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.

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.

Common diagnoses and factors associated with abnormal neuroimaging in headache patients in the emergency department.

OBJECTIVES: To determine causes of headaches in patients who presented to the emergency department (ED) and underwent neuroimaging, and to determine the clinical features associated with abnormal neuroimaging. METHODS: Patients were retrospectively selected from a database between June, 2015 and May, 2019. Patients were included if they had neuroimaging requested from the ED mainly for headache. Associations between clinical characteristics and abnormal neuroimaging were assessed. RESULTS: We included 329 patients (33.4% men, 66.6% women). The mean (SD) age was 39.7 (18.4) years. Neurological signs were reported in 43.8% of the patients, head-computed tomography was requested in 79.6%, magnetic resonance imaging in 77.5%, and both in 57.1%. Abnormal neuroimaging was reported in 31.9%. The most common reported diagnoses were secondary headache disorders (48.9%), followed by primary headache disorders (16.4%). The remainder were nonspecific-headaches (35%). Variables associated with abnormal neuroimaging were headache onset ≤1 month (OR 3.37, CI 1.47-7.70, p=0.004), and presence of an abnormal neurological sign (OR 3.60, CI 1.89-6.83, p<0.001). CONCLUSION: Secondary headache disorders are common in patients who undergo neuroimaging in the ED. Those who have a neurological sign and recent onset of headache are more likely to have abnormal neuroimaging.

The American Registry for Migraine Research: Research Methods and Baseline Data for an Initial Patient Cohort.

BACKGROUND: The American Registry for Migraine Research (ARMR) is a multicenter, prospective, longitudinal patient registry, biorepository, and neuroimaging repository that collects clinical data, electronic health record (EHR) data, blood samples, and brain imaging data from individuals with migraine or other headache types. In this manuscript, we outline ARMR research methods and report baseline data describing an initial cohort of ARMR participants. METHODS: Adults with any International Classification of Headache Disorders (ICHD) diagnosis were prospectively enrolled from one of the 8 participating headache specialty centers. At baseline, ARMR participants complete web-based questionnaires, clinicians enter the participant's ICHD diagnoses, an optional blood specimen is collected, and neuroimaging data are uploaded to the ARMR neuroimaging repository. Participants maintain the ARMR daily headache diary longitudinally and follow-up questionnaires are completed by participants every 3 months. EHR data are integrated into the ARMR database from a subset of ARMR sites. Herein, we describe the ARMR methodology and report the summary data from ARMR participants who had, from February 2016 to May 2019, completed at least 1 baseline questionnaire from which data are reported in this manuscript. Descriptive statistics are used to provide an overview of patient's sociodemographics, headache diagnoses, headache characteristics, most bothersome symptoms other than headache, headache-related disability, comorbidities, and treatments. RESULTS: Data were available from 996 ARMR participants, enrolled from Mayo Clinic Arizona, Dartmouth-Hitchcock Medical Center, University of Utah, University of Colorado, Thomas Jefferson University, University of Texas Health Science Center at Houston, Georgetown University Medical Center, and DENT Neurological Institute. Among ARMR participants, 86.7% (n = 864) were female and the mean age at the time of enrollment was 48.6 years (±13.9; range 18-84). The most common provider-reported diagnosis was chronic migraine (n = 622), followed by migraine without aura (n = 327), migraine with aura (n = 196), and medication overuse headache (n = 65). Average headache frequency was 19.1 ± 9.2 days per month (n = 751), with 68% reporting at least 15 headache days per month. Sensitivity to light was the most frequent (n = 222) most bothersome symptom overall, other than headache, but when present, cognitive dysfunction was most frequently (n = 157) the most bothersome symptom other than headache. Average migraine disability assessment (MIDAS) score was 52 ± 49 (n = 760), (very severe headache-related disability); however, 17% of the ARMR population had MIDAS scores suggesting "no" or "mild" disability. The most common non-headache health issues were allergies (n = 364), back pain (n = 296), neck pain (n = 296), depression (n = 292), and anxiety (n = 278). Nearly 85% (n = 695) of patients were using preventive medications and 24.7% were using non-medication preventive therapy (eg, vitamins and neuromodulation). The most common preventive medication classes were neurotoxins, anticonvulsants, antidepressants, vitamins/supplements, and anticalcitonin gene-related peptide ligand or receptor-targeted monoclonal antibodies. Nearly 90% (n = 734) of ARMR participants was taking medications to treat migraine attacks, with the most common classes being triptans, non-steroidal anti-inflammatory drugs, antiemetics, acetaminophen, and combination analgesics. CONCLUSIONS: ARMR is a source of real-world patient data, biospecimens, and brain neuroimaging data that provides comprehensive insight into patients with migraine and other headache types being seen in headache specialty clinics in the United States. ARMR data will allow for longitudinal and advanced analytics that are expected to lead to a better characterization of patient heterogeneity, healthcare resource utilization, identification of endophenotypes, factors that predict treatment outcomes and clinical course, and ultimately advance the field toward precision headache medicine.

