Characterization of the Safety Profile of the Triple Monoamine Reuptake Inhibitor Dasotraline Based on Clinical Trial Data and Disproportionality Analyses of Four Related Pharmacological Classes Using Real-World Data from the FDA Adverse Event Reporting System.

IF 3.1 3区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical Drug Investigation Pub Date : 2026-04-01 Epub Date: 2026-02-16 DOI:10.1007/s40261-026-01525-3

Solomiya Gumenyuk, Ajay Ogirala, Steven T Szabo, Kenneth Koblan, Seth C Hopkins, Mike Ufer

{"title":"Characterization of the Safety Profile of the Triple Monoamine Reuptake Inhibitor Dasotraline Based on Clinical Trial Data and Disproportionality Analyses of Four Related Pharmacological Classes Using Real-World Data from the FDA Adverse Event Reporting System.","authors":"Solomiya Gumenyuk, Ajay Ogirala, Steven T Szabo, Kenneth Koblan, Seth C Hopkins, Mike Ufer","doi":"10.1007/s40261-026-01525-3","DOIUrl":null,"url":null,"abstract":"Background and objectives: The safety profile of single or dual monoamine reuptake inhibitors (MRIs) is based on longstanding post-marketing experience but remains to be established for triple MRIs that may exhibit favorable efficacy as treatment of psychiatric disorders. Here, we characterized the safety profile of the triple MRI dasotraline based on disproportionality analyses and clinical trial data.Methods: The Food and Drug Administration Adverse Event Reporting System was queried for adverse events of commonly prescribed selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), norepinephrine reuptake inhibitors (NRIs), and norepinephrine-dopamine reuptake inhibitors (NDRIs). Bayesian disproportionality analyses were conducted to determine the Empirical Bayes Geometric Mean (EBGM) for each Medical Dictionary for Regulatory Activities (MedDRA®) preferred term (PT) within each drug class. Five randomized, double-blind, placebo-controlled Phase 2/3 studies with dasotraline were utilized to determine the pooled incidence of disproportionally reported PTs (EBGM ≥3) on dasotraline and placebo.Results: A total of 1087, 940, 409, and 714 PTs with an EBGM ≥3 were identified for SSRIs, SNRIs, NRIs, and NDRIs, respectively. The cumulative pooled incidence of these class-related PTs was approximately 2- to 2.5-fold higher for dasotraline than placebo (SSRIs: 24.7%/9.6%; SNRIs: 50.7%/26.3%; NRIs: 56.5%/32.2%; NDRIs: 35.2%/18.2%).Conclusions: The safety profile of the triple MRI dasotraline was not distinct from pharmacologically related classes indicated by a consistently higher incidence of class-related adverse events compared to placebo in randomized, controlled clinical trials. Bayesian disproportionality analyses utilizing post-marketing data from established drug classes can provide meaningful information for qualitative safety evaluation of drugs in clinical development.Clinicaltrials: Gov identifiers: NCT01692782, NCT02428088, NCT02276209, NCT02564588, NCT03107026.","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"455-465"},"PeriodicalIF":3.1000,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Drug Investigation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40261-026-01525-3","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/2/16 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

Background and objectives: The safety profile of single or dual monoamine reuptake inhibitors (MRIs) is based on longstanding post-marketing experience but remains to be established for triple MRIs that may exhibit favorable efficacy as treatment of psychiatric disorders. Here, we characterized the safety profile of the triple MRI dasotraline based on disproportionality analyses and clinical trial data.

Methods: The Food and Drug Administration Adverse Event Reporting System was queried for adverse events of commonly prescribed selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), norepinephrine reuptake inhibitors (NRIs), and norepinephrine-dopamine reuptake inhibitors (NDRIs). Bayesian disproportionality analyses were conducted to determine the Empirical Bayes Geometric Mean (EBGM) for each Medical Dictionary for Regulatory Activities (MedDRA^®) preferred term (PT) within each drug class. Five randomized, double-blind, placebo-controlled Phase 2/3 studies with dasotraline were utilized to determine the pooled incidence of disproportionally reported PTs (EBGM ≥3) on dasotraline and placebo.

