扣带回下深部脑刺激治疗难治性抑郁症：一项多中心、随机、假手术对照试验。
Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial.
作者信息
Holtzheimer Paul E, Husain Mustafa M, Lisanby Sarah H, Taylor Stephan F, Whitworth Louis A, McClintock Shawn, Slavin Konstantin V, Berman Joshua, McKhann Guy M, Patil Parag G, Rittberg Barry R, Abosch Aviva, Pandurangi Ananda K, Holloway Kathryn L, Lam Raymond W, Honey Christopher R, Neimat Joseph S, Henderson Jaimie M, DeBattista Charles, Rothschild Anthony J, Pilitsis Julie G, Espinoza Randall T, Petrides Georgios, Mogilner Alon Y, Matthews Keith, Peichel DeLea, Gross Robert E, Hamani Clement, Lozano Andres M, Mayberg Helen S
机构信息
Department of Psychiatry and Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
Department of Psychiatry, Neurology and Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA; Department of Psychiatry and Behavioral Science, Duke University School of Medicine, Durham, NC, USA.
出版信息
Lancet Psychiatry. 2017 Nov;4(11):839-849. doi: 10.1016/S2215-0366(17)30371-1. Epub 2017 Oct 4.
BACKGROUND
Deep brain stimulation (DBS) of the subcallosal cingulate white matter has shown promise as an intervention for patients with chronic, unremitting depression. To test the safety and efficacy of DBS for treatment-resistant depression, a prospective, randomised, sham-controlled trial was conducted.
METHODS
Participants with treatment-resistant depression were implanted with a DBS system targeting bilateral subcallosal cingulate white matter and randomised to 6 months of active or sham DBS, followed by 6 months of open-label subcallosal cingulate DBS. Randomisation was computer generated with a block size of three at each site before the site started the study. The primary outcome was frequency of response (defined as a 40% or greater reduction in depression severity from baseline) averaged over months 4-6 of the double-blind phase. A futility analysis was performed when approximately half of the proposed sample received DBS implantation and completed the double-blind phase. At the conclusion of the 12-month study, a subset of patients were followed up for up to 24 months. The study is registered at ClinicalTrials.gov, number NCT00617162.
FINDINGS
Before the futility analysis, 90 participants were randomly assigned to active (n=60) or sham (n=30) stimulation between April 10, 2008, and Nov 21, 2012. Both groups showed improvement, but there was no statistically significant difference in response during the double-blind, sham-controlled phase (12 [20%] patients in the stimulation group vs five [17%] patients in the control group). 28 patients experienced 40 serious adverse events; eight of these (in seven patients) were deemed to be related to the study device or surgery.
INTERPRETATION
This study confirmed the safety and feasibility of subcallosal cingulate DBS as a treatment for treatment-resistant depression but did not show statistically significant antidepressant efficacy in a 6-month double-blind, sham-controlled trial. Future studies are needed to investigate factors such as clinical features or electrode placement that might improve efficacy.
FUNDING
Abbott (previously St Jude Medical).
背景
扣带回下白质的深部脑刺激（DBS）已显示出有望成为慢性、难治性抑郁症患者的一种干预措施。为了测试DBS治疗难治性抑郁症的安全性和有效性，开展了一项前瞻性、随机、假手术对照试验。
方法
将难治性抑郁症患者植入靶向双侧扣带回下白质的DBS系统，并随机分为接受6个月的主动DBS或假手术DBS，随后接受6个月的开放标签扣带回下白质DBS。在各研究点开始研究前，通过计算机生成随机序列，每个研究点的区组大小为3。主要结局是双盲期第4至6个月期间反应频率（定义为抑郁严重程度较基线降低40%或更多）的平均值。当约一半的计划样本接受DBS植入并完成双盲期时，进行了无效性分析。在为期12个月的研究结束时，对一部分患者进行了长达24个月的随访。该研究已在ClinicalTrials.gov注册，注册号为NCT00617162。
研究结果
在进行无效性分析之前，2008年4月10日至2012年11月21日期间，90名参与者被随机分配至主动刺激组（n = 60）或假手术刺激组（n = 30）。两组均有改善，但在双盲、假手术对照阶段，两组的反应无统计学显著差异（刺激组12例[20%]患者 vs 对照组5例[17%]患者）。28例患者发生40起严重不良事件；其中8起（7例患者）被认为与研究设备或手术有关。
解读
本研究证实了扣带回下白质DBS作为难治性抑郁症治疗方法的安全性和可行性，但在为期6个月的双盲、假手术对照试验中未显示出统计学显著的抗抑郁疗效。未来需要开展研究以调查可能改善疗效的因素，如临床特征或电极放置位置等。
资助
雅培公司（原圣犹达医疗公司）。
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