Meta-analyses of comparative efficacy of antidepressant medications on peripheral BDNF concentration in patients with depression

Background
Brain derived neurotrophic factor (BDNF) is one of the most important regulatory proteins in the pathophysiology of major depressive disorder (MDD). Increasing numbers of studies have reported the relationship between serum/plasma BDNF and antidepressants (ADs). However, the potential effects of several classes of antidepressants on BDNF concentrations are not well known. Hence, our meta-analyses aims to review the effects of differential antidepressant drugs on peripheral BDNF levels in MDD and make some recommendations for future research.
Methods
Electronic databases including PubMed, EMBASE, the Cochrane Library, Web of Science, and PsycINFO were searched from 1980 to June 2016. The change in BDNF levels were compared between baseline and post-antidepressants treatment by use of the standardized mean difference (SMD) with 95% confidence intervals (CIs). All statistical tests were two-sided.
Results
We identified 20 eligible trials of antidepressants treatments for BDNF in MDD. The overall effect size for all drug classes showed that BDNF levels were elevated following a course of antidepressants use. For between-study heterogeneity by stratification analyses, we detect that length of treatment and blood samples are significant effect modifiers for BDNF levels during antidepressants treatment. While both SSRIs and SNRIs could increase the BDNF levels after a period of antidepressant medication treatment, sertraline was superior to other three drugs (venlafaxine, paroxetine or escitalopram) in the early increase of BDNF concentrations with SMD 0.53(95% CI = 0.13–0.93; P = 0.009).
Conclusions
There is some evidence that treatment of antidepressants appears to be effective in the increase of peripheral BDNF levels. More robust evidence indicates that different types of antidepressants appear to induce differential effects on the BDNF levels. Since sertraline makes a particular effect on BDNF concentration within a short amount of time, there is potential value in exploring its relationship with BDNF and its pharmacological mechanism concerning peripheral blood BDNF. Further confirmatory trials are required for both observations.

背景
脑源性神经营养因子（Brain Derived Neurotrophic Factor，BDNF）是重性抑郁障碍（Major Depressive Disorder，MDD）病理生理学中最重要的调节蛋白之一。目前已有越来越多的研究报道了血清/血浆BDNF与抗抑郁药（Antidepressants，ADs）之间的关联，但目前对于多类抗抑郁药对BDNF浓度的潜在影响仍不甚明确。因此，本项荟萃分析旨在探讨不同抗抑郁药物对重性抑郁障碍患者外周血BDNF水平的影响，并为未来的研究方向提供建议。
方法
本研究检索了1980年至2016年6月期间的电子数据库，包括PubMed、EMBASE、Cochrane图书馆、Web of Science及PsycINFO。采用标准化均数差（Standardized Mean Difference，SMD）及95%置信区间（Confidence Intervals，CIs）比较抗抑郁药治疗基线与治疗后BDNF水平的变化，所有统计检验均为双侧检验。
结果
本研究共纳入20项符合纳入标准的抗抑郁药治疗重性抑郁障碍并检测BDNF水平的临床试验。所有药物类别的合并效应量结果显示，抗抑郁药治疗疗程结束后，患者外周BDNF水平显著升高。针对研究间异质性的分层分析结果显示，治疗时长与血液样本类型是抗抑郁药治疗期间影响BDNF水平的重要效应调节因子。其中，选择性5-羟色胺再摄取抑制剂（Selective Serotonin Reuptake Inhibitors，SSRIs）与5-羟色胺-去甲肾上腺素再摄取抑制剂（Serotonin-Norepinephrine Reuptake Inhibitors，SNRIs）类抗抑郁药治疗一段时间后均可升高BDNF水平；而在BDNF浓度的早期升高效应方面，舍曲林优于其他三种药物（文拉法辛、帕罗西汀及艾司西酞普兰），其标准化均数差为0.53（95%置信区间：0.13~0.93；P=0.009）。
结论
现有证据表明，抗抑郁药治疗可有效升高外周血BDNF水平。更为可靠的证据显示，不同类型的抗抑郁药对BDNF水平的影响存在差异。鉴于舍曲林可在较短时间内对BDNF浓度产生特异性影响，探索其与外周血BDNF的关联及其相关药理学机制具有潜在研究价值。针对上述两项发现，均需开展进一步的验证性临床试验。