Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau (IIB-SantPau), Universitat Autònoma de Barcelona (UAB), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), C/ Sant Antoni Maria Claret, 167, 08025, Barcelona, Spain.
Department of Cardiology, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau (IIB-SantPau), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
Eur Arch Psychiatry Clin Neurosci. 2017 Dec;267(8):815-822. doi: 10.1007/s00406-016-0758-6. Epub 2017 Jan 23.
Despite safety concerns raised by the European Medicines Agency (EMA), evidence supporting QT-lengthening effects of escitalopram is far to be conclusive. We aimed to evaluate the relationship between escitalopram plasma levels (Escit-PL) and corrected QT-interval length (QTc-length) in 91 outpatients recruited from a hospital setting. Fifteen patients had an abnormally prolonged QTc-interval, and 3 had QTc-intervals ≥500 ms. No correlation between Escit-PL and QTc-length was found (r = 0.08; p = 0.45). Linear/logistic regression analyses were also conducted taking into account potential confounders such as age, gender, personal history of heart disease, medication load and concomitant use of antipsychotic/tricyclic antidepressants. Escit-PL did not predict either QTc-length or abnormally prolonged QTc-interval. Only antipsychotics/tricyclics use (adjusted β = 0.26, SE = 9.1; p = 0.01) was an independent predictor of QTc-length (R = 0.096, F = 4.68, df = 2,88; p = 0.01). Only antipsychotics/tricyclics use (OR 3.56 [95% CI 1.01-12.52]; p < 0.05) and medication load (OR 1.32 [95% CI 1.06-1.64]; p < 0.01) were significantly associated with an increased risk of abnormally prolonged QTc-interval (Omnibus test χ = 9.5, df = 2; p < 0.01). Our study did not find a significant relationship between Escit-PL and QTc-length even when recognized modulating factors of the QT-interval were controlled for. Concomitant use of other potentially arrhythmogenic agents may help to explain the apparent link between escitalopram and QT prolongation previously suggested. The advisability of maintaining the EMA warning is once again called into question.
尽管欧洲药品管理局(EMA)提出了安全性担忧,但支持艾司西酞普兰引起 QT 延长的证据远未得出结论。我们旨在评估 91 名从医院环境招募的门诊患者的艾司西酞普兰血浆水平(Escit-PL)与校正 QT 间期长度(QTc-length)之间的关系。15 名患者的 QTc 间期异常延长,3 名患者的 QTc 间期≥500ms。Escit-PL 与 QTc-length 之间未发现相关性(r=0.08;p=0.45)。还进行了线性/逻辑回归分析,考虑了年龄、性别、个人心脏病史、药物负荷和同时使用抗精神病药/三环类抗抑郁药等潜在混杂因素。Escit-PL 既不能预测 QTc-length,也不能预测异常延长的 QTc 间期。只有抗精神病药/三环类抗抑郁药的使用(调整后的β=0.26,SE=9.1;p=0.01)是 QTc-length 的独立预测因子(R ²=0.096,F=4.68,df=2,88;p=0.01)。只有抗精神病药/三环类抗抑郁药的使用(OR 3.56 [95% CI 1.01-12.52];p<0.05)和药物负荷(OR 1.32 [95% CI 1.06-1.64];p<0.01)与异常延长的 QTc 间期风险增加显著相关(整体检验 χ²=9.5,df=2;p<0.01)。即使控制了 QT 间期的调节因素,我们的研究也没有发现 Escit-PL 与 QTc-length 之间的显著关系。同时使用其他潜在致心律失常的药物可能有助于解释先前提示的艾司西酞普兰与 QT 延长之间的明显联系。再次质疑维持 EMA 警告的必要性。