Naming migraine and those who have it.

Medical language has implications for both public perception of and institutional responses to illness. A consensus panel of physicians, academics, advocates, and patients with diverse experiences and knowledge about migraine considered 3 questions: (1) What is migraine: an illness, disease, syndrome, condition, disorder, or susceptibility? (2) What ought we call someone with migraine? (3) What should we not call someone with migraine? Although consensus was not reached, the responses were summarized and analyzed quantitatively and qualitatively. Panelists participated in writing and editing the paper. The panelists agreed that "migraine," not "migraine headache," was generally preferable, that migraine met the dictionary definition for each candidate moniker, terms with psychiatric valence should be avoided, and "sufferer" should be avoided except in very limited circumstances. Overall, while there was no consensus, "disease" was the preferred term in the most situations, and illness the least preferred. Panelists disagreed strongly whether one ought to use the term "migraineur" at all or if "person with migraine" was preferable. Panelists drew upon a variety of principles when considering language choices, including the extent to which candidate monikers could be defended using biomedical evidence, the cultural meaning of the proposed term, and the context within which the term would be used. Panelists strove to balance the need for terms to describe the best science on migraine, with the desire to choose language that would emphasize the credibility of migraine. The wide range of symptoms of migraine and its diverse effects may require considerable elasticity of language.

Depression and anxiety in episodic and chronic cluster headache: a pilot study.

BACKGROUND: In contrast to migraine and tension-type headache, the psychiatric comorbidities of cluster headache (CH) have not been well-studied. OBJECTIVE: We assessed the presence of depression and anxiety in groups of episodic CH (ECH) and chronic CH (CCH) patients and compared CH patients with and without depression and anxiety. METHODS: Sociodemographics, comorbidities, and selected headache features were ascertained from a clinic-based sample in a cross-sectional fashion from January 2007 to July 2010. Active depression and anxiety were assessed using the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder 7-item (GAD-7) scales. RESULTS: Of 49 CH patients, ECH patients (n=32) had an earlier age of onset and consumed less caffeine than CCH patients (n=17). Rates of depression as defined by a PHQ-9 score ≥10 were low in both ECH (6.3%) and in CCH (11.8%) with similar mean PHQ-9 scores (3.1 vs 3.7, P=.69). Rates of anxiety as defined by a GAD-7 score ≥10 were also low in both ECH (15.6%) and CCH (11.8%) with similar mean GAD-7 scores (3.8 vs 3.4, P=.76). ECH patients in and out of active attack periods had similar levels of depression and anxiety. Depression and anxiety usually occurred together in ECH and CCH patients. CH patients who were depressed or anxious were more likely to present at a younger age and have attack-related nausea and prodromal symptoms. Depressed CH patients were also more likely to have another pain disorder and had undertaken twice as many prophylactic medication trials. CONCLUSION: In this clinic-based cross-sectional study, ECH and CCH patients had similarly low rates of depression and anxiety. Rates were lower than those reported for both episodic and chronic migraine.

Post-traumatic stress disorder, drug abuse and migraine: new findings from the National Comorbidity Survey Replication (NCS-R).

BACKGROUND: Post-traumatic stress disorder (PTSD) has been shown to be associated with migraine and drug abuse. METHODS: This was an analysis of data from the National Comorbidity Survey Replication (NCS-R) to evaluate the association of PTSD in those with episodic migraine (EM) and chronic daily headache (CDH). RESULTS: Our sample consisted of 5,692 participants. Lifetime and 12-month prevalence rates of PTSD were increased in those with EM and CDH. After adjustments, the lifetime odds ratio (OR) of PTSD was greater in those with EM (OR 3.07 confidence interval [CI]: 2.12, 4.46) compared to those without headache; was greater in men than women with EM (men: OR 6.86; CI: 3.11, 15.11; women: OR 2.77; CI: 1.83, 4.21); and was comparable or greater than the association between migraine with depression or anxiety. The lifetime OR of PTSD was also increased in CDH sufferers. The OR of illicit drug abuse was not increased in those with EM or CDH unless co-occurring with PTSD or depression. CONCLUSION: The lifetime and 12-month OR of PTSD is increased in those with migraine or CDH, and is greater in men than women with migraine. The lifetime and 12-month OR of illicit drug abuse is not increased in those with migraine or CDH unless co-occurring with PTSD or depression.

Favorable outcome of early treatment of new onset child and adolescent migraine-implications for disease modification.

