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.

Medication-overuse headache overlapping with serotonin syndrome.

Serotonin syndrome (SS) is an iatrogenic, drug-induced clinical syndrome caused by an increase in the intrasynaptic concentration of serotonin. Serotonin plays a significant role in the pathophysiology of migraines. Upregulation of 5-HT2A receptors is found in medication-overuse headache (MOH). Several migraine medications, both preventative and abortive drugs, act on serotonin receptors. We report two patients with chronic migraine who developed MOH. Besides headache, patients had frequent attacks of dizziness, restlessness, irritability, insomnia, excessive sweating, abdominal discomforts and tremors. These symptoms were suggestive of withdrawal headache. However, on physical examinations, we elicited hyperreflexia, hypertonia, clonus, tachycardia, hypertension, mydriasis and hyperactive bowel sound. Both patients also met the criteria for SS. Cyproheptadine was started. All features, including headaches, got better after cyproheptadine administration within 24 hours. In 7 days, there was practically total improvement. Both patients continued to take cyproheptadine as a preventative medicine, and migraine frequency was under control.

Goshuyuto Reduced the Monthly Intake of Anti-headache Drugs and Improved Pain Status in Patients with 20-Year History of Medication Overuse Headache in an Outpatient Setting.

The management of medication overuse headache (MOH) is sometimes challenging, particularly for patients with a long disease duration. We observed that patients who used goshuyuto, a traditional Japanese medicine, exhibited a favorable clinical course. Two women who had a history of MOH for over 20 years were treated using 5.0-7.5 g/day goshuyuto in an outpatient setting. The treatment reduced their use of habitual drugs, including triptan (33-55%) and non-steroidal anti-inflammatory drugs (75-82%), as well as the headache impact test score-6 (16-23%) over 24 weeks. As goshuyuto has a protective effect on chronic headache and is reported not to lead to MOH, it is a good candidate for the treatment of patients with MOH in an outpatient setting, even for those with an over 20-year history of MOH.

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.

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.

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.

Therapies targeting CGRP signaling for medication overuse headache.

PURPOSE OF REVIEW: Medication overuse headache (MOH) affects more than 60 million individuals worldwide causing enormous personal and social burden. Only repurposed drugs are available for MOH that share limited evidence for efficacy. The preclinical data suggesting that activation of the calcitonin gene-related peptide (CGRP) pathway is involved in headache chronification along with clinical evidence that monoclonal antibodies targeting CGRP (anti-CGRP mAbs) have good efficacy in preventing chronic migraine, triggered this review that aims to summarize the current data on the effectiveness and safety of mAbs against CGRP in MOH. RECENT FINDINGS: Post hoc analyses of phase-3 trials of erenumab, fremanezumab, galcanezumab, and eptinezumab for the prevention of chronic migraine revealed that patients with MOH benefit from the treatment over placebo. Several real-world studies confirm the efficacy of erenumab and galcanezumab in patients with MO. However, all published trials evaluated treatments in patients with chronic migraine with MO collectively, not in patients with MOH exclusively. SUMMARY: The available data indicate that anti-CGRP mAbs represent a good mechanism-based and disease-specific therapeutical option with for MOH as long as detoxification and additional nonpharmaceutical interventions are operated. Future research should focus on long-term-controlled trials in MOH populations exclusively.

Characteristics and comorbidities of headache in patients over 50 years of age: a cross-sectional study.

