Prazosin for Noncombat Trauma PTSD

描述（由申请人提供）：我们提出了一项双盲安慰剂对照增强试验，用于一般可用的α -1肾上腺素能拮抗剂吡唑嗪治疗由非战斗（“平民”）创伤引起的慢性创伤后应激障碍（PTSD）。尽管选择性血清素再摄取抑制剂（SSRI）帕罗西汀进行了试验，但创伤后应激障碍的主要症状将是残留的痛苦的创伤相关噩梦和睡眠障碍。尽管有几种SSRIs被fda批准用于治疗PTSD，但SSRIs（和其他药物）通常对这些非常痛苦的夜间PTSD症状没有帮助。对患有慢性创伤后应激障碍的老年男性退伍军人的初步研究表明，吡唑嗪（唯一一种可从血液进入大脑的α -1拮抗剂）消除或大大减少了先前治疗抵抗性创伤相关的噩梦和睡眠障碍，这些噩梦和睡眠障碍多年来一直使人痛苦和衰弱。普拉唑嗪还降低了总体疾病严重程度和功能损害，并且耐受性良好。这些有益的吡嗪效应与PTSD病理生理中脑α -1肾上腺素能受体反应性增加的参与是一致的。在这里，我们将确定这些令人鼓舞的哌唑嗪效果是否也可以在非战斗创伤性PTSD患者中得到证明，这些患者尽管接受了标准的PTSD治疗，但仍继续遭受与创伤相关的残余痛苦的噩梦和睡眠障碍。在一项为期8周的吡唑嗪增强双盲安慰剂对照平行组临床试验中（在标准SSRI和手动心理治疗的12周“导入”之后），将检验以下假设：假设1:PTSD患者表现为与创伤相关的残余痛苦噩梦和睡眠

DESCRIPTION (provided by applicant): We propose a double-blind placebo-controlled augmentation trial of the generically available alpha-1 adrenergic antagonist prazosin in chronic posttraumatic stress disorder (PTSD) caused by noncombat ("civilian") trauma. Primary target PTSD symptoms will be residual distressing trauma-related nightmares and sleep disturbance that persist despite a trial of the selective serotonin reuptake inhibitor (SSRI) paroxetine. Although several SSRIs are FDA-approved for PTSD, SSRIs (and other drugs) often are not helpful for these very distressing nighttime PTSD Symptoms. Preliminary studies in older male combat veterans with chronic PTSD demonstrated that prazosin (the only available alpha-1 antagonist that crosses from blood into brain) eliminated or Substantially reduced previously treatment resistant trauma-related nightmares and sleep disturbance that had been distressing and debilitating for many years. Prazosin also reduced overall illness severity and functional impairment, and was well tolerated. These beneficial prazosin effects are consistent with involvement of increased responsiveness of brain alpha-1 adrenergic receptors in PTSD pathophysiology. Here we will determine if these encouraging prazosin results also can be demonstrated in the generally younger and predominantly female population of persons with noncombat trauma PTSD who continue to suffer from residual distressing trauma related nightmares and sleep disturbance despite standard PTSD treatment. In a double-blind placebo-controlled parallel group 8-week clinical trial of prazosin augmentation (following a 12-week "lead-in" of standard SSRI plus manualized psychotherapy treatment) the following hypotheses will be tested: Hypothesis 1: Persons with PTSD manifested by residual distressing trauma-related nightmares and sleep disturbance (despite SSRI treatment) randomized to prazosin augmentation will manifest a greater reduction in trauma related nightmares and sleep disturbance than those randomized to placebo augmentation. Hypothesis 2: Persons with PTSD manifested by residual distressing trauma-related nightmares and sleep disturbance (despite SSRI treatment) randomized to prazosin augmentation will manifest greater improvement in overall global PTSD severity and function than those randomized to placebo augmentation. Hypothesis 3: The time to study discontinuation ("dropout") due to unacceptable adverse effects will not differ between PTSD subjects randomized to prazosin augmentation and those randomized to placebo augmentation. Primary outcome measures will be the Clinician Administered PTSD Scale (CAPS) Recurrent Distressing Dreams item, the Pittsburgh Sleep Quality Index, and the Clinical Global Impression of Change. Additional outcome measures will be the total CAPS score, the CAPS Difficulty Falling or Staying Asleep item, the three CAPS subscales (Reexperiencing/Intrusions, Avoidance/Numbing, and Hyperarousal), measures of nightmare quality and frequency, depressive signs and symptoms, and quality of life. Number of study days completed and adverse events also will be compared between groups.