Guirguis A, Chiappini S, Papanti P G D, Vickers-Smith R, Harris D, Corkery J M, Arillotta D, Floresta G, Martinotti G, Schifano F
Swansea University, Singleton Campus, The Grove, SA2 8PP, Wales, UK.
UniCamillus University, Via di S. Alessandro 8, 00131, Rome, Italy; Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, University of Hertfordshire, College Lane Campus, Hatfield AL10 9AB, UK.
Eur Neuropsychopharmacol. 2024 May;82:82-91. doi: 10.1016/j.euroneuro.2024.02.003. Epub 2024 Mar 19.
The study addresses concerns about potential psychiatric side effects of Glucagon-like peptide-1 receptor agonists (GLP-1 RA).
The aim of this work was to analyse adverse drug reports (ADRs) from the Food and Drug Administration Adverse Events Reporting System (FAERS) using metformin and orlistat as comparators.
Descriptive and pharmacovigilance disproportionality analyses was performed.
A total of 209,354 ADRs were reported, including 59,300 serious cases. Of those, a total of 5378 psychiatric disorder cases, including 383 'serious' cases related to selected ADRs were registered during 2005-2023. After unmasking, 271 cases where individual GLP-1 RA were implicated showing liraglutide (n = 90; Reported Odds Ratio (ROR) = 1.64), exenatide (n = 67; ROR = 0.80), semaglutide (n = 61; ROR = 2.03), dulaglutide (n = 45; ROR = 0.84), tirzepatide (n = 5; ROR = 1.76) and albiglutide (n = 2; ROR = 0.04). A greater association between these ADRs with metformin was observed, but not orlistat. With regards to selected preferred terms (PTs), 42 deaths including 13 completed suicides were recorded. Suicidal ideation was recorded in n = 236 cases for 6/7 GLP-1 RA (excluding lixisenatide).
Suicide/self-injury reports pertaining to semaglutide; tirzepatide; and liraglutide were characterised, although lower than metformin. It is postulated that rapid weight loss achieved with GLP-1 RA can trigger significant emotional, biological, and psychological responses, hence possibly impacting on suicidal and self-injurious ideations.
With the current pharmacovigilance approach, no causality link between suicidal ideation and use of any GLP-1 RA can be inferred. There is a need for further research and vigilance in GLP-1 RA prescribing, particularly in patients with co-existing psychiatric disorders.
本研究关注胰高血糖素样肽-1受体激动剂（GLP-1 RA）潜在的精神方面副作用。
本研究旨在分析美国食品药品监督管理局不良事件报告系统（FAERS）中的药品不良反应报告（ADR），并以二甲双胍和奥利司他作为对照。
进行描述性分析和药物警戒不均衡性分析。
共报告了209,354例药品不良反应，其中包括59,300例严重病例。在这些病例中，2005年至2023年期间共记录了5378例精神障碍病例，其中包括383例与特定药品不良反应相关的“严重”病例。经过数据解盲，发现271例涉及个别GLP-1 RA的病例，其中利拉鲁肽（n = 90；报告比值比（ROR）= 1.64）、艾塞那肽（n = 67；ROR = 0.80）、司美格鲁肽（n = 61；ROR = 2.03）、度拉鲁肽（n = 45；ROR = 0.84）、替尔泊肽（n = 5；ROR = 1.76）和阿必鲁肽（n = 2；ROR = 0.04）。观察到这些药品不良反应与二甲双胍之间的关联更强，但与奥利司他无关。关于选定的首选术语（PT），记录了42例死亡，其中包括13例自杀身亡。在6/7种GLP-1 RA（不包括利司那肽）中，共记录了236例自杀意念病例。
对与司美格鲁肽、替尔泊肽和利拉鲁肽相关的自杀/自我伤害报告进行了特征分析，尽管其发生率低于二甲双胍。据推测，GLP-1 RA导致的快速体重减轻可能引发显著的情绪、生理和心理反应，从而可能影响自杀和自我伤害意念。
根据目前的药物警戒方法，无法推断出自杀意念与任何GLP-1 RA的使用之间存在因果关系。在开具GLP-1 RA处方时，尤其是对于患有并存精神障碍的患者，需要进一步研究并保持警惕。
