Aebi N, Meier C R, Jick S S, Lang U, Spoendlin J
Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland; Hospital Pharmacy, University Hospital Basel, Basel, Switzerland; University Psychiatric Clinics Basel, University Hospital Basel, Basel, Switzerland.
Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland; Hospital Pharmacy, University Hospital Basel, Basel, Switzerland; Boston Collaborative Drug Surveillance Program, Lexington, MA, USA.
J Affect Disord. 2024 Jun 1;354:152-159. doi: 10.1016/j.jad.2024.03.002. Epub 2024 Mar 12.
Preclinical studies suggested that drugs that functionally inhibit acid sphingomyelinase (FIASMA)may enhance immune cell longevity and potentially offer protection against infections. Many antidepressants have shown FIASMA activity.
We conducted a cohort study using primary-care data from the UK-based Clinical Practice Research Datalink (2000-2021). We assessed the association of composite diagnosed acute infections in new users of fluoxetine, sertraline, paroxetine, or venlafaxine aged 18-80 years compared to citalopram. We compared SARS-CoV-2 infections between groups in a secondary analysis. We estimated incidence rates (IR) and IR ratios (IRR) of acute infections in four pairwise comparisons using negative binomial regression. We applied propensity score (PS) fine stratification to control for confounding.
In the PS-weighted cohorts, we included 353,138 fluoxetine, 222,463 sertraline, 69,963 paroxetine, 32,608 venlafaxine, and between 515,996 and 516,583 new citalopram users. PS-weighted IRs ranged between 76.8 acute infections /1000 person-years (py) (sertraline) and 98.9 infections/1000 py (citalopram). We observed PS-weighted IRRs around unity for paroxetine (0.97, 95 % CI, 0.95-1.00), fluoxetine (0.94, 95 % CI, 0.92-0.95), and venlafaxine (0.90, 95 % CI, 0.87-0.94) vs citalopram. Reduced IRR for sertraline vs citalopram (0.84, 95 % CI, 0.82-0.85), became null within subgroups by cohort entry date. In the analysis of SARS-CoV-2 infection, no statistically relevant risk reduction was seen.
Analysis not limited to patients with diagnosed depression, possible underestimation of infection incidence, and unclear FIASMA activity of citalopram.
Fluoxetine, sertraline, paroxetine, and venlafaxine were not associated with a reduced risk of acute infection when compared with the presumably weak FIASMA citalopram.
临床前研究表明，功能性抑制酸性鞘磷脂酶的药物（FIASMA）可能会延长免疫细胞寿命，并有可能提供抗感染保护。许多抗抑郁药已显示出FIASMA活性。
我们使用来自英国临床实践研究数据链（2000 - 2021年）的初级保健数据进行了一项队列研究。我们评估了18至80岁的氟西汀、舍曲林、帕罗西汀或文拉法辛新使用者与西酞普兰相比，复合诊断急性感染的相关性。在二次分析中，我们比较了各组之间的SARS-CoV-2感染情况。我们使用负二项回归在四个成对比较中估计急性感染的发病率（IR）和发病率比（IRR）。我们应用倾向评分（PS）精细分层来控制混杂因素。
在PS加权队列中，我们纳入了353138名氟西汀使用者、222463名舍曲林使用者、69963名帕罗西汀使用者、32608名文拉法辛使用者，以及515996至516583名新的西酞普兰使用者。PS加权IR范围在76.8例急性感染/1000人年（py）（舍曲林）至98.9例感染/1000 py（西酞普兰）之间。与西酞普兰相比，我们观察到帕罗西汀（0.97，95% CI，0.95 - 1.00）、氟西汀（0.94，95% CI，0.92 - 0.95）和文拉法辛（0.90，95% CI，0.87 - 0.94）的PS加权IRR接近1。舍曲林与西酞普兰相比的IRR降低（0.84，95% CI，0.82 - 0.85），在按队列入组日期划分的亚组中变为无差异。在SARS-CoV-2感染分析中，未观察到统计学上相关的风险降低。
分析不限于诊断为抑郁症的患者，可能低估感染发病率，且西酞普兰的FIASMA活性不明确。
与可能具有较弱FIASMA活性的西酞普兰相比，氟西汀、舍曲林、帕罗西汀和文拉法辛与急性感染风险降低无关。