There is evidence that the prevalence of migraine in children and adolescents may be increasing. Current theories of migraine pathophysiology in adults suggest activation of central cortical and brainstem pathways in conjunction with the peripheral trigeminovascular system, which ultimately results in release of neuropeptides, facilitation of central pain pathways, neurogenic inflammation surrounding peripheral vessels, and vasodilatation. Although several risk factors for frequent episodic, chronic, and refractory migraine have been identified, the causes of migraine progression are not known. Migraine pathophysiology has not been fully evaluated in children. In this review, we will first discuss the evidence that early therapeutic interventions in the child or adolescent new onset migraineur, may halt or limit progression and disability. We will then review the evidence suggesting that many adults with chronic or refractory migraine developed their migraine as children or adolescents and may not have been treated adequately with migraine-specific therapy. Finally, we will show that early, appropriate and optimal treatment of migraine during childhood and adolescence may result in disease modification and prevent progression of this disease.

Ten years of rizatriptan: from development to clinical science and future directions.

The year 2008 marked the 10th anniversary since rizatriptan was first launched for the acute treatment of migraine. In this article we discuss the concepts that motivated the preclinical and clinical development of rizatriptan, the clinical evidence that has driven its use over the past decade, rizatriptan's overall contribution to the field, and future directions for research.

Moving forward - essential questions for the next 10 years.

The future is bright for migraine sufferers. For acute treatment, CGRP antagonists and combination products will provide more complete, longer lasting, and safer relief. "Designer drugs" for migraine prevention will be identified based on their ability to block cortical spreading depression and will improve migraine treatment. Genetic and environmental risk factors that promote migraine progression will be identified and preventing progression will become a standard goal in treatment. Some of the devices intended to treat migraine will be approved and will provide important options for sufferers seeking to avoid drugs. Clinical trials that evaluate behavioral and pharmacologic interventions and their impact on patient centered outcomes will emerge. The emergence of novel treatments, when coupled with strategies for individualizing and optimizing treatment while maximizing adherence, will result in ever improving patient outcomes.

Healthcare provider-patient communication and migraine assessment: results of the American Migraine Communication Study, phase II.

OBJECTIVE: The American Migraine Communication Study I (AMCS I) revealed communication deficits illustrated by differing healthcare professional (HCP) and patient reports about issues such as impairment and frequency. AMCS II was designed to assess an intervention using open-ended questions about impairment and 'ask-tell-ask' sequences to confirm headache frequency in days versus attacks. RESEARCH DESIGN AND METHODS: HCPs who participated in AMCS I completed an internet-based intervention. Researchers were sent to HCPs' offices, and patients likely to discuss migraine were recruited immediately prior to normally-scheduled appointments. Post-consent, visits were recorded without a researcher present. Separate post-visit interviews were conducted with all parties. All interactions were transcribed. MAIN OUTCOME MEASURES: Transcripts were analyzed using validated sociolinguistic techniques, and study results were compared to AMCS I. RESULTS: HCPs assessed impairment in 90% of interactions compared to 10% in AMCS I (p<0.0001) and used open-ended questions to assess impairment in 55% of visits (95% CI: 0.4261-0.6598). Impairment between attacks was discussed in 37% of visits vs. 0% in AMCS I (p<0.0001). HCPs completed full ask-tell-ask sequences in 29% of visits (95% CI: 0.1921-0.4070). AMCS II contained more discussions of migraine preventive therapy with appropriate candidates compared to AMCS I (74 vs. 50%; p=0.069) without statistically increasing median visit length (9:36 vs. 11:00; p=0.668). Post-visit, HCPs and patients were often aligned about impairment and frequency and reported high levels of satisfaction. CONCLUSIONS: Although further research with a larger sample is needed, a brief, internet-based intervention appears to promote positive communication changes not associated with increased visit length.

Headache attributed to hypothyroidism.

Clinical and subclinical hypothyroidisms are common conditions in the population. Clinic-based studies suggest that hypothyroidism may be an exacerbating factor for some primary headaches. Furthermore, hypothyroidism may be a risk factor for incident new daily persistent headache. This article reviews the classification of the headaches attributed to hypothyroidism according to the second edition of the International Classification of Headache Disorders. We also review the prevalence, etiology, and principles of treatment of hypothyroidism. Because hypothyroidism is a treatable cause of secondary headaches, doctors should be aware of this relationship.

Efficacy of eletriptan in migraine-related functional impairment: functional and work productivity outcomes.

