Cardiovascular safety of dihydroergotamine mesylate delivered by precision olfactory delivery (INP104) for the acute treatment of migraine.

OBJECTIVE: To report the cardiovascular (CV) safety of dihydroergotamine mesylate (DHE) administered by precision olfactory delivery (INP104) from two clinical trials. BACKGROUND: Although the absolute risk is low, migraine is associated with an increased risk of CV events. DHE is a highly effective acute treatment for migraine, but due to its theoretical risk of promoting arterial vasoconstriction, DHE is contraindicated in patients with CV disease or an unfavorable risk factor profile. The INP104 is a novel drug-device combination product approved for acute treatment of migraine that delivers DHE to the upper nasal space using precision olfactory delivery (POD®). METHODS: The STOP 101 was a Phase 1 open-label study that assessed the safety, tolerability, and bioavailability of INP104 1.45 mg, intravenous DHE 1.0 mg, and MIGRANAL (nasal DHE) 2.0 mg in healthy participants. The STOP 301 was a pivotal Phase 3, open-label study that assessed the safety, tolerability, and exploratory efficacy of INP104 1.45 mg over 24 and 52 weeks in patients with migraine. In both studies, active or a history of CV disease, as well as significant CV risk factors, were exclusion criteria. RESULTS: In STOP 101, 36 participants received one or more doses of investigational product. Treatment with intravenous DHE, but not INP104 or nasal DHE, resulted in clinically relevant changes from baseline in systolic blood pressure (BP; 11.4 mmHg, 95% confidence interval [CI] 7.9-15.0) and diastolic BP (13.3 mmHg, 95% CI 9.4-17.1) at 5 min post-dose, persisting up to 30 min post-dose for systolic BP (6.3 mmHg; 95% CI 3.0-9.5) and diastolic BP (7.9 mmHg, 95% CI 3.9-11.9). None of the treatments produced any clinically meaningful electrocardiogram (ECG) changes. In STOP 301, 354 patients received one or more doses of INP104. Over 24 weeks, five patients (1.4%) experienced a non-serious, vascular treatment-emergent adverse event (TEAE). Minimal changes were observed for BP and ECG parameters over 24 or 52 weeks. Off-protocol concomitant use of triptans and other ergot derivatives did not result in any TEAEs. CONCLUSION: In two separate studies, INP104 demonstrated a favorable CV safety profile when used in a study population without CV-related contraindications.

Diagnostic accuracy of an artificial intelligence online engine in migraine: A multi-center study.

OBJECTIVE: This study assesses the concordance in migraine diagnosis between an online, self-administered, Computer-based, Diagnostic Engine (CDE) and semi-structured interview (SSI) by a headache specialist, both using International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria. BACKGROUND: Delay in accurate diagnosis is a major barrier to headache care. Accurate computer-based algorithms may help reduce the need for SSI-based encounters to arrive at correct ICHD-3 diagnosis. METHODS: Between March 2018 and August 2019, adult participants were recruited from three academic headache centers and the community via advertising to our cross-sectional study. Participants completed two evaluations: phone interview conducted by headache specialists using the SSI and a web-based expert questionnaire and analytics, CDE. Participants were randomly assigned to either the SSI followed by the web-based questionnaire or the web-based questionnaire followed by the SSI. Participants completed protocols a few minutes apart. The concordance in migraine/probable migraine (M/PM) diagnosis between SSI and CDE was measured using Cohen's kappa statistics. The diagnostic accuracy of CDE was assessed using the SSI as reference standard. RESULTS: Of the 276 participants consented, 212 completed both SSI and CDE (study completion rate = 77%; median age = 32 years [interquartile range: 28-40], female:male ratio = 3:1). Concordance in M/PM diagnosis between SSI and CDE was: κ = 0.83 (95% confidence interval [CI]: 0.75-0.91). CDE diagnostic accuracy: sensitivity = 90.1% (118/131), 95% CI: 83.6%-94.6%; specificity = 95.8% (68/71), 95% CI: 88.1%-99.1%. Positive and negative predictive values = 97.0% (95% CI: 91.3%-99.0%) and 86.6% (95% CI: 79.3%-91.5%), respectively, using identified migraine prevalence of 60%. Assuming a general migraine population prevalence of 10%, positive and negative predictive values were 70.3% (95% CI: 43.9%-87.8%) and 98.9% (95% CI: 98.1%-99.3%), respectively. CONCLUSION: The SSI and CDE have excellent concordance in diagnosing M/PM. Positive CDE helps rule in M/PM, through high specificity and positive likelihood ratio. A negative CDE helps rule out M/PM through high sensitivity and low negative likelihood ratio. CDE that mimics SSI logic is a valid tool for migraine diagnosis.