Clinical Subtypes of Medication Overuse Headache - Findings From a Large Cohort.

BACKGROUND: The International Classification of Headache Disorders lists different subtypes of medication overuse headache (MOH), according to the medication overused. The aim of this study is to evaluate whether the different subtypes correspond to clinically distinguishable phenotypes in a large population. METHOD: This descriptive cross-sectional observational study included 660 patients with MOH referred to headache centers in Europe and Latin America as a part of the COMOESTAS project. Information about clinical features was collected with structured patient interviews and with self-administered questionnaires for measuring disability, anxiety, and depression. RESULTS: Female/male ratio, body mass index, marital status, and level of education were similar among in subjects enrolled in the 5 centers. The mean age was higher among subjects overusing triptans (T-MOH) with respect to subjects overusing simple analgesic (A-MOH). Duration of headache before chronification was longer in T-MOH (19.2 ± 11.9 years) and in subjects overusing ergotamines (E-MOH, 17.8 ± 11.7 years) with respect to the A-MOH group (13.1 ± 10.9; P < .001 and P = .017, respectively) and in T-MOH with respect multiple drug classes (M-MOH, 14.9 ± 11.7; P = .030). Migraine Disability Assessment (MIDAS) score was significantly lower in E-MOH group (33.6 ± 41.6), while T-MOH group (56.8 ± 40.6) had a significant lower MIDAS score with respect to M-MOH (67.2 ± 62.5; P = .016 and P = .037, respectively). Prevalence of depression and anxiety was lower in patients overusing T with respect to other groups of patients (χ2  = 10.953, P = .027 and χ2  = 25.725, P < .001, respectively). CONCLUSION: In this study on a large and very well characterized population of MOH, we describe the distinctive clinical characteristics of MOH subtypes. These findings contribute to more clearly define the clinical picture of a poorly delineated headache disorder. They also provide some insights in the possible trajectories leading to this highly disabling chronic headache, that is classified as a secondary form, but whose occurrence is entirely dependent on an underlying primary headache.

Incontinence and headache in preschool children.

AIMS: Headaches in preschool children are associated with behavioral and gastrointestinal symptoms. As the co-occurrence with incontinence is not known in young children, the aim of the study was to examine associations of headache, psychological symptoms and nocturnal enuresis (NE), daytime urinary incontinence (DUI), and fecal incontinence (FI) in a population-based sample of preschool children. METHODS: All preschool children of a defined geographical area were examined at school-entry. Parents completed a 22-item questionnaire, including 14 headache, 4 incontinence, and 25 items of the Strength and Difficulties Questionnaire (SDQ). Five hundred eighty-five children (50.4% males) with a mean age of 5.8 years were included. RESULTS: In total, 27.2% of all children had headaches. 15.7% had secondary and 11.3% primary headaches. Five children had migraine and five tension-type headaches, while all others were unclassifiable. 9.4% of children had incontinence (7.7% NE; 2.4% DUI, 1.2% FI) and 4.0% constipation. The rates of incontinence did not differ between children with primary and those without headache for NE (12.9% vs 7.5%), DUI (3.1% vs 2.7%) or FI (3.0% vs 1.0%), but for constipation (12.1% vs 2.6%). Incontinent children had significantly more behavioral and externalizing symptoms, children with headache more internalizing problems. Primary headache was a significant predictor for internalizing, while constipation and FI were predictors for externalizing symptoms. CONCLUSIONS: This population-based study showed that headache is associated with constipation, but not with incontinence in preschool children. Headache and incontinence are common risk factors for specific psychological symptoms and should be assessed in clinical practice.

