Medication-Overuse Headache: Results from a Pain Medicine Clinic Cohort

Background and Objective: Medication-overuse headache (MOH) is a common, disabling, and treatable cause of chronic daily headache. This study evaluates the characteristics of a cohort of patients with MOH seen in a pain medicine clinic. Methods: We conducted a retrospective study of consecutive patients seen by a neurologist in the pain medicine clinic at the University of California, San Diego. Demographics, headache diagnoses, and overused medications were extracted from clinical records from 83 patients ≥ 18 years of age where a diagnosis of MOH was entered into the electronic medical record September 12, 2017-March 30, 2020. Results: Opioids were the most overused medications (42/83, 50.6%) followed by caffeine-containing compounds (20/83, 24.1%), triptans (12/83, 14.5%) and non-steroidal anti-inflammatory drugs (10/83, 12.9%). Chronic migraine was the most common underlying headache syndrome (54/83, 65.1%), followed by secondary headache disorder (13/83, 15.7%) and tension-type headache (8/83, 9.6%). Men were more likely to be overusing opioids (OR 3.3, p = 0.026) while women were more likely to be overusing caffeine-containing compounds (OR 5.4, p = 0.041). Discussion and Conclusions: It is crucial for pain specialists to recognize MOH in the pain clinic setting. Opioid overuse headache is more common among men, likely in part due to migraine being underrecognized in men and therefore men not receiving migraine-specific medications. Caffeine-containing compound overuse is more common among women; these are over-the-counter (OTC) and often do not appear on patients’ medications lists. Pain specialists should specifically ask patients with headache whether they are using OTC caffeine-containing compounds.

The Primary Care Management of Headache: Synopsis of the 2020 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline

ABSTRACT Introduction In June of 2020, the U.S. DVA and DoD approved a new joint clinical practice guideline for assessing and managing patients with headache. This guideline provides a framework to evaluate, treat, and longitudinally manage the individual needs and preferences of patients with headache. Methods In October of 2018, the DVA/DoD Evidence-Based Practice Work Group convened a guideline development panel that included clinical stakeholders and conformed to the National Academy of Medicine’s tenets for trustworthy clinical practice guidelines. Results The guideline panel developed key questions, systematically searched and evaluated the literature, created a 1-page algorithm, and advanced 42 recommendations using the Grading of Recommendations Assessment, Development, and Evaluation system. Conclusion This synopsis summarizes the key features of the guideline in three areas: prevention, assessing and treating medication overuse headache, and nonpharmacologic and pharmacologic management of headache.

Efficacy and safety of anti-CGRP(r) monoclonal antibodies in real clinical practice: preliminary analysis after three months of therapy

Monoclonal antibodies inhibiting calcitonin gene related peptide (CGRP) or its receptor have been widely used for migraine prophylactic therapy for the past three years. Evaluation of their efficacy and safety of therapy in real clinical practice is needed.Objective: to evaluate the efficacy and safety of Erenumab, a monoclonal antibody inhibiting the CGRP receptor during three months of therapy.Patients and methods. Sixty-eight patients (58 women and 10 men, mean age 37±10.4 years) with episodic or chronic migraine who were treated with Erenumab were observed. Patients were assessed with MIDAS, WPAI, and HADS scales; the presence of cutaneous allodynia was evaluated with ASC-12 questionnaire. Patients kept a headache diary and marked adverse events during the whole treatment period.Results and discussion. 47 patients (69%) had chronic migraine and 32 (71.9%) had medication overuse headache. In 48 patients (70%) after 3 injections of Erenumab the number of days with migraine decreased by 50% or more. In 7 patients (10%), the reduction in headache days was more than 75%; 20 (29%) did not experience sufficient effect after three months of therapy. Nineteen adverse events were noted in 15 (22%) patients. Severe constipation led to discontinuation of treatment in two patients (3%).Conclusion. The study showed the efficacy and safety of Erenumab for migraine prophylaxis in both patients with episodic and chronic migraine.

