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）是一种慢性精神疾病， 退伍军人的痛苦和残疾。目前的治疗方案对所有退伍军人都不完全有效， 即使他们有效地降低了总的症状负担，许多退伍军人继续经历 显著症状负担和相关功能损害。总症状负担和相关 对于那些患有轻度创伤性脑损伤（mTBI）的患者，功能损害通常特别高。 哌醋甲酯（MPH）是一种广泛使用的精神兴奋剂药物，具有长期的安全记录， 已被用于改善注意力缺陷多动障碍（ADHD）的认知功能， 在中度或重度TBI的研究中显示出对情绪和认知功能的益处， 难治性重度抑郁症在一项关于MPH对主观认知功能的疗效的小型试点研究中， 与PTSD和/或mTBI相关的损伤，我们的研究小组成员发现，MPH不会导致 不仅在认知功能的主观和客观测量方面有显着改善，而且 抑郁症和创伤后应激障碍的症状显著减少。 方法：在这里，我们建议用一个聚合的N-of-1随机 MPH与安慰剂（PBO）治疗退伍军人PTSD和认知症状的安慰剂对照试验， 有无合并脑外伤两个研究中心的N=70名退伍军人将分别接受连续4周的 MPH和PBO，按随机顺序，间隔1周洗脱期，共20周。在此 他们将完成每周或每两周的评估。这个试验设计， 对于预期对治疗的异质反应的条件，将使我们实现许多 具体目标。首先，我们将评估MPH与PBO相比在减少PTSD和抑郁症方面的疗效 有创伤后应激障碍和神经认知障碍的退伍军人的症状。其次，我们将评估MPH的影响 与PBO相比，在同一人群中的神经认知功能。第三，我们将基线 在该人群中对MPH治疗反应的预测因素，包括是否有mTBI病史的退伍军人 显示对MPH的平均治疗反应大于PBO。最后，该试验设计还将允许 系统评估该人群的风险，包括停药效应或疗效丧失的风险 随着时间 重要性：MPH代表了一种耐受性良好的药物，与传统药物相比具有新的作用机制。 目前推荐的PTSD和mTBI的药物治疗通常无效， 认知上的抱怨如果这项研究的结果支持使用MPH来减少PTSD和神经认知功能， 它将为患有创伤后应激障碍的退伍军人提供一种重要的新治疗选择， 迅速融入临床实践。