BACKGROUND: Although headache is a common complaint in younger individuals, it is one of the most common complaints among persons over the age of 50 and is a significant cause of morbidity. As there are differences in the causes and types of headache, the diagnosis and management of headache in older adults differ from that in younger individuals. METHODS: In this cross-sectional study, 570 patients ≥ 50 years were recruited at a university affiliated tertiary headache center between 2016 and 2019. Demographic data, headache characteristics, and comorbid medical conditions were recorded. The presence of depression was explored using the Beck Depression Inventory. The patients were evaluated using the STOP-BANG scale to determine the risk of obstructive sleep apnea. RESULTS: The mean age of the patients was 57.7 years. Seventy-three percent of the patients had primary headache disorders, with the most prevalent types being migraine, followed by tension-type headache. Secondary headaches were primarily the result of overuse of medication, cervical spine disease, and hypertension. Patients with medication-overuse headache were significantly more likely to suffer from hypothyroidism and gastrointestinal problems such as bleeding/ulcers. Irritable bowel syndrome was also more common in patients with medication-overuse headaches and migraines. The risk for obstructive sleep apnea was intermediate in 45.2% of the patients with hypertension-induced headache, but was lower in the majority of others. There was a high tendency for moderate-to-severe depression in the participants; however, the Beck Depression Inventory scores were significantly higher in medication-overuse headache patients. CONCLUSION: Proper treatment of headache in middle-aged and older adults requires the recognition of secondary causes, comorbid diseases, and drug induced or medication overuse headaches. Special attention should be paid to depression and obstructive sleep apnea in such patients suffering from headache disorders.

Detoxification vs non-detoxification before starting an anti-CGRP monoclonal antibody in medication overuse headache.

BACKGROUND: Medication overuse headache significantly contributes to the chronification process and treatment refractoriness of migraine. Currently, abrupt discontinuation of the overused medication still represents the best management strategy for these patients, challenging public health system resources. METHODS: In this prospective study, chronic migraine and medication overuse headache sufferers with at least 28 days of analgesic consumption per month were included. Assessment of efficacy outcomes at three months were compared among patients who underwent in-hospital abrupt discontinuation of overused acute medication (YES-DETOX group) and patients who did not (NO-DETOX group) before starting an anti-CGRP monoclonal antibody. RESULTS: Of 401 patients who received either erenumab or galcanezumab, 28% (n = 111) satisfied inclusion criteria (YES-DETOX n = 28; NO-DETOX n = 83). After three months of treatment, 59% (n = 65; 47/83 YES-DETOX; 18/28 NO-DETOX) patients reverted from medication overuse headache and 51% (n = 57; 42/83 YES-DETOX; 15/28 NO-DEOTX) achieved ≥50% reduction in monthly headache days; yet no statistical differences were observed between the two groups (p = 0.4788 and p = 0.8393, respectively). Monthly consumption of pain medication was the only baseline prognostic factor in multivariate analysis in the overall cohort (p = 0.016). CONCLUSION: Our results support the emerging evidence that anti-CGRP monoclonal antibodies may be effective in medication overuse headache patients irrespective of detoxification, yet further studies are needed to draw definitive conclusions.

The burden of medication overuse headache and patterns of switching and discontinuation among triptan users: a systematic literature review.

BACKGROUND: A synthesis of real-world discontinuation and switching patterns among triptan users and rates of acute medication use among patients with medication overuse headache (MOH) is needed to better understand the burden among patients with migraine. The study objectives were to: (1) synthesize rates of switching and discontinuation from triptans; (2) characterize acute medication use among patients with MOH; and (3) describe the associated burden. METHODS: A systematic literature review was conducted, under the Preferred Reporting Items for Systematic Review guidelines, using MEDLINE/EMBASE from database inception to July 2019. The search strategy targeted studies of adults with migraine, and included terms related to migraine and its treatment. Continuous variables were summarized using means, standard deviations, and ranges. Dichotomous and categorical variables were summarized using the number and proportion of individuals. RESULTS: Twenty studies were included; seven describing patterns of switching and discontinuation among triptan users, and 13 characterizing triptan overuse among patients with MOH. High rates of switching to non-specific acute medications and low two-year retention rates were reported; among US samples switching to opioids at the first refill (18.2%) or after 1-year (15.5%) was frequent. Compared to persistent use of triptans, switchers experienced greater headache related impact and either no improvement or increased headache-related disability. Rates of medication overuse by agent among patients with MOH varied greatly across the included studies, and only one study described factors associated with the risk of MOH (e.g. duration of medication overuse). Medication agent, increased headache frequency (p = .008), and increased disability (p = .045) were associated with unsuccessful withdrawal; patients overusing triptans were more successful at withdrawal than those overusing opioids or combination analgesics (P < .0001). CONCLUSIONS: The evidence summarized here highlights that rates of WCS are low and many patients turn to other acute medication at their first refill. Patients may experience no improvement in disability when switching from one triptan agent to another, or experience increasing disability and/or increasing migraine frequency when turning to traditional acute treatment for migraine. Variability in health care settings, patient severity, and study design contributed to heterogeneity across the synthesis.

Medication overuse headache: Updating of the French recommendations regarding the treatment strategies.

Regular and frequent use of analgesics and acute antimigraine drugs can increase the frequency of headache, and induce the transition from episodic to chronic migraine or medication-overuse headache (MOH). The one-year prevalence of this condition is between 1% and 2% in Europe, provoking substantial burden. MOH is more prevalent in people with comorbid depression, anxiety, and other chronic pain conditions. This paper aims at presenting an updating of French recommendations regarding treatments strategies. Prior French recommendations, published in 2014, were written in French. A literature search in the major medical databases including the terms "medication overuse headache", "symptomatic medication overuse", published between 2010 and 2020 was carried out. Three main strategies can be recommended and conducted in parallel: education and explanations about the negative consequences of overusing acute antimigraine drugs, discontinuation of the overused medication, and finally, preventive drug therapy and non-pharmacological prevention. Medication overuse headache remains a debated problem and evidence for the most effective treatment strategy is needed.

Candidate Genes and Proteomic Biomarkers of Serum and Urine in Medication-Overuse Headache.

Chronic headache is a topical problem of neurology, psychiatry and general practice. The medication-overuse headache (MOH) is one of the leading pathologies in the structure of chronic headache. However, early diagnosis of the MOH is challenging. We analyzed potential proteomic biomarkers of serum and urine in patients with MOH. METHODS: We searched PubMed, Springer, Scopus, Web of Science, ClinicalKey, and Google Scholar databases for English publications over the past 10 years using keywords and their combinations. RESULTS: We found and analyzed seven studies that met the search criteria for the purpose of the review, including 24 serum proteomic biomarkers and 25 urine proteomic biomarkers of MOH. Moreover, the candidate genes and locus of the studied serum (vitamin D-binding protein, lipocalin-type prostaglandin D2 synthase, apolipoprotein E, etc.) and urine proteomic biomarkers (uromodulin, alpha-1-microglobulin, zinc-alpha-2-glycoprotein, etc.) of MOH are presented in this review. CONCLUSIONS: The serum and urine proteomic biomarkers of MOH can potentially help with the identification of patients with MOH development. Due to the relevance of the problem, the authors believe that further investigation of the MOH proteomic biomarkers in different ethnic and racial groups of patients with primary headache is necessary. In addition, it is important to investigate whether medications of different drug classes influence the levels of serum and urine proteomic biomarkers.

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.

Medication overuse and drug addiction: a narrative review from addiction perspective.

Chronic headache is particularly prevalent in migraineurs and it can progress to a condition known as medication overuse headache (MOH). MOH is a secondary headache caused by overuse of analgesics or other medications such as triptans to abort acute migraine attacks. The worsening of headache symptoms associated with medication overuse (MO) generally ameliorates following interruption of regular medication use, although the primary headache symptoms remain unaffected. MO patients may also develop certain behaviors such as ritualized drug administration, psychological drug attachment, and withdrawal symptoms that have been suggested to correlate with drug addiction. Although several reviews have been performed on this topic, to the authors best knowledge none of them have examined this topic from the addiction point of view. Therefore, we aimed to identify features in MO and drug addiction that may correlate. We initiate the review by introducing the classes of analgesics and medications that can cause MOH and those with high risk to produce MO. We further compare differences between sensitization resulting from MO and from drug addiction, the neuronal pathways that may be involved, and the genetic susceptibility that may overlap between the two conditions. Finally, ICHD recommendations to treat MOH will be provided herein.

Medication overuse headache.