Medication Overuse Headache in a Patient with Myasthenia Gravis: a Case Report on Successful Intervention by an Acupuncturist

In this case of medication overuse headache in a patient with myasthenia gravis, an acupuncturist identified the use of an over-the-counter analgesic that was not revealed to the attending physician. This case highlights the potential role of an acupuncturist as part of the medical care team involved in headache management.

Comprehensive approach for the treatment of medication-overuse headache

Background: Medication-overuse headache (MOH) is defined by the International Classification of Headache Disorders as a headache in patients with a pre-existing primary headache disorder that occurs on 15 or more days per month for more than 3 months. It is caused by overuse of medication for acute or symptomatic headache treatment. Regular and frequent use of acute or symptomatic medications can worsen headaches and lead to chronic headache or MOH. MOH is a burdensome medical condition that is difficult to treat, and the frequent recurrence of headaches may result in disability in individuals and impair socioeconomic outcomes.Current Concepts: Awareness of MOH and the education of patients, the general population, and healthcare providers are important for the first step of treatment. Scientific research regarding the treatment of MOH has been published in the past few years.Discussion and Conclusion: Physicians should educate and counsel patients to stop or at least reduce the intake of acute or symptomatic medications that can be discontinued abruptly or tapered slowly. During the period after the discontinuation of the overused medications, some withdrawal symptoms including headache might be manageable with bridging therapy. Evidence-based preventive therapies including anticonvulsants (topiramate and divalproex sodium), botulinum toxin A, and medications acting by antagonism of the calcitonin generelated peptide pathway might be helpful in patients with MOH for both avoiding the overused medication and preventing the relapse of overuse. A comprehensive and multidisciplinary approach may improve the outcomes of patients with MOH.

PACAP-PAC1 Receptor Inhibition is Effective in Models of Opioid-Induced Medication Overuse Headache

Opioids are regularly prescribed for migraine and can result in medication overuse headache and dependence. We recently showed that pituitary adenylate cyclase activating polypeptide (PACAP) is upregulated following opioid administration or in a model of chronic migraine. The goal of this study was to determine if PACAP was a link between opioid use and headache chronification. We tested the effect of PACAP-PAC1 receptor inhibition in novel models of opioid-exacerbated migraine pain and aura; and examined the co-expression between mu opioid receptor (MOR), PAC1, and PACAP in headache-associated brain and peripheral regions.To model opioid exacerbated migraine pain, mice were injected daily with morphine (10 mg/kg) or vehicle for 11 days. On days 3,5,7,9, and 11 they also received the known human migraine trigger nitroglycerin (0.1 mg/kg) or vehicle. To model opioid exacerbated aura, mice were treated with vehicle or morphine twice daily for 4 days (20 mg/kg on days 1-3, 40 mg/kg on day 4), a well-established paradigm for causing opioid-induced hyperalgesia. On day 5 they underwent cortical spreading depression, a physiological correlate of migraine aura. The effect of the PAC1 inhibitor, M65 (0.1 mg/kg), was tested in these models. Fluorescent in situ hybridization was used to investigate the expression of MOR, PAC1, and PACAP.Only mice treated with combined morphine and nitroglycerin developed chronic cephalic allodynia (n=18/group). M65 reversed this hypersensitivity (n=9/group). Morphine significantly increased the number of CSD events (n=8-9/group); and M65 decreased this exacerbation by morphine (n=8-12/group). PAC1 and/or PACAP were highly co-expressed with MOR, and varied by region (n=6/group). MOR and PACAP were co-expressed in the trigeminal ganglia, while MOR and PAC1 receptor showed near complete overlap in the trigeminal nucleus caudalis and periaqueductal gray. The cortex showed similar cellular co-expression between MOR-PACAP and MOR-PAC1.These results show that opioids facilitate the transition to chronic headache through induction of PACAPergic mechanisms. Antibodies or pharmacological agents targeting PACAP or PAC1 receptor may be particularly beneficial for the treatment of opioid-induced medication overuse headache.

