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将基因检测(5-HTTLPR)纳入治疗重度抑郁症的药理学治疗模型。

A model to incorporate genetic testing (5-HTTLPR) in pharmacological treatment of major depressive disorders.

机构信息

Institute of Psychiatry, University of Bologna, Bologna, Italy.

出版信息

World J Biol Psychiatry. 2011 Oct;12(7):501-15. doi: 10.3109/15622975.2011.572998. Epub 2011 May 19.

Abstract

OBJECTIVE

To evaluate the benefit of pharmacogenetics in antidepressant treatment.

METHODS

In a simulated trial 100,000 subjects in a current episode of major depressive disorder (MDD) received citalopram or bupropion based on the clinician's decision (algorithm A) or following indications from 5-HTTLPR genetic testing (algorithm B), which effect size of was estimated from a meta-analysis of pharmacogenetic trials. A and B were compared in a cost-utility analysis (12 weeks). Costs (international $, 2010) were drawn from official sources. Treatment effects were expressed as quality-adjusted life weeks (QALWs). Outcome was incremental cost-effectiveness ratio (ICER).

RESULTS

Under base-case conditions, genetic test use was associated with increases in antidepressant response (0.062 QALWs) and tolerability (0.016 QALWs) but cost benefit was not acceptable (ICER = $2,890; $1,800-$4,091). However, when the joint effect on antidepressant response and tolerability was analyzed in two recurrent episodes, ICER dropped to $1,392 ($837-$1,982). Cost-effectiveness acceptability curve (CEAC) showed a >80% probability that ICER value fell below the commonly accepted 3 times Gross Domestic Product (GDP) threshold (World Health Organization) and therefore suggesting cost-effectiveness.

CONCLUSION

Notwithstanding some caveats (exclusion of gene-gene and gene-environment interactions; simple 5-HTTLPR architecture), this simulation is favourable to incorporate pharmacogenetic test in antidepressant treatment.

摘要

目的

评估药物遗传学在抗抑郁治疗中的获益。

方法

在一项模拟试验中,10 万名当前患有重度抑郁症(MDD)的患者根据临床医生的决策(算法 A)或 5-HTTLPR 基因检测结果(算法 B)接受西酞普兰或安非他酮治疗,后者的疗效大小是根据药物遗传学试验的荟萃分析估计的。在成本-效用分析(12 周)中比较了 A 和 B。成本(国际美元,2010 年)来自官方来源。治疗效果以质量调整生命周数(QALWs)表示。结果为增量成本效益比(ICER)。

结果

在基础条件下,基因检测的使用与抗抑郁药反应(0.062 QALWs)和耐受性(0.016 QALWs)的增加有关,但成本效益不可接受(ICER = 2890 美元;1800-4091 美元)。然而,当在两个复发性发作中分析对抗抑郁反应和耐受性的联合影响时,ICER 降至 1392 美元(837-1982 美元)。成本效益可接受性曲线(CEAC)显示,ICER 值低于普遍接受的 3 倍国内生产总值(GDP)阈值(世界卫生组织)的可能性大于 80%,因此表明具有成本效益。

结论

尽管存在一些注意事项(排除基因-基因和基因-环境相互作用;简单的 5-HTTLPR 结构),但该模拟结果有利于将药物遗传学检测纳入抗抑郁治疗。

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