Abstract：
BACKGROUND: The comparative effectiveness of selective serotonin reuptake inhibitors (SSRIs) has been subjected to relatively little research. However, a recent study based on target trial emulation suggested that sertraline may be more effective than escitalopram.
OBJECTIVE: To investigate whether sertraline, citalopram, and escitalopram differ in their effectiveness-assessed via the risk of psychiatric hospital admission and suicide following treatment initiation. The choice to focus on sertraline, citalopram, and escitalopram was made to limit confounding by indication, as the Danish depression treatment guideline from 2007 specifically listed these three SSRIs as first choice.
METHODS: We conducted a target trial emulation based on data from Danish registers. We identified all individuals that initiated treatment for depression with sertraline, citalopram, or escitalopram in the period from January 1, 2007, to March 1, 2019. These individuals were followed until psychiatric hospital admission or suicide (separate analyses), death, 1 year after treatment initiation or end of data. Cox proportional hazards regression adjusted for relevant baseline covariates was performed to emulate randomized treatment allocation, comparing the rate of psychiatric hospital admission and suicide for individuals treated with sertraline (used as reference), citalopram or escitalopram, respectively. For escitalopram, we conducted a sensitivity analysis excluding data from the period during which the drug was sold under patent, as the price of the drug during that time likely entailed a different prescription pattern, increasing the risk of (\"patent-related\") confounding by indication.
RESULTS: We identified 56,865, 118,145, and 31,083 individuals initiating treatment with sertraline, citalopram, and escitalopram, respectively. Using sertraline as reference, the adjusted hazard rate ratio (aHRR) for psychiatric admission was 0.98 (95% CI = 0.91-1.05) for citalopram and 1.21 (95% CI = 1.10-1.32) for escitalopram. Notably, in the sensitivity analysis only including patients initiating treatment after the escitalopram patent had expired, the increased risk of psychiatric hospital admission associated with escitalopram treatment was no longer present (aHRR = 0.98, 95% CI = 0.82-1.18). The results of the analyses of suicide were inconclusive, due to few outcome events.
CONCLUSIONS: Sertraline, citalopram, and escitalopram do not seem to have differential effectiveness in the treatment of depression. Taking potential patent-related, time varying, confounding by indication (via severity) into account is critical for pharmacoepidemiological studies, including those employing target trial emulation.
OBJECTIVE: To investigate whether sertraline, citalopram, and escitalopram differ in their effectiveness-assessed via the risk of psychiatric hospital admission and suicide following treatment initiation. The choice to focus on sertraline, citalopram, and escitalopram was made to limit confounding by indication, as the Danish depression treatment guideline from 2007 specifically listed these three SSRIs as first choice.
METHODS: We conducted a target trial emulation based on data from Danish registers. We identified all individuals that initiated treatment for depression with sertraline, citalopram, or escitalopram in the period from January 1, 2007, to March 1, 2019. These individuals were followed until psychiatric hospital admission or suicide (separate analyses), death, 1 year after treatment initiation or end of data. Cox proportional hazards regression adjusted for relevant baseline covariates was performed to emulate randomized treatment allocation, comparing the rate of psychiatric hospital admission and suicide for individuals treated with sertraline (used as reference), citalopram or escitalopram, respectively. For escitalopram, we conducted a sensitivity analysis excluding data from the period during which the drug was sold under patent, as the price of the drug during that time likely entailed a different prescription pattern, increasing the risk of (\"patent-related\") confounding by indication.
RESULTS: We identified 56,865, 118,145, and 31,083 individuals initiating treatment with sertraline, citalopram, and escitalopram, respectively. Using sertraline as reference, the adjusted hazard rate ratio (aHRR) for psychiatric admission was 0.98 (95% CI = 0.91-1.05) for citalopram and 1.21 (95% CI = 1.10-1.32) for escitalopram. Notably, in the sensitivity analysis only including patients initiating treatment after the escitalopram patent had expired, the increased risk of psychiatric hospital admission associated with escitalopram treatment was no longer present (aHRR = 0.98, 95% CI = 0.82-1.18). The results of the analyses of suicide were inconclusive, due to few outcome events.
CONCLUSIONS: Sertraline, citalopram, and escitalopram do not seem to have differential effectiveness in the treatment of depression. Taking potential patent-related, time varying, confounding by indication (via severity) into account is critical for pharmacoepidemiological studies, including those employing target trial emulation.
