Unit of Medical Toxicology, Headache Centre and Drug Abuse, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via del Pozzo, 71, 41124 Modena, Italy.
Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Clin Ther. 2021 Apr;43(4):654-670. doi: 10.1016/j.clinthera.2021.01.020. Epub 2021 Feb 16.
This narrative review provides an update on the research that led to the development of ditans and lasmiditan for the acute treatment of migraine in adults and discusses the potential advantages and disadvantages of lasmiditan in clinical use.
The electronic databases PubMed, Scopus, and ClinicalTrials.gov were searched from database inception through January 9, 2021, to identify relevant studies. Search results were assessed for their overall relevance to this review.
Because part of the effect of the triptans is mediated by the serotonin 1F receptors, which are not present in the smooth muscle, a pure agonist of these receptors, lasmiditan, was developed. Lasmiditan is hypothesized to act on antinociceptive pathways and inhibit the calcitonin gene-related peptide release. Lasmiditan was approved by the US Food and Drug Administration in 2019 based on the results of 2 pivotal trials that found a significant difference from placebo in the percentage of patients who achieved freedom from pain and most bothersome symptom at 2 h. The main concern of lasmiditan derives from its central nervous system-related adverse effects, mainly dizziness and paraesthesia, probably attributable to its high blood brain barrier penetration. These central nervous system adverse effects impair driving performance for hours and might be suboptimal for individuals with migraine who want to quickly stop the migraine attack to resume their activities as soon as possible.
Despite the advantage of being beneficial in the acute treatment of migraine without vasocostrictive action, lasmiditan also presents limitations, in particular the central nervous system adverse effects. Moreover, head-to-head trials against triptans and gepants are indispensable to determine the better option for patients.
本综述性文章介绍了促使 ditans 和 lasmiditan 研发的研究进展，用于治疗成人偏头痛急性发作，并讨论了 lasmiditan 在临床应用中的潜在优势和劣势。
从数据库建立至 2021 年 1 月 9 日，检索电子数据库 PubMed、Scopus 和 ClinicalTrials.gov，以确定相关研究。评估检索结果与本综述的整体相关性。
由于部分曲坦类药物的作用是通过不存在于平滑肌中的 5-羟色胺 1F 受体介导的，因此研发了 lasmiditan 这种该受体的纯激动剂。推测 lasmiditan 通过作用于镇痛通路并抑制降钙素基因相关肽的释放来发挥作用。基于两项关键性试验的结果，美国食品和药物管理局于 2019 年批准 lasmiditan 上市，该两项试验发现与安慰剂相比，lasmiditan 组患者在 2 小时时达到无痛和最困扰症状缓解的比例有显著差异。人们对 lasmiditan 的主要担忧源于其与中枢神经系统相关的不良反应，主要是头晕和感觉异常，这可能归因于其较高的血脑屏障通透性。这些中枢神经系统不良反应会在数小时内影响驾驶能力，可能对那些希望尽快停止偏头痛发作以尽快恢复活动的偏头痛患者来说并不理想。
尽管 lasmiditan 在没有血管收缩作用的情况下对偏头痛急性发作有益，但它也存在局限性，特别是中枢神经系统不良反应。此外，有必要开展与曲坦类药物和 gepants 的头对头试验，以确定哪种药物对患者更好。
