Triggers, Protectors, and Predictors in Episodic Migraine.

PURPOSE OF REVIEW: A wide variety of triggers prompt attacks in episodic migraine. Although experimental triggers such as glyceryl trinitrate reliably produce migraine, natural triggers are much less predictable and vary in importance between individuals. This review describes the most common triggers in episodic migraine and provides strategies for managing them in clinical practice. RECENT FINDINGS: Multiple migraine attack triggers have been established based on patient surveys, diary studies, and clinical trials. Stress, menstrual cycle changes, weather changes, sleep disturbances, alcohol, and other foods are among the most common factors mentioned. Clinical studies have verified that fasting, premenstrual periods in women, letdown after stress, and most likely low barometric pressures are migraine triggers. Premonitory symptoms such as neck pain, fatigue, and sensitivity to lights, sounds, or odors may mimic triggers. Multiple studies clearly demonstrate triggers in episodic migraine, often related to change in homeostasis or environment. Many common migraine triggers are not easily modifiable, and avoiding triggers may not be realistic. Healthy lifestyle choices such as exercise, adequate sleep, stress management, and eating regularly may prevent triggers and transformation to chronic migraine over time

Safety of topiramate for treating migraines.

INTRODUCTION: Migraine is a very common medical disorder characterized by attacks of moderate-severe headache, nausea and disability. Topiramate is an effective, popular prophylactic migraine treatment, which is approved for use in adults and adolescents. Due to its multiple mechanisms of action, topiramate has multiple potential safety issues, including systemic and CNS adverse events, which may complicate therapy. AREAS COVERED: This review evaluates common adverse events as seen in the pivotal trials of topiramate for migraine as well as those observed in postmarketing studies. These include weight loss, metabolic acidosis, renal calculi, acute angle closure glaucoma, visual distortions and cognitive slowing. Topiramate use during pregnancy is associated with an increased risk of cleft lip. This review highlights both common and unusual safety issues associated with topiramate use, including important drug interactions and a comparison with other migraine prophylactic agents. EXPERT OPINION: Topiramate is highly effective in migraine prophylaxis but clinicians using the drug need to be aware of the potential for bothersome or serious adverse events. When treating with topiramate, use a slow titration to the goal dose of 100 mg or the lowest dose, which helps prevent migraine

Metabolic syndrome and migraine.

Migraine and metabolic syndrome are highly prevalent and costly conditions. The two conditions coexist, but it is unclear what relationship may exist between the two processes. Metabolic syndrome involves a number of findings, including insulin resistance, systemic hypertension, obesity, a proinflammatory state, and a prothrombotic state. Only one study addresses migraine in metabolic syndrome, finding significant differences in the presentation of metabolic syndrome in migraineurs. However, controversy exists regarding the contribution of each individual risk factor to migraine pathogenesis and prevalence. It is unclear what treatment implications, if any, exist as a result of the concomitant diagnosis of migraine and metabolic syndrome. The cornerstone of migraine and metabolic syndrome treatments is prevention, relying heavily on diet modification, sleep hygiene, medication use, and exercise

Inpatient management of migraine

Migraine is a frequently disabling disorder which may require inpatient treatment. Admission criteria for migraine include intractable migraine, nausea and/or vomiting, severe disability, and dependence on opioids or barbiturates. The inpatient treatment of migraine is based on observational studies and expert opinion rather than placebo-controlled trials. Well-established inpatient treatments for migraine include dihydroergotamine, neuroleptics/antiemetics, lidocaine, intravenous aspirin, and non-pharmacologic treatment such as cognitive-behavioral therapy. Short-acting treatments possibly associated with medication overuse, such as triptans, opioids, or barbiturate-containing compounds, are generally avoided. While the majority of persons with migraine are admitted on an emergency basis for only a few days, outcome studies and infusion protocols during elective admissions at tertiary headache centers suggest a longer length of stay may be needed for persons with intractable migraine

Dynamic mechanical (brush) allodynia in cluster headache: a prevalence study in a tertiary headache clinic.

