Treating Suicidal Behavior and Self-Mutilation in BPD

描述(申请人提供)：本申请是对PA-07-079“减少和预防自杀的研究”的回应，是R01MH 61017“治疗BPD中的自杀行为和自残”的竞争性延续。自杀行为、非自杀自残行为和抑郁是临界性人格障碍(BPD)的主要问题。高达10%的患有这种疾病的人死于自杀，然而，针对自杀行为和自我伤害的有效治疗方法的发展以及对治疗作用机制的了解几乎没有受到关注。该项目是氟西汀和辩证行为疗法(DBT)治疗自杀行为和非自杀自我伤害(NSSI)的随机临床试验的继续。与接受治疗的前一年相比，我们的自杀未遂率降低了近80%。与支持性治疗和安慰剂相比，DBT和氟西汀在6个月后总体改善方面具有特定的疗效。虽然在12个月时，总体改善的差异不再存在，但由于正在治疗的问题的严重性，反应的速度很重要。此外，在使用DBT和氟西汀的药物使用障碍患者中，NSSI显著降低。此外，在DBT条件下的自杀企图是支持性治疗条件下的一半。大剂量的氟西汀与自杀企图有关，因此，虽然有助于总体改善和NSSI，但应将氟西汀维持在较低剂量，以避免自杀行为。根据我们小组其他人最近的研究，我们现在知道，在相对较低的剂量下可以实现几乎完全的5-羟色胺受体阻断，因此，较高的剂量可能会影响其他系统，并对副作用负责，而不会带来额外的治疗益处。在我们的后续研究中，我们计划通过将DBT与临床上经常使用的策略进行比较，将DBT与临床实践中经常使用的策略进行比较，即使用较低剂量(不超过40 mg)的氟西汀进行临床治疗，并选择改用另一种SSRI。该项目还在基线和治疗结束时使用翻译神经科学测量、神经心理测试、生物行为测量和功能磁共振成像来评估情绪调节和冲动，这是BPD的两个关键组成部分，作为治疗变化的调节和预测因素。此外，我们的初步数据显示，6个月的治疗在治疗这些行为方面可能同样有效，我们计划测试这一模型。拟议的研究结果将有助于为自杀和自伤的BPD患者提供一种可获得的和合理的治疗策略。该项目的创新之处在于：它是第一次将DBT与标准药物策略进行比较的试验；它使用了有充分理由的6个月模型，而不是12个月；它结合了基线和治疗结束时的生物行为和成像测量，以评估变化的预测因素和调节因素；它解决了与自杀相关的结果和抗抑郁药紧急自杀的风险。在边缘型人格障碍中，自杀、自杀企图和抑郁的发生率很高。拟议研究的结果将有助于为自杀和自伤的个人提供可获得的和合理的治疗策略，并将提供关于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.