Nguyen Charles T, Zhou Sharon, Shanahan William, Fain Randi
Department of Psychiatry and Human Behavior, School of Medicine, University of California, Irvine, California; Department of Mental Health, Veterans Affairs Long Beach Healthcare System, Long Beach, California.
Eisai Inc, Woodcliff Lake, New Jersey.
Clin Ther. 2016 Jun;38(6):1498-1509. doi: 10.1016/j.clinthera.2016.04.004. Epub 2016 May 17.
Lorcaserin is a selective serotonin 2C receptor (5-HT2C) agonist approved in the United States for use in chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity. Its pharmacologic activity is limited to 5-HT subtype 2 receptors. The potency of lorcaserin for the 5-HT2C receptor is 14-fold greater than its potency for the 5-HT2A receptor and 61-fold greater than its potency for the 5-HT2B receptor. Although 5-HT receptors have been implicated in serotonin syndrome, the precise pathogenesis is unknown. Given a theoretic risk for this syndrome in patients administered lorcaserin either alone or in combination with certain serotonergic agents (eg, selective serotonin reuptake inhibitors [SSRIs] and serotonin-norepinephrine reuptake inhibitors [SNRIs]), patients taking prohibited serotonergic agents were excluded from the Phase III clinical trials. This retrospective analysis evaluated the tolerability of lorcaserin in patients who took protocol-allowed or proscribed serotonergic agents for varying durations of up to 1 year during the BLOOM, BLOSSOM, and BLOOM-DM studies.
Patients randomly assigned to receive either lorcaserin 10 mg QD, lorcaserin 10 mg BID, or placebo and who took a spectrum of serotonergic agents were evaluated at week 52 of treatment (814 and 624 patients receiving lorcaserin and placebo, respectively, were found to have taken allowed or prohibited serotonergic agents during these trials). After the use of a proscribed serotonergic agent was discovered, these patients were discontinued from the trial and followed.
None of the patients in the serotonergic agent subpopulation or in the overall safety population met the clinical criteria of serotonin syndrome. The proportions of patients experiencing any adverse event (AE) were balanced in the lorcaserin and placebo groups in the prohibited serotonergic agent subpopulation. The prevalences of the most common AEs were similar between the serotonergic agent subpopulation and the overall safety population.
The concurrent use of lorcaserin and prohibited or allowed serotonergic agents did not appear to have increased the spectrum or intensity of AEs potentially associated with serotonin excess in this limited dataset. However, the sample population was too small to rule out an effect on a rare event such as serotonin syndrome. ClinicalTrials.gov identifiers: NCT00395135, NCT00603902, and NCT00603291.
氯卡色林是一种选择性5-羟色胺2C受体（5-HT2C）激动剂，在美国被批准用于慢性体重管理，作为低热量饮食和增加体育活动的辅助手段。其药理活性仅限于5-HT 2型受体。氯卡色林对5-HT2C受体的效力比对5-HT2A受体的效力高14倍，比对5-HT2B受体的效力高61倍。尽管5-HT受体与血清素综合征有关，但其确切发病机制尚不清楚。鉴于单独或与某些血清素能药物（如选择性血清素再摄取抑制剂[SSRIs]和血清素-去甲肾上腺素再摄取抑制剂[SNRIs]）联合使用氯卡色林的患者存在该综合征的理论风险，服用禁用血清素能药物的患者被排除在III期临床试验之外。这项回顾性分析评估了在BLOOM、BLOSSOM和BLOOM-DM研究中，服用方案允许或禁止的血清素能药物长达1年的不同时间段的患者中氯卡色林的耐受性。
随机分配接受氯卡色林10毫克每日一次、氯卡色林10毫克每日两次或安慰剂且服用一系列血清素能药物的患者在治疗第52周时接受评估（在这些试验中，分别发现814名和624名接受氯卡色林和安慰剂的患者服用了允许或禁止的血清素能药物）。在发现使用了禁用血清素能药物后，这些患者被停止试验并进行随访。
血清素能药物亚组或总体安全人群中的患者均未达到血清素综合征的临床标准。在禁用血清素能药物亚组中，氯卡色林组和安慰剂组出现任何不良事件（AE）的患者比例相当。血清素能药物亚组和总体安全人群中最常见不良事件的发生率相似。
在这个有限的数据集中，氯卡色林与禁用或允许的血清素能药物同时使用似乎并未增加可能与血清素过量相关的不良事件的范围或强度。然而，样本量太小，无法排除对血清素综合征等罕见事件的影响。ClinicalTrials.gov标识符：NCT00395135、NCT00603902和NCT00603291。
