Yuan Ziqi, Chen Zhenlei, Xue Maoqiang, Zhang Jie, Leng Lige
Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, Fujian 361102, PR China.
Department of Basic Medical Science, School of Medicine, Xiamen University, Xiamen, Fujian 361102, PR China.
J Clin Neurosci. 2020 Oct;80:169-181. doi: 10.1016/j.jocn.2020.08.013. Epub 2020 Aug 19.
The type and quantities of antidepressants are increasing, but the efficacy and safety of first-line and emerging drugs vary between studies. In this article, we estimated the efficacy and safety of first-line and emerging antidepressants (anti-inflammatory drugs and ketamine).
ystematic search of EMBASE, ERIC, MEDLINE, psycARTICLES, and psycINFO without language restriction for studies on the depression, depressive symptoms, antidepressants, fluoxetine (Prozac), paroxetine, escitalopram, sertraline, fluvoxamine, venlafaxine, duloxetine, NSAIDs, anti-cytokine drugs or pioglitazone published before May 1st, 2019. Information on study characteristics, depression or depressive symptoms, antidepressants and the descriptive statistics (including efficacy and safety of antidepressants) was extracted independently by 2 investigators. Estimates were pooled using random-effects meta-analysis. Differences by study-level characteristics were estimated using stratified meta-analysis and meta-regression. The response and remission of antidepressants were used as clinical evaluation indicators, and the evaluation criteria were clinical depression scales. OR value of antidepressants as assessed by meta-analysis.
The literature search retrieved 5529 potentially relevant articles of which 49 studies were finally included. We compared the efficacy of antidepressants (seven first-line antidepressants (fluoxetine, paroxetine, escitalopram, sertraline, fluvoxamine, venlafaxine, duloxetine), there kinds of anti-inflammatory drugs(NASIDs, cytokine-inhibitor, pioglitazone) and ketamine) by comparing the OR values.
The three drugs with the highest OR value in response were NASID (OR = 3.62(1.58, 8.32)), venlafaxin (OR = 3.50(1.83, 6.70)) and ketamine (OR = 3.28(1.89, 5.68)), while the highest OR value in remission were NASID (OR = 3.17(1.60, 6.29)), ketamine (OR = 2.99(1.58, 5.67)) and venlafaxin (OR = 2.55(1.72, 3.78)). Through reading the literature, we found 69 SNPs associated with depression. Major depression was a debilitating disorder that could ultimately lead to enormous societal and economical challenge [1]. The number of person which affected by depression was up to 16% of the population worldwide. More than 300 million individuals were estimated to suffer depression these days [1,2]. Therefore, it is apparent that safety and effective treatments for depression are necessary. In the 1930 s, the first drug for schizophrenia was discovered. This finding was a landmark for the emerging of biological psychiatry. In the 1950 s, pharmacologists had stumbled upon the antidepressant effect of imipramine. Since then, every 30 years, the use of antidepressants had made a pulsatile leap. Selective serotonin reuptake inhibitors (SSRIs) are the most widely-prescribed psychiatric drugs for the treatment of depression. However, the efficacy was variable and incomplete: 60%-70% of the patients do not experience remission, while 30%-40% do not show a significant response [3,4]. Nevertheless, SSRIs, SNRIs (selective serotonin-norepinephrine reuptake inhibitors, which can block norepinephrine at the same time) and NaSSAs (norepinephrine and selective serotonin receptor agonist), constituted the first-line clinical drugs. Nearly 30 years after the outbreak of SSRIs, antidepressants have ushered in a new chapter. It has been found that anti-inflammatory drugs could also have the small and moderate antidepressant effect and it's widely discussed [5]. More than 40 anti-inflammatory drugs have been certificated to have antidepressant effects in preclinical and clinical studies [6]. The antidepressant that has been approved for use recently is ketamine. There is no comprehensive comparison of the efficacy of all these drugs. In this review, we tried to estimate the efficacy and safety of first-line antidepressants, anti-inflammatory drugs and ketamine. On the other hand, with the development of GWAS, SNPs related to depression have been reported, and the corresponding mechanisms have been elaborated, respectively. However, patients with these SNPs have not been treated with individualized drugs according to the mechanisms. We hope to push this process forward through the summary of this article.
