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.

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

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

Involvement of Plasma Melatonin in Medication-Overuse Headache: A Cross-Sectional Study.

OBJECTIVES: Patients with medication-overuse headache (MOH) are often complicated with anxiety, depression, and sleep disorders and are associated with dependence behavior and substance abuse. Melatonin has physiological properties including analgesia, regulation of circadian rhythms, soporific, and antidepressant and affects drug preference and addiction. This study aimed to investigate the role of melatonin in MOH compared with episodic migraine (EM) and healthy controls and to verify the relationship between plasma melatonin levels and psychiatric symptoms. METHODS: Thirty patients affected by MOH, 30 patients with EM, and 30 matched healthy controls were enrolled. All subjects completed a detailed headache questionnaire and scales including the Hospital Anxiety and Depression Scale (HADS), the Pittsburgh Sleep Quality Index, the Leeds Dependence Questionnaire. Melatonin levels in plasma samples were measured by enzyme immunoassay method. RESULTS: The levels of plasma melatonin were significantly different among 3 groups of subjects (MOH, 7.74 [5.40-9.89]; EM, 9.79 [8.23-10.62]; Control, 10.16 [8.60-17.57]; H = 13.433; P = 0.001). Significantly lower levels of melatonin were found in MOH patients compared with healthy controls ( P = 0.001). The level of plasma melatonin inversely correlated with the scores of HADS-Anxiety ( r = -0.318, P = 0.002), HADS-Depression ( r = -0.368, P < 0.001), Pittsburgh Sleep Quality Index ( r = -0.303, P = 0.004), and Leeds Dependence Questionnaire ( r = -0.312, P = 0.003). CONCLUSIONS: This study innovatively detects the plasma melatonin levels in MOH patients and explores the association between melatonin levels and psychiatric symptoms. Melatonin may be potential complementary therapy in the treatment of MOH considering its comprehensive role in multiple aspects of MOH.

Medication Overuse Headache: an Updated Review and Clinical Recommendations on Management.

OVERVIEW: Medication overuse headache (MOH) is highly prevalent among individuals with primary headache disorders. PURPOSE OF REVIEW: (1) Provide an update on epidemiology, risk factors, and treatment strategies of MOH and (2) provide recommendations on the management of MOH. RECENT FINDINGS: The prevalence of MOH ranges from 0.5 to 7.2%. Risk factors for MOH include female sex, lower socioeconomic status, some psychiatric conditions, and substance use disorders, among others. Recent large clinical trials support preventative therapy as an integral component of MOH management. Emerging clinical trial evidence supports anti-CGRP mAbs as effective preventative treatments among individuals with migraine and MOH. Among the large clinical trials, candesartan, topiramate, amitriptyline, and onabotulinumtoxinA were the most used preventative therapies, providing further support for these agents. MOH management requires a multifaceted and patient-centered approach that involves patient education, behavioral interventions, withdrawal of the overused medication, and initiation of preventative medication.

Medication-overuse headache: clinical profile and management strategies.

Medication-overuse headache (MOH) is a disabling secondary headache disorder, with challenging consequences for affected patients and health care resources. It is defined as headache that occurs on ≥ 15 days per month in a patient known to have primary headache disorder due to regular overuse of acute or abortive headache medication for more than 3 months. MOH affects 1-2% of the world's population in their productive age. New advances in headache neurosciences and development of new treatment options specific for headache, along with an understanding of the clinical profile and pathophysiological mechanisms of MOH, can help improve patient outcomes and decrease the burden on the health care system. This work will review MOH, identify updated clinical assessments and recent management approaches.

Secondary Headache Disorders: Approach, Workup, and Special Considerations for Select Populations.

Headache is one of the most common diagnoses in neurology. A thorough understanding of the clinical presentation of secondary headache, which can be life-threatening, is critical. This review provides an overview of the diagnostic approach to a patient with headache, including discussion of "red," "orange," and "green" flags. We emphasize particular scenarios to help tailor the clinical workup to individual circumstances such as in pregnant women, when particular attention must be paid to the effects of blood pressure and hypercoagulability, as well as in older adults, where there is a need for higher suspicion for an intracranial mass lesion or giant cell arteritis. Patients with risk factors for headache secondary to alterations in intracranial pressure, whether elevated (e.g., idiopathic intracranial hypertension) or decreased (e.g., cerebrospinal fluid leak), may require more specific diagnostic testing and treatment. Finally, headache in patients with COVID-19 or long COVID-19 is increasingly recognized and may have multiple etiologies.

