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Background: Clinical trials and observational studies with anti-calcitonin gene-related peptide antibodies poorly investigated their impact on migraine prodromal and accompanying symptoms. This information might help deciphering the biologics' pharmacodynamic and provide hints on migraine pathogenesis. Herein, we report the effects of erenumab, fremanezumab and galcanezumab on attack prodromal and accompanying symptoms and on neurological and psychiatric traits. Methods: An explorative, prospective, questionnaire-based study was completed by a cohort (n = 80) of patients with chronic migraine patients presenting a sustained reduction of ≥50% of Migraine Disability Assessment Score and ≥30% of monthly migraine days three months after anti-calcitonin gene-related peptide antibodies treatment. Results: The majority of patients experienced a complete prevention of migraine symptoms without evidence of initial onset followed by attack abortion. Few patients reported the recurrence of prodromal (from 10% to 12.5%) or accompanying (from 1.3% to 8.8%) symptoms without headache. All patients with migraine with aura reported a decrease of aura incidence. Sleep changes (51.2%), increase in appetite (20.0%) and weight (18.8%) as well as a reduction in stress (45.0%), anxiety (26.3%), and panic attacks (15%) were also reported. Conclusion: Anti-calcitonin gene-related peptide antibodies seems to significantly impact brain functions of migraineurs, preventing not only migraine headache but also its anticipatory and accompanying symptoms. [ABSTRACT FROM AUTHOR]

Background: A novel formulation of diclofenac, complexed with hydroxypropyl-β-cyclodextrin (HPβCD) as a solubility enhancer, in a prefilled syringe for self-administered subcutaneous injection may overcome the limitations of acute migraine treatments administered by oral, rectal, intramuscular, or intravenous routes. Methods: This multicentre, phase 2, double-blind, randomized, placebo-controlled, dose-finding pilot study evaluated the efficacy, safety and tolerability of three different doses (25/50/75 mg/1 mL) of subcutaneous diclofenac sodium in the treatment of an acute migraine attack in 122 subjects. The primary efficacy endpoint was the percentage of patients pain-free at 2 hours after the study drug injection. Results: A significantly higher percentage of patients in the 50 mg diclofenac group 14 (46.7%) were pain-free at 2 hours when compared with placebo: 9 (29.0%) (p = 0.01). The 50 mg dose proved superior to placebo also in the majority of the secondary endpoints. The overall global impression favoured diclofenac vs placebo. There were no adverse events leading to study withdrawal. The majority of treatment-emergent adverse events were mild. Conclusions: The 50 mg dose of this novel formulation of diclofenac represents a valuable self-administered option for the acute treatment of migraine attacks. Trial registration: EudraCT Registration No. 2017-004828-29. [ABSTRACT FROM AUTHOR]

Background: A pharmacological class effect was initially proposed for monoclonal antibodies against the calcitonin gene related peptide pathway. However, preliminary evidence shows that switching patients who were non-responding to one monoclonal antibody to another could provide some benefit. Herein, we assess treatment response to an anticalcitonin gene related peptide/receptor monoclonal antibody in patients who have failed to respond to anti-calcitonin gene related peptide/ligand monoclonal antibodies calcitonin gene related peptide/ligand monoclonal antibodies and vice versa. In addition, we select non-responders to the first anti-monoclonal antibody by three or five more stringent variables. Methods: Retrospective cohort study including outpatients treated consecutively with two anti-calcitonin gene related peptide monoclonal antibodies. Ineffectiveness to the first monoclonal antibody was assessed using three (MIDAS score, monthly headache days, and analgesic monthly days) variables or five (monthly headache days, MIDAS score, analgesic monthly days, analgesic monthly number and HIT-6 score) variables in the same cohort of patients. The primary endpoints were the absolute change from baseline in monthly headache days, response rate, and persistence in medication overuse at three months of treatment with the second anti-CGRP mAb. Results: In patients selected by three variables, a sustained reduction in monthly headache days, analgesic monthly days, MIDAS and HIT-6 scores was observed at month-3 of treatment with the second monoclonal antibody. Ten (45.4%) patients achieved at least a -30% response rate. No difference was reported switching anti-CGRP mAb against ligand or receptor. In the patient subgroup selected by five variables, only HIT-6 was reduced from baseline at month-3. However, a trend toward a reduction in monthly headache days, analgesic monthly days, and MIDAS score was observed at month-3. Conclusions: Switching anti-calcitonin gene related peptide monoclonal antibodies in selected patients might be an option to achieve or improve clinical benefit. More studies are required to establish the effectiveness of switching these treatments. Conclusions: Switching anti-calcitonin gene related peptide monoclonal antibodies in selected patients might be an option to achieve or improve clinical benefit. More studies are required to establish the effectiveness of switching these treatments. [ABSTRACT FROM AUTHOR]

