Optimising first- and second-line treatment strategies for untreated major depressive disorder - the SUN☺D study: a pragmatic, multi-centre, assessor-blinded randomised controlled trial.
Optimising first- and second-line treatment strategies for untreated major depressive disorder - the SUN☺D study: a pragmatic, multi-centre, assessor-blinded randomised controlled trial.
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DOI：
10.1186/s12916-018-1096-5
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发表时间：
2018-07-11
期刊：
影响因子：
9.3
通讯作者：
SUN☺D Investigators
中科院分区：
文献类型：
--
作者：
Kato T;Furukawa TA;Mantani A;Kurata K;Kubouchi H;Hirota S;Sato H;Sugishita K;Chino B;Itoh K;Ikeda Y;Shinagawa Y;Kondo M;Okamoto Y;Fujita H;Suga M;Yasumoto S;Tsujino N;Inoue T;Fujise N;Akechi T;Yamada M;Shimodera S;Watanabe N;Inagaki M;Miki K;Ogawa Y;Takeshima N;Hayasaka Y;Tajika A;Shinohara K;Yonemoto N;Tanaka S;Zhou Q;Guyatt GH;SUN☺D Investigators
对于开始治疗抑郁症的患者，目前的指南建议在耐受的情况下将抗抑郁药剂量滴定至许可范围的最大剂量。当患者在几周内没有获得缓解时，建议包括添加或改用另一种抗抑郁药。然而，这些指导策略的相对优点仍未确定。这项多中心、开放标签、评估者盲法、务实的试验涉及两个步骤。第 1 步使用开放整群随机化，将诊所分配到第 3 周将舍曲林滴定至 50 mg/天或 100 mg/天的诊所。第 2 步使用中心随机化将治疗 3 周后病情未缓解的患者分配至继续使用舍曲林、添加米氮平或改用米氮平。主要结局是第 9 周时通过患者健康问卷 9 (PHQ-9) 测量的抑郁严重程度（分数在 0 到 27 之间；分数越高，抑郁程度越严重）。我们应用了针对关键基线协变量进行调整的混合模型重复测量分析。 2010 年 12 月至 2015 年 3 月期间，我们在日本 48 家诊所招募了 2011 名尚未接受治疗的重度抑郁症参与者。在第 1 步中，970 名参与者被分配到 50 毫克/天组，1041 名参与者被分配到 100 毫克/天组； 1927 (95.8%) 提供了主要结果。第 9 周时，50 mg/天组和 100 mg/天组之间调整后的 PHQ-9 评分没有统计学上的显着差异（0.25 分，95% 置信区间 (CI)，- 0.58 至 1.07，P = 0.55）。两组的其他结果相似。在第 2 步中，第 3 周未缓解的 1646 名参与者被随机分配继续使用舍曲林 (n = 551)、添加米氮平 (n = 537) 或改用米氮平 (n = 558)：1613 名 (98.0%) 提供了主要结果。第 9 周，添加米氮平使 PHQ-9 分数降低了 0.99 分（0.43 至 1.55，P = 0.0012）；与继续舍曲林相比，转换治疗的疗效降低了 1.01 个百分点（0.46 至 1.56，P = 0.0012）。联合用药使缓解率提高 12.4%（6.1% 至 19.0%），转换率提高 8.4%（2.5% 至 14.8%）。不良反应没有差异。对于新发抑郁症患者，我们发现将舍曲林滴定至 100 毫克与 50 毫克相比没有优势。通过将舍曲林换成米氮平或添加米氮平，第 3 周未缓解的患者在第 9 周的抑郁症状减轻方面获得了小幅获益。 ClinicalTrials.gov，NCT01109693。注册于 2010 年 4 月 23 日。本文的在线版本 (10.1186/s12916-018-1096-5) 包含补充材料，可供授权用户使用。
For patients starting treatment for depression, current guidelines recommend titrating the antidepressant dosage to the maximum of the licenced range if tolerated. When patients do not achieve remission within several weeks, recommendations include adding or switching to another antidepressant. However, the relative merits of these guideline strategies remain unestablished. This multi-centre, open-label, assessor-blinded, pragmatic trial involved two steps. Step 1 used open-cluster randomisation, allocating clinics into those titrating sertraline up to 50 mg/day or 100 mg/day by week 3. Step 2 used central randomisation to allocate patients who did not remit after 3 weeks of treatment to continue sertraline, to add mirtazapine or to switch to mirtazapine. The primary outcome was depression severity measured with the Patient Health Questionnaire-9 (PHQ-9) (scores between 0 and 27; higher scores, greater depression) at week 9. We applied mixed-model repeated-measures analysis adjusted for key baseline covariates. Between December 2010 and March 2015, we recruited 2011 participants with hitherto untreated major depression at 48 clinics in Japan. In step 1, 970 participants were allocated to the 50 mg/day and 1041 to the 100 mg/day arms; 1927 (95.8%) provided primary outcomes. There was no statistically significant difference in the adjusted PHQ-9 score at week 9 between the 50 mg/day arm and the 100 mg/day arm (0.25 point, 95% confidence interval (CI), − 0.58 to 1.07, P = 0.55). Other outcomes proved similar in the two groups. In step 2, 1646 participants not remitted by week 3 were randomised to continue sertraline (n = 551), to add mirtazapine (n = 537) or to switch to mirtazapine (n = 558): 1613 (98.0%) provided primary outcomes. At week 9, adding mirtazapine achieved a reduction in PHQ-9 scores of 0.99 point (0.43 to 1.55, P = 0.0012); switching achieved a reduction of 1.01 points (0.46 to 1.56, P = 0.0012), both relative to continuing sertraline. Combination increased the percentage of remission by 12.4% (6.1 to 19.0%) and switching by 8.4% (2.5 to 14.8%). There were no differences in adverse effects. In patients with new onset depression, we found no advantage of titrating sertraline to 100 mg vs 50 mg. Patients unremitted by week 3 gained a small benefit in reduction of depressive symptoms at week 9 by switching sertraline to mirtazapine or by adding mirtazapine. ClinicalTrials.gov, NCT01109693. Registered on 23 April 2010. The online version of this article (10.1186/s12916-018-1096-5) contains supplementary material, which is available to authorized users.
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DOI：
10.1176/appi.focus.16407
发表时间：
2018-10-01
期刊：
Focus (American Psychiatric Publishing)
影响因子：
--
作者：
Cipriani, Andrea;Furukawa, Toshi A;Geddes, John R
通讯作者：
Geddes, John R
影响因子：
6.7
作者：
Kjosavik, S. R.;Hunskaar, S.;Ruths, S.
通讯作者：
Ruths, S.
影响因子：
4.1
作者：
Chaudhry, I. B.;Neelam, K.;Husain, N.
通讯作者：
Husain, N.
DOI：
10.1001/jama.2015.13766
发表时间：
2015-11-03
期刊：
JAMA
影响因子：
--
作者：
Kantor ED;Rehm CD;Haas JS;Chan AT;Giovannucci EL
通讯作者：
Giovannucci EL
影响因子：
6.6
作者：
Furukawa, Toshi A.;Onishi, Yoshie;Kawakami, Koji
通讯作者：
Kawakami, Koji