Comparison of chronic daily headache with and without medication overuse headache using ICHD II R and ICHD 3 beta criteria.

OBJECTIVE: To evaluate the frequency of Medication Overuse Headache (MOH) in the patients with Chronic Daily Headache (CDH) using International Classification of Headache Disorder II Revision (ICHD II R) and International Classification of Headache Disorder 3 Beta (ICHD-3 beta) criteria. We also compare the CHD patients with and without MOH using both the criteria. PATIENTS AND METHODS: Consecutive CDH patients from neurology service between 2014 and 2015 were included. The patients with CDH was categorised to MOH was based on ICHDIIR and ICHD-3 beta criteria. Their demographic and headache characteristics including frequency, duration, severity and disability were noted. Severity of headache was assessed using Visual Analogue Scale (VAS). Predictors of MOH were evaluated by multivariate analysis. Demographic and headache characteristics of CDH patients without MOH were compared with those with MOH. RESULTS: 202 patients were included whose median age was 32 (range 18-65) years, and 151(74.8%) were females. 12.3% patients fulfilled ICHDIIR criteria for MOH and 46.5% fulfilled ICHD-3 beta criteria. The predictors of MOH were female gender (OR = 3.72; 95% CI 1.72-8.02, p = 0.001), low education level (OR = 1.07, 95%CI 1.02-1.13; p = 0.007) and higher VAS score (OR = 0.67, 95%CI 0.51-0.88; p = 0.004). MOH patients as per ICHD-3 beta criteria had higher education (p = 0.02) and consumed lesser abortive drugs (p = 0.03) as compared with ICHDIIR criteria. CONCLUSION: The frequency of MOH increases by four-fold when using ICHD-3 beta criteria instead of ICHDIIR criteria. Females with lower education level predispose to MOH.

Cognitive Decline in Chronic Migraine with Nonsteroid Anti-inflammation Drug Overuse: A Cross-Sectional Study.

Background: Chronic migraine with medication overuse headache (CM-MOH) is the most common type of chronic migraine, and it increases risk of stroke and white matter lesions. These pathologic changes could induce cognitive decline. However, the alteration of cognitive function in CM-MOH patients is not established. Therefore, we took this study to reveal the cognitive performances in CM-MOH. Methods: This cross-sectional study was conducted between December 2015 and January 2017. Patients were divided into CM-MOH, CMwoMOH (chronic migraine without medication overuse), and MO (migraine without aura) groups. Cognitive function was assessed in all cases during interictal periods using Addenbrooke's Cognitive Examination Test (ACE-R), Trail Making Test A/B (TMT A/B), and Digit Symbol Test (DST). Detailed headache characteristics and evaluation of anxiety, depression, and living and sleep quality were collected. Results: 116 patients were included in this study. There were 21 CM-MOHs, 20 CMwoMOHs, 35 MOs, and 40 controls. Age and education were the independent risk factors of cognitive decline (P < 0.05). After adjusting, the risk of cognitive decline was higher in CM compared with control in ACE-R score and language fluency (P < 0.05). In addition, CM-MOH sufferers were in higher risk of memory and executive dysfunction (P < 0.05). The cognitive function had no difference between CM-MOH and CMwoMOH (P > 0.05). Meanwhile, CM-MOH got significantly higher scores than MO in anxiety and depression, with poorer performances in sleep and life quality (P < 0.05). Conclusion: The risk of cognitive decline increased in chronic migraine patients. Nonsteroid anti-inflammatory drugs overuse had no influence on cognitive performances among chronic migraine sufferers.

Sleep disorder-related headaches.

