Background

Stimulation adjustment is required to optimise outcomes of deep brain stimulation (DBS) for treatment-resistant depression, but controlled data for ideal stimulation parameters are poor or insufficient. We aimed to establish the efficacy and safety of short pulse width (SPW) and long pulse width (LPW) subcallosal cingulate DBS in depression.

Methods

We did a double-blind, randomised, crossover trial in an academic hospital in Calgary, AB, Canada. Patients had DSM IV-defined major depressive disorder and bipolar depression (20–70 years old, both sexes) and did not respond to treatment for more than 1 year, with a score of 20 or more on the 17-item Hamilton Depression Rating Scale (HDRS) at recruitment. Patients underwent bilateral DBS implantation into the subcallosal cingulate white matter using diffusion tensor imaging tractography. Patients were randomly assigned 1:1 without stratification using a computerised list generator to receive either SPW (90 μs) or LPW (210–450 μs) stimulation for 6 months. Patients and the clinician assessing outcomes were masked to the stimulation group. Keeping frequency constant (130 Hz), either pulse width or voltage was increased monthly, based on response using the HDRS. Patients who did not respond to treatment (<50% reduction in HDRS from baseline) at 6 months crossed over to the opposite stimulation for another 6 months. All patients received individualised cognitive behavioural therapy (CBT) for 12 weeks. The primary outcome was change in HDRS at 6 months and 12 months using intention-to-treat analysis. This study is registered with ClinicalTrials.gov, NCT01983904.

Findings

Between Dec 5, 2013, and Sept 30, 2016, of 225 patients screened for eligibility, 23 patients were selected for DBS surgery. After one patient withdrew, 22 (mean age 46·4 years, SEM 3·1; 10 [45%] female, 12 [55%] male) were randomly assigned, ten (45%) to LPW stimulation and 12 (55%) to SPW stimulation. Patients were followed up at 6 months and 12 months. There was a significant reduction in HDRS scores (p<0·0001) with no difference between SPW and LPW groups (p=0·54) in the randomisation phase at 6 months. Crossover groups did not show a significant decrease in HDRS within groups (p=0·15) and between groups (p=0·21) from 6–12 months. Adverse events were equal between groups. Worsening anxiety and depression were the most common psychological adverse events. One patient in the SPW group died by suicide.

Interpretation

Both LPW and SPW stimulation of subcallosal cingulate white matter tracts carried similar risks and were equally effective in reducing depressive symptoms, suggesting a role for both pulse width and amplitude titration in optimising clinical outcomes in patients with treatment-resistant depression.

Funding

Alberta Innovates Health Solutions.

中文翻译：

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长与短脉宽sub部扣带回刺激可治疗难治性抑郁症：一项随机，双盲，交叉试验。

背景

需要进行刺激调整以优化对难治疗性抑郁症的深部脑刺激（DBS）的结果，但是理想刺激参数的受控数据很差或不足。我们旨在建立短脉冲宽度（SPW）和长脉冲宽度（LPW）call骨扣带扣带DBS在抑郁症中的疗效和安全性。

方法

我们在加拿大艾伯塔省卡尔加里市的一家学术医院进行了一项双盲，随机，交叉试验。患者患有DSM IV定义的重度抑郁症和双相抑郁症（20-70岁，男女），对治疗无反应超过1年，汉密尔顿抑郁评估量表的17个项目得分为20分以上（HDRS）招聘时。患者使用弥散张量成像术将双侧DBS植入call骨下扣带回白质。使用计算机列表生成器以分层方式随机分配患者1：1，以接受SPW（90μs）或LPW（210–450μs）刺激6个月。患者和评估结局的临床医生被掩盖在刺激组中。保持频率恒定（130 Hz），脉冲宽度或电压每月增加一次，基于使用HDRS的响应。在6个月对治疗无反应的患者（HDRS与基线水平相比降低了50％以下）又在6个月内接受了相反的刺激。所有患者均接受了为期12周的个性化认知行为疗法（CBT）。主要结果是使用意向性治疗分析得出的在6个月和12个月时HDRS的变化。该研究已在ClinicalTrials.gov注册，NCT01983904。

发现

在2013年12月5日至2016年9月30日之间，筛选出225例符合资格的患者，其中23例被选择进行DBS手术。一名患者退出后，随机分配22名（平均年龄46·4岁，SEM 3·1； 10名[45％]女性，12名[55％]男​​性），LPW刺激十名（45％）和12名（55％） ）对SPW的刺激。在6个月和12个月时对患者进行了随访。在6个月的随机化阶段，SPW组和LPW组之间的HDRS得分显着降低（p <0·0001），差异无统计学意义（p = 0·54）。在6到12个月内，交叉组在组内（p = 0·15）和组间（p = 0·21）的HDRS没有显着降低。两组之间的不良事件相等。焦虑和抑郁加剧是最常见的心理不良事件。SPW组的一名患者死于自杀。

解释

LPW和SPW刺激call门下扣带回白质束具有相似的风险，并且在减轻抑郁症状方面同样有效，表明脉宽和振幅滴定在优化具有治疗抵抗力的抑郁症患者的临床结局中均具有作用。

资金

艾伯塔省（Alberta）创新健康解决方案。