AbstractThis systematic review and network meta-analysis (NMA) sought to compare different antidepressant treatments for treatment-resistant depression (TRD) in order to facilitate evidence-based choices. A literature search of PubMed, Cochrane Library, and Embase from inception until April 13th, 2023 identified randomized, controlled trials (RCTs) of adults with depression who had not responded to at least two antidepressant trials; all RCTs had ≥10 participants per study arm, and participants with bipolar or psychotic depression were excluded.

摘要本系统评价和网络荟萃分析（NMA）试图比较不同的抗抑郁药治疗难治性抑郁症（TRD），以促进循证选择。PubMed，Cochrane图书馆和Embase从开始到2023年4月13日的文献检索确定了对至少两项抗抑郁药试验没有反应的抑郁症成年人的随机对照试验（RCT）；所有随机对照试验每个研究组都有≥10名参与者，排除了躁郁症或精神病性抑郁症的参与者。

The Cochrane Risk of Bias Tool-2 was used to assess study quality. Response rate was the primary outcome measure. Odds ratios (ORs) using a random effects NMA are reported. From 8234 records, 69 RCTs were included in this analysis, encompassing 10,285 participants (5662 F/4623 M) and 25 separate treatments.

Cochrane偏倚风险工具-2用于评估研究质量。。报告了使用随机效应NMA的优势比（OR）。从8234份记录中，69项随机对照试验被纳入分析，包括10285名参与者（5662 F/4623 M）和25项单独治疗。

Six of the 25 treatments demonstrated a higher response rate versus placebo or sham treatment: electroconvulsive therapy (ECT), minocycline, theta-burst stimulation (TBS), repetitive transcranial magnetic stimulation (rTMS), ketamine, and aripiprazole. ORs ranged from 1.9 (95%CI = [1.25; 2.91]) for aripiprazole to 12.86 (95%CI = [4.07; 40.63]) for ECT.

与安慰剂或假治疗相比，25种治疗中有6种表现出更高的缓解率：电惊厥治疗（ECT），米诺环素，θ爆发刺激（TBS），重复经颅磁刺激（rTMS），氯胺酮和阿立哌唑。OR范围从阿立哌唑的1.9（95%CI=[1.25；2.91]）到ECT的12.86（95%CI=[4.07；40.63]）。

Moderate heterogeneity of the model was observed (I2 = 47.3% (95%CI [26.8–62%]). Of the included studies, 12.5% were rated as having high risk of bias, 28.13% as having low risk, and 59.38% as showing some concerns. Several effective treatments for TRD showed robust treatment effects across outcomes (ECT, TBS, rTMS, and ketamine), and others showed promising results for some, but not all, outcomes (minocycline, aripiprazole).

观察到模型的中度异质性（I2=47.3%（95%CI[26.8-62%]）。在纳入的研究中，12.5%被评为偏倚风险高，28.13%被评为低风险，59.38%被评为有一些担忧。TRD的几种有效治疗方法在整个结果（ECT，TBS，rTMS和氯胺酮）中显示出强大的治疗效果，而其他方法对某些但不是全部结果（米诺环素，阿立哌唑）显示出有希望的结果。

These findings may help guide evidence-based treatment choices for TRD. Study Registration: PROSPERO (#CRD42023420584)..

这些发现可能有助于指导TRD的循证治疗选择。研究注册：PROSPERO（#CRD42023420584）。。

IntroductionDespite the availability of numerous treatments for major depressive disorder (MDD), nearly half of individuals do not respond to at least two antidepressants, thereby meeting criteria for treatment resistance [1, 2]. Strategies to address treatment-resistant depression (TRD) include optimizing dosages, switching antidepressants, or augmenting treatment with a nonstandard agent.

引言尽管有许多治疗重度抑郁症（MDD）的方法，但近一半的人对至少两种抗抑郁药没有反应，因此符合治疗抵抗的标准[1，2]。解决难治性抑郁症（TRD）的策略包括优化剂量，转换抗抑郁药或增加非标准药物的治疗。

Another treatment approach involves augmenting monoaminergic drugs like selective serotonin reuptake inhibitors (SSRIs) with mood stabilizers or second-generation antipsychotics. In addition, administration of subanesthetic-dose ketamine, which has been shown to alleviate depressive symptoms within hours, led to the approval of its enantiomer, (S)-ketamine, for the treatment of TRD in 2019 [3].