Search Strategy and Study Eligibility.
抗抑郁药的种类和数量不断增加,但一线药物和新型药物的疗效和安全性在不同研究中存在差异。在本文中,我们评估了一线和新型抗抑郁药(抗炎药和氯胺酮)的疗效和安全性。
对EMBASE、ERIC、MEDLINE、psycARTICLES和psycINFO进行系统检索,不限语言,检索2019年5月1日前发表的关于抑郁症、抑郁症状、抗抑郁药、氟西汀(百忧解)、帕罗西汀、艾司西酞普兰、舍曲林、氟伏沙明、文拉法辛、度洛西汀、非甾体抗炎药、抗细胞因子药物或吡格列酮的研究。由2名研究人员独立提取有关研究特征、抑郁症或抑郁症状、抗抑郁药以及描述性统计数据(包括抗抑郁药的疗效和安全性)的信息。使用随机效应荟萃分析汇总估计值。使用分层荟萃分析和荟萃回归估计研究水平特征的差异。将抗抑郁药的反应和缓解作为临床评估指标,评估标准为临床抑郁量表。通过荟萃分析评估抗抑郁药的OR值。
文献检索共获得5529篇潜在相关文章,最终纳入49项研究。我们通过比较OR值,比较了抗抑郁药(七种一线抗抑郁药(氟西汀、帕罗西汀、艾司西酞普兰、舍曲林、氟伏沙明、文拉法辛、度洛西汀)、三种抗炎药(非甾体抗炎药、细胞因子抑制剂、吡格列酮)和氯胺酮)的疗效。
反应中OR值最高的三种药物是非甾体抗炎药(OR = 3.62(1.58, 8.32))、文拉法辛(OR = 3.50(1.83, 6.70))和氯胺酮(OR = 3.28(1.89, 5.68)),而缓解中OR值最高的是非甾体抗炎药(OR = 3.17(1.60, 6.29))、氯胺酮(OR = 2.99(1.58, 5.67))和文拉法辛(OR = 2.55(1.72, 3.78))。通过阅读文献,我们发现69个与抑郁症相关的单核苷酸多态性。重度抑郁症是一种使人衰弱的疾病,最终可能导致巨大的社会和经济挑战[1]。受抑郁症影响的人数占全球人口的16%。目前估计有超过3亿人患有抑郁症[1,2]。因此,显然需要安全有效的抑郁症治疗方法。20世纪30年代,发现了第一种治疗精神分裂症的药物。这一发现是生物精神病学兴起的一个里程碑。20世纪50年代,药理学家偶然发现了丙咪嗪的抗抑郁作用。从那时起,每30年,抗抑郁药的使用就有一次脉冲式飞跃。选择性5-羟色胺再摄取抑制剂(SSRIs)是治疗抑郁症最广泛使用的精神科药物。然而,疗效参差不齐且不完全:60%-70%的患者没有缓解,而30%-40%的患者没有显著反应[3,4]。尽管如此,SSRI、SNRI(选择性5-羟色胺-去甲肾上腺素再摄取抑制剂,可同时阻断去甲肾上腺素)和NaSSA(去甲肾上腺素和选择性5-羟色胺受体激动剂)构成了一线临床药物。在SSRI出现近30年后,抗抑郁药迎来了新的篇章。已发现抗炎药也可能具有轻度至中度抗抑郁作用,这一点已得到广泛讨论[5]。超过40种抗炎药在临床前和临床研究中被证明具有抗抑郁作用[6]。最近被批准使用的抗抑郁药是氯胺酮。目前尚无对所有这些药物疗效的全面比较。在本综述中,我们试图评估一线抗抑郁药、抗炎药和氯胺酮的疗效和安全性。另一方面,随着全基因组关联研究(GWAS)的发展,已报道了与抑郁症相关的单核苷酸多态性,并分别阐述了相应的机制。然而,携带这些单核苷酸多态性的患者尚未根据这些机制接受个体化药物治疗。我们希望通过本文的总结推动这一进程。
检索策略和研究纳入标准。