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Frequencies of genetic polymorphisms related to triptans metabolism in chronic migraine.

ABSTRACT: Chronic migraine (CM) prevalence ranges around 1-5%. Most of these patients usually treat their acute attacks with triptans, whose efficacy is extremely variable. A genetic basis for migraine is evident and many susceptibility genes have been described, as well as gene polymorphisms possibly implied in therapy response. Several factors could be involved in the evolution of episodic migraine into a chronic form, such as natural history, psychiatric comorbidity, and the individual's response to therapy. During a study aimed at detecting connections between genotype and response to triptans administration, we characterized a CM population for polymorphisms in the genes coding for monoamine oxidase A, g-protein beta 3 and the cytochromes CYP3A4 and CYP1A2. Alleles and genotypes distributions were compared with known frequencies of healthy Caucasian populations. A significant association with CM was found for the long allele of monoamine oxidase A 30 bp VNTR and CYP1A2*1F variant. Such genomic analysis is part of an integrated platform able to evaluate different levels of metabolic pathways of drugs in CM and their influence in the chronicization process.

SUBMITTER: Gentile G

PROVIDER: S-EPMC3452288 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Frequencies of genetic polymorphisms related to triptans metabolism in chronic migraine.

Gentile Giovanna G Missori Serena S Borro Marina M Sebastianelli Alisa A Simmaco Maurizio M Martelletti Paolo P

The journal of headache and pain 20100306 2

Chronic migraine (CM) prevalence ranges around 1-5%. Most of these patients usually treat their acute attacks with triptans, whose efficacy is extremely variable. A genetic basis for migraine is evident and many susceptibility genes have been described, as well as gene polymorphisms possibly implied in therapy response. Several factors could be involved in the evolution of episodic migraine into a chronic form, such as natural history, psychiatric comorbidity, and the individual's response to th ...[more]

PMID: 20213484

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Project description:IntroductionAs 5-HT1B receptor agonists, triptans produce vasoconstriction and have cardiovascular contraindications and precautions. Lasmiditan, a selective 5-HT1F receptor agonist, has a low affinity for 5-HT1B receptors, does not cause vasoconstriction, and is free of cardiovascular contraindications and precautions. The objective of this post hoc analysis was to evaluate the efficacy and safety of lasmiditan in patients with and without at least one triptan contraindication.MethodsPatient subgroups, with and without triptan contraindications, were analyzed from pooled patient data from four randomized, double-blind, placebo-controlled clinical trials (SAMURAI, SPARTAN, CENTURION, and MONONOFU). Patients experiencing a single migraine attack of moderate or severe intensity were treated with lasmiditan 50 mg (SPARTAN and MONONOFU only), 100 mg, 200 mg, or placebo, and efficacy data were recorded in an electronic diary.ResultsOf 5704 patients, 207 (3.6%) patients had at least one contraindication to triptans. Overall subgroup analysis revealed that the effects of lasmiditan on pain freedom, pain relief, freedom from most bothersome symptom, disability freedom, and Patient Global Impression of Change at 2 h post-dose did not differ in patient groups with and without triptan contraindications. These outcomes generally showed a similar benefit pattern for lasmiditan in both subgroups, with all results being statistically significant in patients without contraindications, and pain relief being statistically significant in patients with contraindications. The safety and tolerability profiles of patients with triptan versus without triptan contraindications were similar, including dizziness in 18.3 to 22.8% and somnolence in 7.9 to 9.9% of patients at the highest dose of lasmiditan.ConclusionsIn pooled analyses from four trials, patients with and without triptan contraindications did not differ in their patterns of lasmiditan efficacy. Lasmiditan may be a treatment option in patients with contraindications to triptans.Trial registration numbersSAMURAI, NCT:02439320; SPARTAN, NCT:02605174; CENTURION, NCT:03670810; and MONONOFU, NCT:03962738.

Project description:ObjectiveTo characterize nationwide utilization patterns of migraine pharmacotherapy before, during, and after pregnancy in women with triptan use.MethodsPopulation-based data were obtained by linking the Medical Birth Registry of Norway and the Norwegian Prescription Database from 2006 to 2017. We included 22,940 pregnancies among 19,669 women with at least one filled triptan prescription, a proxy for migraine, in the year before pregnancy or during pregnancy. The population was classified into four groups: i) continuers; ii) discontinuers; iii) initiators, and vi) post-partum re-initiators. Participant characteristics and prescription fills for other drugs such as analgesics, antinauseants, and preventive drugs among the groups were examined, along with an array of triptan utilization parameters.ResultsIn total, 20.0% of the women were classified as triptan continuers, 54.1% as discontinuers, 8.0% as initiators, and 17.6% as re-initiators. Extended use of triptans (≥15 daily drug doses/month) occurred among 6.9% of the continuers in the first trimester. The top 10% of triptan continuers and initiators accounted for 41% (95% CI: 39.2% - 42.5%) and 33% (95% CI: 30.3% - 35.8%) of the triptan volume, respectively. Triptan continuers and initiators had similar patterns of acute co-medication during pregnancy, but use of preventive drugs was more common among the continuers before, during, and after pregnancy.ConclusionAmong women using triptans before and during pregnancy, one in four continued triptan treatment during pregnancy, and extended triptan use was relatively low. Triptan discontinuation during and in the year after pregnancy was common. Use of other acute migraine treatments was higher among both continuers and initiators of triptans. Women using preventive migraine treatment were most commonly triptan continuers and re-initiators after pregnancy. Prescribing to and counseling of women with migraine should be tailored to the condition severity and their information needs to promote optimal migraine management in pregnancy.

Dataset Information

Frequencies of genetic polymorphisms related to triptans metabolism in chronic migraine.

Publications

Frequencies of genetic polymorphisms related to triptans metabolism in chronic migraine.

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