另一种治疗方法是用情绪稳定剂或第二代抗精神病药物增加单胺能药物，如选择性5-羟色胺再摄取抑制剂（SSRIs）。此外，服用麻醉下剂量的氯胺酮（已被证明可在数小时内缓解抑郁症状）导致其对映体（S）-氯胺酮在2019年被批准用于治疗TRD（3）。

There has also been a resurgence of clinical trials investigating serotonergic psychedelics (SPs) such as psilocybin and N,N-dimethyltryptamine (DMT) for various psychiatric conditions, including depression. Another potential treatment for TRD is neuromodulatory procedures, which can be either invasive (e.g., deep brain stimulation (DBS)) or non-invasive (e.g., repetitive transcranial magnetic stimulation (rTMS) or electroconvulsive therapy (ECT)).

针对包括抑郁症在内的各种精神疾病，研究血清素能迷幻剂（SP）的临床试验也再次兴起，例如裸盖菇素和N，N-二甲基色胺（DMT）。TRD的另一种潜在治疗方法是神经调节程序，它可以是侵入性的（例如，深部脑刺激（DBS））或非侵入性的（例如，重复经颅磁刺激（rTMS）或电惊厥治疗（ECT））。

Despite considerable research evidence surrounding these treatment modalities—some novel, some in use for decades— it is unclear how their efficacies compare.While previous NMAs have investigated treatment strategies for TRD [4,5,6], to date none have also compared recent evidence drawn from ketamine or SP studies or compared pharmacological augmentation to neuromodulatory procedures such as ECT, DBS, rTMS, or transcranial direct current stimulation (tDCS).

尽管围绕这些治疗方式的大量研究证据-一些新颖的，一些已经使用了几十年-尚不清楚它们的疗效如何比较。虽然之前的NMA已经研究了TRD的治疗策略[4,5,6]，但迄今为止，还没有人比较最近从氯胺酮或SP研究中获得的证据，或者将药物增强与神经调节程序（如ECT，DBS，rTMS或经颅直流电刺激（tDCS））进行比较。

This NMA compared the effectiveness of a variety of available antidepressant treatments for T.

该NMA比较了各种可用抗抑郁药治疗T的有效性。

Data availability

数据可用性

Data not included in the article or supplementary materials can be obtained from the corresponding author upon request.

文章或补充材料中未包含的数据可以根据要求从通讯作者那里获得。

ReferencesEuropean Medicines Agency. Guideline on clinical investigation of medicinal products in the treatment depression. Available at: https://www.ema.europa.eu/en/news/european-medicines-agency-publishes-guideline-clinical-investigation-medicines-depression. 2013.U. S. Food Drug Administration. Major depressive disorder: developing drugs for treatment guidance for industry.

参考欧洲药品管理局。。网址：https://www.ema.europa.eu/en/news/european-medicines-agency-publishes-guideline-clinical-investigation-medicines-depression.2013年。美国食品药品管理局。重性抑郁症：为行业开发治疗药物指导。

Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/major-depressive-disorder-developing-drugs-treatment. 2018.U. S. Food Drug Administration. FDA approves new nasal spray medication for treatment-resistant depression; available only at a certified doctor’s office or clinic.

网址：https://www.fda.gov/regulatory-information/search-fda-guidance-documents/major-depressive-disorder-developing-drugs-treatment.2018年。美国食品药品管理局。FDA批准用于治疗难治性抑郁症的新型鼻喷雾剂；仅在注册医生的办公室或诊所可用。

Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-new-nasal-spray-medication-treatment-resistant-depression-available-only-certified. 2019.Papadimitropoulou K, Vossen C, Karabis A, Donatti C, Kubitz N. Comparative efficacy and tolerability of pharmacological and somatic interventions in adult patients with treatment-resistant depression: a systematic review and network meta-analysis.

网址：https://www.fda.gov/news-events/press-announcements/fda-approves-new-nasal-spray-medication-treatment-resistant-depression-available-only-certified.2019年。Papadimitropoulou K，Vossen C，Karabis A，Donatti C，Kubitz N.药物和躯体干预对成年难治性抑郁症患者的比较疗效和耐受性：系统评价和网络荟萃分析。

Curr Med Res Opin. 2017;33:701–11.Article .