OBJECTIVE: To provide a multidimensional assessment of the extent of functional impairment during an acute migraine attack, and of the improvement in functioning in response to treatment, using 4 concurrently administered scales: the 7-item work productivity questionnaire (PQ-7), the functional assessment in migraine (FAIM) activities and participation (FAIM-A&P) subscale, the FAIM-impact of migraine on mental functioning (FAIM-IMMF) subscale, and the traditional 4-point global functional impairment scale (FIS). METHODS: Outpatients with an International Classification of Headache Disorders diagnosis of migraine were randomized to double-blind treatment of a single attack with either oral eletriptan 20 mg (n = 192) once-daily, eletriptan 40 mg (N = 213) once-daily, or placebo (n = 208). Patients were encouraged to take study medication as soon as they were sure they were experiencing a typical migraine headache, after the aura phase (if present) had ended. Patients with moderate-to-severe functional impairment were identified on each of the 4 disability scales, and 2-hour functional response was compared between treatments. RESULTS: At baseline, the PQ-7 and FAIM-IMMF items that assessed ability to perform tasks requiring concentration, sustained work or attention, and ability to think quickly or spontaneously, were especially sensitive to the effects of mild headache pain, with 27% to 48% of patients (n = 92-112) reporting moderate-to-severe impairment. Only 11.3% of patients (n = 112) reported this level of impairment due to mild pain on the FIS. Functional response at 2 hours was significantly higher on eletriptan 40 mg versus placebo on the FAIM-A&P (63% vs 36%; n = 218; P < .0001); on the PQ-7 (56% vs 34%; n = 116; P= .0052); and on the FAIM-IMMF (50% vs 34%; n = 215; P= .017). These rates were all lower than the functional response rates on the FIS for eletriptan 40 mg (75%) and eletriptan 20 mg (70%) versus placebo (45%; P < .001). Conclusions.-In this exploratory analysis, use of multidimensional scales was found to provide a sensitive measure of headache-related functional impairment, especially for detecting clinically meaningful cognitive effects, and for detecting drug versus placebo differences.

Medications associated with probable medication overuse headache reported in a tertiary care headache center over a 15-year period.

OBJECTIVES: To evaluate the substances associated with medication overuse headache (MOH) in a headache center, over the course of the past 15 years. BACKGROUND: The acute treatment of migraine has substantially changed over the past 15 years, and therefore, the substances associated with MOH may have changed as well. METHODS: We randomly reviewed charts of subjects seen during the years of 2005, 2000, 1995, and 1990, to identify substances associated with MOH. Since the criteria proposed by the second edition of the International Classification of Headache Disorders require causal attribution, demonstrated by improvement after withdrawal (and this was not assessed in this study), herein we refer to probable MOH (PMOH). We contrasted the substances associated with PMOH over the studied years. RESULTS: Our sample consists of 1200 individuals, 300 per year of interest. The proportions of subjects with a diagnosis of PMOH remained stable over the years, varying from 64% of all cases seen in the center in 1990, to 59.3% in 2005. We found a significant decrease in the relative frequency of probable ergotamine overuse headache (from 18.6% to 0%, P < .0001), and in probable combination analgesic overuse headache (from 42.2% to 13.6%, P < .0001). The differences were not significant for opioid overuse headache. The relative frequency increased significantly for the triptans (from 0% to 21.6%, P < .0001), simple analgesics (from 8.8% to 31.8%, P < .05), and for combinations of acute medications (from 9.8% to 22.7%, P = .01). CONCLUSION: While overuse of acute medications remains an important problem in the tertiary care arena, the substances associated with the overuse have dramatically changed over the past 15 years. Educational initiatives should emphasize that the newer specific acute migraine medications (triptans) may also be associated with PMOH.

Naratriptan in the preventive treatment of refractory transformed migraine: a prospective pilot study.

