Maljuric Nevena M, Noordam Raymond, Aarts Nikkie, Niemeijer Maartje N, van den Berg Marten E, Hofman Albert, Kors Jan A, Stricker Bruno H, Visser Loes E
Department of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam.
Department of Internal Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam.
Br J Clin Pharmacol. 2015 Oct;80(4):698-705. doi: 10.1111/bcp.12681. Epub 2015 Jul 29.
Selective serotonin re-uptake inhibitors (SSRIs), specifically citalopram and escitalopram, are thought to cause QTc prolongation, although studies have shown contradictory results. Nevertheless, a maximum citalopram dosage of 20 mg in high risk patients (e.g. >60 years of age) is recommended. We aimed to investigate the association between use of (individual) SSRIs and QTc in a population-based study in older adults.
This study, which was part of the prospective Rotterdam Study (period 1991-2012), included participants with up to five electrocardiograms (ECGs). We used linear mixed models to compare QTc F (QT corrected according to Fridericia) measured during use of individual SSRIs with QTc F measured during non-use of any antidepressant. For citalopram, analyses were additionally restricted to a maximum dosage of 20 mg in participants aged 60 years and older.
We included 12 589 participants with a total of 26 620 ECGs of which 436 ECGs were made during SSRI use. The mean QTc F was similar during use of any drugs from the SSRI class and during non-use. After stratifying to individual SSRIs, ECGs recorded during use of citalopram had the longest QTc compared with ECGs recorded during non-use (+12.8 ms, 90% CI 7.5, 18.2). This result remained similar in the analysis comprising participants aged 60 years and older with a maximum prescribed daily dosage of 20 mg citalopram.
Although no SSRI class effect was observed, use of citalopram was associated with a longer QTc F, even after considering the recommended restrictions. Other SSRIs may not give a clinically relevant QTc F prolongation.
选择性5-羟色胺再摄取抑制剂(SSRI),尤其是西酞普兰和艾司西酞普兰,被认为会导致QTc延长,尽管研究结果相互矛盾。然而,对于高危患者(如年龄>60岁),建议西酞普兰最大剂量为20mg。我们旨在通过一项针对老年人的基于人群的研究,调查(个体)SSRI的使用与QTc之间的关联。
本研究是前瞻性鹿特丹研究(1991 - 2012年)的一部分,纳入了最多有五份心电图(ECG)的参与者。我们使用线性混合模型,将使用个体SSRI期间测量的QTc F(根据弗里德里西亚校正的QT)与未使用任何抗抑郁药期间测量的QTc F进行比较。对于西酞普兰,分析还仅限于60岁及以上参与者,最大剂量为20mg。
我们纳入了12589名参与者,共有26620份ECG,其中436份ECG是在使用SSRI期间进行的。使用SSRI类药物期间和未使用期间的平均QTc F相似。按个体SSRI分层后,与未使用期间记录的ECG相比,使用西酞普兰期间记录的ECG的QTc最长(+12.8ms,90%CI 7.5,18.2)。在包括60岁及以上、西酞普兰最大每日处方剂量为20mg的参与者的分析中,这一结果仍然相似。
虽然未观察到SSRI类药物的整体效应,但即使考虑了推荐的限制,使用西酞普兰仍与较长的QTc F相关。其他SSRI可能不会导致临床上有意义的QTc F延长。