Chiappini Stefania, Vickers-Smith Rachel, Guirguis Amira, Corkery John Martin, Martinotti Giovanni, Schifano Fabrizio
Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, London AL10 9EU, UK.
Department of Epidemiology, College of Public Health, University of Kentucky, 111 Washington Avenue, Lexington, KY 40536, USA.
Pharmaceuticals (Basel). 2022 May 1;15(5):565. doi: 10.3390/ph15050565.
Despite increasing reports, antidepressant (AD) misuse and dependence remain underestimated issues, possibly due to limited epidemiological and pharmacovigilance evidence. Thus, here we aimed to determine available pharmacovigilance misuse/abuse/dependence/withdrawal signals relating to the Selective Serotonin Reuptake Inhibitors (SSRI) citalopram, escitalopram, paroxetine, fluoxetine, and sertraline. Both EudraVigilance (EV) and Food and Drug Administration-FDA Adverse Events Reporting System (FAERS) datasets were analysed to identify AD misuse/abuse/dependence/withdrawal issues. A descriptive analysis was performed; moreover, pharmacovigilance measures, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the information component (IC), and the empirical Bayesian geometric mean (EBGM) were calculated. Both datasets showed increasing trends of yearly reporting and similar signals regarding abuse and dependence. From the EV, a total of 5335 individual ADR reports were analysed, of which 30% corresponded to paroxetine ( = 1592), 27% citalopram ( = 1419), 22% sertraline ( = 1149), 14% fluoxetine ( = 771), and 8% escitalopram ( = 404). From FAERS, a total of 144,395 individual ADR reports were analysed, of which 27% were related to paroxetine, 27% sertraline, 18% citalopram, 16% fluoxetine, and 13% escitalopram. Comparing SSRIs, the EV misuse/abuse-related ADRs were mostly recorded for citalopram, fluoxetine, and sertraline; conversely, dependence was mostly associated with paroxetine, and withdrawal to escitalopram. Similarly, in the FAERS dataset, dependence/withdrawal-related signals were more frequently reported for paroxetine. Although SSRIs are considered non-addictive pharmacological agents, a range of proper withdrawal symptoms can occur well after discontinuation, especially with paroxetine. Prescribers should be aware of the potential for dependence and withdrawal associated with SSRIs.
尽管相关报告日益增多，但抗抑郁药（AD）的滥用和依赖问题仍未得到充分重视，这可能是由于流行病学和药物警戒证据有限。因此，我们旨在确定与选择性5-羟色胺再摄取抑制剂（SSRI）西酞普兰、艾司西酞普兰、帕罗西汀、氟西汀和舍曲林相关的药物警戒滥用/误用/依赖/戒断信号。我们分析了欧洲药物警戒数据库（EudraVigilance，EV）和美国食品药品监督管理局不良事件报告系统（Food and Drug Administration - FDA Adverse Events Reporting System，FAERS）数据集，以识别抗抑郁药的滥用/误用/依赖/戒断问题。我们进行了描述性分析；此外，还计算了药物警戒指标，包括报告比值比（ROR）、比例报告比值（PRR）、信息成分（IC）和经验贝叶斯几何均值（EBGM）。两个数据集均显示年度报告呈上升趋势，且在滥用和依赖方面有类似信号。在EV数据集中，共分析了5335份个体不良反应报告，其中30%对应帕罗西汀（n = 1592），27%对应西酞普兰（n = 1419），22%对应舍曲林（n = 1149），14%对应氟西汀（n = 771），8%对应艾司西酞普兰（n = 404）。在FAERS数据集中，共分析了144,395份个体不良反应报告，其中27%与帕罗西汀有关，27%与舍曲林有关, 18%与西酞普兰有关, 16%与氟西汀有关, 13%与艾司西酞普兰有关。比较各SSRI药物，EV中与滥用/误用相关的不良反应大多记录于西酞普兰、氟西汀和舍曲林；相反，依赖大多与帕罗西汀相关，戒断则与艾司西酞普兰相关。同样，在FAERS数据集中，与帕罗西汀相关的依赖/戒断信号报告更为频繁。尽管SSRI被认为是非成瘾性药物，但停药后很长一段时间内仍可能出现一系列典型的戒断症状，尤其是帕罗西汀。处方医生应意识到SSRI存在依赖和戒断的可能性。