PURPOSE OF REVIEW: Medication overuse headache (MOH)is a disabling problem worldwide with areas of controversy regarding its cause. This article reviews the recent ideas regarding the development of this disorder and its effective management. RECENT FINDINGS: It has been proposed that all acute migraine medications can lead to MOH, with differences in the propensity of different agents to cause the problem. Early data suggests that gepants, which are small-molecule calcitonin gene-related peptide antagonists used for the acute treatment of migraine, may be an exception. Recent studies show that practitioners and the general public are still largely unaware of the problem of medication overuse and its damaging effects. SUMMARY: MOH is an accepted concept of an increase in headaches driven by the frequent administration of acute antimigraine drugs. The impressions of providers, and studies documenting the concept may be flawed. Although it is likely that MOH does occur, and restricting the amount of acute medications is necessary to prevent it, it is also possible that increasing amounts of acute medications are simply a reflection of poorly controlled headaches, rather than a cause. Objective markers need to be developed to identify those who have MOH, which does not include all with chronic migraine, and to use these markers in diagnosis and management, particularly in those patients where the frequent acute drugs might only be a reflection of frequent headaches, rather than a cause.

Use of medicinal plants for headache, and their potential implication in medication-overuse headache: Evidence from a population-based study in Nepal.

BACKGROUND: In Nepal, traditional treatment using medicinal plants is popular. Whereas medication-overuse headache is, by definition, caused by excessive use of acute headache medication, we hypothesized that medicinal plants, being pharmacologically active, were as likely a cause. METHODS: We used data from a cross-sectional, nationwide population-based study, which enquired into headache and use of medicinal plants and allopathic medications. We searched the literature for pharmacodynamic actions of the medicinal plants. RESULTS: Of 2100 participants, 1794 (85.4%) reported headache in the preceding year; 161 (7.7%) reported headache on ≥15 days/month, of whom 28 (17.4%) had used medicinal plants and 117 (72.7%) allopathic medication(s). Of 46 with probable medication-overuse headache, 87.0% (40/46) were using allopathic medication(s) and 13.0% (6/46) medicinal plants, a ratio of 6.7:1, higher than the overall ratio among those with headache of 4.9:1 (912/185). Of 60 plant species identified, 49 were pharmacodynamically active on the central nervous system, with various effects of likely relevance in medication-overuse headache causation. CONCLUSIONS: MPs are potentially a cause of medication-overuse headache, and not to be seen as innocent in this regard. Numbers presumptively affected in Nepal are low but not negligible. This pioneering project provides a starting point for further research to provide needed guidance on use of medicinal plants for headache.

Secondary headache attributed to exposure to or overuse of a substance.

BACKGROUND: Secondary headaches attributed to exposure to or the overuse of a substance are classified under chapter eight in the International Classification of Headache Disorders 3rd edition. Three distinct sub-chapters consider: 1. Headache attributed to exposure to a substance, 2. Medication overuse headache, and 3. Headache attributed to substance withdrawal. Headache attributed to exposure to a substance refers to a headache with onset immediately or within hours after the exposure, while medication overuse headache is a headache occurring on 15 or more days per month that has developed as a consequence of regular usage of acute headache medication(s) for more than three consecutive months in a patient with a pre-existing primary headache disorder. The withdrawal of caffeine, oestrogen, and opioids is most often associated with the development of headache. DISCUSSION: Despite the current headache classification, there is no certainty of a causal relationship between the use of any substance and the development of headache. Some substances are likely to provoke headache in patients that suffer from a primary headache disorder like migraine, tension-type headache or cluster headache, while others were described to cause headache even in people that generally do not get headaches. Toxic agents, such as carbon monoxide (CO) are difficult to investigate systematically, while other substances such as nitric oxide (NO) were specifically used to induce headache experimentally. If a patient with an underlying primary headache disorder develops a headache, in temporal relation to exposure to a substance, which is significantly worse than the usual headache it is considered secondary. This is even more the case if the headache phenotype is different from the usually experienced headache characteristics. Medication overuse headache is a well-described, distinct disease entity with only marginally understood pathophysiology and associated psychological factors. Managing medication overuse headache patients includes education, detoxification, prophylactic treatments and treating comorbidities, which is reflected in available guidelines. Viewing medication overuse headache as a separate entity helps clinicians and researchers better recognise, treat and study the disorder. CONCLUSION: Identification of substances that may cause or trigger secondary headache is important in order to educate patients and health care professionals about potential effects of these substances and prevent unnecessary suffering, as well as deterioration in quality of life. Treatment in case of medication overuse and other chronic headache should be decisive and effective.

