Previously, some allergic conditions involving pruritus have been linked to migraine, raising the possibility that migraine and itching may be governed by similar underlying mechanisms. We aimed to investigate the efficacy of Lasmiditan, a highly selective agonist of the 5-hydroxytryptamine 1F (5-HT1F) receptor and a recently approved medication for the treatment of migraine headaches, in ameliorating serotonergic itching. Forty animals were employed in the present study (n = 40). Eight animals were randomly assigned to each of the following study groups (n = 8, in each group): (1) \"Normal Saline\": This group was given intradermal injections of normal saline (2) \"5-HT\": The animals were injected with intradermal 5-HT, which was used to induce itching. (3) \"Lasmiditan 0.3\", \"Lasmiditan 1\", and \"Lasmiditan 3\" groups: injected with 5-HT as well as intraperitoneal Lasmiditan at different dose levels (0.3, 1, and 3 mg/kg, respectively). Scratching behavior was recorded for 60 min, and the skin tissue of three mice was sampled at the end of the behavioral experiment to assess the levels of TLR-4, IL-31, 5-HT1F receptor, CGRP & TRPV4. In the present study, we found that Lasmiditan when administered at 1 mg/kg effectively reduced serotonin-induced itching compared to the \"5-HT\" group (P < 0.0001). Following the administration of Lasmiditan (1 mg/kg), the expression levels of the 5-HT1F receptor significantly increased (P < 0.01). Further, the levels of TLR-4, IL-31, CGRP & TRPV4 were substantially reduced upon the administration of Lasmiditan (1 mg/kg). We found that Lasmiditan is effective in reducing serotonergic itch in mice through its interaction with the 5-HT1F receptor in the skin tissue of mice.

The combined use of lasmiditan and triptan is unexplored in medical literature. This study aimed to investigate whether the intake of lasmiditan following triptan improves migraine pain. Following triptan intake, if headache relief was less than 50% at 1 h, patients took 50 mg of lasmiditan within 2 h of migraine onset. Patients recorded headache intensity and adverse events (AEs) caused by lasmiditan at 1, 2, and 4 h after the intake of an additional 50 mg of lasmiditan. A significant reduction in pain scale was observed post 50 mg lasmiditan intake (p < 0.001, t-test). Pain relief was reported for 32 migraine attacks (80%) at 1 h after additional lasmiditan intake. Although AEs were observed in 63% of the patients who took an additional lasmiditan, most were mild and resolved 1 h after lasmiditan intake. Our study revealed the significant headache relief provided by an additional lasmiditan for patients who did not achieve satisfactory results following initial triptan intake for treating migraine. The AEs associated with this treatment strategy were mild and lasted for a short time. This study suggested that the combination of triptan and lasmiditan is promising for the treatment of migraine and should be studied in a randomized placebo-controlled trial.

UNASSIGNED: Lasmiditan offers a promising option for the treatment of migraines, particularly for individuals with cardiovascular concerns. It is crucial to gather comprehensive safety information of lasmiditan through large-scale post market monitoring.
UNASSIGNED: This study assessed the safety profile of lasmiditan based on real-world data of FDA Adverse Event Reporting System (FAERS) database. Four disproportionality analysis methods were applied to mining the significant signals. The differences in adverse event signals among different subgroups were investigated concerning race, sex, age, weight, dose, and concomitant drug.
UNASSIGNED: A total of 820 reports and 1,661 adverse events with lasmiditan as the primary suspected drug were identified. Two new adverse event signals related to nervous system disorders emerged. Females and males were more likely to develop paresthesia and dizziness, respectively. Most common adverse events were more likely to occur in the elderly patients and at high doses.
UNASSIGNED: It is essential to be vigilant about the relation of potential nervous system disorders with lasmiditan. The importance of heightened clinical vigilance regarding paresthesia in females and dizziness in males was underscored. Additionally, it is advised to administer a lower initial dose for elderly patients.

BACKGROUND: Real-world data on the effectiveness and safety of lasmiditan, a new medication for acute migraine attacks, is necessary.
METHODS: We performed a prospective, observational, multi-center, real-world study. A total of 48 patients with migraine (44 females, 44.6 ± 12.9 years old) were included in this study.
RESULTS: Twenty-three patients (47.9%) reported they were headache-free two hours after taking lasmiditan and were categorized into the responder group. In total, 44 patients (91.7%) experienced at least one side effect within two hours of taking the medication. Dizziness, somnolence, malaise, nausea, and palpitations were reported by 56.3% (n = 27), 45.8% (n = 22), 37.5% (n = 18), 20.8% (n = 10), and 14.6% (n = 7) of patients respectively. Of 48 patients, 20 (41.7%) indicated that they preferred lasmiditan to their previous acute treatment. There were no predictive factors for efficacy.
CONCLUSIONS: This real-world study demonstrated the efficacy and safety of lasmiditan. More than 90% of patients experienced side effects from lasmiditan. Approximately 40% of patients preferred lasmiditan despite the occurrence of side effects.