医学研究开放。2017;33:701-11.条款[联合王国]。

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Carter B, Strawbridge R, Husain MI, Jones BDM, Short R, Cleare AJ, et al. Relative effectiveness of augmentation treatments for treatment-resistant depression: a systematic review and network meta-analysis. Int Rev Psychiatry. 2020;32:477–90.Article

Carter B，Strawbridge R，Husain MI，Jones BDM，Short R，Cleare AJ等。增强治疗对难治性抑郁症的相对有效性：系统评价和网络荟萃分析。Int Rev精神病学。2020年；32:477–90.文章

PubMed

PubMed

Google Scholar

谷歌学者

Li H, Cui L, Li J, Liu Y, Chen Y. Comparative efficacy and acceptability of neuromodulation procedures in the treatment of treatment-resistant depression: a network meta-analysis of randomized controlled trials. J Affect Disord. 2021;287:115–24.Article

Li H，Cui L，Li J，Liu Y，Chen Y.神经调节程序治疗难治性抑郁症的比较疗效和可接受性：随机对照试验的网络荟萃分析。J影响混乱。2021年；287:115–24.文章

PubMed

PubMed

Google Scholar

谷歌学者

Zhou X, Ravindran AV, Qin B, Del Giovane C, Li Q, Bauer M, et al. Comparative efficacy, acceptability, and tolerability of augmentation agents in treatment-resistant depression: systematic review and network meta-analysis. J Clin Psychiatry. 2015;76:e487–e98.Article

Zhou X，Ravindran AV，Qin B，Del Giovane C，Li Q，Bauer M等。增强剂在难治性抑郁症中的比较疗效，可接受性和耐受性：系统评价和网络荟萃分析。J临床精神病学。2015年；76:e487–e98.文章

PubMed

PubMed

Google Scholar

谷歌学者

Nuñez NA, Joseph B, Pahwa M, Kumar R, Resendez MG, Prokop LJ, et al. Augmentation strategies for treatment resistant major depression: a systematic review and network meta-analysis. J Affect Disord. 2022;302:385–400.Article

Nuñez NA，Joseph B，Pahwa M，Kumar R，Resendez MG，Prokop LJ等。难治性抑郁症的增强策略：系统评价和网络荟萃分析。J影响混乱。2022年；302:385–400.文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015;349:g7647.Article

Shamseer L，Moher D，Clarke M，Ghersi D，Liberati A，Petticrew M等。系统评价和荟萃分析协议的首选报告项目（PRISMA-P）2015：阐述和解释。英国医学杂志。2015年；349:g7647.文章

Google Scholar

谷歌学者

Zimmerman M, Posternak MA, Chelminski I. Derivation of a definition of remission on the Montgomery-Asberg depression rating scale corresponding to the definition of remission on the Hamilton rating scale for depression. J Psychiatr Res. 2004;38:577–82.Article

Zimmerman M，Posternak MA，Chelminski I.推导蒙哥马利-阿斯伯格抑郁评定量表上缓解的定义，对应于汉密尔顿抑郁评定量表上缓解的定义。J Psychiatric Res.2004；38:577–82.文章

PubMed

PubMed

Google Scholar

谷歌学者

Drahota A, Beller E RevMan Calculator. Available at: https://training.cochrane.org/resource/revman-calculator. 2019.Mutz J, Vipulananthan V, Carter B, Hurlemann R, Fu CHY, Young AH. Comparative efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults: systematic review and network meta-analysis.

Drahota A，Beller E RevMan计算器。网址：https://training.cochrane.org/resource/revman-calculator.2019年。穆茨J，维普拉南坦五世，卡特B，赫尔曼R，富希，扬AH。非手术脑刺激对成人重度抑郁发作急性治疗的比较疗效和可接受性：系统评价和网络荟萃分析。

BMJ. 2019;364:1079.Article .

