A Double-blind Sham Controlled Trial of rTMS in Treatment Resistant Major Depression
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 67
- 试验地点
- 1
- 主要终点
- The 17- item Hamilton Rating Scale for Depression (HAM-D)
研究概览
简要总结
The main treatment option for Treatment Resistant Depression is electroconvulsive therapy (ECT) which is often effective but complicated by cognitive side effects, need for anaesthesia and considerable stigma.
In recent years considerable efforts have been made to increase public awareness about depression and increase access to services. However, the increasing number of patients accessing treatment for depression in clinical services is also likely to be accompanied by a sizeable increase in the number of patients with TRD. Despite the demand, relatively few treatment options are available to such patients. One of the only substantially new treatments developed for TRD in recent years has been the advent of repetitive transcranial magnetic stimulation (rTMS). Repetitive TMS has been evaluated in over 20 trials conducted over the last 10 years. Previous research indicates that rTMS has antidepressant activity; however, the proportion of patients who respond to rTMS and the degree of treatment response demonstrated in trials to date is limited. The limitations of these studies include relatively small samples and limited duration of treatment (i.e., 2 weeks) as well as a lack of long term follow-up. As rTMS is gradually entering use in routine clinical practice (for example, recent regulation of its use in Canada), research is urgently required to establish ways to enhance treatment response both in regards to the extent of response within individuals and the proportion of individuals in whom rTMS has effects.
Stimulation site is another important treatment factor; thus far almost all of the trials of rTMS in TRD conducted have evaluated the utility of high frequency left prefrontal cortex (PFC) rTMS (HFL-TMS). In addition, several studies have evaluated the treatment efficacy of low frequency rTMS to right PFC (LFR-TMS). In a previously published study we have demonstrated that these two approaches have similar therapeutic benefit and both were superior to sham stimulation.
A promising new approach to enhance efficacy involves combining LFR-TMS and HFL-TMS in a sequential manner. We describe this as sequential bilateral rTMS (SB-rTMS). We have recently published the results of the first substantial evaluation of SB-rTMS showing not only a superiority to placebo in TRD but also a therapeutic response that is substantially superior to response rates in most of the published studies of unilateral rTMS (>50% of patients achieving standard criteria for clinical response compared to usually <30% in most studies). In this proposed research study, we will directly test the hypothesis that SB-rTMS produces a greater therapeutic response than HFL-TMS and compare both of these forms of stimulation to placebo (i.e., sham) stimulation.
详细描述
Justification for project
TRD is clearly a major health issue - depression is common, results in marked morbidity and mortality and a large percentage of patients do not respond to, or cannot tolerate standard treatment. The development of new treatments for this condition is undoubtedly required. International efforts are underway to try and establish the efficacy of HFL-TMS to the point where the technique may be approved by regulatory authorities and clinically introduced. However, clearly the response rate to HFL-TMS is suboptimal for its widespread use.
The overall goal of this research program is to develop rTMS methods to the point at which they are highly relevant and applicable to clinical practice. None of the substantial international studies is focusing on novel applications such as SBrTMS. As an outcome, we expect positive results to change the focus of rTMS application and practice nationally and internationally. If we can follow our well received initial study of this technique with a substantial comparative trail as planned here, it will provide enough evidence for the more widespread adoption and testing of SBrTMS as a viable alternative to HFL-TMS. Ultimately, this or a modification of it, may become the rTMS administration method of choice.
Additionally, we will have a sufficient sample size to start to explore meaningful predictors of clinical response including biological, psychosocial/personality variable predictors.
Hypotheses / Research Questions
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients will be included if they:
- •Have a DSM-IV diagnosis of a major depressive episode (SCID 11).
- •Have treatment resistant depression at Stage II of the Thase and Rush classification [31]; .e. have failed to achieve a clinical response, or did not tolerate, at least two separate antidepressant trials of sufficient dose for at least 6 weeks.
- •Have a Hamilton Depression Rating Scale Score of > 20 (moderate - severe depression). Including only a severely ill group of subjects limits the placebo response rate [32]. Moreover, this will allow us to address the application of rTMS methods in the most clinically relevant subgroup of patients (in addition helping to constrain group heterogeneity, a major issue in depression research).
- •Have had no increase or initiation of new antidepressant (or other psychoactive) therapy in the 4 weeks prior to screening.
排除标准
- •Patients who have an unstable medical condition, neurological disorder or any history of a seizure disorder or are currently pregnant or lactating.
- •In the opinion of the investigator, are a sufficient suicidal risk to require immediate electro-convulsive therapy.
- •Have a current DSM IV diagnosis of substance abuse or dependence disorder, a diagnosis of a personality disorder (SCID II) or another axis 1 disorder.
- •Please note: several of these criteria (e.g. inclusion criteria 1 & 2, exclusion criteria 3) have been selected to explicitly constrain the heterogeneity of the sample to increase the likely power of the study to detect differences between the groups given the potentially subtle difference between the treatment methods.
研究组 & 干预措施
1
active TMS
干预措施: TMS (Drug)
2
Sham TMS
干预措施: Sham TMS (Device)
结局指标
主要结局
The 17- item Hamilton Rating Scale for Depression (HAM-D)
时间窗: every 3 weeks
次要结局
未报告次要终点