OBJECTIVE: To assess the efficacy, safety, and tolerability of daily naratriptan in the preventive treatment of transformed migraine (TM) refractory to previous first line therapies. BACKGROUND: Limited evidence suggests that the triptans can be used in the preventive treatment of refractory headaches. DESIGN/METHODS: We included subjects from 18 to 65 years old, with TM, with or without medication overuse (Silberstein and Lipton, 1996). All participants had previously failed at least two preventive medications. Concomitant, preventive medications were allowed if on a stable dose. After the baseline period, all patients received naratriptan 2.5 mg bid. The treatment phase lasted 3 months. The primary endpoint was change in headache frequency per month. Safety assessment included monthly ECGs, complete ophthalmologic exam, and monthly blood tests. Statistical analyses were performed using the intent-to-treat (ITT) population. We also conducted per-protocol (PP) analyses. RESULTS: Our ITT population consisted of 30 subjects (79% female, mean age of 46.5 years). Mean headache frequency per month at baseline was 27.1 days and a significant reduction of headache frequency was obtained in 1 month (20.4, P < .001), 2 months (18.9, P < .001), and 3 months (19.0, P < .001). HIT scores were 64.3 at baseline, 57.4 after 1 month (P < .001), 55.7 after 2 months (P < .01), and 60 at 3 months (P < .05). The mean number of days using rescue medication was reduced from 17.7 at baseline, to 9.7 at 3 months (P < .001). Our PP population consisted of 22 subjects, and 54% had fewer than 15 headaches per month at the end of the study (converted to an episodic pattern). No serious adverse events were reported. No significant changes were observed in blood pressure or in heart rate. ECGs and ophthalmologic exam were unchanged from baseline. CONCLUSIONS: (1) Daily use of naratriptan provided good preventive efficacy in an important subset of subjects with TM refractory to other preventive treatments. (2) The tolerability of this treatment was excellent. (3) Over a short period of time (3 months), no serious adverse events were reported, nor significant changes were found in the ECG or ophthalmologic evaluation.

Tinnitus in migraine: an allodynic symptom secondary to abnormal cortical functioning?

Tinnitus is not a common auditory symptom in migraine. Recent research suggests that central sensitization (CS) develops in most migraneurs during the course of a migraine attack. Herein we describe 3 patients with primary headache disorders and tinnitus as their chief complaint, in whom the tinnitus intensity consistently increased during headache attacks. In headache patients, tinnitus may be related to spontaneous and aberrant neural activity at any level along the auditory axis, with abnormal reorganization processes in the auditory cortex following hearing receptor damage. We hypothesize that the tinnitus intensity increase could be an allodynic symptom related to CS, or alternatively could be associated with cortical hyperexcitability.

Optimizing the diagnosis and treatment of migraine.

PURPOSE: To describe and discuss short headache questionnaires, which can simplify and improve the diagnosis of migraine. DATA SOURCES: Review of the worldwide scientific literature on short diagnostic questionnaires for migraine. CONCLUSIONS: A new three-question Headache Screen addressing disability due to recurring headaches, headache duration, and changes in headache characteristics and/or pattern over the previous 6 months displayed high sensitivity when used to survey >3000 migraineurs, correctly identifying 77% of migraineurs diagnosed by International Headache Society (IHS) criteria, clinical impression, or the presence of recurring, disabling headaches. IMPLICATIONS FOR PRACTICE: The underdiagnosis and undertreatment of migraine are problems that may be attributed to many causes involving both patients and medical providers. These include stringent diagnostic criteria established by the IHS, which fail to easily classify many common migraine presentations, the lack of clear outcome measures of successful management of migraine, and failure to recognize the iatrogenic role of prescription and nonprescription medications as an etiologic factor in chronic daily headache. The recent development of reliable, clinically useful, short headache questionnaires that are focused on headache impact facilitates the understanding and diagnosis of migraine for both patients and healthcare professionals. As a diagnostic tool, the Headache Screen has the potential to expand appropriate medication use, leading to improved functional status and quality of life for migraineurs.

Two replicate randomized, double-blind, placebo-controlled trials of the time to onset of pain relief in the acute treatment of migraine with a fast-disintegrating/rapid-release formulation of sumatriptan tablets.