Headache secondary to cerebrovascular disease.

OBJECTIVES: To discuss headache secondary to cerebrovascular disease. BACKGROUND: Headache is an important symptom in cerebrovascular diseases. In some conditions, headache is the leading symptom. Migraine is associated with an increased risk of stroke. METHODS: The authors undertook a literature search for the terms "headache" and "cerebrovascular diseases". RESULTS: We report studies on headache in subarachnoidal hemorrhage, intracerebral hemorrhage, ischemic stroke, TIA, basilar artery thrombosis, cervical artery dissection, cerebellar stroke, arteritis and cerebral sinus venous thrombosis. In addition, we discuss migraine and stroke and thunderclap headache. CONCLUSIONS: Headache is a leading symptom in many cerebrovascular diseases. Headache in combination with focal neurological deficits requires immediate diagnosis and treatment.

Prognosis Following Discontinuation of OnabotulinumA Therapy in "Super-responding" Chronic Migraine Patients.

OBJECTIVE: To determine whether the successful treatment of chronic migraine (CM) with onabotulinumA (BotoxA) may be followed by a continued respite from headache once therapy has been discontinued. BACKGROUND: The optimal duration of prophylactic therapy for migraine generally and for CM treated with BotoxA specifically is unknown. METHODS: We conducted a prospective cohort study evaluating a series of patients with CM at a university-affiliated headache subspecialty clinic in Reno, Nevada, all of whom were treated according to a uniform protocol involving serial injections of BotoxA. We followed all positively responding patients who met our stopping rule for a minimum of 6 months after discontinuation of BotoxA, and we assessed the incidence of clinical worsening in that group. RESULTS: A total of 105/131 patients (80%) for whom complete follow-up was available reported no clinical worsening or need to resume prophylactic therapy over the 6 months following discontinuation of BotoxA therapy. Patients with pre-treatment baseline chronic daily headache (CDH) of greater than 6 months duration were more likely to report clinical deterioration within 6 months of stopping treatment, as compared to patients with CDH of less than 6 months. A greater number of BotoxA treatments required to achieve our stopping rule correlated with clinical deterioration within 6 months of stopping treatment. CONCLUSIONS: In many CM patients who experience an especially positive response to serial BotoxA injection therapy, clinical improvement may be sustained for a period of at least 6 months following discontinuation of prophylactic therapy.

FORWARD Study: Evaluating the Comparative Effectiveness of OnabotulinumtoxinA and Topiramate for Headache Prevention in Adults With Chronic Migraine.

OBJECTIVE: To compare effectiveness of onabotulinumtoxinA and topiramate for chronic migraine (CM) prevention. BACKGROUND: The efficacy* of onabotulinumtoxinA and topiramate has been established in placebo-controlled randomized clinical trials (*defined as the benefit of treatment under ideal conditions). The effectiveness* of the 2 preventive treatments, however, has not been established (*the benefit of treatment under real-world conditions, representing a blend of efficacy and tolerability). METHODS: In this multicenter, randomized, parallel-group, post-authorization, open-label prospective study (FORWARD; ClinicalTrials.gov, NCT02191579), we randomized adults with CM (1:1) to onabotulinumtoxinA 155 U every 12 weeks for 3 cycles or topiramate "immediate release" 50-100 mg/day to week 36. Primary outcome measure was proportion of patients achieving ≥50% reduction in headache days (weeks 29-32). Missing values were imputed using baseline observation carried forward (BOCF) methodology. After 12 weeks, patients initially randomized to topiramate could cross over to onabotulinumtoxinA treatment. We monitored and recorded all adverse events (AEs). RESULTS: We enrolled 282 patients (onabotulinumtoxinA, n = 140; topiramate, n = 142) and 148 patients completed randomized treatment (onabotulinumtoxinA, n = 120 [86%]; topiramate, n = 28 [20%]). Primary reasons for withdrawal were ineffective treatment (onabotulinumtoxinA, n = 7 [5%]; topiramate, n = 27 [19%]) and AEs (onabotulinumtoxinA, n = 5 [4%]; topiramate, n = 72 [51%]). Eighty topiramate patients crossed over to onabotulinumtoxinA. In the BOCF analysis, a significantly higher proportion of patients randomized to onabotulinumtoxinA experienced ≥50% reduction in headache frequency compared with those randomized to topiramate (40% [56/140] vs 12% [17/142], respectively; adjusted OR, 4.9 [95% CI, 2.7-9.1]; P < .001). OnabotulinumtoxinA was superior to topiramate in meeting secondary endpoints. In a post hoc analysis using observed data, the 50% responder rates at week 12 were 45.6% for onabotulinumtoxinA (n = 125) and 29.4% for topiramate (n = 109) (P = .015). AEs were reported by 48% (105/220) of onabotulinumtoxinA and 79% (112/142) of topiramate patients. Results were similar in those who crossed over to onabotulinumtoxinA. CONCLUSIONS: While using imputation methods of accounting for differences in discontinuation rates, we found onabotulinumtoxinA to have greater clinical utility than topiramate, largely because of tolerability issues associated with the latter and a relatively higher number of onabotulinumtoxinA patients remaining on treatment.