Migraine with and without aura, cluster headache, hypnic headache, and paroxysmal hemicranias are each reported as intrinsically related to sleep. Chronic migraine, chronic tension-type headache, and medication overuse headache may cause sleep disturbance. Otherwise, both headache and sleep disorder may be manifestations of a same systemic dysfunction. There is a vicious cycle linking sleep disorders and migraine. The poor quality or poor duration of sleep could be a trigger of migraine attack and migraineurs with poor sleep reported a higher headache frequency. Moreover, coping behaviors of migraineurs (e.g., going to sleep early to relieve migraine attacks) can be factors precipitating and perpetuating sleep disturbances themselves. During cluster headache, patients report a poor quality of sleep correlated with the amount of daylight. In particular, it was demonstrated that melatonin levels have influences on cluster headache attacks. Concerning the pathophysiology of hypnic headache, it has been hypothesized a possible role of obstructive sleep apnea in triggering nocturnal attacks: an increased number of apnea episodes has been reported in hypnic headache patients, but a lack of a temporal correlation of headache attacks with the drop of oxygen saturation has been observed. Tension-type headache is the most common headache with sleep dysregulation (lack of sleep or oversleeping) frequently reported as a triggering factor for acute attacks: management of sleep disturbances seems crucial in this form of headache.

Dramatic placebo effect of high frequency repetitive TMS in treatment of chronic migraine and medication overuse headache.

Chronic migraine (CM) is often associated with medication overuse headache (MOH). Few small trials have been conducted on Transcranial Magnetic Stimulation for CM treatment, but results are conflicting. Aim of the study was to investigate the effects of high frequency of repetitive Transcranial Magnetic Stimulation (hf-rTMS) in the dorsolateral prefrontal cortex combined with strongly suggesting to avoid medications overuse in patients suffering with CM and MOH. A six-month single-centre perspective randomized double-blinded study was conducted at the Headache Centre of Trieste. Patients suffering with CM and MOH were randomly enrolled in two groups to receive active hf-rTMS in DLPFC or sham hf-rTMS. Headache days (HD), headache hours (HH) and symptomatic drug intake (SDI) were recorded for 30 days before the beginning of stimulation (T0) and during the three following months (T3). Disability (MIDAS score) was evaluated at T0 and at the three-month follow-up visit. The primary outcome was the evaluation of reduction of HD. Reduction of SDI, HH and disability were considered as secondary outcomes. Out of 26 patients enrolled, 14 completed the study, 7 underwent hf-rTMS and 7 sham-TMS. There were no significant differences between groups at T0 in demographic data and headache measures. Mean number of HD, HH, SDI, and MIDAS similarly reduced in the two groups. Our study failed in demonstrating that hf-rTMS with detoxification advice could be better than detoxification advice alone in CM treatment. hf-rTMS carries a high potential of inducing placebo effect and this can be usefully leveraged to enhance patients' coping strategies.

Headache characteristics in multiple sclerosis.

OBJECTIVES: The aims of this study were to study the prevalence and characteristics of headache in patients with multiple sclerosis and to clarify the relationship between headache and multiple sclerosis therapies. METHOD: 782 MS patients were consecutively admitted. All patients filled out a detailed headache questionnaire and 754 patients were included. RESULTS: Of 754 patients, 515 (68%) reported having headache. According to the International Headache Society criteria, we detected 202 (39%) suffering from migraine, 103 (20%) suffering from tension-type headache and 198 (38%) with medication overuse headache. Twelve patients (2%) had unclassified headache. Three hundred and seventy seven patients (73%) were treated with interferon beta, 81 (16%) with fingolimod, 35 (7%) with teriflunamide and 22 (4%) with natalizumab, respectively. One hundred and one (20%) reported that onset of headache occured prior to onset of multiple sclerosis therapies, while 414 (80%) had headaches occured after therapy. A higher incidence of headache was found in patients treated with interferon beta. We found a significant association between migraine and the age of onset of multiple sclerosis therapies. The age of onset of headache was the earliest in the patients with migraine. In migraine patients, the duration of medication use until the headache onset was the shortest when compared to other headache groups. Four hundred and fifty nine patients (89%) have sought help from a physician because of the severity and frequency of headache. CONCLUSION: In our study, the prevalence of headache among all multiple sclerosis patients was 68%. The results of this study indicate a possible relationship may exist between headache and multiple sclerosis therapies since 80% of patients described headaches after the onset of treatments. The younger start and the shorter duration of interferon beta use caused the higher incidence of headache, but this correlation was not observed in other drugs. Interestingly, medication overuse headache was far more prevalent in multiple sclerosis patients than in previously reported community populations.

