A Double-blind Pilot Trial of the Effect of Ketamine vs. Active Placebo on Suicidal Ideation in Depressed Inpatients With Major Depressive Disorder or Bipolar Depression.
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Montgomery-Aspberg Depression Rating Scale (MADRS)
研究概览
简要总结
Depression and suicidal ideation/attempt/death are major causes of morbidity and mortality from psychiatric illnesses. In 2009, the World Health Organization listed depression as the leading cause of years lost due to disability worldwide. Suicide is the 9th most common cause of death in Canada with 1.6% of Canadians ultimately dying from suicide (Statistics Canada, 2012) and the 2nd most common cause of death in young people after accidental deaths. This information highlights the importance of finding treatments to prevent suicidal deaths.
Ketamine has been shown to provide rapid treatment response for major depressive episodes both in major depressive disorder (MDD) and bipolar disorder (BD), via a single intravenous infusion which persists for at least 72 hours.
The purpose of this study is to conduct a pilot trial of IV ketamine + treatment as usual (TAU) vs. midazolam (an active placebo) + TAU to estimate sample size for a full-scale RCT examining these treatments for decreasing suicidal ideation among depressed inpatients with major depressive disorder and bipolar depression.
A total of 52 patients will be recruited for this trial. All subjects will be inpatients at Sunnybrook Health Sciences Centre with a diagnosis of either major depressive disorder or bipolar disorder type I or II currently depressed. Suicidal ideation must be present at baseline assessment in order to be included in the study. Thirteen subjects will be randomized to each treatment arm in each treatment stream - that is, 13 will be recruited to ketamine + TAU in the major depressive disorder stream, and 13 will be recruited to the midazolam + TAU in the major depressive stream. Likewise, 26 subjects with bipolar depression will be randomized to these two treatments.
详细描述
Depression and suicidal ideation/attempt/death are major causes of morbidity and mortality from psychiatric illness. The World Health Organization (2009) lists depression as the leading cause of years lost due to disability worldwide. Suicide is the 9th most common cause of death in Canada with 1.6% of Canadians ultimately dying from suicide (Statistics Canada, 2012) and the 2nd most common cause of death in young people after accidental deaths. The investigators' data show that at least 50% of people dying from suicide in Toronto suffer from depression with a small proportion ~12% suffering from BD. These data underscore the urgency of developing new treatments for both MDD and BD but also the suicidality that is often associated with them.
Ketamine treatment represents a potentially viable, safe and effective treatment for MDD/bipolar depression + SI. The Investigators therefore propose to conduct a pilot trial in preparation for a full- scale randomized controlled trial (RCT) which would aim to determine the efficacy of IV ketamine + a standard medication treatment (Treatment As Usual; TAU) vs. midazolam, an "active" placebo + TAU in treating SI among inpatients with MDD and in inpatients with bipolar depression. If the full-scale RCT demonstrates ketamine's efficacy, it would have important implications for both future research as well as inpatient treatment.
The primary objective is to conduct a pilot trial of IV ketamine + TAU vs. midazolam + TAU to estimate sample size for a full-scale RCT examining these treatments for decreasing SI among depressed inpatients with MDD and bipolar depression.
The primary hypothesis is that the effect size for reducing SI in the ketamine group vs. the midazolam group will be in the moderate range or above (d > 0.5 at 14 and 42 days) in terms of reduction in scores on the Scale of Suicidal Ideation (SSI) and the Columbia-Suicide Severity Rating Scale (CSSRS) for both subjects with MDD and subjects with bipolar depression.
Further, there are secondary objectives and secondary hypotheses. The secondary objectives are:
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision of written informed consent
- •[MDD stream only] Diagnosis of major depressive disorder, currently depressed as determined by DSM-IV diagnostic criteria (confirmed using the MINI)
- •[BD stream only] Diagnosis of bipolar disorder, type I or type II, currently depressed as determined by DSM-IV diagnostic criteria (confirmed using the MINI)
- •Both females and males, aged 18 to 65 years
- •Inpatient status
- •Female patients of childbearing potential must have a negative urine human chorionic gonadotropin (hCG) test at enrolment and must be taking or willing to take some acceptable form of birth control during the course of the study if they are or plan to be sexually active
- •The ability to understand and comply with the requirements of the study and capable of providing informed consent
- •Suffering from suicidal ideation/attempts as evidenced by a score of >0 on either of the SSI or CSSRS or both.
排除标准
- •Current or past psychotic symptoms
- •Substance or alcohol dependence at enrollment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria
- •Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM-IV criteria within 4 weeks prior to enrollment
- •Any pervasive developmental disorder (according to DSM-IV criteria)
- •Diagnosis of dementia (according to DSM-IV criteria)
- •Known intolerance or hypersensitivity to ketamine or midazolam as judged by the investigator
- •Significant medical condition that would contraindicate the use of ketamine, midazolam or that is untreated and would need urgent attention (as determined by treating physician)
- •Medical conditions that would significantly affect absorption, distribution, metabolism, or excretion of ketamine or midazolam
- •Unstable or inadequately treated medical illness (e.g. congestive heart failure, angina pectoris, hypertension) as judged by the investigator
- •Any clinically significant deviation from the reference range in clinical laboratory test results as judged by the investigator
- •Pregnancy (or female of child-bearing age not using adequate contraception) or lactation
- •A positive β-hCG test at enrollment
- •Involvement in the planning and conduct of the study
- •Previous enrollment or randomisation of treatment in the present study
- •Participation in another drug trial within 4 weeks prior enrollment into this study or longer in accordance with local requirements
研究组 & 干预措施
ketamine + TAU - BD
Ketamine + treatment as usual (TAU) in BD inpatients with SI
干预措施: Ketamine (Drug)
ketamine+TAU - MDD
Ketamine + treatment as usual (TAU) in MDD inpatients with SI
干预措施: Ketamine (Drug)
ketamine+TAU - MDD
Ketamine + treatment as usual (TAU) in MDD inpatients with SI
干预措施: Treatment as usual (TAU) (Other)
midazolam + TAU - MDD
Midazolam + treatment as usual (TAU) in MDD inpatients with SI
干预措施: Midazolam (Drug)
midazolam + TAU - MDD
Midazolam + treatment as usual (TAU) in MDD inpatients with SI
干预措施: Treatment as usual (TAU) (Other)
ketamine + TAU - BD
Ketamine + treatment as usual (TAU) in BD inpatients with SI
干预措施: Treatment as usual (TAU) (Other)
midazolam + TAU - BD
Midazolam + treatment as usual (TAU) in BD inpatients with SI
干预措施: Midazolam (Drug)
midazolam + TAU - BD
Midazolam + treatment as usual (TAU) in BD inpatients with SI
干预措施: Treatment as usual (TAU) (Other)
结局指标
主要结局
Montgomery-Aspberg Depression Rating Scale (MADRS)
时间窗: two weeks
次要结局
- Clinical Global Impression of Severity/Improvement (CGI-S, CGI-I)(two weeks)
- Scale of Suicidal Ideation (SSI)(two weeks)
- Columbia-Suicide Severity Rating Scale (CSSRS)(two weeks)
研究者
Mark Sinyor
Associate Scientist
Sunnybrook Health Sciences Centre