Effects of onabotulinumtoxinA treatment in patients with and without allodynia: results of the COMPEL study.

BACKGROUND: OnabotulinumtoxinA is effective in treating chronic migraine (CM), but there are limited data assessing how allodynia affects preventive treatment responses. This subanalysis of the 108-week, multicenter, open-label COMPEL Study assessed the efficacy and safety of onabotulinumtoxinA in people with CM with and without allodynia. METHODS: Patients (n = 715) were treated with onabotulinumtoxinA 155 U every 12 weeks for 9 treatment cycles. The Allodynia Symptom Checklist was used to identify patients with allodynia (scores ≥3). The primary outcome for this subanalysis was reduction in monthly headache days from baseline for weeks 105 to 108 in groups with and without allodynia. Other outcomes included assessments of moderate to severe headache days, disability (using the Migraine Disability Assessment [MIDAS] questionnaire), and health-related quality of life (Migraine-Specific Quality-of-Life Questionnaire [MSQ] v2). Adverse events and their relation to treatment were recorded. RESULTS: OnabotulinumtoxinA was associated with a significant mean (SD) reduction in headache day frequency at week 108 relative to baseline in patients with (n = 289) and without (n = 426) allodynia (- 10.8 [7.1] and - 12.5 [7.4], respectively; both P < 0.001) that was significantly greater in patients without allodynia (P = 0.044 between-subgroup comparison). Moderate to severe headache days were significantly reduced at week 108 in patients with and without allodynia (- 9.6 [6.9] and - 10.5 [7.2]; both P < 0.001); reduction was similar between groups. MIDAS scores improved significantly at week 108 (- 53.0 [50.3] and - 37.7 [53.0]; both P < 0.001), with a significant between-group difference in favor of those with allodynia (P = 0.005). Similarly, MSQ subscale scores (Role Function Preventive, Role Function Restrictive, Emotional Function) significantly improved at week 108 for patients with and without allodynia: 20.6 (21.9) and 16.9 (20.7), 28.0 (23.3) and 24.7 (22.7), and 27.6 (26.5) and 24.9 (26.1), respectively (all P < 0.001). OnabotulinumtoxinA was well tolerated in patients with and without allodynia. CONCLUSION: Results indicate that onabotulinumtoxinA is associated with reductions from baseline in multiple efficacy outcomes for up to 108 weeks whether or not allodynia is present. The allodynia group showed a smaller treatment response for reduction in headache days, but a similar or greater treatment response for improvement in other measures. No new safety concerns were identified.

Effects of onabotulinumtoxinA treatment in chronic migraine patients with and without daily headache at baseline: results from the COMPEL Study.

