Zhi-Yong Cao1, Yun-Zi Liu2, Jia-Mei Li2, Yi-Ming Ruan3, Wen-Jie Yan2, Shi-Yang Zhong2, Ting Zhang2, Lin-Lin Liu4, Ran Wu2, Bo Wang2, Wei Wang2, Xiao-Ying Bi5, Yun-Xia Wang2, Wen-Jun Su6, Chun-Lei Jiang7. 1. Department of Stress Medicine, Faculty of Psychology, Second Military Medical University, 800 Xiangyin Road, Shanghai, China; Department of Psychiatry, The 904th Hospital of PLA, 55 North Heping Road, Changzhou, China. 2. Department of Stress Medicine, Faculty of Psychology, Second Military Medical University, 800 Xiangyin Road, Shanghai, China. 3. Department of Health Statistics, Second Military Medical University, 800 Xiangyin Road, Shanghai, China. 4. Department of Stress Medicine, Faculty of Psychology, Second Military Medical University, 800 Xiangyin Road, Shanghai, China; Department of Nursing, The 474th Hospital of PLA, 757 Beijing Road, Urumqi, China. 5. Department of Neurology, Changhai Hospital, 168 Changhai Road, Shanghai, China. 6. Department of Stress Medicine, Faculty of Psychology, Second Military Medical University, 800 Xiangyin Road, Shanghai, China. Electronic address: suwenjun1992@163.com. 7. Department of Stress Medicine, Faculty of Psychology, Second Military Medical University, 800 Xiangyin Road, Shanghai, China. Electronic address: cljiang@vip.163.com.
Abstract
BACKGROUND: Recently, abundant evidence indicated proinflammatory cytokines might play a crucial role in pathophysiology and treatment of depression. According to our preclinical research, we propose glycyrrhizic acid (GZA) for an adjunctive treatment owing to its safety, economical and anti-inflammatory profile. METHODS:Eligible participants were recruited and randomly allocated into independent treatment groups of SSRI+GZA (n = 30) and SSRI+PBO (placebo, n = 26). Depressive symptoms and specific serum biomarkers were detected during the 4-week treatment course. Afterward, the relationships between biomarkers and clinical effects were explored. RESULTS:Depressive symptoms relieved more in SSRI+GZA than SSRI+PBO, both at week 2 (P = 0.003) and week 4 (P = 0.016). Meanwhile, at week 4, both response rate (P = 0.035) and remission rate (P = 0.031) acutely became higher in SSRI+GZA compared with SSRI+PBO. Mediation analysis further demonstrated that TNF-α reduction mediated the association between GZA treatment and clinical improvement, the indirect effect lay between 0.124 and 3.514 (95% CI). The exploratory analysis also suggested that the symptomatic improvement existed in patients with high-inflammation (baseline CRP > 3 mg/L) rather than those with low-inflammation (baseline CRP ≤ 3 mg/L). LIMITATIONS: The sample size in this study was not large enough and the follow-up duration was relatively short. CONCLUSIONS: This study offers a novel strategy for the diagnosis, categorization, individualization and prognosis regarding upgrading traditional antidepressant therapy, which is from biomarkers to diagnostic indicator and therapeutic target. Patients are necessary to be classified according to the inflammatory state, those with high levels of baseline inflammation should receive combined treatment with anti-inflammatory agents like GZA.
RCT Entities:
BACKGROUND: Recently, abundant evidence indicated proinflammatory cytokines might play a crucial role in pathophysiology and treatment of depression. According to our preclinical research, we propose glycyrrhizic acid (GZA) for an adjunctive treatment owing to its safety, economical and anti-inflammatory profile. METHODS: Eligible participants were recruited and randomly allocated into independent treatment groups of SSRI+GZA (n = 30) and SSRI+PBO (placebo, n = 26). Depressive symptoms and specific serum biomarkers were detected during the 4-week treatment course. Afterward, the relationships between biomarkers and clinical effects were explored. RESULTS:Depressive symptoms relieved more in SSRI+GZA than SSRI+PBO, both at week 2 (P = 0.003) and week 4 (P = 0.016). Meanwhile, at week 4, both response rate (P = 0.035) and remission rate (P = 0.031) acutely became higher in SSRI+GZA compared with SSRI+PBO. Mediation analysis further demonstrated that TNF-α reduction mediated the association between GZA treatment and clinical improvement, the indirect effect lay between 0.124 and 3.514 (95% CI). The exploratory analysis also suggested that the symptomatic improvement existed in patients with high-inflammation (baseline CRP > 3 mg/L) rather than those with low-inflammation (baseline CRP ≤ 3 mg/L). LIMITATIONS: The sample size in this study was not large enough and the follow-up duration was relatively short. CONCLUSIONS: This study offers a novel strategy for the diagnosis, categorization, individualization and prognosis regarding upgrading traditional antidepressant therapy, which is from biomarkers to diagnostic indicator and therapeutic target. Patients are necessary to be classified according to the inflammatory state, those with high levels of baseline inflammation should receive combined treatment with anti-inflammatory agents like GZA.
Authors: Harald Murck; Lisa Lehr; Johannes Hahn; Matthias C Braunisch; Daniela Jezova; Maxim Zavorotnyy Journal: Front Psychiatry Date: 2020-12-10 Impact factor: 4.157