Results: A total of 1087, 940, 409, and 714 PTs with an EBGM ≥3 were identified for SSRIs, SNRIs, NRIs, and NDRIs, respectively. The cumulative pooled incidence of these class-related PTs was approximately 2- to 2.5-fold higher for dasotraline than placebo (SSRIs: 24.7%/9.6%; SNRIs: 50.7%/26.3%; NRIs: 56.5%/32.2%; NDRIs: 35.2%/18.2%).

Conclusions: The safety profile of the triple MRI dasotraline was not distinct from pharmacologically related classes indicated by a consistently higher incidence of class-related adverse events compared to placebo in randomized, controlled clinical trials. Bayesian disproportionality analyses utilizing post-marketing data from established drug classes can provide meaningful information for qualitative safety evaluation of drugs in clinical development.

Clinicaltrials:

Gov identifiers: NCT01692782, NCT02428088, NCT02276209, NCT02564588, NCT03107026.

查看原文本刊更多论文

基于临床试验数据的三重单胺再摄取抑制剂Dasotraline的安全性特征和使用FDA不良事件报告系统中真实数据的四种相关药理学类的歧化分析。

背景和目的：单胺再摄取抑制剂或双单胺再摄取抑制剂（mri）的安全性基于长期的上市后经验，但仍有待建立三重mri，可能显示出良好的治疗精神疾病的疗效。在这里，我们根据歧化分析和临床试验数据对三次MRI检查的安全性进行了描述。方法：查询美国食品药品监督管理局不良事件报告系统中常用的选择性5 -羟色胺再摄取抑制剂（SSRIs）、5 -羟色胺-去甲肾上腺素再摄取抑制剂（SNRIs）、去甲肾上腺素再摄取抑制剂（NRIs）和去甲肾上腺素-多巴胺再摄取抑制剂（NDRIs）的不良事件。进行贝叶斯歧化分析，以确定每个药物类别中每个监管活动医学词典（MedDRA®）首选术语（PT）的经验贝叶斯几何平均（EBGM）。五项随机、双盲、安慰剂对照的2/3期研究使用达索曲林来确定达索曲林和安慰剂的不成比例报告PTs （EBGM≥3）的合并发生率。结果：共有1087、940、409和714名EBGM≥3的患者分别被鉴定为SSRIs、SNRIs、NRIs和NDRIs。这些类别相关PTs的累积总发生率达索曲林比安慰剂高约2- 2.5倍（SSRIs: 24.7%/9.6%; SNRIs: 50.7%/26.3%; NRIs: 56.5%/32.2%; NDRIs: 35.2%/18.2%）。结论：在随机对照临床试验中，三重MRI达索曲林的安全性与药理学相关类别没有明显区别，与安慰剂相比，其类别相关不良事件的发生率始终较高。贝叶斯歧化分析利用已建立药物类别的上市后数据，可以为临床开发中药物的定性安全性评估提供有意义的信息。临床试验：政府标识符：NCT01692782， NCT02428088, NCT02276209, NCT02564588, NCT03107026。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Clinical Drug Investigation 医学-药学

CiteScore

5.90

自引率

3.10%

发文量

108

审稿时长

6-12 weeks

期刊介绍： Clinical Drug Investigation provides rapid publication of original research covering all phases of clinical drug development and therapeutic use of drugs. The Journal includes: -Clinical trials, outcomes research, clinical pharmacoeconomic studies and pharmacoepidemiology studies with a strong link to optimum prescribing practice for a drug or group of drugs. -Clinical pharmacodynamic and clinical pharmacokinetic studies with a strong link to clinical practice. -Pharmacodynamic and pharmacokinetic studies in healthy volunteers in which significant implications for clinical prescribing are discussed. -Studies focusing on the application of drug delivery technology in healthcare. -Short communications and case study reports that meet the above criteria will also be considered. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Clinical Drug Investigation may be accompanied by plain language summaries to assist readers who have some knowledge, but non in-depth expertise in, the area to understand important medical advances.