Headache and non-headache symptoms provoked by nitroglycerin in migraineurs: A human pharmacological triggering study

Background Studying a spontaneous migraine attack is challenging, particularly the earliest components. Nitroglycerin is a potent, reliable and reproducible migraine trigger of the entirety of the migraine attack, making its use experimentally attractive. Methods Fifty-three subjects with migraine with a history of spontaneous premonitory symptoms were exposed to a 0.5 mcg/kg/min nitroglycerin infusion. Eighty-three percent (n = 44) developed typical premonitory and headache symptomatology. Fifty-seven percent (n = 25) were invited back to further study visits, during which they were re-exposed to nitroglycerin or placebo infusion in a double-blind randomised design. The phenotype of premonitory symptoms and headache was captured and compared to spontaneous attacks and between triggered attacks using agreement analysis. Results More premonitory symptoms were triggered with nitroglycerin than placebo (mean symptom difference = 4, t20 = 7.06, p < 0.001). The agreement in triggering for the most commonly reported premonitory symptoms (concentration difficulty and tiredness) was >66%. The retriggering agreement for all but one premonitory symptom was >60%. The agreement in timing to onset of premonitory symptoms was reliable across two triggered attacks. The agreement with spontaneous attacks and between attacks for headache and its associated symptoms, including laterality, was less reliable. Conclusions Nitroglycerin can reliably and reproducibly provoke premonitory symptomatology associated with migraine. This forms an ideal model to study the earliest manifestations of migraine attacks.

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The premonitory phase of migraine and migraine management

Cephalalgia ◽

10.1177/0333102412437390 ◽

2012 ◽

Vol 33 (13) ◽

pp. 1117-1121 ◽

Cited By ~ 21

Author(s):

Werner J Becker

Keyword(s):

Literature Review ◽

Migraine Attack ◽

Management Strategy ◽

Controlled Study ◽

Open Label ◽

Double Blind ◽

Open Label Study ◽

Label Study ◽

Medication Treatment ◽

Premonitory Symptoms

Objective: The objective was to determine, through a literature review, whether treatment during the premonitory phase of migraine is a potentially useful migraine management strategy. Methods: A general literature review was done with regard to the nature of migraine premonitory symptoms, their frequency, their reliability in predicting migraine attacks, and the effectiveness of medication treatment when given during the premonitory phase. Results: Many different symptoms have been reported as premonitory symptoms that occur before migraine attacks. Up to 87% of patients with migraine may experience premonitory symptoms, although some studies have provided estimates as low as 33%. In selected patients, premonitory symptoms may be relatively reliable predictors of a migraine attack to follow. Both naratriptan (open-label study) and domperidone (double-blind, randomized, placebo-controlled study) have been reported to be effective when given during the premonitory phase. Conclusions: More research is needed, but there is some evidence that medication treatment during the premonitory phase has the potential to be helpful in selected patients with migraine.

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Randomized, controlled trial of telcagepant over four migraine attacks

Cephalalgia ◽

10.1177/0333102410370878 ◽

2010 ◽

Vol 30 (12) ◽

pp. 1443-1457 ◽

Cited By ~ 57

Author(s):

Andrew P Ho ◽

Carl GH Dahlöf ◽

Stephen D Silberstein ◽

Joel R Saper ◽

Messoud Ashina ◽

...

Keyword(s):

Pain Relief ◽

Migraine Attack ◽

Controlled Trial ◽

Control Treatment ◽

Double Blind ◽

Calcitonin Gene ◽

Associated Symptoms ◽

Cgrp Receptor Antagonist ◽

Severe Migraine ◽

Treatment Sequences

Methods: This study evaluated the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant (tablet formulation) for treatment of a migraine attack and across four attacks. Adults with migraine were randomized, double-blind, to telcagepant 140 mg, telcagepant 280 mg, or control treatment sequences to treat four moderate-to-severe migraine attacks. Control patients received placebo for three attacks and telcagepant 140 mg for one attack. Efficacy for the first attack (Attack 1) and consistency of efficacy over multiple attacks were assessed. For an individual patient, consistent efficacy was defined as ≥3 successes, and lack of consistent efficacy was defined as ≥2 failures, in treatment response. A total of 1677 patients treated ≥1 attack and 1263 treated all four attacks. Results: Based on Attack 1 data, telcagepant 140 mg and 280 mg were significantly ( p < .001) more effective than placebo for 2-hour pain freedom, 2-hour pain relief, 2-hour absence of migraine-associated symptoms (phonophobia, photophobia, nausea), and 2–24 hours sustained pain freedom. The percentage of patients with 2-hour pain freedom consistency and 2-hour pain relief consistency was significantly ( p < .001) higher for both telcagepant treatment sequences versus control. Adverse events within 48 hours for telcagepant with an incidence ≥2% and twice that of placebo were somnolence (placebo = 2.3%, 140 mg = 5.9%, 280 mg = 5.7%) and vomiting (placebo = 1.4%, 140 mg = 1.0%, 280 mg = 2.9%). Conclusion: Telcagepant 140 mg and 280 mg were effective for treatment of a migraine attack and were more consistently effective than control for intermittent treatment of up to four migraine attacks. Telcagepant was generally well tolerated. (Clinicaltrials.gov; NCT00483704)

