Randomized Placebo-Controlled Trial of Methylphenidate for the Treatment of Post-Traumatic Stress Disorder with Associated Neurocognitive Complaints

哌醋甲酯治疗创伤后应激障碍及相关神经认知症状的随机安慰剂对照试验

• 批准号: 10588946
• 负责人: LORI L. DAVIS
• 金额: --
• 依托单位: VA PUGET SOUND HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10588946
• 关键词: Acceleration; Address; Attention Deficit Disorder; Attention deficit hyperactivity disorder; Back; Benefits and Risks; Chronic; Clinical; Clinical Sciences; Code; Cognitive; DSM-V; Development; Diagnosis; Digit structure; Double-Blind Method; Healthcare Systems; Heterogeneity; Impaired cognition; Impairment; Major Depressive Disorder; Measures; Memory; Mental Depression; Mental disorders; Methods; Moods; Neurobehavioral Manifestations; Neurocognitive; Participant; Persons; Pharmaceutical Preparations; Pharmacological Treatment; Pilot Projects; Placebo Control; Placebos; Population; Post-Traumatic Stress Disorders; Prediction of Response to Therapy; Psychopharmacology; Publishing; Randomized; Randomized, Controlled Trials; Recommendation; Recording of previous events; Reporting; Research; Research Personnel; Resistance; Risk; Risk Assessment; Ritalin; Safety; Sampling; Short-Term Memory; Site; Stimulant; Symptoms; Testing; Time; Traumatic Brain Injury; Veterans; Work; clinical practice; cognitive control; cognitive function; comorbidity; depressive symptoms; design; diagnostic criteria; disability; efficacy evaluation; efficacy study; evidence base; experience; follow-up; functional disability; improved; innovation; member; mild traumatic brain injury; novel; pilot trial; predicting response; prescription stimulants; processing speed; psychostimulant; randomized placebo controlled trial; randomized placebo-controlled clinical trial; research and development; stimulant use; sustained attention; treatment duration; treatment response; trial design; verbal

Background: Posttraumatic stress disorder (PTSD) is a chronic psychiatric illness that is associated with significant suffering and disability in Veterans. Current treatment options are not fully effective for all Veterans, and even when they are effective in lowering total symptom burden, many Veterans continue to experience significant symptom burden and associated functional impairment. Total symptom burden and associated functional impairment is often particularly high for those with comorbid mild traumatic brain injury (mTBI). Methylphenidate (MPH) is a widely available psychostimulant medication with a long track record of safety, which has been used to improve cognitive functioning in attention deficit hyperactivity disorder (ADHD) and has also shown benefit for mood and cognitive functioning in studies of moderate or severe TBI and as augmentation in treatment-resistant major depressive disorder. In a small pilot study of the efficacy of MPH for subjective cognitive impairment associated with PTSD and/or mTBI, members of our research team found that MPH resulted in not only a significant improvement in subjective and objective measures of cognitive functioning, but also a significant decrease in symptoms of both depression and PTSD. Methods: Here, we propose to follow up this promising initial finding with an aggregated N-of-1 randomized placebo-controlled trial of MPH versus placebo (PBO) for PTSD and cognitive symptoms in Veterans with PTSD, with or without comorbid TBI. N=70 Veterans across two sites will each receive sequential 4-week periods of MPH and PBO, in randomized order and separated by a 1-week washout, for a total of 20 weeks. During this time, they will complete weekly or biweekly assessments. This trial design, which is particularly well-optimized for conditions in which a heterogeneous response to treatment is expected, will let us achieve a number of specific aims. First, we will assess the efficacy of MPH compared to PBO for reducing PTSD and depression symptoms in Veterans with PTSD and neurocognitive complaints. Second, we will assess the impact of MPH compared to PBO on neurocognitive functioning in this same population. And third, we characterize the baseline predictors of treatment response to MPH in this population, including whether Veterans with a history of mTBI show greater average treatment response to MPH versus PBO. Finally, this trial design will also allow a systematic assessment of risks in this population, including the risk of discontinuation effects or loss of efficacy over time. Significance: MPH represents a well-tolerated medication with a novel mechanism of action compared to the currently recommended and often ineffective pharmacologic treatments for PTSD and mTBI with associated cognitive complaints. If the results of this study support the use of MPH to decrease PTSD and neurocognitive symptoms in Veterans, it would provide an important new treatment option for Veterans with PTSD, which could be rapidly integrated into clinical practice.

背景：创伤后应激障碍（PTSD）是一种慢性精神病，与 退伍军人的重大苦难和残疾。当前的治疗选择对所有退伍军人都不是完全有效的 即使他们有效地降低了总症状负担，许多退伍军人仍在继续体验 重大症状负担和相关的功能障碍。总症状负担和相关 对于合并症轻度创伤性脑损伤（MTBI）的人来说，功能障碍通常特别高。 哌醋甲酯（MPH）是一种可广泛可用的精神刺激药物，具有长长的安全记录， 已被用来改善注意力缺陷多动障碍（ADHD）的认知功能，并且也有 在中度或重度TBI的研究中显示出对情绪和认知功能的好处 耐治疗的重度抑郁症。在一项小型试点研究中，MPH对主观认知的功效 与PTSD和/或MTBI相关的障碍，我们的研究小组的成员发现MPH并没有导致 仅在认知功能的主观和客观度量方面有了显着改善，但也有一个 抑郁症和PTSD症状的显着减少。 方法：在这里，我们建议使用汇总的1个随机n-fandizal PTSD的退伍军人的PTSD和认知症状的MPH与安慰剂（PBO）的安慰剂对照试验 有或没有合并症TBI。 n =两个地点的70名退伍军人将分别接收4周的连续时间 MPH和PBO以随机顺序为单位，并通过1周的冲洗分开，共20周。在此期间 时间，他们将每周或每两周完成评估。这个试验设计，特别优化 对于预期对治疗的异质反应的条件，我们将使我们实现多个 具体目标。首先，我们将评估与PBO减少PTSD和抑郁症的MPH的功效 具有PTSD和神经认知投诉的退伍军人的症状。第二，我们将评估MPH的影响 与PBO在同一人群中的神经认知功能上相比。第三，我们表征了基线 预测该人群中对MPH的治疗反应因素，包括有MTBI史的退伍军人是否是否 显示对MPH与PBO的平均治疗反应更大。最后，该试验设计还将允许 系统评估该人群的风险，包括停用效果或效力丧失的风险 随着时间的推移。 意义：MPH代表一种具有良好耐受性的药物，具有新颖的作用机理 目前推荐的，通常是无效的PTSD和MTBI的药理学治疗 认知投诉。如果这项研究的结果支持使用MPH降低PTSD和神经认知的使用 退伍军人的症状，它将为具有PTSD的退伍军人提供重要的新治疗选择，这可能 迅速融入临床实践。