Addressing the cost of chronic and episodic migraine and its main drivers: a short-term longitudinal analysis from a third-level Italian center.

BACKGROUND: Chronic migraine (CM) is one of the most disabling neurological diseases, often associated to medication overuse headache (MOH). These patients make high use of pharmacological and non-pharmacological treatments, and experience high work-related indirect costs. The aim of this study was to address and compare the main driver of cost associated to CM-MOH and EM, and to evaluate the effect of improvement in migraine profile on disease cost. METHODS: We selected patients with baseline CM-MOH who reverted to an episodic pattern by 3 months after structured withdrawal. Paired sample t-test was used to explore the variation in headache frequency and its costs. Regression models were run to address the impact of single cost categories on total migraine cost. RESULTS: A total of 261 patients were included. Significant reductions in headache frequency and its costs were observed, with the exception of medical prophylaxis cost. The cost of migraine from chronic to episodic pattern is reduced by 533€ per month and 80% of this reduction is accountable to reduced indirect costs, i.e., loss of productive time. CONCLUSIONS: The results of our study open to future considerations on future approaches to the treatment of CM-MOH in which new migraine-specific treatments, i.e., monoclonal antibodies, should be combined with other pharmacological and non-pharmacological ones.

Interim analysis of the Registry for Load and Management of Medication Overuse Headache (RELEASE): A multicenter, comprehensive medication overuse headache registry.

BACKGROUND: Characteristics, disabilities, and optimal management of medication overuse headache remain uncertain. This study aimed to elucidate the clinical characteristics of patients with medication overuse headache enrolled in a medication overuse headache registry in Korea. METHODS: The Registry for Load and Management of MEdicAtion OveruSE Headache (RELEASE), a cross-sectional prospective observational study including seven referral headache centers in Korea, started enrolling adult patients with medication overuse headache in April 2020. Data included information on headache characteristics, burden on daily function, depression, anxiety, history of acute and preventive medications, and treatment strategies. RESULTS: A total of 229 patients (85.6% females; mean age, 45.5 ± 13.5 years) were enrolled by June 2021. The average durations of chronic headaches and medication overuse were 6.5 and 4.3 years, respectively. In the past month before enrollment, patients had headaches for 25 days and severe headaches for 12 days, and used acute medications for 20 days. Patients were disabled in 66.8 days in the past 3 months and had moderate/severe depression and anxiety in 56% and 35%, respectively. The proportion of patients on preventive treatments increased from 38% to 93% during the study period. CONCLUSIONS: RELEASE study reflects the current management status and opportunities to improve the quality of care in patients with medication overuse headache.

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.

Headache in transgender and gender-diverse patients: A narrative review.

OBJECTIVE: To summarize the unique aspects of managing headache in gender minorities and current research in this area including the potential relationship between gender-affirming hormone therapy (GAHT) and headache. BACKGROUND: The study of headache in gender minorities is intrinsically important. Gender minorities are medically underserved, and their medical care to date has been limited by socioeconomic disadvantages including stigma and an unsupportive clinical environment. Despite the rising population of transgender and gender-diverse adults and youth, headache research has also been limited. Knowledge of hormonal effects on headache in cisgender patients raises the question of possible effects of GAHT on transgender patients. METHODS/RESULTS: The manuscript is a narrative review of current best practices in treating transgender patients, including the use of appropriate terminology and ways to create a supportive environment. It also contains current guidelines on GAHT and reviews drug-drug interactions and secondary headache related to hormone therapy. We also review transgender headache research and related research on hormonal effects on headache in cisgender individuals. CONCLUSION: Creating a supportive environment for transgender and gender-diverse patients and being knowledgeable about GAHT are key to providing quality headache care. This review identifies further research needs for this population including the epidemiology of headache disorders in sexual minorities and the potential effects of GAHT on headache disorders in transgender patients.

