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.

Migraine

Migraine is the most common disabling brain disorder. Chronic migraine, a condition characterized by the experience of migrainous headache on at least 15 days per month, is highly disabling. Patients with chronic migraine present to primary care, are often referred for management to secondary care, and make up a large proportion of patients in specialist headache clinics. Many patients with chronic migraine also have medication overuse, defined as using a compound analgesic, opioid, triptan or ergot derivative on at least 10 days per month. All doctors will encounter patients with chronic headaches. A basic working knowledge of the common primary headaches, and a rational manner of approaching the patient with these conditions, allows a specific diagnosis of chronic migraine to be made quickly and safely, and by making this diagnosis one opens up a substantial number of acute and preventive treatment options. This article discusses the current state of management of 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.

Discontinuing monoclonal antibodies targeting CGRP pathway after one-year treatment: an observational longitudinal cohort study

Background Monoclonal antibodies anti-calcitonin gene-related peptide (mAbs anti-CGRP) pathway are effective and safe on migraine prevention. However, some drug agencies limited these treatments to one year due to their high costs. This study aimed at evaluating the effect of discontinuing mAbs anti-CGRP on monthly migraine days (MMDs) and disability in high-frequency episodic (HFEM) and chronic migraine (CM) patients. Methods This observational longitudinal cohort study was conducted at 10 Italian headache centres. Consecutive adult patients were followed-up for three months (F-UP1–3) after discontinuation of a one-year erenumab/galcanezumab treatment. The primary endpoint was the change in F-UP MMDs. Secondary endpoints included variation in pain intensity (Numerical Rating Scale, NRS), monthly acute medication intake (MAMI), and HIT-6 scores. We also assessed from F-UP1 to 3 the ≥50% response rate, relapse rate to CM, and recurrence of Medication Overuse (MO). Results We enrolled 154 patients (72.1% female, 48.2 ± 11.1 years, 107 CM, 47 HFEM); 91 were treated with erenumab, 63 with galcanezumab. From F-UP1 to F-UP3, MMDs, MAMI, NRS, and HIT-6 progressively increased but were still lower at F-UP3 than baseline (Friedman’s analysis of rank, p < .001). In the F-UP1–3 visits, ≥50% response rate frequency did not differ significantly between CM and HFEM patients. However, the median reduction in response rate at F-UP3 was higher in HFEM (− 47.7% [25th, − 79.5; 75th,-17.0]) than in CM patients (− 25.5% [25th, − 47.1; 75th, − 3.3]; Mann-Whitney U test; p = .032). Of the 84 baseline CM patients who had reverted to episodic migraine, 28 (33.3%) relapsed to CM at F-UP1, 35 (41.7%) at F-UP2, 39 (46.4%) at F-UP3. Of the 64 baseline patients suffering of medication overuse headache ceasing MO, 15 (18.3%) relapsed to MO at F-UP1, 26 (31.6%) at F-UP2, and 30 (42.3%, 11 missing data) at F-UP3. Lower MMDs, MAMI, NRS, and HIT-6 and higher response rate in the last month of therapy characterized patients with ≥50% response rate at F-UP1 and F-UP3 (Mann-Whitney U test; consistently p < .01). Conclusion Migraine frequency and disability gradually increased after mAbs anti-CGRP interruption. Most patients did not relapse to MO or CM despite the increase in MMDs. Our data suggest to reconsider mAbs anti-CGRP discontinuation.