Combination of Paroxetine CR and Quetiapine for the Treatment of Refractory Generalized Anxiety Disorder
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Hamilton Anxiety Scale (HAM-A) Score at Study Endpoint.
研究概览
简要总结
The purpose of this study is to examine the safety and efficacy of quetiapine for generalized anxiety disorder patients who remain symptomatic despite treatment with paroxetine CR.
详细描述
Generalized anxiety disorder (GAD) is a relatively common condition affecting 5% of the population, with a typically chronic course and associated with significant psychosocial impairment and decreased quality of life (Schweizer, 1995). Although a number of therapeutic agents demonstrate some efficacy in the treatment of generalized anxiety disorder, only a minority of anxious patients experience remission with initial treatment.
The purpose of this study is to examine the efficacy of one strategy, the addition of quetiapine, for the treatment of patients with GAD who remain refractory despite an adequate treatment trial with a selective serotonin reuptake inhibitor (SSRI). This is an investigator-initiated augmentation study of an already approved drug for a different indication. Quetiapine is a novel antipsychotic agent with potent effects at the serotonergic, as well as dopaminergic receptor, and a more favorable side effect profile than standard neuroleptics, including a low potential to cause extrapyramidal symptoms.
This is a two phase, 18-week research study in which participants who remain symptomatic at the end of one phase (10 weeks) enter into the next phase. In phase I, all participants receive paroxetine CR (Paxil CR) for 10 weeks. Participants who continue to have anxiety symptoms will enter the 8-week Phase II, in which they continue taking Paxil CR and they will also be randomly assigned (by chance, like a flip of a coin) to receive quetiapine (Seroquel) or placebo (contains no active medication).
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 72 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female outpatients, age 18-
- •Primary diagnosis of generalized anxiety disorder.
- •Patients on concurrent benzodiazepines will be entered into the trial if they remain symptomatic despite stable doses for at least one month
排除标准
- •Pregnant or lactating women or other women of child bearing potential not using acceptable means of birth control
- •Patients with a primary diagnosis of major depression, dysthymia, panic disorder or social phobia.
- •Patients with current or history of bipolar disorder, schizophrenia or other psychotic conditions
- •Patients with post-traumatic stress disorder or obsessive-compulsive disorder current in the past 6 months.
- •Patients with a history of alcohol or substance abuse or dependence within the last six months.
- •Patients with significant unstable medical illness.
- •Ongoing psychotherapy directed toward the treatment of generalized anxiety disorder.
- •History of hypersensitivity to paroxetine CR, paroxetine or quetiapine.
- •History of cataracts.
- •Concurrent use of psychotropic medications including buspirone and antidepressants. Patients must have discontinued buspirone or antidepressant therapy at least two weeks prior to study entry, and fluoxetine at least four weeks prior, but no patient will be taken off effective medication.
- •Concomitant use of herbs and dietary supplements with known psychotropic properties, including St John's Wort, Kava, Valerian, Gingko, Ginseng, ephedra and weight loss supplements. Other than such agents with known psychotropic properties, no over the counter medications are exclusionary.
研究组 & 干预措施
Paroxetine CR and Placebo
Eleven individuals were randomized to plaecbo augmentation of continued paroxetine CR at the week 10 dose level. In the first phase of the study, individuals started at 12.5 mg/day of paroxetine and flexibly titrated up to a maximum of 62.5 mg/day by week 10. Individuals who did not achieve remission and were randomized into the placebo group received placebo augmentation of continued paroxetine CR at the week 10 dose level.
干预措施: Continued Paroxetine CR (Drug)
Paroxetine CR and Placebo
Eleven individuals were randomized to plaecbo augmentation of continued paroxetine CR at the week 10 dose level. In the first phase of the study, individuals started at 12.5 mg/day of paroxetine and flexibly titrated up to a maximum of 62.5 mg/day by week 10. Individuals who did not achieve remission and were randomized into the placebo group received placebo augmentation of continued paroxetine CR at the week 10 dose level.
干预措施: Placebo (Drug)
Quetiapine and continued paroxetine CR
Eleven individuals were randomized to quetiapine augmentation of continued paroxetine CR at the week 10 dose level. In the first phase of the study, individuals started at 12.5 mg/day of paroxetine and flexibly tirated up to a maximum of 62.5 mg/day by week 10. Individuals who did not receive remission and were randomized to receive quetiapine started at 25 mg at bedtime for the first week, then flexibly dosed based on response and tolerability to a maximum of 200 mg BID by week 16.
干预措施: Continued Paroxetine CR (Drug)
Quetiapine and continued paroxetine CR
Eleven individuals were randomized to quetiapine augmentation of continued paroxetine CR at the week 10 dose level. In the first phase of the study, individuals started at 12.5 mg/day of paroxetine and flexibly tirated up to a maximum of 62.5 mg/day by week 10. Individuals who did not receive remission and were randomized to receive quetiapine started at 25 mg at bedtime for the first week, then flexibly dosed based on response and tolerability to a maximum of 200 mg BID by week 16.
干预措施: Quetiapine (Drug)
结局指标
主要结局
Hamilton Anxiety Scale (HAM-A) Score at Study Endpoint.
时间窗: Baseline and Week 18
Symptoms of generalized anxiety disorder as measured by the Hamilton Anxiety Scale (HAM-A) at week 18/study endpoint. Each item is scored on a scale from 0 (not present) to 4 (severe) with a total score range of 0-56. Changes in HAM-A scores are calculated as the difference between the baseline HAM-A scores and scores at week 18/study endpoint. The 14-item Hamilton Anxiety Rating Scale (HAM-A) (Hamilton, 1959) was developed to assess anxiety in a clinical population. It is considered a measure of general anxiety across anxiety disorders, in addition to being a gold standard measure for GAD.
次要结局
- Remission (HAM-A ≤ 7)(Week 18 (Study Endpoint))
- The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q).(Week 10 (Phase 1 Endpoint) and Week 18 (Phase 2 Endpoint))
- Response, Clinical Global Impression of Improvement (CGI-I)(Week 18 (Phase 2 Endpoint))
- Depressive Symptoms, Montgomery-Asberg Depression Rating Scale (MADRS)(Week 10 (Phase 1 Endpoint) and Week 18 (Phase 2 Endpoint))
研究者
Naomi M. Simon
Director, Center for Anxiety and Traumatic Stress Disorders
Massachusetts General Hospital