[Chronic and Refractory Migraine: How to Diagnose and Treat]. / Enxaqueca Crónica e Refratária: Como Diagnosticar e Tratar.

Migraine is highly prevalent and carries a significant personal, social and economic burden. It is the second cause of disability (years living with disability) worldwide and the first cause under 50 years of age. Chronic migraine (occurring for more than 15 days a month) and refractory migraine (treatment resistant), especially when there is also analgesic overuse, are the most disabling forms of migraine. These three disorders (chronic migraine, refractory migraine and medication overuse headache) are particularly difficult to treat. This article reviews their epidemiology, clinical presentation, diagnostic criteria, risk factors, comorbidities and social and personal impact. The therapeutic options available are discussed and focused on a multidisciplinary approach, non-pharmacological interventions treatment of comorbidities and avoiding analgesic overuse. Prophylactic treatments are mandatory and include the oral prophylactic treatments (topiramate), botulinum toxin type A and the novel monoclonal antibodies against calcitonin gene related peptide or its receptor, which are the first migraine preventive medicines developed specifically to target migraine pathogenesis. In refractory cases, multiple therapies are required including neurostimulation.

A enxaqueca é uma cefaleia muito prevalente na população com importantes custos pessoais, sociais e económicos e é a segunda causa a nível mundial de anos vividos com incapacidade. As suas variantes, crónica (aquela que ocorre mais de 15 dias por mês) e refratária (resistente ao tratamento), sobretudo quando se complicam de uso excessivo de analgésicos, embora mais raras, constituem as formas que causam maior incapacidade. Os autores revêm estes três tipos de cefaleias (enxaqueca refratária, enxaqueca crónica e cefaleia secundária a utilização excessiva de analgésicos) que constituem um grupo de cefaleias de difícil terapêutica. São revistos a epidemiologia, os aspetos clínicos, os critérios de diagnóstico, as comorbilidades, os fatores de agravamento e o impacto destas cefaleias sobre a qualidade de vida dos doentes. O tratamento de cada uma destas entidades é abordado, ressalvando a importância de uma abordagem abrangente, considerando o tratamento das comorbilidades, a utilidade de medidas não farmacológicas, o imperativo de evitar o abuso de analgésicos e a necessidade absoluta de tratamento profilático. São revistos os diferentes tratamentos profiláticos disponíveis (e a evidência científica da sua eficácia), tais como os fármacos preventivos orais (neuromodeladores como o topiramato), a toxina botulínica tipo A e os novos medicamentos preventivos para a enxaqueca (anticorpos monoclonais que atuam sobre o péptido relacionado com o gene da calcitonina ou o seu recetor, e que são os primeiros medicamentos preventivos desenvolvidos especificamente para atuar na fisiopatogenia da enxaqueca. Para os casos refratários são consideradas outras alternativas terapêuticas como a neuroestimulação.

Evaluation of LY573144 (lasmiditan) in a preclinical model of medication overuse headache.

