Prescribing antidepressants post Cipriani et al
Prescribing antidepressants post Cipriani et al
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Cipriani 等人之后开出抗抑郁药
DOI：
10.1177/0269881109106958
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发表时间：
2009
影响因子：
4.1
通讯作者：
D. Nutt
中科院分区：
文献类型：
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作者：
D. Nutt
你们很多人都看过《柳叶刀》上最近发表的一篇论文，其中对新型抗抑郁药的相对疗效和可接受性进行了复杂的荟萃分析（Cipriani et al., 2009）。这篇论文的作者使用了一种新的统计方法，使得估计抗抑郁药物的相对疗效成为可能，即使大多数药物没有被专门地相互比较。通过比较不同药物与常用比较物的疗效，可以对抗抑郁药的相对疗效和可接受性做出有意义的推断。这种新的荟萃分析过程允许作者根据这两个维度对抗抑郁药进行排序，如图1所示。那么关键信息是什么呢？最明显的是相对疗效，其中米氮平、艾司西酞普兰、文拉法辛和舍曲林的疗效显著高于其他药物[相对优势比约为1.3]；参见图1。瑞波西汀的疗效明显低于其他药物。第二个维度与相对可接受性有关，艾司西酞普兰排名第一，其次是舍曲林和安非他酮，文拉法辛和米氮平排名较低。基于这两个维度，作者认为艾司西酞普兰和舍曲林应该是首选抗抑郁药，舍曲林可能以较低的获取成本为优先选择。这些发现意味着什么？它们对临床实践有什么影响？从英国精神药理学协会（BAP）的角度来看，艾司西酞普兰和文拉法辛比大多数其他新型抗抑郁药具有更好的疗效，这一发现强化了最近BAP抑郁症治疗指南中的信息（Anderson et al., 2008）。鉴于艾司西酞普兰是最有效的选择性5 -羟色胺再摄取抑制剂（SSRI），艾司西酞普兰是最容易被接受的抗抑郁药之一，这一点可能不那么明显。与西酞普兰和其他短效SSRIs（如帕罗西汀和氟伏沙明）相比，它可能反映出其更长的再摄取位点动力学的一些积极益处。艾司西酞普兰与再摄取位点的缓慢分离似乎是由于其与5HT转运体上的另一个（所谓的“变构”）位点结合（Sánchez et al., 2004）。舍曲林相对较高的疗效是出乎意料的，尽管它的良好接受性和药物-药物相互作用的低倾向是公认的。是否许多精神科医生会同意Cipriani等人（2009）的建议，即舍曲林应该是一线抗抑郁药物，目前尚不清楚，只有时间才能证明处方做法是否会改变。目前，西酞普兰和氟西汀是最常用的新型抗抑郁药，总处方数分别为770万和500万，尽管西酞普兰处方中有30%（230万）是10毫克片剂，仅这两种片剂就具有亚治疗作用。令人惊讶的是，低剂量阿米替林也很常见，有超过600万份处方，剂量为10毫克和25毫克，但由于这些剂量远远低于有效的抗抑郁药剂量，我们推测它们一定是出于其他原因使用的)（2008年处方成本分析）。西酞普兰和氟西汀如此受欢迎的原因可能反映了它们是第一批成为通用的ssri类药物的事实。在NICE（2004）对抗抑郁药的回顾中，建议处方SSRIs/ 5 -羟色胺-去甲肾上腺素再摄取抑制剂（SNRIs）的“考虑因素”如下：
Many of you will have seen the recent paper in the Lancet in which a sophisticated meta-analysis of the relative efficacy and acceptability of new antidepressants was conducted (Cipriani et al., 2009). The authors of this paper used a new statistical approach that makes it possible to estimate the relative efficacy of antidepressant drugs even though the majority have not been specifically compared against each other. By comparing the efficacy of different drugs against common comparators, meaningful inferences of relative antidepressant efficacy and acceptability can be made. This new meta-analytical process allowed the authors to rank antidepressants according to these two dimensions as shown in Figure 1. So what are the key messages? The most obvious ones relate to relative efficacy where mirtazapine escitalopram venlafaxine and sertraline demonstrated significantly greater efficacy than the other drugs [relative odds ratios of about 1.3]; see Figure 1. Reboxetine was significantly less efficacious than the others. The second dimension relates to relative acceptability where escitalopram came top followed by sertraline and bupropion, with venlafaxine and mirtazapine lower down. Based on these two dimensions the authors conclude that escitalopram and sertraline should be the first choice antidepressants with sertraline possibly being preferred on the grounds of lower acquisition costs. What do these findings mean and what are their implications for clinical practice? From the perspective of the British Association for Psychopharmacology (BAP) the finding that escitalopram and venlafaxine have better efficacy than most other new antidepressants reinforces the message in the recent BAP guidelines on the treatment of depression (Anderson et al., 2008). That escitalopram was among the antidepressants with greatest acceptability was perhaps less obvious given it is the most potent selective serotonin reuptake inhibitor (SSRI). It may reflect some positive benefit of its more prolonged reuptake site kinetics as compared with those of citalopram and other shorter-acting SSRIs such as paroxetine and fluvoxamine. This slow dissociation of escitalopram from the reuptake site appears to be due to its binding to another (the so-called ‘allosteric’) site on the 5HT transporter (Sánchez et al., 2004). The relatively high efficacy of sertraline was unexpected although its good acceptability and low propensity for drug– drug interactions is well recognised. Whether many psychiatrists will agree with the recommendations of Cipriani et al. (2009) that sertraline should be the first-line antidepressant drug is not known and only time will tell if prescribing practice changes. Currently citalopram and fluoxetine are the most commonly used of the new antidepressants with total script numbers of 7.7 and 5 million, respectively although 30% of citalopram scripts (2.3 million) are for 10 mg tablets which alone would be subtherapeutic. Surprisingly amitriptyline at low dose is also very common with over 6 million scripts for 10 and 25 mg doses but as these are so far below the effective antidepressant dose we presume that they must be being used for other reasons) (prescription cost analysis 2008). The reason for citalopram and fluoxetine being so popular probably reflects the fact they were the first of the SSRIs to become generic. In the NICE (2004) review of antidepressants the ‘considerations’ suggested for the prescribing of SSRIs/ serotonin–norepinephrine reuptake inhibitors (SNRIs) were: