Department of Psychiatry and Psychotherapy, University Medical Centre Mainz, Germany.
Prog Neuropsychopharmacol Biol Psychiatry. 2011 Mar 30;35(2):415-20. doi: 10.1016/j.pnpbp.2010.08.011. Epub 2010 Aug 20.
In the treatment of patients with major depressive disorder (MDD), early non-improvement of symptoms after initiation of antidepressant treatment is a highly sensitive and specific marker for final treatment failure. On the other hand, meta-analyses of clinical studies investigating serum BDNF (sBDNF) concentration before and after antidepressant treatment showed an increase of sBDNF during treatment, which was correlated with amelioration of depressive symptoms. No study has yet investigated the predictive value of early changes of sBDNF for final treatment outcome of the individual patient. The aim of this study was to investigate in patients with MDD, whether i) the non-increase of sBDNF in the early course of treatment is a specific and sensitive marker for final treatment failure, ii) whether the sensitivity and specificity of early non-improvement for treatment failure can be increased by combining it with the marker "early non-increase of sBDNF". For this purpose, we performed a pilot study with 41 inpatients with MDD according to DSM-IV, who were treated in a naturalistic setting. Depression severity and sBDNF were measured in weekly intervals from baseline to week six with the 21-item Hamilton Depression Rating Scale (HAMD-21) and ELISA, respectively. The individual markers sBDNF non-increase and HAMD-21 non-improvement from baseline to day 7 or 14 predicted later non-response and non-remission with moderate to high specificity. The combined marker sBDNF non-increase plus HAMD-21 non-improvement at day 14 increased the specificity for non-response and non-remission to 100%. Our data provide the first evidence that the absence of an early increase of sBDNF in conjunction with early non-improvement might be a highly specific peripheral marker predictive for treatment failure in patients with MDD. If replicated, this combined marker could be considered useful for prospective confirmatory trials in patients with MDD.
在治疗重度抑郁症（MDD）患者时，抗抑郁治疗开始后症状早期无改善是最终治疗失败的高度敏感和特异性标志物。另一方面，对抗抑郁治疗前后血清脑源性神经营养因子（sBDNF）浓度进行的临床研究的荟萃分析表明，治疗期间 sBDNF 增加，与抑郁症状改善相关。尚无研究调查 sBDNF 的早期变化对个体患者最终治疗结果的预测价值。本研究旨在调查 MDD 患者中，i）治疗早期 sBDNF 无增加是否是最终治疗失败的特异性和敏感性标志物，ii）是否可以通过将其与“早期 sBDNF 无增加”标志物相结合来提高早期无改善对治疗失败的敏感性和特异性。为此，我们对 41 名符合 DSM-IV 标准的 MDD 住院患者进行了一项试点研究，这些患者在自然环境中接受治疗。采用汉密尔顿抑郁评定量表（HAMD-21）和 ELISA 分别在基线至第 6 周的每周间隔测量抑郁严重程度和 sBDNF。从基线到第 7 天或第 14 天的个体标志物 sBDNF 无增加和 HAMD-21 无改善预测了后期无反应和无缓解，具有中到高度特异性。第 14 天 sBDNF 无增加加 HAMD-21 无改善的联合标志物将无反应和无缓解的特异性提高到 100％。我们的数据首次提供了证据，即早期 sBDNF 无增加与早期无改善相结合可能是 MDD 患者治疗失败的高度特异性外周标志物。如果得到复制，这种联合标志物可用于 MDD 患者的前瞻性确证性试验。