BACKGROUND: OnabotulinumtoxinA is effective in preventing chronic migraine (CM); however, the benefit of onabotulinumtoxinA in patients with CM with daily headache is unknown because these patients are typically excluded from clinical trials. This subanalysis of the COMPEL Study assessed the efficacy and safety of onabotulinumtoxinA in people with CM with and without daily headache. METHODS: In total, 715 patients received onabotulinumtoxinA 155 U with or without concomitant oral preventive treatment. Patients who had complete daily diary records for the 28 days of the baseline period were stratified based on daily headache status. The primary outcome variable was reduction in headache-day frequency per 28-day period at 108 weeks (after 9 treatment cycles) relative to baseline. Exploratory outcomes included moderate to severe headache days, migraine disability (using the Migraine Disability Assessment [MIDAS] questionnaire), and health-related quality of life (Migraine-Specific Quality-of-Life Questionnaire v2 [MSQ]). Adverse events and their relatedness were recorded. RESULTS: Overall, 641 patients had complete daily diary records at baseline. In patients with daily headache (n = 138) versus without (n = 503), treatment with onabotulinumtoxinA was associated with a significant mean (SD) reduction in 28-day headache-day frequency relative to baseline at week 108 (- 10.5 [9.2] vs - 12.2 [6.7], respectively; both P < 0.001) with no significant between-group difference (P = 0.132). The mean (SD) reduction in moderate to severe headache days at week 108 was significant in patients with and without daily headache (- 11.5 [9.4] and - 9.9 [6.4]; P < 0.001) with no significant between-group difference (P = 0.153). Mean (SD) MIDAS scores significantly improved from baseline at week 108 (- 43.3 [73.4] and - 43.6 [46.7]; both P < 0.001), with no significant between-group difference (P = 0.962). Similarly, mean (SD) MSQ subscale scores significantly improved from baseline at week 108 for patients with and without daily headache. OnabotulinumtoxinA was well tolerated in patients with and without daily headache. CONCLUSION: Results indicate that onabotulinumtoxinA is associated with reductions from baseline in headache-day frequency and improvements in disability and quality of life for up to 108 weeks in people with CM with daily headache; however, a longer duration of treatment was required to fully realize the treatment effect on headache. No new safety concerns were identified.

What Are We Missing in the Diagnostic Criteria for Migraine?

PURPOSE OF REVIEW: This review is intended to examine how the diagnostic criteria for migraine have evolved over the past 45 years and to evaluate the strengths and weaknesses of the current diagnostic criteria promulgated by the International Classification of Headache Disorders (ICHD). RECENT FINDINGS: The ICHD is a comprehensive and systematic classification system for headache disorders. As the pathophysiology of migraine is more fully elucidated and more sophisticated diagnostic technologies are developed (e.g., the identification of biomarkers), the current diagnostic criteria for migraine will likely be further refined. The ICHD has allowed for more precise research study design in the field of headache medicine. The current diagnostic criteria for migraine outlined in the 3rd version of the ICHD are far more sensitive and specific than the clinical criteria proposed in 1962. In future iterations, dividing episodic and chronic migraine into subtypes based on frequency (i.e., low frequency vs high frequency; near-daily vs daily) potentially could assist in guiding clinical management. In addition, a better understanding of aura, vestibular migraine, migrainous infarction, and hemiplegic migraine likely will lead to more refined diagnostic criteria for those entities.

Cerebral Sinus Thrombosis.

BACKGROUND: Although cerebral venous thrombosis/cerebral sinus thrombosis (CVT/CST) remains a relatively uncommon cause of stroke and other neurologic complications, the widespread availability of noninvasive brain imaging has led to an increase in its diagnosis. PURPOSE: Through a review and description of its epidemiology, clinical features and treatment, to heighten awareness of CVT/CST. METHODOLOGY: Via a systematic review of the more recently published medical literature relevant to the topic and focusing in particular on primary sources, we compiled data related to the incidence of CVT/CST and its diagnosis, treatment and prognosis. RESULTS: Thrombosis of a cerebral vein or sinus may occur in individuals of any age and may be caused by a myriad of prothrombotic conditions, both primary and acquired. The clinical presentation of CVT/CST is widely variable, but headache is present in the great majority of cases, and the predominant symptom in many. The headache associated with CVT/CST may be acute, severe, and even "thunderclap" in character, or it may be chronic, pervasive, and of lower intensity. CONCLUSIONS: Given its eclectic epidemiology, its potential to produce a highly unfavorable clinical outcome, and evidence suggesting that specific treatment improves outcome, CVT/CST is a disorder whose salient features should be familiar to virtually all clinicians.

Hemiplegia and headache: a review of hemiplegia in headache disorders.