BACKGROUND: Medication overuse is a significant issue that complicates the treatment of headache disorders. The most effective medications for the acute treatment of migraine all have the capacity to induce medication overuse headache (MOH). Novel acute migraine-specific treatments are being developed. However, because the mechanism(s) underlying medication overuse headache are not well understood, it is difficult to predict whether any particular acute medication will induce MOH in susceptible individuals. LY573144 (lasmiditan), a 5-HT1F receptor agonist, has recently been shown to be effective in the acute treatment of migraine in phase 3 trials. The aim of this study is to determine whether frequent administration of lasmiditan induces behaviors consistent with MOH in a pre-clinical rat model. METHODS: Sprague Dawley rats were administered six doses of lasmiditan (10 mg/kg), sumatriptan (10 mg/kg), or sterile water orally over 2 weeks and cutaneous allodynia was evaluated regularly in the periorbital and hindpaw regions using von Frey filaments. Testing continued until mechanosensitivity returned to baseline levels. Rats were then submitted to bright light stress (BLS) or nitric oxide (NO) donor administration and were again evaluated for cutaneous allodynia in the periorbital and hindpaw regions hourly for 5 hours. RESULTS: Both lasmiditan and sumatriptan exhibited comparable levels of drug-induced cutaneous allodynia in both the periorbital and hindpaw regions, which resolved after cessation of drug administration. Both lasmiditan and sumatriptan pre-treatment resulted in cutaneous allodynia that was evoked by either BLS or NO donor. CONCLUSIONS: In a pre-clinical rat model of MOH, oral lasmiditan, like sumatriptan, induced acute transient cutaneous allodynia in the periorbital and hindpaw regions that after resolution could be re-evoked by putative migraine triggers. These results suggest that lasmiditan has the capacity to induce MOH through persistent latent peripheral and central sensitization mechanisms.

Comparison of 3 Treatment Strategies for Medication Overuse Headache: A Randomized Clinical Trial.

Importance: Medication overuse headache (MOH) is a disabling, globally prevalent disorder representing a well-known and debated clinical problem. Evidence for the most effective treatment strategy is needed. Objective: To compare 3 treatment strategies for MOH. Design, Setting, and Participants: This open-label, randomized clinical trial with 6 months of follow-up was conducted in the tertiary sector at the Danish Headache Center, Glostrup, from October 25, 2016, to June 28, 2019. Of 483 patients with MOH referred during the inclusion period, 195 met the criteria consisting of migraine and/or tension-type headache, 18 years or older, eligibility for outpatient treatment, no severe physical or psychiatric disorder, no other addiction, and not pregnant or breastfeeding. Of these, 75 refused participation and 120 were included. Data were analyzed from July 3 to September 6, 2019. Interventions: Random assignment (1:1:1 allocation) to 1 of the 3 outpatient treatments consisting of (1) withdrawal plus preventive treatment, (2) preventive treatment without withdrawal, or (3) withdrawal with optional preventive treatment 2 months after withdrawal. Main Outcomes and Measures: The primary outcome was change in headache days per month after 6 months. Predefined secondary outcomes were change in monthly migraine days, use of short-term medication, pain intensity, number of responders, patients with remission to episodic headache, and cured MOH. Results: Of 120 patients, 102 (mean [SD] age, 43.9 [11.8] years; 81 women [79.4%]) completed the 6-month follow-up. Headache days per month were reduced by 12.3 (95% CI, 9.3-15.3) in the withdrawal plus preventive group, by 9.9 (95% CI, 7.2-12.6) in the preventive group, and by 8.5 (95% CI, 5.6-11.5) in the withdrawal group (P = .20). No difference was found in reduction of migraine days per month, use of short-term medication, or headache intensity. In the withdrawal plus preventive group, 23 of 31 patients (74.2%) reverted to episodic headache, compared with 21 of 35 (60.0%) in the preventive group and 15 of 36 (41.7%) in the withdrawal group (P = .03). Moreover, 30 of 31 patients (96.8%) in the withdrawal plus preventive group were cured of MOH, compared with 26 of 35 (74.3%) in the preventive group and 32 of 36 (88.9%) in the withdrawal group (P = .03). These findings corresponded to a 30% (relative risk, 1.3; 95% CI, 1.1-1.6) increased chance of MOH cure in the withdrawal plus preventive group compared with the preventive group (P = .03). Conclusion and Relevance: All 3 treatment strategies were effective, but based on these findings, withdrawal therapy combined with preventive medication from the start of withdrawal is recommended as treatment for MOH. Trial Registration: ClinicalTrials.gov Identifier: NCT02993289.