A Randomized, Double-blind, Double-dummy, Controlled Trial of Lithium Versus Paroxetine in Subjects With Major Depression Who Have a Family History of Bipolar Disorder or Completed Suicide - a Pilot Study
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Remission will be defined as MADRS ≤ 12.
研究概览
简要总结
This study is being done to look at how well people respond to two very different drug treatments for depression. Clinically, people with depression can respond differently to drug treatments for reasons which are not always clear. Some of our own recent research suggests that people with depression who have a family history of bipolar disorder or completed suicide, may react differently to standard antidepressant medications than those without such a family history. Our data shows that family history of completed suicide, as well as the known predictor of family history of bipolar disorder, may help identify a pre-bipolar high risk group i.e. they currently have depression but at some future date will declare a bipolar illness (manic-depression) by virtue of development of a manic episode also. Our research suggests that treatment- emergent symptoms in response to a trial of antidepressant, such as agitation may be strong predictors of future bipolarity and inherently dangerous particularly as they are not ascribed to the antidepressant treatment. Finally, it is possible that this subgroup of those with depressive illness may respond better and more safely to lithium, a mood stabiliser used in known bipolar depression.
The objective of this proposal is to investigate response to acute lithium treatment in subjects who meet the diagnostic criteria for major depression, but who are potentially at risk for bipolar disorder, by virtue of family history of bipolarity or completed suicide.
详细描述
Introduction: Bipolar disorder is an illness that consists of distinct episodes or "poles" of both major depression and mania (bipolar I) or major depression and hypomania (bipolar II). Both poles of the illness may be fully present simultaneously in what is referred to as a "Mixed episode". The "poles" of Major depression, Mania and Mixed mood are currently defined by descriptive criteria in the psychiatric diagnostic manual, DSMIV.
Estimates of the prevalence of Bipolar disorder are as high as 6% of the population.(1) It is a severe and potentially lethal illness which has a different course and treatment profile to unipolar depression, commonly known simply as "major depression". In 50-60% of cases however, the initial presentation of bipolar disorder is one of major depression, and several episodes of depression may occur before declaration of bipolarity, by virtue of a manic or hypomanic episode (pre-bipolar depression).(2,3) The mainstay of treatment for unipolar major depression is antidepressants. In contrast, antidepressant monotherapy is contraindicated in Bipolar I depression and must be used very cautiously in Bipolar II illness (4) with much concern for an "unacceptable cost /benefit ratio' because of the risk of antidepressant induction of mania and rapid cycling (increase in frequency of episodes as a consequence of antidepressants). (5). Hence treatment of the early depressive episodes of bipolar illness requires recognition of depression specific to bipolar disorder and appropriate choice of medication.
Unfortunately, efforts to clearly distinguish bipolar from unipolar depression cross-sectionally have been mostly disappointing. Most evidence supports the value of family history(6) and there is variable predictive value for specific phenomenological and course descriptors such as hypersomnia, psychomotor retardation, early-onset and psychotic sub types(7,8).
The dilemma then is two-fold:
- Identifying patients suffering from major depression who are at high risk of bipolar disorder.
- Choosing appropriate pharmacological treatment.
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, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Not currently participating in a drug or medical device clinical trial
- •Male or female over the age of 18
- •DSM - IV Diagnosis of major depression
- •Positive family history of bipolar disorder or completed suicide
排除标准
- •Not able to give informed consent
- •Pregnant or breast-feeding
- •Current additional psychiatric diagnoses including Panic Disorder, Post -Traumatic Stress Disorder (PTSD) or Psychosis
- •History of mania or hypomania
- •Active substance abuse or dependence in the last 6 months
- •Current depressive episode less than 4 weeks or greater than 12 months in duration
- •Current or prior adequate trial of lithium or paroxetine
- •Current use of other medications such as antidepressants for the treatment of depression
- •Clinically significant medical illness, in particular kidney problems
研究组 & 干预措施
lithium group
Start at 600 mg po hs. Dose titrated up to a serum level of between 0.6 and 1.1 mmol/l.
干预措施: lithium (Drug)
paroxetine group
Start dose at 20 mg po od. If no clinical improvement(<20% reduction in MADRS score) by week 4 dose to be increased to 40 mg po od.
干预措施: paroxetine (Drug)
结局指标
主要结局
Remission will be defined as MADRS ≤ 12.
时间窗: weekly
The MADRS will be done at week 0,1,2,3,4,5,6.
时间窗: weekly
Response will be defined as 50% reduction in MADRS score.
时间窗: weekly
次要结局
- The Young Mania Rating Scale (YMRS), at weeks 0,1,2,3,4,5,6.(weekly)
- Checklist of DSM IV symptoms of mania/ hypomania, with additional questions assessing the presence of mood lability, abnormally high energy, abnormally high libido, and rage. Done at weeks 0,1,2,3,4,5,6.(weekly)
- The Beck Suicide Scale (BSS), at weeks 0, 1, 2,3,4,5, 6.(weekly)
- The Hamilton Depression Rating Scale (HAM -D)-17 item scale, at weeks 0 and 6.(weeks 0 and 6)
- Hamilton Anxiety Rating Scale (HAM-A),at weeks 0 and 6.(weeks 0 and 6)
- The Bipolar Depression Rating Scale (BDRS) (42),at weeks 0,1,2,3,4,5,6.(weekly)
研究者
Julie Garnham
Dr. Claire O'Donovan
Nova Scotia Health Authority