ABSTRACT
Background: Two new classes of drugs approved by USFDA for the treatment of acute migraine are non-peptide Calcitonin Gene-Related Peptide (CGRP) receptor antagonists (rimegepant and ubrogepant) and 5-HT1F receptor agonist lasmiditan. There are no clinical trials comparing these two classes of newer drugs. Aim and Objectives: The present network meta-analysis was conducted with the objective to compare the efficacy of orally administered lasmiditan versus CGRP-receptor antagonists (rimegepant and ubrogepant) in the treatment of acute migraine. Materials and Methods: Electronic database search in PUBMED and Cochrane library was conducted using MeSH search terms “Lasmiditan” AND “Migraine” for articles on lasmiditan; while MeSH terms “Ubrogepant” AND “Migraine;” “Rimegeapnt” AND “Migraine” were used for articles on CGRP-antagonists. Randomized or cross-over studies comparing efficacy of oral lasmiditan and two FDA approved CGRP-antagonists (rimegepant, and ubrogepant) versus other active treatment or placebo in adults with acute attack of migraine were included in the analysis. Incidence of 2 h pain-free event was the primary outcome measure while the incidence of 24 h pain-free was the secondary outcome measure compared. Both frequent and Bayesian network meta-analysis were conducted by CRSU MetaInsight software. Results: In 12 eligible studies, seven interventions were compared with total 13795 patients analyzed in the network. Higher treatment ranking for 2 h and 24 h pain-free events was observed for lasmiditan 200 mg and rimegepant 150 mg, respectively. Conclusions: There is strong evidence to conclude that lasmiditan at 200 mg is better drug for immediate (2 h) headache freedom. There is limited evidence to support rimegepant for sustained effect (beyond 24 h).
ABSTRACT
Background: Acute migraine is the most common disabling chronic neurological disorder in the world. There are a huge proportion of unmet needs in treatment efficacy and satisfaction with currently available drugs and hence need for newer agents. One such FDA-approved drug is 5-HT1F Agonist lasmiditan. Aim and Objective: The present review and meta-analysis were conducted with the objectives to analyze and review safety and efficacy of lasmiditan. Materials and Methods: Electronic database search in PUBMED and Cochrane Library was conducted using search terms ?Lasmiditan? OR ?5-HT1F Agonist.? Randomized or cross-over studies comparing safety and/or efficacy of oral lasmiditan versus other active treatment or placebo in adults with acute attack of migraine were included in the analysis. Incidences of ?2 h pain-free? events were the primary outcome measure while the incidences of adverse drug events and control of other migraine-associated symptoms were the secondary outcome measures compared. Inverse variance method and both random and fixed effect models were used in the analysis by RevMan 5.3 software. Results: At 2 h, freedom from pain (odds ratio: 2.02, 95% CI: 1.76, 2.31, n = 4395), most bothersome symptom, photophobia, and phonophobia were observed at significantly highest rates in 200 mg lasmiditan group than in placebo group. In decreasing order, incidences of dizziness, fatigue, ?1 serious adverse drug reaction, paresthesia, and somnolence were significantly higher with 200 mg lasmiditan than placebo. Conclusion: Higher the dose of lasmiditan used, rapid and stronger is its pain aborting action. Lasmiditan has effective and sustained effect up to 48 h, and hence, there is a need to analyze its potential migraine preventive effects.
ABSTRACT
Background: Autism spectrum disorders (ASD) is diagnosed primarily by the presence of impaired social interaction, social communication, and stereotypical behaviors. Bumetanide, a loop diuretic which acts by inhibiting Na+-K+-2Cl co-transporters (NKCC): NKCC1 and NKCC2 are explored as a pharmacological agent for treatment of ASD. Aim and Objectives: The aim of the study was to analyze safety and efficacy of bumetanide in treatment of ASD. Materials and Methods: Electronic database search in PUBMED and Cochrane library was conducted using MeSH search terms “Autism” AND “Bumetanide.” Randomized or cross-over trials comparing efficacy of bumetanide versus placebo in ASD patients of any age group were included in analysis. Quantity of reduction in total Childhood Autism Rating Scale (CARS) score after 90 days of treatment with bumetanide was the primary outcome measure analyzed. Efficacy outcome measures were estimated by calculating the Mean Difference (MD) values and their 95% Confidence Intervals (CI) by both fixed and random effect models using Revman 5.4.1 software. Results: A total of six trials were found to be eligible and included in quantitative synthesis of efficacy. Small but significant decrease in total CARS score (MD: ?1.86, 95% CI: ?3.20, ?0.15, n = 352) and total social responsive scale score (MD: ?9.38, 95% CI: ?16.45, ?2.31, n = 171) on day 91 was evident in bumetanide treated group. Conclusions: Bumetanide appears to provide small but significant benefits in relieving ASD symptoms. These benefits are lesser in Chinese patients compared to European patients.