Prospective real-world analysis of OnabotulinumtoxinA in chronic migraine post-National Institute for Health and Care Excellence UK technology appraisal.

BACKGROUND AND PURPOSE: The National Institute for Health and Care Excellence (NICE) in the UK recommends the use of OnabotulinumtoxinA (BoNTA, Botox® ) in the management of chronic migraine (CM) following specific guidelines within the National Health Service. In view of the lack of data on the efficacy of this therapy following implementation of these guidelines in clinical practice and on the evaluation of guidance compliance, we aimed to evaluate the effectiveness and safety of BoNTA in patients with CM following the NICE guidelines. METHODS: This was a prospective real-life audit study. RESULTS: After two treatments, 127 of 200 patients (63.5%) obtained at least a 30% reduction in headache days. Those who continued the treatment up to 3 years reported a stable beneficial effect compared with baseline. Amongst responders, 68 patients (53.5%) were reclassified as episodic migraineurs. A total of 57 of these patients (83.8%) converted to an episodic migraine pattern at 6-month follow-up. The majority of those whose migraine became episodic after BoNTA extended the treatment intervals beyond 3 months (range 4-8 months) before noticing any worsening of headache. We observed no significant differences in the efficacy measures in patients treated with 155 U BoNTA compared with those treated with >155 U BoNTA. CONCLUSIONS: When administered according to the NICE guidance, BoNTA produced a clinically meaningful effect in the long-term management of CM with and without medication overuse headache. Treatment discontinuation when CM becomes episodic may be useful in clinical practice to identify those who may benefit from extended treatment intervals. Our clinical experience indicates a lack of additional benefit from using the 'follow-the-pain' paradigm.

Early management of patients with medication-overuse headache: results from a multicentre clinical study.

BACKGROUND AND PURPOSE: Educational intervention has proved to be effective in reducing drug abuse in uncomplicated medication-overuse headache (MOH). This ancillary of the SAMOHA multicentre study aimed to assess any differences in phenotypic characteristics, type and amount of drugs overused, and comorbidities between patients with MOH who responded to simple advice and those who did not. METHODS: Demographic and clinical headache data of the last 3 months before enrollment of patients were collected and patients were then asked to fill out a daily headache diary for 4 weeks. Patients were then divided into two subgroups, i.e. those with confirmed MOH continued in the study [randomized (R) group], whereas those who did not still show any features of MOH dropped out of the study. RESULTS: A total of 88 (67.7%) patients still met the inclusion criteria after the baseline 4 weeks (R group). Conversely, 42 (32.3%) patients dropped out of the study. A detailed analysis of those who dropped out revealed that only 34 were not randomized at visit 2 because they no longer satisfied the inclusion criteria for MOH [screening failures (SF) group]. The SF group was significantly younger and had fewer years of migraine history than the R group. Moreover, the SF group had a significantly shorter history of chronicity compared with the R group. CONCLUSIONS: Our findings suggest that in MOH trials, after an educational session, an observational period is needed in order to confirm the diagnosis of MOH and to avoid overestimation of the effect of other treatments used to manage MOH. Future research should focus mainly on those patients with MOH who do not respond to simple advice and with unsuccessful withdrawal.

Lower hippocampal subfields volume in relation to anxiety in medication-overuse headache.