BMJ。2019年；364:1079.文章。

Google Scholar

谷歌学者

Ekstrand J, Fattah C, Persson M, Cheng T, Nordanskog P, Åkeson J, et al. Racemic ketamine as an alternative to electroconvulsive therapy for unipolar depression: a randomized, open-label, non-inferiority trial (KetECT). Int J Neuropsychopharmacol. 2022;25:339–49.Article

Ekstrand J，Fattah C，Persson M，Cheng T，Nordanskog P，Åkeson J等。外消旋氯胺酮替代电惊厥治疗单相抑郁症：一项随机，开放标签，非劣效性试验（KetECT）。Int J神经精神药理学。2022年；25:339–49.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Anand A, Mathew SJ, Sanacora G, Murrough JW, Goes FS, Altinay M, et al. Ketamine versus ECT for nonpsychotic treatment-resistant major depression. N. Engl J Med. 2023;388:2315–25.Article

Anand A，Mathew SJ，Sanacora G，Murrough JW，Goes FS，Altinay M等。氯胺酮与ECT治疗非精神病治疗抵抗性抑郁症。N、 英国医学杂志2023；388:2315–25.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Ren J, Li H, Palaniyappan L, Liu H, Wang J, Li C, et al. Repetitive transcranial magnetic stimulation versus electroconvulsive therapy for major depression: a systematic review and meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2014;51:181–9.Article

Ren J，Li H，Palaniyappan L，Liu H，Wang J，Li C等。重复经颅磁刺激与电惊厥治疗重度抑郁症：系统评价和荟萃分析。Prog Neuropsychopharmacol Biol精神病学。2014年；51:181–9.文章

PubMed

PubMed

Google Scholar

谷歌学者

Strawbridge R, Carter B, Marwood L, Bandelow B, Tsapekos D, Nikolova VL, et al. Augmentation therapies for treatment-resistant depression: systematic review and meta-analysis. Br J Psychiatry. 2019;214:42–51.Article

Strawbridge R，Carter B，Marwood L，Bandelow B，Tsapekos D，Nikolova VL等。难治性抑郁症的增强疗法：系统评价和荟萃分析。Br J精神病学。2019年；214:42-51.文章

PubMed

PubMed

Google Scholar

谷歌学者

Reif A, Bitter I, Buyze J, Cebulla K, Frey R, Fu D-J, et al. Esketamine nasal spray versus quetiapine for treatment-resistant depression. N. Engl J Med. 2023;389:1298–309.Article

Reif A，Bitter I，Buyze J，Cebulla K，Frey R，Fu D-J等。艾司氯胺酮鼻喷雾剂与喹硫平治疗难治性抑郁症。N、 英国医学杂志2023；389:1298–309.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Bahji A, Vazquez GH, Zarate CA Jr. Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis. J Affect Disord. 2021;278:542–55.Article

Bahji A，Vazquez GH，Zarate CA Jr.外消旋氯胺酮和依氯胺酮治疗抑郁症的比较疗效：系统评价和荟萃分析。J影响混乱。2021年；278:542-55.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Kojic M, Saelens J, Kadriu B, Zarate CA Jr., Kraus C. Ketamine for depression: advances in clinical treatment, rapid antidepressant mechanisms of action, and a contrast with serotonergic psychedelics. Curr Top Behav Neurosci. 2022;56:141–67.Article

Kojic M，Saelens J，Kadriu B，Zarate CA Jr.，Kraus C.氯胺酮治疗抑郁症：临床治疗进展，快速抗抑郁作用机制以及与5-羟色胺能迷幻药的对比。Curr Top Beav Neurosci。2022年；56:141–67.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Soczynska JK, Mansur RB, Brietzke E, Swardfager W, Kennedy SH, Woldeyohannes HO, et al. Novel therapeutic targets in depression: minocycline as a candidate treatment. Behav Brain Res. 2012;235:302–17.Article

Soczynska JK，Mansur RB，Brietzke E，Swardfager W，Kennedy SH，Woldeyohannes HO等。抑郁症的新治疗靶点：米诺环素作为候选治疗。Behav Brain Res.2012；235:302–17.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Al Jumaili W, Vora D, Trivedi C, Jain S. Role of minocycline as an adjunct neuroinflammatory modulator in treatment-resistant depression: A systematic review of randomized controlled trials. Prim Care Companion CNS Disord. 2023;25:22r03467.Article

Al-Jumaili W，Vora D，Trivedi C，Jain S.米诺环素作为辅助神经炎症调节剂在难治性抑郁症中的作用：随机对照试验的系统评价。Prim Care Companion中枢神经系统疾病。2023年；25:22r03467.文章