FRAMES protocol versus simple advice for medication-overuse headache: a prospective, randomized, controlled clinical trial.

It is central to the management of patients with Medication-overuse headache that they reverse their behavior regarding the frequent use of pain medication. The objective of this study was to compare two counseling techniques for treating patients with Medication-overuse headache (MOH). This was a randomized, blind, controlled clinical trial that compared a structured (FRAMES) and unstructured counseling, for the treatment of MOH. Patients were assessed before the counseling and then again four and eight weeks after it. Semi-structured interview, headache diary, the Headache Impact Test (HIT-6) and the Hospital Anxiety and Depression Scale were used. Primary endpoints were the following: number of patients who stopped medication overuse; days with acute medication use; HIT-6; the number of patients who returned for consultations. Secondary endpoints were as follows: days per month of headache; 50% reduction in monthly days with acute medication use; the number of patients with less than 15 days of headache. Thirty-seven patients were allocated to the "FRAMES Group" and 33 to the "Control Group". There was no difference regarding primary or secondary outcomes between the two groups. There was a significant reduction in the frequency of headache and the number of days using pain medication in the first and second months of follow-up compared to baseline in both groups. There was a significant reduction in the HIT-6 in the first and second months of follow-up compared to baseline in the FRAMES Group, but not in the control group. Patients in both counseling groups significantly decreased the use of pain medications and the frequency of their headaches.

Treatment of medication overuse headache: Effect and predictors after 1 year-A randomized controlled trial.

BACKGROUND: Combined withdrawal and early preventive medication was the most effective treatment for medication overuse headache (MOH) within the first 6 months in a previous study, but results from a longer follow-up period are lacking. OBJECTIVE: (1) To measure the efficacy at 1 year of three different treatment approaches to MOH; (2) to compare withdrawal and early preventives (W+P), preventives with potential withdrawal therapy after 6 months (P+pW), and withdrawal with delayed potential preventives (W+pP); and (3) to identify predictors of chronic headache after 1 year. METHODS: Patients with MOH and migraine and/or tension-type headache were randomly assigned to one of the three outpatient treatments. Headache calendar and questionnaires were filled out. Primary outcome was a reduction in headache days/month after 1 year. RESULTS: Of 120 patients, 96 completed 1-year follow-up, and all were included in our analyses. Overall headache days/month were reduced from 24.6 (23.4-25.8) to 15.0 (13.0-17.0) (p < 0.0001), and only 11/96 patients (11%) relapsed. Reduction in monthly headache days was 10.3 days (95% CI: 6.7-13.9) in the W+P group, 10.8 days (95% CI: 7.6-14) in the P+pW group, and 7.9 days (95% CI: 5.1-10.7) in the W+pP group. No significant differences in treatment effect were seen between the three groups (p = 0.377). After 1 year, 39/96 (41%) had chronic headache. Predictors of chronic headache after 1 year were higher headache frequency (aOR 1.19; 1.09-1.31), more days with acute medication (aOR 1.11; 1.03-1.19), higher pain intensity (aOR 1.04; 1.01-1.08), and depression (aOR 4.7; 1.38-18.95), whereas higher self-rated health (aOR 0.61; 0.36-0.97) and high caffeine consumption (aOR 0.40; 0.16-0.96) were predictors of a lower risk of chronic headache. No adverse events were reported. CONCLUSIONS: All treatment strategies proved effective in treating MOH with a low relapse rate. The W+P strategy leads to the fastest effect, confirming earlier treatment recommendations. Identification of predictors for chronic headache may help identify more complex patients.

Medication Overuse Headache.

