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

BackgroundBrain 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.MethodsElectronic 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.ResultsWe 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).ConclusionsThere 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）是重度抑郁症（major depressive disorder, MDD）病理生理过程中最重要的调控蛋白之一。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浓度的潜在调控作用尚不清楚。因此，本荟萃分析旨在探讨不同抗抑郁药物对重度抑郁症患者外周血BDNF水平的影响，并为未来的研究方向提供建议。
方法：检索1980年至2016年6月期间PubMed、EMBASE、Cochrane图书馆、Web of Science及PsycINFO等电子数据库。采用标准化均数差（standardized mean difference, SMD）结合95%置信区间（confidence intervals, CIs）比较抗抑郁药治疗前后BDNF水平的变化，所有统计检验均采用双侧检验。
结果：本研究共纳入20项符合纳入标准的抗抑郁药治疗重度抑郁症患者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表明，治疗时长与血液样本类型是抗抑郁药治疗期间BDNF水平的重要效应调节因素。尽管选择性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）在经一段时间的抗抑郁药物治疗后均可升高BDNF水平，但舍曲林在短期内提升BDNF浓度的效果优于其他三种药物（文拉法辛、帕罗西汀或艾司西酞普兰），其标准化均数差为0.53（95%CI=0.13–0.93；P=0.009）。
结论：现有研究证据表明，抗抑郁药治疗可有效升高重度抑郁症患者外周血BDNF水平。更充分的证据显示，不同类型的抗抑郁药对BDNF水平的调控作用存在差异。鉴于舍曲林可在短时间内对BDNF浓度产生显著影响，探究其与外周血BDNF的关联及其相关药理学机制具有潜在研究价值。上述两项发现均需开展进一步的验证性试验予以确认。