摘要：
背景：对选择性5-羟色胺再摄取抑制剂（SSRIs）的相对有效性进行了相对较少的研究。然而,最近一项基于目标试验模拟的研究表明,舍曲林可能比艾司西酞普兰更有效.
目的：调查舍曲林是否，西酞普兰,和艾司西酞普兰在通过精神科住院风险和治疗开始后自杀评估的有效性方面存在差异。选择专注于舍曲林，西酞普兰,艾司西酞普兰是为了通过适应症来限制混杂，2007年的丹麦抑郁症治疗指南特别列出了这三种SSRIs作为首选。
方法：我们根据丹麦注册的数据进行了一项目标试验仿真。我们确定了所有开始使用舍曲林治疗抑郁症的个体，西酞普兰,或艾司西酞普兰在2007年1月1日至2019年3月1日期间。这些人被跟踪直到精神病住院或自杀（单独分析），死亡,治疗开始或结束后1年的数据。对相关基线协变量进行Cox比例风险回归调整，以模拟随机治疗分配，比较接受舍曲林治疗的个人的精神病住院率和自杀率（用作参考），西酞普兰或艾司西酞普兰，分别。对于依他普仑，我们进行了敏感性分析，不包括专利销售期间的数据，因为这段时间的药物价格可能需要不同的处方模式，通过适应症增加(“专利相关”)混淆的风险。
结果：我们确定了56,865、118,145和31,083名开始使用舍曲林治疗的个体，西酞普兰,还有艾司西酞普兰,分别。使用舍曲林作为参考，西酞普兰和艾司西酞普兰的精神科住院校正风险率比(aHRR)分别为0.98(95%CI=0.91-1.05)和1.21(95%CI=1.10-1.32).值得注意的是,在敏感性分析中，仅包括艾司西酞普兰专利过期后开始治疗的患者，与艾司西酞普兰治疗相关的精神科住院风险增加不再存在(aHRR=0.98,95%CI=0.82~1.18).自杀的分析结果尚无定论，由于结果事件很少。
结论：舍曲林，西酞普兰,和艾司西酞普兰在治疗抑郁症方面似乎没有不同的效果。考虑到潜在的专利相关，时变,考虑到适应症(通过严重程度)的混淆对药物流行病学研究至关重要，包括那些采用目标试验仿真的人。
目的：调查舍曲林是否，西酞普兰,和艾司西酞普兰在通过精神科住院风险和治疗开始后自杀评估的有效性方面存在差异。选择专注于舍曲林，西酞普兰,艾司西酞普兰是为了通过适应症来限制混杂，2007年的丹麦抑郁症治疗指南特别列出了这三种SSRIs作为首选。
方法：我们根据丹麦注册的数据进行了一项目标试验仿真。我们确定了所有开始使用舍曲林治疗抑郁症的个体，西酞普兰,或艾司西酞普兰在2007年1月1日至2019年3月1日期间。这些人被跟踪直到精神病住院或自杀（单独分析），死亡,治疗开始或结束后1年的数据。对相关基线协变量进行Cox比例风险回归调整，以模拟随机治疗分配，比较接受舍曲林治疗的个人的精神病住院率和自杀率（用作参考），西酞普兰或艾司西酞普兰，分别。对于依他普仑，我们进行了敏感性分析，不包括专利销售期间的数据，因为这段时间的药物价格可能需要不同的处方模式，通过适应症增加(“专利相关”)混淆的风险。
结果：我们确定了56,865、118,145和31,083名开始使用舍曲林治疗的个体，西酞普兰,还有艾司西酞普兰,分别。使用舍曲林作为参考，西酞普兰和艾司西酞普兰的精神科住院校正风险率比(aHRR)分别为0.98(95%CI=0.91-1.05)和1.21(95%CI=1.10-1.32).值得注意的是,在敏感性分析中，仅包括艾司西酞普兰专利过期后开始治疗的患者，与艾司西酞普兰治疗相关的精神科住院风险增加不再存在(aHRR=0.98,95%CI=0.82~1.18).自杀的分析结果尚无定论，由于结果事件很少。
结论：舍曲林，西酞普兰,和艾司西酞普兰在治疗抑郁症方面似乎没有不同的效果。考虑到潜在的专利相关，时变,考虑到适应症(通过严重程度)的混淆对药物流行病学研究至关重要，包括那些采用目标试验仿真的人。