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Domperidone Plus Paracetamol in The Treatment of Migraine

Cephalalgia ◽

10.1046/j.1468-2982.1993.1302124.x ◽

1993 ◽

Vol 13 (2) ◽

pp. 124-127 ◽

Cited By ~ 39

Author(s):

E Anne MacGregor ◽

Marcia Wilkinson ◽

K Bancroft

Keyword(s):

Adverse Events ◽

Pain Intensity ◽

Migraine Attack ◽

Double Blind ◽

Safety And Efficacy ◽

Significant Difference ◽

Associated Symptoms ◽

City Of London ◽

The City ◽

Efficacy Of Treatment

This study was designed to evaluate the safety and efficacy of domperidone in combination with paracetamol in the treatment of migraine. Severity of headache, duration of migraine attack and overall efficacy of treatment were amongst the variables assessed in a randomized, double-blind, three-way cross-over comparison of 1 g paracetamol plus either domperidone 30 mg, domperidone 20 mg or placebo, taken at onset of headache. Forty-six patients attending the City of London Migraine Clinic completed the study. A significant difference was observed in the duration of the migraine attack: a median of 17.5 h with paracetamol alone was reduced to 12.0 h with the addition of domperidone 20 mg, and to 12.0 h with domperidone 30 mg. No significant adverse events were reported. A reduction in pain intensity and nausea was noted but this was not statistically significant. It was concluded that domperidone shortens the duration of a migraine attack and may help reduce headache and associated symptoms.

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A Combination of Lactoplantibacillus plantarum Strains CECT7527, CECT7528 and CECT7529 Plus Monacolin K Reduces Blood Cholesterol: Results from a Randomized, Double-Blind, Placebo-Controlled Study

Nutrients ◽

10.3390/nu13041206 ◽

2021 ◽

Vol 13 (4) ◽

pp. 1206

Author(s):

Rafael Guerrero-Bonmatty ◽

Guadalupe Gil-Fernández ◽

Francisco José Rodríguez-Velasco ◽

Jordi Espadaler-Mazo

Keyword(s):

Intervention Group ◽

Study Groups ◽

Statin Treatment ◽

Blood Cholesterol ◽

Controlled Study ◽

Controlled Clinical Trial ◽

Red Yeast Rice ◽

Monacolin K ◽

Double Blind ◽

History Of

Background: Dietary supplements have been proposed to help manage blood cholesterol, including red yeast rice (RYR) extracts, plant sterols and stanols, beta-glucans, and some probiotics. This study was conducted to evaluate the efficacy of RYR (containing 10 mg of monacolin K) combined with 109 CFU of three Lactoplantibacillus plantarum strains (CECT7527, CECT7528, and CECT7529). Methods: A 12-week randomized, double-blinded, placebo-controlled clinical trial was conducted. In total, 39 adult patients were enrolled, having total cholesterol (TC) ≥200 mg/dL, and being statin-naïve or having recently stopped statin treatment because of intolerance. Active product or placebo were taken once daily, and subjects were evaluated at baseline, 6, and 12 weeks. Results: Study groups were comparable at baseline, except for history of recent hypercholesterolemia treatment (81% in active vs. 22% in placebo). Changes in LDL cholesterol and TC became significant compared to placebo (mean difference between groups and standard error of the mean = 23.6 ± 1.5 mg/dL, p = 0.023 and 31.4 ± 1.9 mg/dL, p = 0.011, respectively) upon adjusting for the baseline imbalance in hypercholesterolemia treatment. No adverse effects were noted during the study. Conclusion: This combination of 10 mg of monacolin K and L. plantarum strains was well tolerated and achieved a statistically significant greater reduction in LDL-C and TC in the intervention group compared to the placebo, once adjusting for recent history of hypercholesterolemia treatment.

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Efficacy of galcanezumab in patients with episodic cluster headaches and a history of preventive treatment failure

Cephalalgia Reports ◽

10.1177/25158163211015654 ◽

2021 ◽

Vol 4 ◽

pp. 251581632110156

Author(s):

Brian Plato ◽

J Scott Andrews ◽

Mallikarjuna Rettiganti ◽

Antje Tockhorn-Heidenreich ◽

Jennifer Bardos ◽

...