Cutaneous allodynia (CA) has been described in migraine and has been related to treatment failure. There are little data about the incidence of CA in other primary headache syndromes such as cluster headache (CH). The objectives of this study are to evaluate the prevalence of dynamic mechanical (brush) allodynia (BA) in CH patients attending a tertiary headache clinic, and to assess its relation to disease characteristics. Adult patients with episodic or chronic CH were recruited. We obtained demographic data and data on disease characteristics through a structured questionnaire, and tested the patients for brush allodynia BA by applying a 4 x 4 gauze pad over the V1, C2/C3 and C8 skin areas bilaterally. The prevalence of allodynia in the entire study population and in the different sub-groups was calculated. We also examined the association between CA and demographic parameters, and its association with disease characteristics. Forty-one patients were recruited (22 men, 19 women; mean age 44.9 years). Twenty-two had chronic CH (CCH) and 19 had episodic CH (ECH). Mean disease duration was 14.1 years (12.3 the CCH group and 15.7 in the ECH group). Overall, 20 (49%) patients were allodynic. There was no statistically significant association between the presence of allodynia and age, gender, diagnosis (episodic vs. chronic CH), disease duration or disease severity. In conclusion, BA was common in this CH patient sample. The therapeutic implications of the presence of BA in CH need to be further studied

Olfactory Acuity in Chronic Migraine: A Cross-Sectional Study.

OBJECTIVE/BACKGROUND: This study aims to measure olfactory acuity in chronic migraine subjects, at baseline and on migraine days, and compare to age- and sex-matched controls. Olfactory impairment is common in neurological disorders. While smell hypersensitivity has been established with chronic migraine, olfactory acuity has not been well studied. METHODS: We recruited 50 subjects with chronic migraine from the Jefferson Headache Center and 50 age- and sex-matched controls. Using the University of Pennsylvania Smell Identification Test (UPSIT), a validated test of olfaction, olfactory acuity was measured at baseline and during a migraine for subjects, and compared to controls at baseline and at home 2 weeks later. All subjects were additionally screened for odor sensitivity and allodynia. RESULTS: The mean UPSIT score for migraine subjects was 34.5 on non-migraine days and 34.7 on migraine days (mean difference = -0.4, 95% confidence interval [CI; -1.3, 0.6] P = .45). Controls had a mean of 35.9 and 36.1 for each test day (mean difference = -0.1, 95% CI [-0.9, 0.7] P = .87). On average, migraineurs performed worse than their matched control counterparts in both test sittings (test 1: P = .047; test 2: P = .01). The great majority of subjects were allodynic (42/50) compared with only 9 of 50 controls, and the majority of subjects (41/50) found more than one listed odor to be bothersome, compared with only 10/50 controls. On non-migraine days, 18/48 chronic migraine subjects had abnormal olfaction and on migraine days 14/42 had abnormal olfaction, compared with only 9/50 controls who had abnormal olfaction on their first UPSIT. CONCLUSIONS: While chronic migraine patients do not appear to have a significant change in olfactory acuity between migrainous and non-migrainous periods, they do appear to be more likely to have abnormal olfactory acuity at baseline compared to age- and sex-matched controls

Olfactory function in migraine both during and between attacks.

INTRODUCTION: People with migraine often report being osmophobic, both during and between acute migraine attacks. It is not clear, however, whether such reports are associated with changes in olfaction such as hyperosmia, as measured by psychophysical testing. In this case-control study we quantitatively assessed olfactory identification ability, which correlates with threshold tests of olfactory acuity, in patients with migraine at baseline (no headache), during migraine episodes, and after a treated attack and compared the test scores to those of matched control subjects. METHODS: Fifty episodic migraine subjects and 50 and sex- and age-matched controls without headache were tested. All completed the University of Pennsylvania Smell Identification Test (UPSIT), a standardized and well-validated olfactory test. RESULTS: At baseline, the UPSIT scores did not differ significantly between the migraine and control study groups (median paired score difference: -1, p = 0.18). During migraine attacks, a minority of migraine subjects (eight of 42) developed microsmia (i.e. lower test scores by at least four points), suggesting that, as compared to their matched controls, olfactory acuity was somewhat impaired during migraine attacks (p = 0.02). This difference was less pronounced and not statistically significant after a successfully treated attack (p = 0.15). DISCUSSION: People with episodic migraine were found to have similar olfactory function as age- and sex-matched controls, but a minority exhibit microsmia or hyposmia during acute attacks. The cause of this dysfunction is unknown, but could relate to autonomic symptoms, limbic system activation, or disorders of higher order sensory processing

Electronic Medical Records as a Research Tool: Evaluating Topiramate Use at a Headache Center.