BACKGROUND: Recently, US Food and Drug Administration (FDA) has approved calcitonin gene-related peptide receptor antagonists (rimegepant, and ubrogepant), and selective serotonin receptor agonists (lasmiditan) in the management of migraine. However, the exact safety and efficacy profile of these drugs is unclear so far.
METHODS: The study\'s primary objective was to determine the exact safety and efficacy profile. The overall estimate was calculated in terms of risk ratios using a suitable model. The subgroup analysis was also performed to check the effect of individual drugs on the outcome, whereas sensitivity analysis was performed to check the effects of outliers on the outcome. All the analyses were performed using Rev Man 5. The drugs have shown significant improvement in efficacy parameters (pain freedom, most bothersome symptoms, phonophobia, nausea, and photophobia).
RESULTS: The subgroup analysis results have shown significant improvement in all efficacy parameters in the rimegepant and ubrogepant groups. The effect of ubrogepant on safety parameters was found to be non-significant, indicating a better safety profile of ubrogepant than lasmiditan.
CONCLUSIONS: The sensitivity analysis results have shown no effect of outliers on the efficacy parameters. Based on the available evidence, recently approved drugs are effective in the treatment of migraine, however, associated with few adverse drug reactions.

Migraine is a disease with a high prevalence and incidence, in addition to being highly disabling, causing a great impact on the patient\'s quality of life at a personal, family and work level, but also social, given its high expense due to its direct (care) and indirect (presenteeism and work absenteeism) costs. The multiple and recent developments in its pathophysiological knowledge and in its therapy require updating and, therefore, in this article the Spanish scientific societies most involved in its study and treatment (SEN, SEMFYC and SEMERGEN), together with the Association Spanish Association for Patients with Migraine and other Headaches (AEMICE), we have developed these updated care recommendations. We reviewed the treatment of migraine attacks, which consisted mainly of the use of NSAIDs and triptans, to which ditans and gepants have been added. We also discuss preventive treatment consisting of oral preventive drugs, botulinum toxin, and treatments that block the action of calcitonin-related peptide (CGRP). Finally, we emphasize that pharmacological treatments must be complementary to carrying out general measures consisting of identifying and managing/deletion the precipitating factors of the attacks and the chronicizing factors, controlling the comorbidities of migraine and eliminating analgesic overuse.

BACKGROUND: The objective of this analysis was to gain new insights into the patient characteristics and other factors associated with lasmiditan usage and clinical outcomes under conditions resembling the real-world setting.
METHODS: This was a post hoc analysis of data from the 12-month, open-label extension (OLE) of the phase 3, double-blind, randomized, controlled CENTURION trial, which examined the efficacy and safety of lasmiditan as acute treatment across four migraine attacks. Patients completing the main study who treated ≥ 3 attacks could continue in the OLE. The initial lasmiditan dose was 100 mg, with dose adjustments to 50 mg or 200 mg allowed at the investigator\'s discretion. Patient and clinical characteristics were summarized by dosing pattern and completion status. Safety was assessed based on adverse event (AE) frequency by number of doses.
RESULTS: In total, 445 patients treated ≥ 1 migraine attacks with lasmiditan during the OLE, 321 of whom (72.1%) completed the study. Forty-seven percent of patients remained on the 100-mg initial dose during the OLE whereas 20.2% used both 100 mg and 50 mg, 30.6% used both 100 mg and 200 mg, and 6 (1.3%) used multiple dose levels. All dosing patterns were associated with clinical and patient-reported improvement; however, the 100-mg group had the highest proportion of patients reporting improvement in the Patient Global Impression of Change - Migraine Headache Condition (56.5% vs 33.4%-52.2%). In comparison, all three groups that made dose adjustments had higher rates of completion compared to the 100-mg group (72.1%-83.3% vs 68.9%). The frequency of AEs decreased with continued use of lasmiditan. Concomitant triptans and lasmiditan use did not increase AE frequency.
CONCLUSIONS: Based on high persistence and patient satisfaction rates, the 100-mg dose appears optimal for most patients. For those who adjusted dose levels, dose adjustments appeared beneficial to improve efficacy or tolerability, retaining patients on treatment. Collectively, the data suggest that patients who experienced efficacy continued to use lasmiditan regardless of the occurrence or frequency of AEs, and continued use appeared associated with fewer AEs.
BACKGROUND: European Union Drug Regulating Authorities Clinical Trials Database (EudraCT): 2018-001661-17; ClinicalTrials.gov: NCT03670810; registration date: September 12, 2018.

