Anti-Estrogens - A Potential Treatment for Bipolar Affective Disorder in Women?

抗雌激素——女性双相情感障碍的潜在治疗方法？

• 批准号: nhmrc : 284319
• 负责人: Prof Jayashri Kulkarni
• 金额: $ 15.95万
• 依托单位: Monash University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2004
• 资助国家: 澳大利亚
• 起止时间: 2004-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/anti-estrogens-potential-disorder-women/76679
• 关键词: Anti; Estrogens; Potential; Treatment; Bipolar

Bipolar Affective Disorder (BPAD) or Manic-Depressive Illness is a serious mental illness with high morbidity and mortality. The cause of the illness is still unclear and the underlying neurochemical changes are different for the manic phase compared with the depressive phase. The current treatments for BPAD are limited in scope and not biochemically well understood. There are gender differences in the presentation and outcomes for BPAD which adds to the complexity of the illness. We are proposing a study to develop a new type of treatment for the manic phase of BPAD and are exploring the use of anti-estrogens in women with mania. The background to our proposed study comes from a few case reports suggesting that anti-estrogen agents such as progesterone and tamoxifen may be useful adjuncts to treatment. We conducted a small pilot study comparing the addition of oral tamoxifen with oral progesterone and placebo in 10 women with mania and found that the women who received tamoxifen made significantly better improvements in their manic symptoms over a 28-day trial. The research study we are now proposing is a larger, three-arm, double blind, placebo controlled, 28-day adjunctive study in women with mania to expand and clarify our pilot study findings. Patients in our proposed study would receive either 40mg per day tamoxifen or 20mg per day progesterone or placebo in addition to standardised lithium medication. We will measure enzyme activity (protein kinase C) and estrogen-progesterone levels to understand more about the mechanisms of action by these new hormone treatments. BPAD is a crippling disorder and if we are successful, then tamoxifen treatment may be an important new treatment. This proposed study will also shed new light on some of the neurochemical mechanisms underlying BPAD as well as opening up the new area of hormone treatments for serious mental illness.

双相情感障碍（BPAD）或躁狂抑郁症是一种严重的精神疾病，具有高发病率和死亡率。这种疾病的原因尚不清楚，与抑郁阶段相比，躁狂阶段的潜在神经化学变化是不同的。目前BPAD的治疗范围有限，生物化学方面也不清楚。BPAD的表现和结局存在性别差异，这增加了疾病的复杂性。我们正在提出一项研究，以开发一种新型的治疗躁狂阶段的BPAD，并正在探索使用抗雌激素的妇女与躁狂症。我们提出的研究的背景来自于一些病例报告，这些病例报告表明抗雌激素药物如黄体酮和他莫昔芬可能是治疗的有效药物。我们进行了一项小型的试点研究，比较了10名躁狂症妇女口服他莫昔芬与口服黄体酮和安慰剂的添加，发现接受他莫昔芬的妇女在28天的试验中躁狂症状有明显改善。我们现在提出的研究是一个更大的，三臂，双盲，安慰剂对照，28天的连续性研究，在女性躁狂症，以扩大和澄清我们的初步研究结果。在我们建议的研究中，患者除了标准化的锂药物外，还将接受每天40 mg他莫昔芬或每天20 mg黄体酮或安慰剂。我们将测量酶活性（蛋白激酶C）和雌激素-孕酮水平，以了解更多关于这些新激素治疗的作用机制。BPAD是一种致残性疾病，如果我们成功，那么他莫昔芬治疗可能是一种重要的新治疗方法。这项拟议中的研究也将为BPAD的一些神经化学机制提供新的线索，并开辟严重精神疾病激素治疗的新领域。