McAllister-Williams R Hamish, Sousa Soraia, Kumar Arun, Greco Teresa, Bunker Mark T, Aaronson Scott T, Conway Charles R, Rush A John
Northern Centre for Mood Disorders, Newcastle University, Newcastle upon Tyne, UK.
Regional Affective Disorders Service, Cumbria, Northumberland Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, UK.
Int J Bipolar Disord. 2020 May 2;8(1):13. doi: 10.1186/s40345-020-0178-4.
To compare illness characteristics, treatment history, response and durability, and suicidality scores over a 5-year period in patients with treatment-resistant bipolar depression participating in a prospective, multicenter, open-label registry and receiving Vagus Nerve Stimulation Therapy (VNS Therapy) plus treatment-as-usual (VNS + TAU) or TAU alone.
Response was defined as ≥ 50% decrease from baseline Montgomery-Åsberg Depression Rating Scale (MADRS) total score at 3, 6, 9, or 12 months post-baseline. Response was retained while MADRS score remained ≥ 40% lower than baseline. Time-to-events was estimated using Kaplan-Meier (KM) analysis and compared using log-rank test. Suicidality was assessed using the MADRS Item 10 score.
At baseline (entry into registry), the VNS + TAU group (N = 97) had more episodes of depression, psychiatric hospitalizations, lifetime suicide attempts and higher suicidality score, more severe symptoms (based on MADRS and other scales), and higher rate of prior electroconvulsive therapy than TAU group (N = 59). Lifetime use of medications was similar between the groups (a mean of 9) and was consistent with the severe treatment-resistant nature of their depression. Over 5 years, 63% (61/97) in VNS + TAU had an initial response compared with 39% (23/59) in TAU. The time-to-initial response was significantly quicker for VNS + TAU than for TAU (p < 0.03). Among responders in the first year after implant, the KM estimate of the median time-to-relapse from initial response was 15.2 vs 7.6 months for VNS + TAU compared with TAU (difference was not statistically significant). The mean reduction in suicidality score across the study visits was significantly greater in the VNS + TAU than in the TAU group (p < 0.001).
The patients who received VNS + TAU included in this analysis had severe bipolar depression that had proved extremely difficult to treat. The TAU comparator group were similar though had slightly less severe illnesses on some measures and had less history of suicide attempts. Treatment with VNS + TAU was associated with a higher likelihood of attaining a response compared to TAU alone. VNS + TAU was also associated with a significantly greater mean reduction in suicidality.
In this registry study, participants were not randomized to the study treatment group, VNS Therapy stimulation parameters were not controlled, and there was a high attrition rate over 5 years. Trial registration ClinicalTrials.gov NCT00320372. Registered 3 May 2006, https://clinicaltrials.gov/ct2/show/NCT00320372 (retrospectively registered).
为比较参与一项前瞻性、多中心、开放标签登记研究并接受迷走神经刺激疗法（VNS疗法）加常规治疗（VNS + TAU）或仅接受常规治疗（TAU）的难治性双相抑郁症患者在5年期间的疾病特征、治疗史、反应及持久性，以及自杀倾向评分。
反应定义为自基线起3、6、9或12个月时蒙哥马利-奥斯伯格抑郁评定量表（MADRS）总分较基线降低≥50%。只要MADRS评分仍比基线低≥40%，则维持反应状态。采用Kaplan-Meier（KM）分析估计事件发生时间，并使用对数秩检验进行比较。使用MADRS第10项评分评估自杀倾向。
在基线期（进入登记研究时），VNS + TAU组（N = 97）比TAU组（N = 59）有更多的抑郁发作、精神科住院、终生自杀未遂次数及更高的自杀倾向评分，症状更严重（基于MADRS及其他量表），且既往接受电休克治疗的比例更高。两组终生用药次数相似（平均9种），这与其抑郁症严重难治的性质相符。在5年期间，VNS + TAU组63%（61/97）有初始反应，而TAU组为39%（23/59）。VNS + TAU组达到初始反应的时间显著快于TAU组（p < 0.03）。在植入后第一年的反应者中，VNS + TAU组与TAU组相比，从初始反应到复发的中位时间的KM估计值分别为15.2个月和7.6个月（差异无统计学意义）。在整个研究访视期间，VNS + TAU组自杀倾向评分的平均降低幅度显著大于TAU组（p < 0.001）。
纳入本分析的接受VNS + TAU治疗的患者患有严重的双相抑郁症，已证明极难治疗。TAU对照组成员情况相似，但在某些指标上病情稍轻，自杀未遂史较少。与单独使用TAU相比，VNS + TAU治疗获得反应的可能性更高。VNS + TAU还与自杀倾向的平均降低幅度显著更大相关。
在本登记研究中，参与者未随机分配至研究治疗组，VNS疗法刺激参数未得到控制，且5年期间损耗率较高。试验注册ClinicalTrials.gov NCT00320372。于2006年5月3日注册，https://clinicaltrials.gov/ct2/show/NCT00320372（追溯注册）。