Background Hippocampus (HIP) was an important limbic structure, and concurrent emotion disorders may occur in medication-overuse headache patients. The aim of this study is to investigate altered HIP and HIP subfields volume in relation with the anxiety in medication-overuse headache patients using a state-of-the-art hippocampal segment method. Results The current study presented that a significant lower HIP and HIP subfields volume were identified in medication-overuse headache compared with that in normal controls except right HIP tail, bilateral parasubiculums, and HIP fissure. The left HIP and right subiculum presented negative correlation with headache variables, and the right subiculum, Cornu Ammonis 4, granule cell layer of dentate gyrus, bilateral Cornu Ammonis 1, molecular layer, and whole HIP presented negative correlation with Hamilton Anxiety Scale score, which were further confirmed by the linear regression analysis with the exclusion of psychological variables and headache variables, respectively. Conclusions The lower HIP and HIP subfields volume were identified in medication-overuse headache patients, and negatively related with anxiety condition. The potential mechanism for the comorbidity medication-overuse headache and anxiety might be interpreted as the reciprocal causation relationship and co-occurrence relationship.

Personality Traits and Anxiety and Depressive Disorders in Patients With Medication-Overuse Headache Versus Episodic Migraine.

OBJECTIVE: An episodic migraine (EM) may lead to medication-overuse headache (MOH), an abnormal behavioral pattern of noncompliance. Anxiety disorders, mood disorders, and disorders caused by psychoactive substances other than analgesics all have been reported with MOH at higher rates than with EM. The objective of this study was to evaluate the relationships between personality traits and anxiety and depressive disorders and headache type. METHODS: In this cross-sectional study, 55 patients with EM and 50 patients with MOH were recruited from were recruited from 2 university hospital clinics in Tehran, Iran, from January 2013 to November 2015. Personality traits were assessed with the Temperament and Character Inventory (TCI-125). Patients were assessed for depression with the 9-item Patient Health Questionnaire (PHQ-9) and anxiety with the 7-item Generalized Anxiety Disorder scale (GAD-7). RESULTS: There was no significant difference between the 2 groups regarding sex, age, or educational level. The TCI-125 analysis between the 2 groups showed a significant mean ± SD difference in reward dependence (EM: 9.77 ± 2.06, MOH: 8.69 ± 2.15, P = .01) and self-transcendence (EM: 8.42 ± 2.45, MOH: 6.83 ± 3.90, P = .03). The GAD-7 and PHQ-9 analyses demonstrated no significant difference between the 2 groups. CONCLUSIONS: Reward-dependence and self-transcendence scores were significantly lower in patients with MOH than in those with EM. These results suggest that people with lower reward-dependence and self-transcendence scores may not adequately respond to prescribed medications, leading them to the frequent use of multiple drugs at higher doses. A multidisciplinary approach to management may be suggested for migraine patients, and it is reasonable to consider behavioral therapy in conjunction with pharmacotherapy to ameliorate comorbid conditions.

Onabotulinumtoxin A for chronic migraine with medication overuse: clinical results of a long-term treatment.

The use of Onabotulinumtoxin A as treatment for different neurological conditions is more common in the last decades; its application has been consolidated on the basis of significant clinical results. The clinical experiences with Onabotulinumtoxin A for chronic migraine are on the increase in Italy: at the moment, clinical results are encouraging and enforce the application of the toxin for chronic migraine, according to the results of the PREEMPT studies. The possibility for the patients to be treated with a second cycle of therapy after the first year of treatment is under discussion, in particular for patients who obtained significant clinical benefit from the first period of treatment. In this report, a group of patients treated with Onabotulinumtoxin A for 1 year, according to the PREEMPT protocol, has been retreated for one more year in order to confirm the clinical benefit obtained after the first year of treatment.

Usefulness of an occlusal device in the treatment of medication overuse headache and persistent idiopathic facial pain: preliminary results.

There is a debate in literature about the therapeutic usefulness of oral devices in patients suffering from Medication Overuse Headache (MOH) or in patients suffering from Persistent Idiopathic Facial Pain (PIFP). From the case histories of 3356 patients, referred to us with a diagnosis of chronic craniofacial pain for assessment of the eventual application of an occlusal device to correct an impaired neuromuscular relationship between the mandible and the maxilla, we selected, following the criteria of the International Classification of Headache Disorders (ICHD-3beta), two groups of patients suffering from MOH and PIFP. All patients of the two groups underwent a Kinesiographic exam and an EMG to evaluate the freeway space (FWS). Patients presenting an impaired FWS were placed in treatment with the application of an occlusal device. At the follow-up after 6 months and after 1 year, we found a significant decrease in pain with regard to the intensity resulting in the reduction of clinical disability. The preliminary data collected using the VAS scale and the MIDAS questionnaire confirm that the neuromuscular cranio-mandibular system can have an important role in the diagnostic process of the MOH and the PIFP, suggesting the usefulness of treatment with an occlusal device, where there is adequate FWS.

