Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial
Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial
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DOI：
10.1016/s2215-0366(17)30371-1
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发表时间：
2017-11-01
影响因子：
64.3
通讯作者：
Mayberg, Helen S.
中科院分区：
文献类型：
--
作者：
Holtzheimer, Paul E.;Husain, Mustafa M.;Mayberg, Helen S.
背景 对胼胝体下扣带回白质进行深部脑刺激 (DBS) 已显示出有望作为慢性、持续性抑郁症患者的干预措施。为了测试 DBS 对难治性抑郁症的安全性和有效性，进行了一项前瞻性、随机、假对照试验。 方法 难治性抑郁症参与者被植入针对双侧胼胝体下扣带回白质的 DBS 系统，并随机接受 6 个月的主动或假 DBS，随后接受 6 个月的开放标签胼胝体下扣带回 DBS。在开始研究之前，随机化是由计算机生成的，每个中心的区块大小为三。主要结局是双盲阶段第 4-6 个月的平均缓解频率（定义为抑郁症严重程度较基线降低 40% 或更多）。当大约一半的拟议样本接受 DBS 植入并完成双盲阶段时，进行了无效分析。在为期 12 个月的研究结束时，部分患者接受了长达 24 个月的随访。该研究已在临床试验中注册。 gov，编号NCT00617162。调查结果在无效性分析之前，90名参与者被随机分配到2008年4月10日至2012年11月21日之间的主动刺激（n = 60）或假刺激（n = 30）组。两组均显示出改善，但在双盲、假对照阶段期间，反应没有统计学上的显着差异（刺激组中的12名患者[20％]对照组有 5 名 [17%] 患者）。 28名患者经历了40次严重不良事件；其中 8 例（7 名患者）被认为与研究设备或手术有关。 解释 这项研究证实了胼胝体下扣带回 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、假对照试验中并未显示出具有统计学意义的抗抑郁功效。未来的研究需要调查可能提高疗效的临床特征或电极放置等因素。
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.