BACKGROUND: Medication overuse headache (MOH) is one of the highly disabling headache disorder and affects about 1% of the population of the world. It is associated with the development of headache for 15 days or more, with consumption of acute symptomatic medications for 10-15 days (depending on the class of drug, like, simple analgesics, triptans, and opioids) in a month, used for relief of headache for three or more months, in a known patient of primary headache disorder. OBJECTIVE: The aim of this study was to review the topic of MOH and present the details of this disorder with an emphasis on recent updates in the field of pathophysiology and treatment. MATERIAL AND METHODS: Literature search was performed in the PubMed/MEDLINE and Cochrane database with appropriate keywords and relevant full-text articles were reviewed for writing this article. RESULTS: Over the years, the concept of MOH has evolved, although the exact pathophysiology is still being explored. In a susceptible individual interplay of genetics, change in pain pathways, changes in areas of the brain associated with the perception of pain, and changes in the neurotransmitters have been implicated. It has to be differentiated from other secondary chronic daily headache disorders, by a careful history, targeted examination, details of intake of medications. Treatment predominantly involves patient education, removal of the offending agent, and initiation of prophylactic medications for primary headache disorder in the outpatient or inpatient services. CONCLUSIONS: MOH is a secondary headache disorder, which should be considered in any chronic headache patient. There are various pathophysiological mechanisms attributed to its development. Management includes educating the patients about the disorder, detoxification, and prophylactic therapy.

Breaking the cycle of medication overuse headache.

Care of this disorder can be complex-from ruling out another secondary cause of headache to supervising detox from abortives, providing preventives, and educating often-fearful patients.

Anodal transcranial direct current stimulation in chronic migraine and medication overuse headache: A pilot double-blind randomized sham-controlled trial.

OBJECTIVES: Little evidence is available on the role of transcranial direct current stimulation (tDCS) in patients affected by chronic migraine (CM) and medication overuse headache (MOH). We aim to investigate the effects of tDCS in patients with CM and MOH as well as its role on brain activity. METHODS: Twenty patients with CM and MOH were hospitalized for a 7-day detoxification treatment. Upon admission, patients were randomly assigned to anodal tDCS or sham stimulation delivered over the primary motor cortex contralateral to the prevalent migraine pain side every day for 5 days. Clinical data were recorded at baseline (T0), after 1 month (T2) and 6 months (T3). EEG recording was performed at T0, at the end of the tDCS/Sham treatment, and at T2. RESULTS: At T2 and T3, we found a significant reduction in monthly migraine days (p = 0.001), which were more pronounced in the tDCS group when compared to the sham group (p = 0.016). At T2, we found a significant increase of alpha rhythm in occipital leads, which was significantly higher in tDCS group when compared to sham group. CONCLUSIONS: tDCS showed adjuvant effects to detoxification in the management of patients with CM and MOH. The EEG recording showed a significant potentiation of alpha rhythm, which may represent a correlate of the underlying changes in cortico-thalamic connections. SIGNIFICANCE: This study suggests a possible role for tDCS in the treatment of CM and MOH. The observed clinical improvement is coupled with a potentiation of EEG alpha rhythm.

The impact of an online adult headache guideline on headache referrals to the neurology clinic.

BACKGROUND: Headache is a common problem in primary care and one of the main reasons general practitioners (GP) consult the neurology service. We developed an online adult headache guideline (Supporting Information Appendix S1) for the greater Wellington Region as a resource for GP to guide identification of concerning headaches, initiation of prophylactic medications for migraine and management of analgesic overuse headache. AIMS: To examine the effectiveness of this adult headache guideline in reducing demand on the neurology outpatient service for headache patients that could readily be managed in primary care. METHODS: We reviewed electronic referrals to Wellington Hospital's neurology department before and after the implementation of the online headache guideline. The primary outcome was the proportion of referrals for headache. Secondary outcomes included proportion of referrals requiring clinic review, rate of pre-referral trial of headache prophylactic medication and medication overuse headache diagnosed at neurological consultation. RESULTS: Nine hundred neurology referrals before and 801 referrals after the publication of the online headache guideline were included. There was a statistically significant reduction in proportion of referrals for headache (15.4% vs 11.7%; P = 0.026). There was neither an increased rate of pre-referral adequate prophylactic medication trial (33.8% vs 27.7%; P = 0.320) nor fewer medication overuse headaches diagnosed during the neurology assessment (21.9% vs 25.0%; P = 0.674). CONCLUSION: The launch of an online headache guideline was associated with a reduction in demand on neurology service. Further education could improve the utilisation of this guideline, to avoid delays in prophylactic treatment and reduce the harm of medication overuse.