UNASSIGNED: Vascular and mitochondrial dysfunction are well-established consequences of multiple central nervous system (CNS) disorders, including neurodegenerative diseases and traumatic injuries. We previously reported that 5-hydroxytryptamine 1F receptor (5-HT1FR) agonism induces mitochondrial biogenesis (MB) in multiple organ systems, including the CNS.
UNASSIGNED: Lasmiditan is a selective 5-HT1FR agonist that is FDA-approved for the treatment of migraines. We have recently shown that lasmiditan treatment induces MB, promotes vascular recovery and improves locomotor function in a mouse model of spinal cord injury (SCI). To investigate the mechanism of this effect, primary cerebral microvascular endothelial cells from C57bl/6 mice (mBMEC) were used.
UNASSIGNED: Lasmiditan treatment increased the maximal oxygen consumption rate, mitochondrial proteins and mitochondrial density in mBMEC, indicative of MB induction. Lasmiditan also enhanced endothelial cell migration and tube formation, key components of angiogenesis. Trans-endothelial electrical resistance (TEER) and tight junction protein expression, including claudin-5, were also increased with lasmiditan, suggesting improved barrier function. Finally, lasmiditan treatment decreased phosphorylated VE-Cadherin and induced activation of the Akt-FoxO1 pathway, which decreases FoxO1-mediated inhibition of claudin-5 transcription.
UNASSIGNED: These data demonstrate that lasmiditan induces MB and enhances endothelial cell function, likely via the VE-Cadherin-Akt-FoxO1-claudin-5 signaling axis. Given the importance of mitochondrial and vascular dysfunction in neuropathologies, 5-HT1FR agonism may have broad therapeutic potential to address multiple facets of disease progression by promoting MB and vascular recovery.

OBJECTIVE: To compare the outcomes associated with the use of lasmiditan, rimegepant, ubrogepant, and zavegepant for the acute management of migraine headaches.
METHODS: We searched four electronic databases from database inception to August 31, 2023, to identify randomized controlled trials (RCTs) that report efficacy and safety for the acute treatment of migraine. The risk of bias in the included RCTs was evaluated according to the Cochrane tool, and the certainty of evidence using the CINeMA approach. We conducted frequentist network meta-analyses (NMA) to summarise the evidence. Data were analyzed using R-4.3.1.
RESULTS: A total of 18 eligible studies including 10 different types of interventions with 22,429 migraine patients were included. NMA results showed that compared to ubrogepant (25 mg and 50 mg) and zavegepant, lasmiditan (100 mg and 200 mg) exhibits an elevated probability of achieving pain relief within a 2-hour interval. Similarly, relative to zavegepant, rimegepant (75 mg) and ubrogepant (50 mg and 100 mg) demonstrate an enhanced likelihood of sustaining pain relief over a 24-hour period. Furthermore, in contrast to ubrogepant (25 mg) and lasmiditan (50 mg), rimegepant (75 mg) presents a heightened probability of achieving freedom from photophobia within 2 h. Regarding safety, lasmiditan carries the highest risk of adverse events, which are associated with an increased incidence of adverse effects, including dizziness, somnolence, asthenia, paresthesia, and fatigue.
CONCLUSIONS: In this NMA, a spectrum of evidence ranging from very low to high levels underscores the favorable efficacy and tolerability of rimegepant 75 mg and ubrogepant 100 mg, positioning them as potential candidates for the acute management of migraine. Concurrently, lasmiditan (100 mg and 200 mg) exhibits notable efficacy, albeit accompanied by an increased susceptibility to adverse events. These findings should still be approached with caution, primarily due to the intrinsic limitations associated with indirect comparisons.

5-Hydroxytryptamine (HT)/serotonin receptor agonism has been a long-recognized property of triptan medications, and more recently, the study and development of medications with selective binding to the 1F receptor subtype have been explored. While the exact mechanism contributing to decreased symptoms of an acute migraine attack remains unclear, selective 5-HT1F agonists have demonstrated clinical efficacy with lasmiditan as the only approved medication from this class to date. Lasmiditan lacks vasoconstrictive properties, giving it utility in specific patient populations in whom triptans should be avoided. Availability, central nervous system (CNS) side effects, and 8-hour driving restriction may affect its clinical use.