Keyword(s):

Cluster Headache ◽

Treatment Failure ◽

Preventive Treatment ◽

Mean Difference ◽

Least Square ◽

Double Blind Study ◽

Double Blind ◽

Cluster Headache Attack ◽

Episodic Cluster Headache ◽

History Of

Objective: The efficacy of galcanezumab was evaluated in patients with episodic cluster headache and history of preventive treatment failure. Methods: In the randomized, 8-week, double-blind study (CGAL), patients with episodic cluster headache received once-monthly subcutaneous injections of galcanezumab 300 mg or placebo. Patients who completed CGAL and enrolled in an open-label study were queried for preventive treatment history. In a subset of patients with a known history of failure of verapamil or any other prior preventive treatment, a post hoc analysis of least square mean change from baseline in weekly cluster headache attack frequency across Weeks 1 to 3 was assessed. Results: Fifteen patients provided data for known history of prior preventive treatment failure (6 placebo, 9 galcanezumab), of whom 11 failed verapamil. The mean reduction in the weekly frequency of cluster headache attacks was greater with galcanezumab compared to placebo among patients with prior preventive treatment failure (8.2 versus 2.4); mean difference 5.8 (95% confidence interval [CI] 2.0, 13.6) and among patients with verapamil failure (10.1 versus 1.6); mean difference 8.5 (95% CI 0.4, 16.7). Conclusion: In this exploratory analysis of patients with a known history of prior preventive treatment failures, treatment with galcanezumab resulted in greater mean reductions in weekly cluster headache attacks compared with placebo. ClinicalTrials.gov: NCT02397473 (I5Q-MC-CGAL) NCT02797951 (I5Q-MC-CGAR)

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Effect of galcanezumab on severity and symptoms of migraine in phase 3 trials in patients with episodic or chronic migraine

The Journal of Headache and Pain ◽

10.1186/s10194-021-01215-9 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Michael Ament ◽

Kathleen Day ◽

Virginia L Stauffer ◽

Vladimir Skljarevski ◽

Mallikarjuna Rettiganti ◽

...

Keyword(s):

Chronic Migraine ◽

Migraine Headache ◽

Randomized Clinical Trials ◽

Episodic Migraine ◽

Double Blind Study ◽

Double Blind ◽

Prodromal Symptoms ◽

Link Type ◽

Associated Symptoms ◽

Severe Migraine

Abstract Background Galcanezumab, a humanized monoclonal antibody that binds calcitonin gene-related peptide, has demonstrated a significant reduction in monthly migraine headache days compared with placebo. Here, we analyze data from 3 randomized clinical trials (2 episodic trials [EVOLVE-1, EVOLVE-2] and 1 chronic trial [REGAIN]), to examine if galcanezumab also alleviates the severity and symptoms of migraine. Methods The episodic migraine trials were 6-month, double-blind studies in patients with episodic migraine (4–14 monthly migraine headache days). The chronic migraine trial was a 3-month, double-blind study in patients with chronic migraine (≥ 15 headache days per month, where ≥ 8 met criteria for migraine). Patients (18–65 years) were randomized to placebo or galcanezumab 120 mg with a 240-mg loading dose or 240 mg. Patients recorded headache characteristics, duration, severity, and presence of associated symptoms with each headache. The outcomes analyzed were changes from baseline in number of monthly migraine headache days with nausea and/or vomiting, photophobia and phonophobia, aura, and prodromal symptoms other than aura. Additional outcomes analyzed included the number of moderate-to-severe monthly migraine headache days, number of severe migraine headache days, and mean severity of remaining migraine headache days. Change from baseline in the proportion of days with nausea and/or vomiting and the proportion of days with photophobia and phonophobia among the remaining monthly migraine headache days were also analyzed. Results Galcanezumab was superior to placebo in reducing the frequency of migraine headache days with associated symptoms of migraine such as nausea and/or vomiting, photophobia and phonophobia, and prodromal symptoms. Galcanezumab reduced the frequency of migraine headache days with aura in the episodic migraine studies. There was a significant reduction in the proportion of remaining migraine headache days with nausea and/or vomiting for the episodic and chronic migraine studies, and with photophobia and phonophobia for the episodic migraine studies. Galcanezumab was superior to placebo in reducing the number of monthly moderate-to-severe migraine headache days and the overall and monthly severe migraine headache days. Conclusions Galcanezumab reduces the frequency of migraine headache days and can alleviate potentially disabling non-pain symptoms on days when migraine is present in patients with episodic or chronic migraine. Trial registration NCT, NCT02614183 (EVOLVE-1), registered 25 November 2015; NCT, NCT02614196, (EVOLVE-2), registered 25 November 2015; NCT, NCT02614261 (REGAIN), registered 25 November 2015.

