The Efficacy and Prediction of Deep Brain Stimulation for Treatment-resistant Depression
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- the comparison between the Hamilton Depression Scale(HAMD-17) scores after active and sham phase
研究概览
简要总结
Several open-label trials have shown the therapeutic promise of deep brain stimulation (DBS) targeted to striatal and surrounding capsular areas in treatment-resistant depression (TRD). However, the results of placebo-controlled trials have been mixed, with one showing a large difference between active and sham DBS and another finding no difference.
Main aim of this study is establishing whether active DBS results in more treatment responders than sham DBS. Secondary aims are establishing an adverse events profile, establishing effects on quality of life,neuropsychological and neuroimaging measures, and finding predictors of response.
详细描述
Major Depressive Disorder (MDD) is a highly prevalent psychiatric disorder, with an estimated lifetime prevalence of 14.6% across high-income countries.Effective therapeutic options for MDD include psychotherapy, different classes of antidepressants, and electroconvulsive therapy (ECT). Nevertheless, up to 30% of patients do not respond to four consecutive antidepressant strategies and 52% of pharmacotherapy resistant patients do not respond to ECT.Such patients are designated an advanced stage of Treatment Resistant Depression (TRD), which is associated with more hospitalizations, more suicide attempts, and higher costs than non-TRD patients.
Deep Brain Stimulation (DBS) is a promising therapeutic option for TRD patients. DBS consists of implanting electrodes in specific brain areas and then optimizing stimulation parameters (e.g. voltage, frequency, pulse width) to modulate brain activity of the targeted area. Since 2005, several open label trials have reported promising effects of DBS in TRD, targeting different brain structures involved in the neurobiology of MDD: the Subcallosal Cingulate Gyrus (SCG),Medial Forebrain Bundle (MFB),Ventral Capsule/Ventral Striatum (VC/VS), and Nucleus Accumbens (NAc). Response rates, defined as a symptom decrease of at least 50%, range from 30% to 90% with most studies finding a response rate around 50%.
However, results of the first two randomized trials are mixed. The first randomized, controlled trial (RCT) of VC/VS DBS in TRD did not find differences in response rates following active (3 of 14 patients) or sham stimulation (2 of 15 patients) after four months of stimulation. In contrast, another group found a strong antidepressant effect in 16 patients with TRD following active ventral Anterior Limb of the Internal Capsule (vALIC) DBS compared to sham stimulation in a randomized crossover phase.
Therefore, this trial aims to establishing whether active DBS results in more treatment responders than sham DBS. Secondary aims are establishing an adverse events profile, establishing effects on quality of life,neuropsychological and neuroimaging measures, and finding predictors of response.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Primary diagnosis: Major Depressive Disorder according to the ICD-10 criteria based on a psychiatric interview
- •Age: 18-65 years old
- •HAMD-17 total ≥17
- •Chronic illness with current episode ≥ 24 months duration and/or Illness with at least a total of 4 lifetime episodes (including current episode≥ 12 months) and a minimum of 5 years since the onset of the first depressive episode
- •Treatment refractory defined as failure of: at least 3 adequate treatments from at least two distinctly different classes (SSRI, SNRI, NaSSA, TCA +, lithium-addition) for a period of 6-8 weeks or more weeks. Adequate psychotherapy. At least 1 session of ECT, for which the series of ECT was terminated either due to adverse effects or insufficient response (including at least 6 sessions of bilateral ECT); unavailable, rejective or intolerable to ECT
- •remain stable with the current anti-depressive medicine for the last month
- •Able and willing to give written informed consent
- •Able to fully understand the consequences of the procedure
排除标准
- •Schizophrenia /history of psychosis unrelated to MDD
- •Severe personality disorder (assessed by SCID-II)
- •Abnormal brain MRI
- •Neurological disease (e.g., Parkinson's disease)
- •Previous sterosurgery
- •Any medical contraindication to surgery
研究组 & 干预措施
Active DBS then Sham DBS
After more than 6 months open-lable period, some patients will take DBS ON for two weeks with the optimal stimulation parameters and then take DBS OFF for two weeks.
干预措施: Deep brain stimulation(Active) (Device)
Active DBS then Sham DBS
After more than 6 months open-lable period, some patients will take DBS ON for two weeks with the optimal stimulation parameters and then take DBS OFF for two weeks.
干预措施: Deep brain stimulation(Sham) (Device)
Sham DBS then Active DBS
After more than 6 months open-lable period, some patients will take DBS OFF for two weeks and then take DBS ON for two weeks with the optimal stimulation parameters.
干预措施: Deep brain stimulation(Active) (Device)
Sham DBS then Active DBS
After more than 6 months open-lable period, some patients will take DBS OFF for two weeks and then take DBS ON for two weeks with the optimal stimulation parameters.
干预措施: Deep brain stimulation(Sham) (Device)
结局指标
主要结局
the comparison between the Hamilton Depression Scale(HAMD-17) scores after active and sham phase
时间窗: Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months
Effect size of comparison between HAMD-17 scores at two weeks when the active and sham phase end. The score of HAMD-17 ranges from 0 to 50. Higher HAMD-17 score indicates more severe depression.
次要结局
- changes in the Quick Inventory of Depression Scale(QIDS-SR16)(Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months)
- changes in the Depression and Somatic Symptoms Scale(DSSS)(Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months)
- changes in the Dimensional Anhedonia Rating Scale(DARS)(Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months)
- changes in the MOS item short from health survey (SF-36)(Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months)
- changes in the Montgomery-Asberg Depression Rating Scale(MADRS)(Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months)
- changes in Hamilton Anxiety Scales(HAMA)(Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months)
- changes in World Health Organization Quality of Life-BREF(WHO-BREF)(Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months)
- changes in Neuropsychological measures(Scores of Thinc-it tasks)(Baseline (preoperative), 6.25 months, 6.5 months, 18months)
- changes in Sheehan Disability Scale(Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months)
研究者
Bomin Sun
Principal Investigator
Ruijin Hospital