Serotonin Receptor agonist and Risk of Paresthesia in Migraine Patients: A Dose-Response Model-Based (Network) Meta-Analysis

Background: Migraine may be an important factor for paresthesia in the limbs, especially in the upper limbs. In several patients, paresthesia is responsible for a low quality of life. Treatment with the serotonin agonist may be a triggering factor for paresthesia in certain patients. Various serotonin receptor agonists are available for migraine treatment. We performed a meta-analysis of updated clinical trials of the serotonin agonist to figure out the risk of paresthesia.

Methods: PubMed, Embase, and Cochrane Library databases were searched for clinical trials that evaluated the serotonin agonist for migraine treatment versus placebo. The main outcomes were to perform dose-response model-based network meta-analysis of different serotonin agonists and to compute the relative risk for paresthesia. In addition, probability of paresthesia among various treatments was estimated by the Surface Under the Cumulative Ranking (SUCRA) method. The R 4.30 and Rev Man 5.3 softwares were used to perform meta-analysis.

Results: A total of 30 placebo-controlled clinical trials (29,154 subjects) were included in the study to perform dose-response model-based network meta-analysis to explore the risk of paresthesia with different serotonin agonists versus placebo. The drugs Topiramate 200 mg, Lasmiditan 400 mg, and Zolmitriptan 10 mg showed higher relative risks for paraesthesia as 2.71, 2.2, and 2.42, respectively. However, the SUCRA probabilities of paresthesia for each treatment in the network were higher for Lasmiditan.

Conclusions: This meta-analysis of reported placebo-controlled clinical trials suggests that the SUCRA probabilities for the manifestation of paresthesia are higher with Lasmiditan. The relative risk of paresthesia is higher with the use of Topiramate 200 mg, Lasmiditan 400 mg, and Zolmitriptan 10 mg. In addition, Lasmiditan exhibited a gradual dose-response of relative risk for the manifestation of paresthesia.