Early improvement and response to antidepressant medications in adults with major depressive disorder. Meta-analysis and study of a sample with treatment-resistant depression
Early improvement and response to antidepressant medications in adults with major depressive disorder. Meta-analysis and study of a sample with treatment-resistant depression
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DOI：
10.1016/j.jad.2017.11.004
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发表时间：
2018-02-01
影响因子：
6.6
通讯作者：
Mendlewicz, Julien
中科院分区：
文献类型：
--
作者：
Olgiati, Paolo;Serretti, Alessandro;Mendlewicz, Julien
背景：抗抑郁药（AD）治疗前几周的初始改善是AD完全缓解的有用早期预测因子。我们对AD研究进行了一项荟萃分析，以调查在重度抑郁症（MDD）中，第4周抑郁症状的部分减少是否与第6-14周的反应和缓解相关。最后，我们专注于难治性抑郁症（TRD：缺乏反应，以前的AD），以测试早期改善对第二次AD治疗结果的影响，并比较不同的转换strategies.Methods：荟萃分析进行了AD自然主义的研究之间发表01.01.2000和06.30.2017。TRD为排除标准。对407例接受文拉法辛治疗6周的MDD患者进行TRD分析。MADRS用于定义极早期改善（VEI：第2周下降> 20%）、早期改善（EI：第4周下降> 30%）和缓解（第6周MADRS < 10）。结果：9项研究（N = 6185）显示早期改善、缓解（OR：3.28 95% C.）、VEI（算法B）和EI（算法C）与AD转换有显著相关性（P < 0.05）。I：2.06-5.20）和缓解（OR：2.10 ~ 95%C. I：1.53-2.87）。24.6%的TRD样本缓解。VEI是不良结局预测因子：敏感性= 0.52（0.40-0.63）;特异性= 0.82（0.76-0.86）; AUC = 0.67（0.62-0.71）。EI具有中等预测能力：敏感性= 0.87（0.77-0.93）;特异性= 0.71（0.66-0.77）; AUC = 0.76（0.71-0.80）。最佳治疗方案为方案C（4周后转换），其中缓解率略微增加（35.1% vs方案A的33.7%）。算法B（2周后转换）与算法A相比，缓解率下降4.3%。局限性：纳入了没有对照组的自然样本;模拟治疗。结论：虽然文献数据表明，在AD治疗期间，抑郁症状的最初改善与后来的反应和缓解之间存在相关性，我们的分析表明，这种早期改善并不是TRD的可靠预后预测因素。TRD的性质是复杂的，TRD患者可能需要不同的生物学机制和治疗。
Background: Initial improvement in the first weeks of antidepressant (AD) treatment is a useful early predictor of complete AD response. We performed a meta-analysis of AD studies to investigate whether a partial decrease in depressive symptoms by week 4 was associated with response and remission by weeks 6-14 in major depressive disorder (MDD). Finally, we focused on treatment-resistant depression (TRD: lack of response to prior AD) to test the impact of early improvement on a second AD treatment outcome and to compare different switching strategies.Methods: Meta-analysis was conducted on AD naturalistic studies published between 01.01.2000 and 06.30.2017. TRD was an exclusion criterion. TRD was analyzed in 407 MDD patients treated with venlafaxine for 6 weeks. The MADRS was used to define very early improvement (VEI: > 20% decrease at week 2), early improvement (EI: > 30% decrease at week 4) and remission (week 6 MADRS < 10). A theoretical model was used to simulate AD switch in TRD patients who failed to achieve remission (Algorithm A), VEI (Algorithm B) or EI (Algorithm C).Results: Our meta-analysis (9 studies; N = 6185) showed significant associations between early improvement, response (OR: 3.28 95% C. I: 2.06-5.20) and remission (OR: 2.10 95% C. I: 1.53-2.87). 24.6% of TRD sample remitted. VEI was a poor outcome predictor: sensitivity = 0.52 (0.40-0.63); specificity = 0.82 (0.76-0.86); AUC = 0.67 (0.62-0.71). EI had a moderate predictive power: sensitivity = 0.87 (0.77-0.93); specificity = 0.71 (0.66-0.77); AUC = 0.76 (0.71-0.80). The best treatment scenario was Algorithm C (switch after 4 weeks) in which remission rate was marginally increased (35.1% vs 33.7% of Algorithm A). Algorithm B (switch after 2 weeks) led to a 4.3% decrease in remission compared to Algorithm A.Limitations: Inclusion of a naturalistic sample without a control arm; simulation of treatments.Conclusion: Although literature data suggest a correlation between an initial improvement of depressive symptoms and later response and remission during AD treatment, our analysis shows that such an early improvement is not a reliable outcome predictor in TRD. The nature of TRD is complex and different biological mechanisms and treatments might be necessary for TRD patients.