Initial experience with novel CGRP-receptor inhibitor therapy in Migraine in the United Arab Emirates: a retrospective observational study

Background Erenumab is a calcitonin gene-related peptide (CGRP)-receptor antibody inhibiting CGRP function. CGRP is prominently involved in the pathophysiology of migraine through nociceptive modulation in the trigeminovascular system. This study aims to explore the treatment effect of erenumab in a real-life setting. Methods In this retrospective observational study, we analyzed the data of 91 patients with migraine receiving at least three consecutive monthly injections of erenumab and followed up for 3–12 months. The primary objective was to describe the reduction in monthly migraine days throughout the follow-up period. To identify patients who responded to treatment, we analyzed the association between different patient characteristics and their treatment outcomes. Results Seventy-three patients (80.2%) responded to erenumab treatment, defined as ≥50% reduction of migraine days per month, across all migraine types. It was noted that ethnicity (p-value = 0.015) and older age (p-value = 0.035) were associated with clinically relevant improvement of symptoms. Middle Eastern ethnicity was related to less improvement of symptoms while Europeans were more likely to benefit from erenumab therapy (odds ratio: 12.788, p = 0.037). Patients aged from 31 to 40 and 41–65 years benefited most from erenumab treatment with a response rate of 77.8 and 89.9%, respectively, also confirmed by logistic regression (p = 0.047). Neither gender nor dose increase of erenumab showed association with the reported clinically relevant improvement of the symptoms. An association between clinically relevant improvement of headaches and the type of migraine was also noted. Around 87.9% of patients with episodic migraine responded to treatment, followed by 84.1% of chronic migraine patients and 50% of medication overuse headache patients. Medication overuse headache showed a lower probability of therapy success with erenumab (odds ratio: 0.126, p = 0.039). An improvement of headaches was eminent in patients who received 140 mg erenumab monthly (2 × 70 mg injections) and patients who had one injection every two weeks. Conclusions Erenumab is a novel preventive treatment for all migraine types. Clinically relevant improvement of headaches and reduction of monthly migraine days were demonstrated in patients that continued the treatment course. In real-life, a substantial number of patients suspended therapy early, reasons for which need further investigation.

The relationship between headache-attributed disability and lost productivity: 2. Empirical evidence from population-based studies in nine disparate countries

Background Headache disorders are disabling, with major consequences for productivity, yet the literature is silent on the relationship between headache-attributed disability and lost productivity, often erroneously regarding the two as synonymous. We evaluated the relationship empirically, having earlier found that investment in structured headache services would be cost saving, not merely cost-effective, if reductions in headache-attributed disability led to > 20% pro rata recovery of lost productivity. Methods We used individual participant data from Global Campaign population-based studies conducted in China, Ethiopia, India, Nepal, Pakistan and Russia, and from Eurolight in Lithuania, Luxembourg and Spain. We assessed relationships in migraine and probable medication-overuse headache (pMOH), the most disabling common headache disorders. Available symptom data included headache frequency, usual duration and usual intensity. We used frequency and duration to estimate proportion of time in ictal state (pTIS). Disability, in the sense used by the Global Burden of Disease study, was measured as the product of pTIS and disability weight for the ictal state. Impairment was measured as pTIS * intensity. Lost productivity was measured as lost days (absence or < 50% productivity) from paid work and corresponding losses from household work over the preceding 3 months. We used Spearman correlation and linear regression analyses. Results For migraine, in a linear model, we found positive associations with lost paid worktime, significant (p < 0.05) in many countries and highly significant (p < 0.001) in some despite low values of R2 (0–0.16) due to high variance. With lost household worktime and total lost productivity (paid + household), associations were highly significant in almost all countries, although still with low R2 (0.04–0.22). Applying the regression equations for each country to the population mean migraine-attributed disability, we found pro rata recoveries of lost productivity in the range 16–56% (> 20% in all countries but Pakistan). Analysing impairment rather than disability increased variability. For pMOH, with smaller numbers, associations were generally weaker, occasionally negative and mostly not significant. Conclusion Relief of disability through effective treatment of migraine is expected, in most countries, to recover > 20% pro rata of lost productivity, above the threshold for investment in structured headache services to be cost saving.