The most common scenario wherein the practicing neurologist is likely to encounter a patient with headache and hemiplegia will vary depending on his/her specific type of practice. A neurologist providing consultative service to an emergency department is far more likely to see patients with "secondary" headache and hemiplegia in the setting of either ischemic or hemorrhagic stroke than hemiplegia as a transient feature of a primary headache disorder. Neurologists subspecializing in headache medicine who practice in a tertiary referral headache clinic are more likely to encounter hemiplegic migraine, but even in that clinical setting hemiplegic migraine is by no means a frequent diagnosis. The acute onset of hemiplegia can be very frightening not only to the patient but also to the medical personnel. Given the abundance of mimicry, practitioners must judiciously ascertain the correct diagnosis as treatment may greatly vary depending on the cause of both headache and hemiplegia. In this review, we will address the most common causes of hemiplegia associated with headache.

Real-world economic impact of onabotulinumtoxinA in patients with chronic migraine.

OBJECTIVE: To determine whether the utilization of healthcare resources is reduced after chronic migraine patients are treated for 6 months with onabotulinumtoxinA. BACKGROUND: OnabotulinumtoxinA is indicated for headache prophylaxis in patients with chronic migraine, but its effect on healthcare resource use is unknown. METHODS: We analyzed data from an open-label study of 230 chronic migraine patients refractory to ≥2 oral prophylactics who presented to a headache specialty clinic and who were treated with two cycles of onabotulinumtoxinA. Frequency and cost of migraine-related healthcare resource use, including visits to emergency departments, urgent care, or hospitalization, were compared for the 6 months before and after initial treatment. Costs were based on publicly available sources. RESULTS: Compared with the 6 months predating initial treatment, patients had 55% fewer emergency department visits (174 vs 385), 59% fewer urgent care visits (61 vs 150), and 57% fewer hospitalizations (19 vs 45) during the 6-month treatment period (P < .01 for all). Analysis of treatment-related costs yielded an average reduction of $1219.33/patient, off-setting 49.7% of the total estimated cost for 6 months of treatment with onabotulinumtoxinA. CONCLUSIONS: Although we are unable to distinguish onabotulinumtoxinA's treatment effect from other potential confounding variables, our analysis showed that severely afflicted, treatment-refractory patients with chronic migraine experienced a significant cost-offset through reduced migraine-related emergency department visits, urgent care visits, and hospitalizations in the 6 months following treatment initiation of onabotulinumtoxinA. Future analyses will assess the longer-term effect of onabotulinumtoxinA treatment and the potential contribution of regression to the mean.

Headache due to Vascular Disorders.

Headache and cerebrovascular disease (CVD) are inextricably linked. Although in some cases headache complicating CVD may be little more than a symptomatic afterthought, in other cases, early recognition of headache's role in the CVD process is critical to effective management. In other words, headaches secondary to CVD span a spectrum, and in this article, we will review that spectrum.

A review of needle-free sumatriptan injection for rapid control of migraine.

The treatment of migraine was transformed in 1992 with the introduction of the first triptan-based therapy, subcutaneous (SC) sumatriptan. SC sumatriptan has high efficacy and a rapid onset of action compared with other available triptans and formulations presumably because of its short Tmax, high Cmax, and avoidance of enteral absorption. Because of these characteristics, SC sumatriptan is still considered the most reliably and rapidly effective self-administered medication available for acute migraine. Even so, it is relatively little used possibly in part because of patient "needle-phobia." The needle-free sumatriptan injection system (Sumavel DosePro) was developed to address this concern. Clinical trials have shown that the needle-free system is bioequivalent to needle-based injection systems, easy to use, and capable of providing rapid and effective symptom relief for many migraine episodes. Sumavel DosePro is an effective treatment for migraine and should be part of the therapeutic armamentarium, particularly in cases where a rapid onset of action is critical or where oral administration is problematic.

"Mixing triptans": patient satisfaction.

