different between the two groups: 6/89 (6.7%) and 9/88 (10.2%) among those in TaU and TaU + MIND, respectively. A significant effect of time for all variables was shown, together with a significant effect of time by group, favoring TaU + MIND condition for headache frequency (p = 0.025) and NSAID intake (p = 0.007), controlling for age and CM duration. In total, 45/83 (54.2%) and 69/79 (75.9%) of the patients allocated to TaU and TaU + MIND, respectively, achieved 50% or more headache-day reduction (chi-squared 8.38, p = 0.004). Our preliminary analysis indicates that adding six mindfulness-based sessions to TaU was feasible and showed short-term efficacy in the treatment of patients with CM and MOH.

Is prednisone still a reasonable option in the treatment of withdrawal headache in patients with chronic migraine and medication overuse headache in the age of CGRP antibodies? A narrative review.

OBJECTIVE: Along with the development of novel migraine therapies as the monoclonal antibodies against calcitonin gene-related peptide (CGRP) and its receptor, the question arises if the treatment of chronic migraine (CM) and medication overuse headache (MOH) must be reconsidered. Have previous therapeutic approaches, including glucocorticoids, lost their role in the management of this debilitating disorder? In this narrative review, we present an overview of the available treatment options in CM and MOH in light of CGRP antibodies as well as an evaluation of the role of glucocorticoids in withdrawal therapy. BACKGROUND: Chronic migraine and medication overuse continues to be a difficult to treat condition. To date, potent treatment options are scarce and algorithms for advising patients with MOH are often still based on expert consensus rather than evidence-based medicine. For years and probably due to lack of effective alternatives, glucocorticoids have been used in MOH, especially to alleviate withdrawal symptoms caused by detoxification. Small case series report positive effects of steroids in this respective patient group; however, randomized controlled trials did not show a consistent benefit, although this may be due to methodological limitations. Because of these discrepancies, their role in MOH has been under debate ever since. METHODS: We searched the electronic database PubMed for articles up to June 1, 2022 on the use of glucocorticoids in CM and MOH. CONCLUSION: Despite popular use in clinical practice, there is currently still no scientific evidence for the efficacy of glucocorticoids in patients with CM and MOH. Treatment with monoclonal antibodies achieved high transition rates from medication overuse to non-overuse. However, further research is needed to evaluate the additional benefit of these new agents.

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.

Quantity changes in acute headache medication use among patients with chronic migraine treated with eptinezumab: subanalysis of the PROMISE-2 study.

BACKGROUND: Patients with chronic migraine (CM) treated with eptinezumab in the PROMISE-2 trial achieved greater reductions in migraine and headache frequency, impact, and acute headache medication (AHM) use than did patients who received placebo. This post hoc analysis examines relationships between headache frequency reductions and changes in AHM use in patients in PROMISE-2. METHODS: PROMISE-2 was a double-blind, placebo-controlled trial conducted in adults with CM. Patients were randomized to eptinezumab 100 mg, 300 mg, or placebo, administered intravenously once every 12 weeks for up to two doses. Patients recorded headache/AHM information daily and for each event in an electronic diary; data from all days with daily reports were included. Shifts in headache frequency and AHM use were assessed in the three populations: total CM population, patients with CM and medication-overuse headache (MOH), and patients with CM and MOH who were ≥ 50% responders during treatment (response over weeks 1-24). RESULTS: A total of 1072 adults with CM received treatment (eptinezumab, n = 706; placebo, n = 366). Mean baseline headache frequency was 20.5 days; mean baseline AHM days was 13.4; 431 patients had MOH, of which 225 (52.2%) experienced ≥50% response over weeks 1-24. Relative to baseline, the proportion of days with both headache and AHM use decreased 25.1% (eptinezumab) versus 17.0% (placebo) in the total population (N = 1072), 29.2% versus 18.4% in the MOH subpopulation (n = 431), and 38.3% versus 31.5% in the CM with MOH population with ≥50% response subgroup (n = 225) during weeks 1-24. The proportion of days with headache and triptan use decreased 9.1% (eptinezumab) versus 5.8% (placebo), 11.8% versus 7.2%, and 14.5% versus 12.6%, respectively. Reductions in other AHM types were smaller. CONCLUSIONS: In this post hoc analysis, eptinezumab use in patients with CM was associated with greater decreases in days with headache with AHM overall and with triptans in particular. The magnitude of effect was greater in the subgroup of CM patients with MOH and ≥ 50% response. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02974153 . Eptinezumab reduces headache frequency and acute medication use in patients with chronic migraine.

A cross-sectional study on the quality of life in migraine and medication overuse headache in a Hungarian sample: understanding the effect of headache characteristics.

Background and purpose: Previous studies using generic and disease specific instruments showed that both migraine and medication overuse headache are associated with lower health-related quality of life (HRQoL). The aim of our study was to assess HRQoL differences in migraineurs and in patients with MOH and to examine how headache characteristics such as years with headache, aura symptoms, triptan use, headache pain severity and headache frequency are related to HRQoL. Methods: In this cross-sectional study 334 participants were examined (248 were recruited from a tertiary headache centre and 86 via advertisements). The Comp-rehensive Headache-related Quality of life Questionnaire (CHQQ) was used to measure the participants' HRQoL. Data showed normal distribution, therefore beside Chi-squared test parametric tests (e.g. independent samples t-test) were used with a two-tailed p<0.05 threshold. Linear regression models were used to determine the independent effects of sex, age, recruitment method, headache type (migraine vs. MOH) and headache characteristics (presence of aura symptoms, years with headache, headache pain severity, headache frequency and triptan use) separately for each domain and for the total score of CHQQ. Significance threshold was adopted to p0.0125 (0.05/4) to correct for multiple testing and avoid Type I error. Results: Independent samples t-tests showed that patients with MOH had significantly lower scores on all CHQQ domains than migraineurs, except on the social subscale. Results of a series of regression analyses showed that triptan use was inversely related to all the domains of HRQoL after correction for multiple testing (p<0.0125). In addition, headache pain severity was associated with lower physical (p=0.001) and total scores (p=0.002) on CHQQ subscales. Conclusion: Based on the results, different headache characteristics (but not the headache type, namely migraine or MOH) were associated with lower levels of HRQoL in patients with headache. Determining which factors play significant role in the deterioration of HRQoL is important to adequately manage different patient populations and to guide public health policies regarding health service utilization and health-care costs.