Neural hyperactivity in the amygdala induced by chronic treatment of rats with analgesics may elucidate the mechanisms underlying psychiatric comorbidities associated with medication-overuse headache.

BACKGROUND: Patients with medication-overuse headache suffer not only from chronic headache, but often from psychiatric comorbidities, such as anxiety and depression. The mechanisms underlying these comorbidities are unclear, but the amygdala is likely to be involved in their pathogenesis. To investigate the mechanisms underlying the comorbidities we used elevated plus maze and open field tests to assess anxiety-like behavior in rats chronically treated with analgesics. We measured the electrical properties of neurons in the amygdala, and examined the cortical spreading depression (CSD)-evoked expression of Fos in the trigeminal nucleus caudalis (TNC) and amygdala of rats chronically treated with analgesics. CSD, an analog of aura, evokes Fos expression in the TNC of rodents suggesting trigeminal nociception, considered to be a model of migraine. RESULTS: Increased anxiety-like behavior was seen both in elevated plus maze and open field tests in a model of medication overuse produced in male rats by chronic treatment with aspirin or acetaminophen. The time spent in the open arms of the maze by aspirin- or acetaminophen-treated rats (53 ± 36.1 and 37 ± 29.5 s, respectively) was significantly shorter than that spent by saline-treated vehicle control rats (138 ± 22.6 s, P < 0.001). Chronic treatment with the analgesics increased the excitability of neurons in the central nucleus of the amygdala as indicated by their more negative threshold for action potential generation (-54.6 ± 5.01 mV for aspirin-treated, -55.2 ± 0.97 mV for acetaminophen-treated, and -31.50 ± 5.34 mV for saline-treated rats, P < 0.001). Chronic treatment with analgesics increased the CSD-evoked expression of Fos in the TNC and amygdala [18 ± 10.2 Fos-immunoreactive (IR) neurons per slide in the amygdala of rats treated with aspirin, 11 ± 5.4 IR neurons per slide in rats treated with acetaminophen, and 4 ± 3.7 IR neurons per slide in saline-treated control rats, P < 0.001]. CONCLUSIONS: Chronic treatment with analgesics can increase the excitability of neurons in the amygdala, which could underlie the anxiety seen in patients with medication-overuse headache.

Predictors of 12-Months Relapse After Withdrawal Treatment in Hospitalized Patients With Chronic Migraine Associated With Medication Overuse: A Longitudinal Observational Study.

BACKGROUND: Studies addressing relapse rates conflate relapse into chronic migraine (CM) and medication overuse (MO), and the consequent need to repeat withdrawal. We aim to identify 12-months predictors of relapse into CM (based on headaches frequency) separately from occurrence of another structured withdrawal. METHODS: Hospitalized patients with CM-MO under withdrawal were enrolled. Candidate predictors included demographic, disability, quality of life, depression scores, general self-efficacy, social support, headaches frequency and intensity, class of overused medications, history of withdrawal treatment in the three years prior to enrollment, attendance to emergency room (ER) between enrollment and follow-up, nonattendance to outpatient neurological examinations. Logistic regressions was used to address the significant predictors for the two outcomes. RESULTS: Complete data were available for 177 patients: 60 (33.9%) relapsed into CM, 38 (21.5%) underwent another withdrawal treatment. Recent history of withdrawal treatments, ER admission after discharge and high baseline BDI-II scores were significant predictors in both models. In addition to this, high baseline headache frequency predicted relapse into another withdrawal treatment. CONCLUSIONS: Predictors or relapse into CM and of occurrence of another withdrawal by 12-months are somehow similar. It is important to assess presence of recent previous withdrawal treatments and to plan regular follow-up afterwards, in particular for patients with high headache frequency and relevant mood disturbances: in this way, it will be more likely that situations requiring further structured withdrawal treatments can be identified before patients have to refer to ER.