Background: The proper identification of chronic migraine is one of the mainstays for general practitioners. This study therefore aims to assess the epidemiology and determinants of chronic migraine in primary care in Italy by testing five operational case definition algorithms. Methods: Five case definition algorithms defining chronic migraine were developed to estimate the prevalence and incidence rate of chronic migraine in the Health Search database. For each algorithm, we conducted a nested case-control analysis to quantify the level of association between certain determinants and incident cases of chronic migraine. Results: Considering a cohort of 1,091,032 patients (52% were females), the prevalence rate of chronic migraine increased from the first to the fifth case definition algorithm ranging from 0.03 to 0.28%. No 95% confidence interval overlapped the others, and every confidence interval reliably maintained 2% precision. Incidence rates showed a growing trend (0.008–0.056 per 100,000 person-years) as well. All case definition algorithms were able to capture sex (i.e. female) and nonsteroidal anti-inflammatory drug (NSAID) overuse as statistically significant determinants of incident cases of chronic migraine. Depression was associated with a statistically significant increase of incidence rate of chronic migraine only for two case definition algorithms. Conclusion: Our findings show that prevalence and incidence rate of chronic migraine are underestimated when compared with current literature. On the other hand, we found acceptable correctness of chronic migraine definition in the light of the association with well-known determinants. [ABSTRACT FROM AUTHOR]

Background: The proper identification of chronic migraine is one of the mainstays for general practitioners. This study therefore aims to assess the epidemiology and determinants of chronic migraine in primary care in Italy by testing five operational case definition algorithms.Methods: Five case definition algorithms defining chronic migraine were developed to estimate the prevalence and incidence rate of chronic migraine in the Health Search database. For each algorithm, we conducted a nested case-control analysis to quantify the level of association between certain determinants and incident cases of chronic migraine.Results: Considering a cohort of 1,091,032 patients (52% were females), the prevalence rate of chronic migraine increased from the first to the fifth case definition algorithm ranging from 0.03 to 0.28%. No 95% confidence interval overlapped the others, and every confidence interval reliably maintained 2% precision. Incidence rates showed a growing trend (0.008-0.056 per 100,000 person-years) as well. All case definition algorithms were able to capture sex (i.e. female) and nonsteroidal anti-inflammatory drug (NSAID) overuse as statistically significant determinants of incident cases of chronic migraine. Depression was associated with a statistically significant increase of incidence rate of chronic migraine only for two case definition algorithms.Conclusion: Our findings show that prevalence and incidence rate of chronic migraine are underestimated when compared with current literature. On the other hand, we found acceptable correctness of chronic migraine definition in the light of the association with well-known determinants. [ABSTRACT FROM AUTHOR]

Background: In spite of the substantial therapeutic efficacy of triptans, their site of action is still debated. Subcutaneous sumatriptan is the most efficacious symptomatic treatment for cluster headache (CH) patients, showing therapeutic onset within a few minutes after injection even in migraine patients. However, whether subcutaneous sumatriptan is able to reach the CNS within this short time frame is currently unknown.Methods: Here, by means of liquid chromatography/mass spectrometry, we investigated peripheral and brain distribution of subcutaneous sumatriptan soon after injection in rats at a dose equivalent to that used in patients. Tissue sumatriptan contents were compared to those of oxazepam, a prototypical lipophilic, neuroactive drug.Results: We report that sumatriptan accumulated within brain regions of relevance to migraine and CH pathogenesis such as the hypothalamus and the brainstem as soon as 1 and 5 minutes after injection. Notably, sumatriptan brain distribution was faster than that of oxazepam, reaching concentrations exceeding its reported binding affinity for 5HT1B/D receptors, and in the range of those able to inhibit neurotransmitter release in vivo.Conclusion: Our findings indicate that sumatriptan distributes within the CNS soon after injection, and are in line with prompt pain relief by parenteral sumatriptan in CH patients. [ABSTRACT FROM AUTHOR]