BACKGROUND: The gastric stasis that commonly accompanies migraine headache may impair absorption of conventional oral tablets in the stomach. A fast-disintegrating/rapid-release formulation of sumatriptan has been developed to enhance tablet disintegration and drug dispersion and potentially improve absorption. OBJECTIVE: Two studies were conducted comparing the time to onset of relief from moderate or severe migraine pain with the fast-disintegrating/rapid-release formulation of sumatriptan tablets 50 and 100 mg and placebo. METHODS: These were 2 identically designed randomized, double-blind, parallel-group studies. Sumatriptan 50 or 100 mg or placebo was taken on an outpatient basis to treat a single moderate or severe migraine attack. Using a personal digital assistant, patients recorded the time of dosing and the time at which pain severity reached none or mild (ie, pain relief) or none (ie, pain free) in real time so that the time to onset of relief could be measured as a continuous variable. Onset of relief was defined as the earliest time point at which a statistically significant difference in pain relief compared with placebo was achieved and maintained through 2 hours after dosing. Before dosing and at pre-determined time points after dosing, patients also provided an assessment of migraine pain as none, mild, moderate, or severe. At a clinic visit within 1 week after treatment of the migraine attack, patients were queried about adverse events. For each adverse event, investigators recorded whether study medication was considered the cause. Data analyses were undertaken for each study individually and, in post hoc analyses of the primary and key secondary end points, on pooled data from both studies. RESULTS: The 2 studies comprised 2696 patients: 902 received sumatriptan 50 mg, 902 received sumatriptan 100 mg, and 892 received placebo. Patients' mean age ranged from 40.2 to 40.8 years across treatment groups, and most patients were female (83%-87%) and white (92%-93%). In the analysis of pooled data, sumatriptan tablets provided significantly more effective pain relief compared with placebo as early as 20 minutes after dosing with the 100-mg dose and as early as 30 minutes after dosing with the 50-mg dose (P < or = 0.05). Similar results were observed for the individual studies: in study 1, sumatriptan tablets were significantly more effective than placebo at 25 minutes with the 100-mg dose and at 50 minutes with the 50-mg dose; in study 2, sumatriptan tablets were significantly more effective than placebo at 17 minutes for the 100-mg dose and at 30 minutes for the 50-mg dose (P < or = 0.05). In the pooled data, the cumulative percentages of patients with pain relief by 2 hours after dosing were 72% for the 100-mg dose and 67% for the 50-mg dose, compared with 42% for placebo (P < or = 0.001, both sumatriptan doses vs placebo). The cumulative percentages of patients with a pain-free response by 2 hours were 47% for the 100-mg dose, 40% for the 50-mg dose, and 15% for placebo (P < or = 0.001, both sumatriptan doses vs placebo). In the individual studies, significantly more patients receiving either sumatriptan dose were migraine free 2 hours after dosing and had sustained pain relief and a sustained pain-free response over 24 hours compared with placebo (P < or = 0.001, both sumatriptan doses vs placebo). The only drug-related adverse events reported in >2% of patients in any treatment group in either study were nausea (both studies: 3% sumatriptan 100 mg, 2% sumatriptan 50 mg, 1% placebo) and paresthesia (study 1: <1% sumatriptan 100 mg, <1% sumatriptan 50 mg, 0% placebo; study 2: 3% sumatriptan 100 mg, 1% sumatriptan 50 mg, <1% placebo). CONCLUSIONS: In these studies, sumatriptan tablets in a fast-disintegrating/rapid-release formulation were effective for the acute treatment of moderate to severe migraine pain, were generally well tolerated, and achieved an onset of pain relief as early as 20 minutes for 100 mg and as early as 30 minutes for 50 mg.

The classification of chronic daily headache in adolescents--a comparison between the second edition of the international classification of headache disorders and alternative diagnostic criteria.

OBJECTIVES: To compare the second edition of the International Classification of Headache Disorders (ICHD-2) and the Silberstein-Lipton (S-L) criteria in the classification of adolescents with chronic daily headache (CDH). METHODS: We reviewed the clinical records and the headache diaries of 170 adolescents (13 to 17 years) seen between 1998 and 2003 at a headache center. Relevant information was transferred to a standardized form that included operational criteria for the ICHD-2. CDH subtypes were classified according the criteria proposed by S-L into transformed migraine (TM) with (TM+) and without medication overuse (TM-), chronic tension-type headache (CTTH), new daily persistent headache (NDPH), and hemicrania continua (HC). RESULTS: From the 69 patients with TM- according the S-L criteria, most (71%) could be classified as chronic migraine (CM), while a minority of patients required a combination of diagnosis, mainly migraine and CTTH (14.4%). Of the patients with TM+, just 39.6% met the criteria for probable CM (PCM) with probable medication overuse (PMO). If instead of 15 migraine days per month, we considered 15 or more days of migraine or probable migraine, 84% of the subjects with TM- and 68.7% of those with TM+ could be classified. Of the 27 subjects classified as NDPH without medication overuse according to the S-L system, the majority (51.2%) were also classified as NDPH according the ICHD-2. Interestingly, three (11.1% of the subjects with NDPH without medication overuse) were classified as CM in the ICHD-2 because these patients had an abrupt onset of 15 or more days of migraine per month. All patients with NDPH with medication overuse according to the S-L criteria required a combination of diagnoses in the ICHD-2. All subjects with CTTH received a single diagnosis in both classification systems. CONCLUSIONS: (i) Among adolescents with TM, the majority (58.1%) could be classified as CM, according to the ICHD-2. These results were driven by TM without medication overuse. (ii) If the ICHD-2 criteria for CM are revised to require 15 days of migraine or probable migraine, the proportion of patients with TM- who meet the criteria for CM increases from 71% to 84%; for TM+, the proportion with probable chronic migraine and PMO increases from 30% to 68%. (iii) About half of the patients with NDPH according to the S-L criteria have too many migraine features to meet ICHD-2 criteria for NDPH.