PubMed

PubMed

Google Scholar

谷歌学者

Hellmann-Regen J, Clemens V, Grözinger M, Kornhuber J, Reif A, Prvulovic D, et al. Effect of minocycline on depressive symptoms in patients with treatment-resistant depression: a randomized clinical trial. JAMA Netw Open. 2022;5:e2230367.Article

Hellmann Regen J，Clemens V，Grözinger M，Kornhuber J，Reif A，Prvulovic D等。米诺环素对难治性抑郁症患者抑郁症状的影响：一项随机临床试验。JAMA网络打开。2022年；5： e2230367。条款

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Fournier JC, Derubeis RJ, Hollon SD, Shelton RC, Fawcett J. Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA. 2010;303:47–53.Article

。杰玛。2010年；303:47–53.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

U.S. Food and Drug Administration. Approval package for seroquel XR. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022047Orig1s011.pdf. 2009.Gerhard T, Stroup TS, Correll CU, Setoguchi S, Strom BL, Huang C, et al. Mortality risk of antipsychotic augmentation for adult depression.

U、 美国食品和药物管理局。seroquel XR的批准包。网址：https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022047Orig1s011.pdf.2009年。Gerhard T，Stroup TS，Correll CU，Setoguchi S，Strom BL，Huang C等。成人抑郁症抗精神病药物增强的死亡风险。

PLoS ONE. 2020;15:e0239206.Article .

PLoS ONE。2020年；15： e0239206。文章。

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Jha MK, Mathew SJ. Pharmacotherapies for treatment-resistant depression: how antipsychotics fit in the rapidly evolving therapeutic landscape. Am J Psychiatry. 2023;180:190–99.Article

Jha MK，Mathew SJ。难治性抑郁症的药物治疗：抗精神病药物如何适应快速发展的治疗环境。Am J精神病学。2023年；180:190–99.文章

PubMed

PubMed

Google Scholar

谷歌学者

Bschor T, Bauer M. Efficacy and mechanisms of action of lithium augmentation in refractory major depression. Curr Pharm Des. 2006;12:2985–92.Article

Bschor T，Bauer M.锂增强治疗难治性抑郁症的疗效和作用机制。Curr Pharm Des公司。2006年；12： 2985–92.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Nelson JC, Baumann P, Delucchi K, Joffe R, Katona C. A systematic review and meta-analysis of lithium augmentation of tricyclic and second generation antidepressants in major depression. J Affect Disord. 2014;168:269–75.Article

Nelson JC，Baumann P，Delucchi K，Joffe R，Katona C.三环类和第二代抗抑郁药在重度抑郁症中锂增强的系统评价和荟萃分析。J影响混乱。2014年；168:269–75.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Quitkin FM, Petkova E, McGrath PJ, Taylor B, Beasley C, Stewart J, et al. When should a trial of fluoxetine for major depression be declared failed? Am J Psychiatry. 2003;160:734–40.Article

Quitkin FM，Petkova E，McGrath PJ，Taylor B，Beasley C，Stewart J等。什么时候应该宣布氟西汀治疗重度抑郁症的试验失败？Am J精神病学。2003年；160:734-40.文章

PubMed

PubMed

Google Scholar

谷歌学者

Ijaz S, Davies P, Williams CJ, Kessler D, Lewis G, Wiles N. Psychological therapies for treatment-resistant depression in adults. Cochrane Database Syst Rev. 2018;5:CD010558.PubMed

Ijaz S，Davies P，Williams CJ，Kessler D，Lewis G，Wiles N.成人难治性抑郁症的心理治疗。Cochrane数据库系统版本2018；5： CD010558.PubMed

Google Scholar

谷歌学者

Download referencesAcknowledgementsThe authors thank Ioline Henter (NIMH) for invaluable editorial assistance, and Dr. Siegfried Kasper for critical discussion of the manuscript.FundingFunding for this work was provided in part by the Intramural Research Program at the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH; ZIAMH002857).

下载参考文献致谢作者感谢Ioline Henter（NIMH）提供了宝贵的编辑帮助，感谢Siegfried Kasper博士对稿件的批判性讨论。资助这项工作的资金部分由国立卫生研究院国家心理健康研究所的校内研究计划（IRP-NIMH-NIH；ZIAMH002857）提供。

The NIMH had no further role in study design; in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. Open access funding provided by Medical University of Vienna.Author informationAuthors and AffiliationsDepartment of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, AustriaJohan Saelens, Anna Gramser, Victoria Watzal, Rupert Lanzenberger & Christoph KrausComprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, AustriaJohan Saelens, Anna Gramser, Victoria Watzal, Rupert Lanzenberger & Christoph KrausExperimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USACarlos A.