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Safety and effectiveness of eculizumab in Japanese patients with generalized myasthenia gravis: interim analysis of post-marketing surveillance

Therapeutic Advances in Neurological Disorders ◽

10.1177/17562864211001995 ◽

2021 ◽

Vol 14 ◽

pp. 175628642110019

Author(s):

Hiroyuki Murai ◽

Shigeaki Suzuki ◽

Miki Hasebe ◽

Yuji Fukamizu ◽

Ema Rodrigues ◽

...

Keyword(s):

Myasthenia Gravis ◽

Interim Analysis ◽

Japanese Patients ◽

Phase Iii ◽

High Dose ◽

Complement Protein ◽

Double Blind ◽

Post Marketing Surveillance ◽

Post Marketing ◽

History Of

Background: Eculizumab, a humanized monoclonal antibody targeted to terminal complement protein C5, is approved in Japan for treatment of patients with anti-acetylcholine receptor antibody-positive (AChR+) generalized myasthenia gravis (gMG) whose symptoms are difficult to control with high-dose intravenous immunoglobulin (IVIg) therapy or plasmapheresis. Methods: This interim analysis of mandatory post-marketing surveillance in Japan assessed the safety and effectiveness of eculizumab at 26 weeks after treatment initiation in patients with AChR+ gMG. Results: Data were available for 40 adult patients in Japan [62.5% (25/40) female; mean age at eculizumab initiation, 51.0 years]. Fifteen patients had a history of thymoma. Six patients were excluded from the effectiveness analysis set due to participation in the open-label extension part of the phase III, randomized, double-blind, placebo-controlled REGAIN study [ClinicalTrials.gov identifier: NCT02301624]. After 26 weeks’ follow up, 32 patients (80%) were continuing eculizumab treatment. Adverse drug reactions were reported by seven patients [most frequently headache ( n = 3)]. One death was reported during eculizumab treatment (relationship unclear as determined by the treating physician) and there was one death 45 days after the last dose (considered unrelated). No meningococcal infections were reported. Mean (standard deviation) changes from baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores were −3.7 (2.61) ( n = 27) and −5.6 (3.50) ( n = 26), respectively, at 12 weeks, and −4.3 (2.72) ( n = 26) and −5.6 (4.02) ( n = 24), respectively, at 26 weeks. Improvements in MG-ADL and QMG scores were generally similar in patients with/without a history of thymoma. Frequency of IVIg use decreased following eculizumab initiation. Conclusion: In a real-world setting, eculizumab was effective and well tolerated for the treatment of AChR+ gMG in adult Japanese patients whose disease was refractory to IVIg or plasmapheresis. These findings are consistent with the efficacy and safety results from the global phase III REGAIN study of eculizumab.

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Episodic versus Chronic Dizziness: An Analysis of Predictive Factors

Annals of Otology Rhinology & Laryngology ◽

10.1177/00034894211025416 ◽

2021 ◽

pp. 000348942110254

Author(s):

Eric J. Formeister ◽

Ricky Chae ◽

Emily Wong ◽

Whitney Chiao ◽

Lauren Pasquesi ◽

...

Keyword(s):

Multivariate Regression ◽

Treatment Options ◽

Depression And Anxiety ◽

Imaging Studies ◽

Comorbid Depression ◽

Cross Sectional ◽

Tertiary Center ◽

Chronic Dizziness ◽

Associated Symptoms ◽

History Of

Objectives: To elucidate differences in demographic and clinical characteristics between patients with episodic and chronic dizziness. Methods: A cross-sectional, observational study of 217 adults referred for dizziness at 1 tertiary center was undertaken. Subjects were split into a chronic dizziness group (>15 dizzy days per month) and an episodic dizziness group (<15 dizzy days per month). Results: 217 adults (average age, 53.7 years; 56.7% female) participated. One-third (n = 74) met criteria for chronic dizziness. Dizziness handicap inventory (DHI) scores were significantly higher in those with chronic dizziness compared to those with episodic dizziness (53.9 vs 40.7; P < .001). Comorbid depression and anxiety were more prevalent in those with chronic dizziness (44.6% and 47.3% vs 37.8% and 35.7%, respectively; P > .05). Abnormal vestibular testing and abnormal imaging studies did not differ significantly between the 2 groups. Ménière’s disease and BPPV were significantly more common among those with episodic dizziness, while the prevalence of vestibular migraine did not differ according to chronicity of symptoms. A multivariate regression that included age, sex, DHI, history of anxiety and/or depression, associated symptoms, and dizziness triggers was able to account for 15% of the variance in the chronicity of dizziness (pseudo- R2 = 0.15; P < .001). Conclusions: Those who suffer from chronic dizziness have significantly higher DHI and high comorbid rates of depression and anxiety than those with episodic dizziness. Our findings show that factors other than diagnosis alone are important in the chronification of dizziness, an observation that could help improve on multimodal treatment options for this group of patients.

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