Treating Suicidal Behavior and Self-Mutilation in BPD

描述（由申请人提供）：本申请是对PA-07-079“减少和预防自杀行为的研究”的回应，是R 01 MH 61017“治疗BPD中的自杀行为和自残”的竞争性延续。自杀行为、非自杀性自伤行为和抑郁是边缘型人格障碍（BPD）的关键问题。高达10%的个体受这种疾病的影响死于自杀，然而，自杀行为和自伤的有效治疗方法的发展以及对治疗作用机制的理解很少受到关注。本项目是氟西汀和辩证行为疗法（DBT）治疗自杀行为和非自杀性自伤（NSSI）的随机临床试验的延续。与进入研究前一年相比，我们实现了近80%的自杀企图率降低。DBT和氟西汀在6个月时相对于支持性治疗和安慰剂在实现总体改善方面具有特定疗效。虽然在12个月时，总体改善的差异不再存在，但由于所治疗问题的严重性，反应速度很重要。此外，在使用DBT和氟西汀的物质使用障碍患者中，NSSI显著降低。此外，DBT条件下的自杀企图是支持性治疗条件下的一半。高剂量氟西汀与自杀企图相关，因此，虽然有助于总体改善和NSSI，但应维持低剂量氟西汀以避免自杀行为。我们现在知道，根据我们小组其他人最近的研究，几乎完全的5-羟色胺受体阻断是在相对较低的剂量下实现的，因此，较高的剂量可能会影响其他系统，并导致副作用，而没有额外的治疗益处。在我们的后续研究中，我们计划通过将DBT与临床实践中常用的策略进行比较，以更低剂量（不超过40 mg）的氟西汀进行临床管理，并选择转换为另一种SSRI，从而建立我们目前的研究结果。该项目还在基线和治疗结束时使用转化神经科学测量，神经心理学测试，生物行为测量和功能磁共振成像，以评估情绪调节和冲动，BPD的两个关键组成部分，作为治疗变化的调节因子和预测因子。此外，我们的初步数据表明，6个月的治疗可能对治疗这些行为同样有效，我们计划测试这个模型。本研究的结果将有助于为自杀和自伤的BPD患者提供一种可行和合理的治疗策略。该项目的创新之处在于：它是第一个将DBT与标准药物治疗策略进行比较的试验;它使用了合理的6个月模型而不是12个月;它在基线和治疗结束时结合了生物行为和成像测量，以评估变化的预测因子和调节因子;它解决了自杀相关结局和抗抑郁药紧急自杀的风险。自杀、自杀未遂和抑郁在边缘型人格障碍中的发生率很高。拟议研究的结果将有助于为自杀和自伤个体提供一种可获得的合理治疗策略，并将提供有关这些治疗的不同疗效和作用机制的信息。

DESCRIPTION (provided by applicant): This application is in response to PA-07-079, "Research on the Reduction and Prevention of Suicidality" and is a competing continuation of R01MH 61017, "Treating Suicidal Behavior and Self-Mutilation in BPD." Suicidal behavior non-suicidal self-injurious behavior and depression are key problems in borderline personality disorder (BPD). Up to 10% of individuals affected with this disorder die by suicide, however, development of effective treatments for suicidal behavior and self-injury and understanding of mechanisms of action of treatment has received little attention. This project is a continuation of a randomized clinical trial of fluoxetine and Dialectical Behavior Therapy (DBT) for the treatment of suicidal behavior and non-suicidal self injury (NSSI). We achieved a nearly 80% reduction in suicide attempt rate comparing the treatment year to the year prior to study entry. DBT and fluoxetine have specific efficacy in achieving overall improvement at six months relative to supportive therapy and placebo. While at 12 months the differences in overall improvement are no longer present, the speed of response is important due to the seriousness of the problems being treated. Also, NSSI was significantly reduced in those with substance use disorders with DBT and fluoxetine. Furthermore, suicide attempts in the DBT condition were half the number of the supportive therapy condition. Fluoxetine at a high dose was associated with suicide attempts, thus, while helpful in overall improvement and NSSI, fluoxetine should be maintained at lower doses in order to avoid suicidal behavior. We now know, based on recent research from others in our group that almost complete serotonin receptor blockade is achieved at relatively low doses and, therefore, higher doses are likely to affect other systems and be responsible for side effects without additional therapeutic benefit. In our continuation, we plan to build on our current findings by comparing DBT to a strategy frequently used in clinical practice, clinical management with fluoxetine at lower dosage (no more than 40mg) with the option of switching to another SSRI. The project also uses translational neuroscience measures, neuropsychological testing, biobehavioral measures and fMRI at baseline and at the end of treatment, to evaluate emotion regulation and impulsivity, two key components of BPD, as moderators and predictors of treatment change. Furthermore, our preliminary data demonstrates that a 6-month treatment may be as effective in treating these behaviors and we plan to test this model. The findings of the proposed study will help to provide an accessible and rational treatment strategy for suicidal and self injuring individuals with BPD. This project is innovative in that: it is the first trial to compare DBT to a standard medication strategy; it uses a well-justified six month model instead of 12 months; it incorporates both biobehavioral and imaging measures at baseline and end of treatment to evaluate predictors and moderators of change; it addresses suicide-related outcomes and the risk of risk of antidepressant emergent suicidality. Suicide, suicide attempts and depression occur at a high rate in borderline personality disorder. The findings of the proposed study will help to provide an accessible and rational treatment strategy for suicidal and self injuring individuals and will also provide information on differential efficacy and mechanisms of action for these treatments.