NIMH在研究设计中没有进一步的作用；在数据的收集，分析或解释中；在撰写报告时；。维也纳医科大学提供的开放获取资金。作者信息作者和附属机构维也纳医科大学精神病学和心理治疗系，维也纳，澳大利亚圣约翰·萨伦斯，安娜·格拉姆瑟，维多利亚·沃特扎尔，鲁珀特·兰岑伯格和克里斯托夫·克劳斯维也纳医科大学临床神经科学和心理健康综合中心，维也纳，澳大利亚圣约翰·萨伦斯，安娜·格拉姆瑟，维多利亚·沃特扎尔，鲁珀特·兰岑伯格和克里斯托夫·克劳斯实验治疗和病理生理学分部，国立卫生研究院，国立卫生研究院，贝塞斯达，马里兰州，美国卡洛斯A。

Zarate Jr. & Christoph KrausAuthorsJohan SaelensView author publicationsYou can also search for this author in.

Zarate Jr.&Christoph KrausAuthorsJohan SaelensView作者出版物您也可以在中搜索这位作者。

PubMed Google ScholarAnna GramserView author publicationsYou can also search for this author in

PubMed Google ScholarAnna GramserView作者出版物您也可以在

PubMed Google ScholarVictoria WatzalView author publicationsYou can also search for this author in

PubMed Google ScholarVictoria WatzalView作者出版物您也可以在

PubMed Google ScholarCarlos A. Zarate Jr.View author publicationsYou can also search for this author in

PubMed Google ScholarCarlos A.Zarate Jr.查看作者出版物您也可以在

PubMed Google ScholarRupert LanzenbergerView author publicationsYou can also search for this author in

PubMed谷歌学术评论LanzenbergerView作者出版物您也可以在

PubMed Google ScholarChristoph KrausView author publicationsYou can also search for this author in

PubMed Google ScholarChristoph KrausView作者出版物您也可以在

PubMed Google ScholarContributionsJS: Conceptualized the study; conducted the literature search, abstract screening, data collection; conducted the quality rating analysis; conducted the statistical analysis; drafted the manuscript. AG: Checked the collected data; revised the manuscript for critical intellectual content.

PubMed谷歌学术贡献JS：将研究概念化；进行了文献检索，摘要筛选，数据收集；进行质量评级分析；进行了统计分析；起草了手稿。AG：检查收集的数据；修改了手稿的关键知识内容。

VW: Conducted the quality rating analysis; revised the manuscript for critical intellectual content. CAZ: Helped interpret the data; edited the manuscript for critical intellectual content. RL: Conceptualized the study; edited the manuscript for critical intellectual content. CK: Conceptualized the study; provided research supervision; screened the abstracts; revised the manuscript for critical intellectual content.

大众：进行质量评级分析；修改了手稿的关键知识内容。CAZ：帮助解释数据；。RL：将研究概念化；编辑了手稿的关键知识内容。CK：将研究概念化；提供研究监督；筛选摘要；修改了手稿的关键知识内容。

All authors had full access to all the data in the study, gave final approval of the version to be published, and accept responsibility for submitting this manuscript for publication.Corresponding authorCorrespondence to.

所有作者都可以完全访问研究中的所有数据，最终批准了要发布的版本，并负责提交这份手稿以供出版。对应作者对应。

Christoph Kraus.Ethics declarations

克里斯托夫·克劳斯。

Competing interests

相互竞争的利益

Dr. Kraus received honoraria from Janssen and LivaNova, as well as travel support from Roche Austria and AOP Orphan. Dr. Lanzenberger received investigator-initiated research funding from Siemens Healthcare regarding clinical research using PET/MR and travel grants and/or conference speaker honoraria from Janssen-Cilag Pharma GmbH in 2023, and Bruker BioSpin, Shire, AstraZeneca, Lundbeck A/S, Dr.