Background.—Electronic medical records (EMRs) are used in large healthcare centers to increase efficiency and accuracy of documentation. These databases may be utilized for clinical research or to describe clinical practices such as medication usage. Methods.—We conducted a retrospective analysis of EMR data from a headache clinic to evaluate clinician prescription use and dosing patterns of topiramate. The study cohort comprised 4833 unique de-identified records, which were used to determine topiramate dose and persistence of treatment. Results.—Within the cohort, migraine was the most common headache diagnosis (n = 3753, 77.7%), followed by tension-type headache (n = 338, 7.0%) and cluster or trigeminal autonomic cephalalgias (n = 287, 5.9%). Physicians prescribed topiramate more often for subjects with migraine and idiopathic intracranial hypertension (P \u3c .0001) than for those with other conditions, and more often for subjects with coexisting conditions including obesity, bipolar disorder, and depression. The most common maintenance dose of topiramate was 100 mg/day; however, approximately 15% of subjects received either less than 100 mg/day or more than 200 mg/day. More than a third of subjects were prescribed topiramate for more than 1 year, and subjects with a diagnosis of migraine were prescribed topiramate for a longer period of time than those without migraine. Conclusions.—Findings from our study using EMR demonstrate that physicians use topiramate at many different doses and for many off-label indications. This analysis provided important insight into our patient populations and treatment patterns

The Importance of an Early Onset of Migraine Preventive Disease Control: A Roundtable Discussion

Background: Newly approved migraine preventive therapies have allowed for rapid control of migraine activity, offering potential to minimize the burden of migraine. This report summarizes a roundtable discussion convened to analyze evidence for early onset of prevention, ascertain its clinical relevance, and provide guidance for healthcare professionals in crafting goals and treatment expectations for patients with migraine initiating preventive therapy. Methods: A virtual roundtable meeting of migraine clinicians, researchers, and patient advocates convened in October 2020. Participants reviewed and discussed data summarizing patient and healthcare professional perceptions of migraine prevention and evidence from the peer-reviewed and gray literature to develop corresponding recommendations. Summary: Evidence from clinical studies of anti-calcitonin gene-related peptide monoclonal antibodies (erenumab, fremanezumab, galcanezumab, and eptinezumab) and the chemodenervation agent onabotulinumtoxinA indicate that patients may experience reduction of migraine activity within 7 days of drug administration and early attainment of disease control is associated with improvements in clinically important outcomes. The roundtable of experts proposes that early onset be defined as demonstration of preventive benefits within 1 week of treatment initiation. We recommend focusing discussion with patients around “disease control” and potential benefits of early onset of prevention, so patients can set realistic preventive therapy goals and expectations

Safety and Tolerability Results of Atogepant for the Preventive Treatment of Episodic Migraine From a 40-Week, Open-Label Multicenter Extension of the Phase 3 ADVANCE Trial

Background: Atogepant is a United States Food and Drug Administration-approved oral calcitonin gene-related peptide receptor antagonist for the preventive treatment of episodic migraine. The study objective was to evaluate the long-term safety and tolerability of atogepant in participants who completed the phase 3 ADVANCE trial (NCT03777059). Methods: This 40-week, open-label extension trial (NCT03939312) monitored safety in participants receiving oral atogepant 60 mg once daily, followed by a four-week safety follow-up period. Results: Of the 685 participants taking at least one dose of atogepant, the treatment period was completed by 74.6% of participants with a mean (standard deviation) treatment duration of 233.6 (89.3) days. Treatment-emergent adverse events occurred in 62.5% of participants, with upper respiratory tract infection (5.5%), urinary tract infection (5.3%), nasopharyngitis (4.8%), sinusitis (3.6%), constipation (3.4%), and nausea (3.4%) occurring at ≥3%. Serious adverse events were observed in 3.4% of participants (none were treatment-related), and there were no deaths. Adverse events leading to discontinuation occurring at \u3e0.1% were nausea (0.4%) and abdominal pain, vomiting, weight decrease, dizziness, and migraine (0.3% each). Conclusion: These results are consistent with atogepant\u27s known safety profile and support long-term use of atogepant 60 mg once daily dosing as safe and well tolerated.ClinicalTrials.gov Registration Number: NCT03939312