Center for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, Rome, Italy.
BIO@SNS lab, Scuola Normale Superiore di Pisa, Pisa, Italy.
Pharmacogenomics J. 2019 Dec;19(6):538-546. doi: 10.1038/s41397-019-0080-6. Epub 2019 Feb 6.
Selective serotonin reuptake inhibitors (SSRIs), the most prescribed antidepressant drugs, have incomplete efficacy and no clear mechanism of action. In addition, no reliable methods to identify patients who will benefit from treatment is available. In this study, we show that citalopram, a commonly used SSRI, produces a dose-dependent amplification of the influence of the environment on mood, making the severity of symptoms dependent on the level of socioeconomic status (SES). As a consequence, based on SES, we were able to predict which patients would show remission following 12 weeks of treatment in the high, but not the low dose group. Our findings support a novel mechanism of action for SSRIs, which calls for a permissive rather than an instructive role of these drugs, and indicate that treatment outcome can be predicted based on SES and dose. Finally, our findings suggest that the patient's social and economic conditions should be considered in setting up personalized strategies aimed at enhancing SSRI efficacy.
选择性 5-羟色胺再摄取抑制剂(SSRIs)是最常被开的抗抑郁药,但疗效并不完全,作用机制也不明确。此外,目前还没有可靠的方法来识别哪些患者将从治疗中受益。在这项研究中,我们表明,西酞普兰是一种常用的 SSRI,它会使环境对情绪的影响产生剂量依赖性的放大,使症状的严重程度取决于社会经济地位(SES)的水平。因此,我们可以根据 SES 预测哪些患者在高剂量而不是低剂量组治疗 12 周后会缓解。我们的研究结果支持了 SSRI 的一种新的作用机制,它需要这些药物起到许可而不是指导的作用,并表明可以根据 SES 和剂量预测治疗效果。最后,我们的研究结果表明,在制定旨在提高 SSRI 疗效的个性化策略时,应考虑患者的社会和经济状况。