BACKGROUND: Although some patients may prefer using an oral triptan other than sumatriptan and injectable sumatriptan to treat an attack of persistent migraine, administration of 2 different triptans within a 24-hour period currently is contradicted. OBJECTIVE: We sought to determine patient satisfaction with an acute migraine treatment regimen wherein patients were permitted to administer an oral triptan other than sumatriptan and injectable sumatriptan within 24 hours of one another METHODS: We evaluated a consecutive series of migraine patients who either had tried and failed oral sumatriptan or were using another oral triptan and were satisfied with it. We advised subjects that they could administer their oral triptan and injectable sumatriptan within a single 24-hour period (but not within 2 hours of one another); we termed such treatment "mixing triptans." We asked all subjects to keep detailed written headache diaries for the 6-month treatment period, and at the 6-month end-of-study visit we asked subjects who had treated at least 3 migraine attacks by mixing triptans to rate their satisfaction with that treatment according to a 5-point Likert scale. RESULTS: Of the 200 subjects enrolled, 132 (66%) used an oral triptan other than sumatriptan and injectable sumatriptan within a 24-hour period on at least 3 occasions. At their final follow-up visits, 117 (89%) of the 132 reported themselves "very satisfied" or "satisfied" with this specific treatment regimen. No serious adverse events were recorded. CONCLUSION: The option of sequentially using an oral triptan other than sumatriptan and injectable sumatriptan to treat a given attack of migraine appears to correlate with a high rate of patient satisfaction. While in our subject population this treatment regimen was well tolerated, our study results do not suffice to establish the safety of "mixing triptans."

Satisfaction with and confidence in needle-free subcutaneous sumatriptan in patients currently treated with triptans.

OBJECTIVE: To evaluate patient satisfaction with and confidence in Sumavel® DosePro® (needle-free subcutaneous sumatriptan) among current triptan users administering Sumavel DosePro for up to 4 migraine attacks. BACKGROUND: Sumavel DosePro is a needle-free, single-use device that facilitates subcutaneous injection of sumatriptan 6 mg and confers relief as early as 10 minutes after dosing. DESIGN/METHODS: In this open-label, multicenter study, Sumavel DosePro was self-administered for ≤4 migraine attacks (over a ≤60-day period) involving moderate or severe baseline pain by adult migraineurs who currently were using triptans (any form, any dosage) and reported being less than very satisfied with their current therapy (i.e., baseline satisfaction ranging from satisfied to very dissatisfied). Treatment satisfaction was measured via the Patient Perception of Migraine Questionnaire, revised (PPMQ-R). RESULTS: Among the 212 patients using Sumavel DosePro to treat ≥1 migraine attack, PPMQ-R Overall Satisfaction (primary endpoint) increased significantly from baseline to the end of treatment (mean ± SD 65.7 ± 19.8 vs. 73.7 ± 29.1, P = .0007), an improvement that met the criterion for clinical significance. From baseline to the end of treatment, PPMQ-R scores also improved significantly for Efficacy (62.2 ± 17.6 vs. 76.2 ± 23.7, P < .0001), Functionality (59.0 ± 22.3 vs. 73.8 ± 25.3, P < .0001), and Tolerability (83.9 ± 13.1 vs. 86.4 ± 15.0, P = .02), but declined for Ease of Use (82.6 ± 15.3 vs 67.8 ± 27.6, P < .0001). For all global satisfaction domains, the percentage of patients satisfied or very satisfied increased from baseline to the end of treatment (Overall Satisfaction 36.3% vs. 64.0%, Satisfaction with Medication Effectiveness 40.1% vs. 68.2%, Satisfaction with Side Effects 48.6% vs. 67.3%). The percentage of patients who were confident or very confident in treating repeated migraine attacks also increased (baseline: 41.0%, 90% confidence interval [CI] 35.4, 46.9 vs. end of treatment: 66.5%, 90% CI 58.9, 70.1). The efficacy results (pain relief, pain-free response, sustained 24-hour pain relief and pain-free response) were consistent with those previously observed with needle-based sumatriptan. CONCLUSIONS: Patients currently treated with triptans and less than very satisfied with their acute migraine therapy experienced a statistically significant and clinically relevant increase in satisfaction with therapy and enhanced confidence in treatment after use of Sumavel DosePro for up to 4 migraine attacks.

Safety and tolerability of preventive treatment options for chronic migraine.

INTRODUCTION: Relative to migraine generally, chronic migraine (CM) imposes greater disability, healthcare utilization and socioeconomic burden. Six therapies currently possess a credible evidence base for prevention/suppression of CM. This review is intended to provide an assessment of their relative utility, defined as a blend of safety, tolerability and efficacy, focusing in particular on their safety and tolerability.Areas Covered: We discuss all six medications currently FDA-approved for migraine prevention which also specifically possess credible evidence of efficacy in treating CM. While we do address the efficacy of each, our primary emphasis involves assessment of safety and tolerability data derived from clinical trials and post-marketing experience.Expert Opinion: Recent research involving CM has led to the identification of highly targeted and typically well-tolerated therapies. For patients who experience obstacles to accessing these newer therapies, topiramate is available as an evidence-based alternative, but contraindications, drug-drug interactions and poor tolerability may limit or prevent its use. Although data to support such intervention presently is limited, clinically challenging CM cases may benefit from combination therapy. 'Real world' studies are needed to evaluate such polytherapy, along with studies intended to assess the long-term safety of the individual therapies and their use during pregnancy and breast-feeding.

An analysis of migraine triggers in a clinic-based population.

BACKGROUND: Many migraineurs report attack "triggers," but relatively few published data exist regarding the relative prevalences of individual triggers, variations related to gender, duration of migraine or migraine subtype, or the existence of any regional variations in the prevalences and distributions of triggers. OBJECTIVE: We sought to determine the prevalence and types of migraine triggers in our clinic population, to determine what influence gender, migraine subtype, or duration of migraine might have on the prevalences and types of triggers reported and to compare our findings with data derived from surveys we previously had conducted involving 2 clinic-based populations and 1 general population sample from other regions of the USA. METHODS: We evaluated 200 consecutive new migraine patients referred to our clinic. All patients specifically were queried as to whether they had noted any of 7 specific factors to serve consistently as migraine attack triggers and additionally were surveyed as to whether they might have "other" triggers not listed on the intake questionnaire. Among the other data collected and analyzed were age, gender, age at time of migraine onset, and migraine subtype (ie, episodic vs chronic). Actively cycling females who reported menses as a trigger were questioned as to whether their menstrual migraine (MM) attacks differed from their non-menstrual migraines and, if so, how they differed. RESULTS: One hundred and eighty-two patients (91%) reported at least 1 migraine trigger, and 165 (82.5%) reported multiple triggers. The most common trigger reported (59%) was "emotional stress," followed by "too much or little sleep" (53.5%), "odors" (46.5%), and "missing meals" (39%). Females or subjects of either gender with chronic migraine were no more likely than males or subjects with episodic migraine to report triggers or multiple triggers. Similarly, longer exposure to migraine did not correlate with a higher likelihood of reporting a trigger or multiple triggers. Fifty-three (62%) of 85 actively cycling females reported menses as a trigger, and of the 51 with menstrually related migraine, 34 (67%) reported their MM to be more severe, more refractory to symptomatic therapy or of longer duration than their non-menstrual attacks; 13 (24.5%) of the 53 women with apparent MM reported their MM to be at least occasionally manifested as status migrainosus. The prevalence and type of triggers reported by this predominantly white female population were similar to those reported by clinic-based populations in San Diego, California and Mobile, Alabama, and in a population-based sample of Hispanics in San Diego County. CONCLUSIONS: A large majority of migraineurs report migraine attack triggers, and the triggers most commonly reported include emotional stress, a disrupted sleep pattern, and various odors. These findings do not appear to vary according to geographic region or race/ethnicity. Among the triggers, MM appears inclined to provoke headache that is more severe, less amenable to treatment, or longer in duration than headaches that occur at other times during the cycle.

Suboccipital nerve blocks for suppression of chronic migraine: safety, efficacy, and predictors of outcome.

BACKGROUND: Approximately 1 in 50 Americans is afflicted by chronic migraine (CM). Many patients with CM describe cervicogenic headache. Options for treating CM effectively are at present quite limited. OBJECTIVE: To determine the safety and efficacy of occipital nerve blocks (ONBs) used to treat cervicogenic chronic migraine (CCM) and to identify variables predictive of a positive treatment response. METHODS: Using a uniform dose and injection paradigm, we performed ONBs consecutively on a series of patients presenting with CCM. Patients were stratified according to specific findings found to be present or absent on physical examination. A positive treatment outcome was defined as a 50% or greater reduction in headache days per month over the 30 days following treatment relative to the 30-day pre-treatment baseline. We used a 5-point Likert scale as one of the secondary outcome variables. RESULTS: We treated 150 consecutive patients with unilateral (37) or bilateral (113) ONBs. At the 1-month follow-up visit 78 (52%) exhibited evidence of a positive treatment response according to the primary outcome variable, and 90 (60%) reported their headache disorder to be "better" (44; 29%) or "much better" (46; 30%). A total of 8 (5%) patients reported adverse events within the ensuing 72 hours, and 3 (2%) experienced adverse events that reversed spontaneously but required emergent evaluation and management. CONCLUSION: For suppression of CCM, ONBs may offer an attractive alternative to orally administered prophylactic therapy.