Clomiphene citrate as a new treatment for SUNCT: hormonal manipulation for hypothalamic-influenced trigeminal autonomic cephalalgias.

We present a patient with treatment refractory short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) who was found to have low levels of serum testosterone supporting the hypothalamic connection to this trigeminal autonomic cephalalgia. Clomiphene citrate therapy induced a significant elevation of testosterone levels (by its effect on hypothalamic estrogen receptors) and led to a dramatic reduction in SUNCT attacks. Hormonal manipulation may be a treatment strategy for hypothalamic-influenced trigeminal autonomic cephalalgias.

Abrupt onset and termination of cutaneous allodynia (central sensitization) during attacks of SUNCT.

The presence of central sensitization and cutaneous allodynia has not been readily studied in other primary headache syndromes outside of migraine. If central sensitization does occur, is the temporal profile any different in the short-lasting more aggressive syndromes such as SUNCT than in migraine? A patient with SUNCT was examined during and in between attacks looking for the presence and duration of cutaneous allodynia.

Levetiracetam in the preventive treatmentof transformed migraine: A prospective, open-label, pilot study.

BACKGROUND: Most preventive agents used for transformed migraine (TM)have not been studied specifically for the treatment of this syndrome. Open-label trials have demonstrated the effectiveness of levetiracetam in the treatment of refractory headaches. OBJECTIVE: The aim of this study was to assess the effectiveness and tolerabilityof levetiracetam in the preventive treatment of refractory TM. METHODS: This prospective, open-label, pilot study was conducted at TheNew England Center for Headache, Stamford, Connecticut. We included patients aged ≥ 18 years with refractory TM according to the criteria proposed by Silberstein et al. All participants had failed on at least 1 but not more than 3 preventive drugs. Other preventive drugs were allowed if they had been received at a stable dose for > 30 days. The dosage of the levetiracetam tablets ranged from 1000 to 3000 mg/d in 2 divided doses. The treatment phase lasted 3 months. The primary end point was headache frequency (expressed as the number of headache days per month), and the secondary end point was the frequency of moderate or severe headache (d/mo). Other end points were headache score, Migraine Disability Assessment (MIDAS) Questionnaire score, and Headache Impact Test (HIT-6) score. Statistical analyses were performed in the intent-to-treat (ITT) population (patients who received at least 1 dose of study medication) using data subjected to the last-observation-carried-forward algorithm. We also conducted per-protocol (PP) analyses in patients who completed the study. RESULTS: The ITT population consisted of 36 patients (26 women, 10 men;mean [SD] age, 46.5 [17.4] years). The mean headache frequency at baseline was 24.9 d/mo, and a significant reduction in headache frequency was obtained at l, 2, and 3 months of treatment (19.4, 18.4, and 16.2 d/mo, respectively; all, P < 0.001 Reproduction in whole or part is not permitted. vs baseline). At baseline, the mean number of moderate or severe headache days was 16.8 d/mo compared with 13.2, 11.9, and 9.7 d/mo at 1, 2, and 3 months, respectively (P=NS, <0.01, and <0.01, respectively). The mean MIDAS score was significantly reduced at 3 months compared with baseline (40.8 vs 62.8 d/mo; P = 0.01). The mean HIT-6 score was 59.4 at 3 months versus 63.4 at baseline (P < 0.01). In the PP population, the mean (SD) headache frequency was reduced from 26.1 (4.1) d/mo at baseline to 14.3 (4.8) d/mo at the end of the study (P < 0.001). The mean (SD) headache score was reduced from 51.3 (17.1) at baseline to 34.0 (22.0) at 3 months (P < 0.016). CONCLUSION: The results of this study in patients with TM support the role of levetiracetam in the preventive treatment of refractory TM.