克劳斯博士获得了杨森和利瓦诺娃的酬金，以及罗氏奥地利公司和AOP孤儿公司的旅行支持。Lanzenberger博士于2023年获得了西门子医疗保健公司（Siemens Healthcare）的研究者发起的研究资金，该资金来自Janssen Cilag Pharma GmbH的PET/MR和旅行补助金和/或会议发言人酬金，以及阿斯利康（AstraZeneca）伦贝克（Lundbeck）夏尔（Shire）Bruker BioSpin博士。

Willmar Schwabe GmbH, Orphan Pharmaceuticals AG, Janssen-Cilag Pharma GmbH, Heel and Roche Austria GmbH., and Janssen-Cilag Pharma GmbH in the years before 2020. He is a shareholder of the start-up company BM Health GmbH, Austria since 2019. Dr. Zarate is listed as a co-inventor on a patent for the use of ketamine in major depression and suicidal ideation; as a co-inventor on a patent for the use of (2 R,6 R)-hydroxynorketamine, (S)-dehydronorketamine, and other stereoisomeric dehydroxylated and hydroxylated metabolites of (R,S)-ketamine metabolites in the treatment of depression and neuropathic pain; and as a co-inventor on a patent application for the use of (2 R,6 R)-hydroxynorketamine and (2S,6S)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorders.

2020年之前的几年，Willmar Schwabe GmbH、Orphan Pharmaceuticals AG、Janssen Cilag Pharma GmbH、Heel and Roche Austria GmbH和Janssen Cilag Pharma GmbH。自2019年以来，他是奥地利BM Health GmbH初创公司的股东。Zarate博士被列为氯胺酮治疗抑郁症和自杀意念专利的共同发明人；作为使用（2R，6R）-羟基去甲氯胺酮，（S）-脱氢氯胺酮和（R，S）-氯胺酮代谢物的其他立体异构体脱羟基和羟基代谢物治疗抑郁症和神经性疼痛的专利的共同发明人；并作为专利申请的共同发明人，使用（2R，6R）-羟基去甲氯胺酮和（2S，6S）-羟基去甲氯胺酮治疗抑郁症，焦虑症，快感缺乏症，自杀意念和创伤后应激障碍。

He has assigned his patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government. All other authors have no conflict of interest to disclose, financial or otherwise..

他已将专利权转让给美国政府，但将分享政府可能收到的任何版税的百分比。所有其他作者都没有利益冲突可以披露，财务或其他方面。。

Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Supplementary informationSupplemental MaterialPRISMA Checklist für NMARights and permissions

Additional informationPublisher的注释Springer Nature在已发布的地图和机构隶属关系中的管辖权主张方面保持中立。补充信息补充材料风险清单für n权利和权限

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

开放获取本文是根据知识共享署名4.0国际许可证授权的，该许可证允许以任何媒体或格式使用，共享，改编，分发和复制，只要您对原始作者和来源给予适当的信任，提供知识共享许可证的链接，并指出是否进行了更改。

The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

本文中的图像或其他第三方材料包含在文章的知识共享许可中，除非在材料的信用额度中另有说明。如果材料未包含在文章的知识共享许可中，并且您的预期用途不受法律法规的许可或超出许可用途，则您需要直接获得版权所有者的许可。

To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/..

要查看此许可证的副本，请访问http://creativecommons.org/licenses/by/4.0/..

Reprints and permissionsAbout this articleCite this articleSaelens, J., Gramser, A., Watzal, V. et al. Relative effectiveness of antidepressant treatments in treatment-resistant depression: a systematic review and network meta-analysis of randomized controlled trials.

转载和许可本文引用本文Aelens，J.，Gramser，A.，Watzal，V。等人。抗抑郁药治疗难治性抑郁症的相对有效性：随机对照试验的系统评价和网络荟萃分析。

Neuropsychopharmacol. (2024). https://doi.org/10.1038/s41386-024-02044-5Download citationReceived: 29 August 2024Revised: 09 December 2024Accepted: 13 December 2024Published: 30 December 2024DOI: https://doi.org/10.1038/s41386-024-02044-5Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

神经精神药理学。（2024年）。https://doi.org/10.1038/s41386-024-02044-5Download引文收到日期：2024年8月29日修订日期：2024年12月9日接受日期：2024年12月13日发布日期：2024年12月30日OI：https://doi.org/10.1038/s41386-024-02044-5Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

Provided by the Springer Nature SharedIt content-sharing initiative

由Springer Nature SharedIt内容共享计划提供