Felbamate for Treatment-Resistant Bipolar Depression

非氨酯治疗难治性双相抑郁症

基本信息

项目摘要

Bipolar affective disorder (BPD, manic-depressive illness) is a common, severe, chronic and often life-threatening illness. Increasingly, it is being recognized that it is the depressive phase of the illness, which contributes much of the morbidity and mortality. Impairment in physical and social functioning resulting from depression can be just as severe as other chronic medical illnesses. Suicide is the cause of death in 10-20% of individuals with either bipolar or recurrent depressive disorders. The treatments for acute unipolar depression have been extensively researched. However, despite the availability of a wide range of antidepressant drugs, clinical trials indicate that 30% to 40% of depressed patients fail to respond to first-line antidepressant treatment, despite adequate dosage, duration, and compliance. Very few studies have examined the efficacy of somatic treatments for the acute phase of bipolar depression. Thus, there is a clear need to develop novel and improved therapeutics for bipolar depression. Recent preclinical studies suggest that antidepressants may exert delayed indirect effects on the glutamatergic system. Furthermore, a growing body of data suggests that mood disorders are associated with regional volumetric reductions, and cell loss and atrophy. It is noteworthy that lamotrigine reduces glutamatergic neurotransmission, has antidepressant effects in bipolar depression, and a pilot study has suggested that NMDA antagonists may have antidepressant effects. Together, this data suggests that the glutamatergic system may play a role in the pathophysiology and treatment of depression, and that agents, which more directly reduce glutamatergic neurotransmission, may represent a novel class of antidepressants. Felbamate (Felbatol?) a dicarbamate, is FDA-approved as monotherapy and adjunctive therapy in adults with partial-onset seizures with or without secondary generalization and in partial and generalized seizures associated with Lennox-Gastaut syndrome in children. Felbamate has significant antiglutamatergic and neuroprotective properties, and may prove to have antidepressant properties in bipolar patients. In this study, we propose to investigate the potential efficacy of felbamate, which reduces glutamatergic throughput via inhibition of glutamate release and NMDA, AMPA, and metabotropic glutamate receptor blockade. This is an 8-week randomized, double-blind, placebo-controlled study that will examine the efficacy and safety of felbamate in acutely depressed bipolar patients who are considered treatment-resistant. This study has two phases. The first phase is the washout phase that will last for 7 days. The second phase is an 8-week acute treatment phase in which the efficacy and tolerability of felbamate and placebo are compared. Lithium can remain during Study Periods I and II if partial response to this agent is documented. Patients who complete the 8-week double-blind phase will receive clinical treatment. Acute efficacy will be determined by demonstrating a greater response rate using specified criteria. Patients, ages 18 or older, with a diagnosis of Bipolar I or II disorder, depressed (without psychotic features), will be randomized to double-blind treatment to receive either felbamate (600-3000 mg/day) or placebo for a period of 8 weeks. Following this acute period, the patients will receive treatment as clinically indicated. Approximately 52 patients with treatment-resistant acute bipolar depression will be enrolled in the study.
双相情感障碍(BPD,躁狂抑郁症)是一种常见的、严重的、慢性的、经常危及生命的疾病。越来越多的人认识到,这种疾病的抑郁阶段是造成发病率和死亡率的主要原因。抑郁症导致的身体和社会功能障碍可能与其他慢性疾病一样严重。自杀是10-20%双相或复发性抑郁症患者死亡的原因。

项目成果

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HUSSEINI K MANJI其他文献

HUSSEINI K MANJI的其他文献

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{{ truncateString('HUSSEINI K MANJI', 18)}}的其他基金

LITHIUM RESPONSIVE BIPOLAR DISORDER AND CNS MYO INOSITOL
锂反应性双相情感障碍和中枢神经系统肌醇
  • 批准号:
    2908653
  • 财政年份:
    1999
  • 资助金额:
    --
  • 项目类别:
PKC SIGNALING AND THE TREATMENT OF BIPOLAR DISORDER
PKC 信号传导和双相情感障碍的治疗
  • 批准号:
    2702902
  • 财政年份:
    1998
  • 资助金额:
    --
  • 项目类别:
PKC SIGNALING AND THE TREATMENT OF BIPOLAR DISORDER
PKC 信号传导和双相情感障碍的治疗
  • 批准号:
    2891036
  • 财政年份:
    1998
  • 资助金额:
    --
  • 项目类别:
Microarray Studies -- Long Term Treatment for Bipolar
微阵列研究——双相情感障碍的长期治疗
  • 批准号:
    6824378
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Antidepressant Efficacy of Antiglutamatergic Agent
抗谷氨酸药的抗抑郁功效
  • 批准号:
    6824387
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Neuronal-Glial Interaction in the Treatment of Bipolar
双相情感障碍治疗中的神经元-胶质细胞相互作用
  • 批准号:
    6824400
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Antidepressant Efficacy of an Antiglutamatergic Agent in
抗谷氨酸药物的抗抑郁功效
  • 批准号:
    7312904
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Glucocorticoid Receptors (GR) in Mitochondria: The Role
糖皮质激素受体 (GR) 在线粒体中的作用
  • 批准号:
    7312914
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Roles of kainate receptors in behavioral plasticity rela
红藻氨酸受体在行为可塑性关系中的作用
  • 批准号:
    7312942
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
The Protein Kinase C Inhibitor Tamoxifen in Acute Mania
蛋白激酶 C 抑制剂他莫昔芬治疗急性躁狂症
  • 批准号:
    6982748
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:

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