Yale School of Medicine Department of Psychiatry, New Haven, CT, USA.
Goucher College Post-Baccalaureate Premedical Program, Baltimore, MA, USA.
Neuropsychopharmacology. 2023 Jun;48(7):991-999. doi: 10.1038/s41386-023-01540-4. Epub 2023 Feb 17.
This study is the first randomized controlled trial to test the effects of ketamine in Borderline Personality Disorder (BPD). BPD remains undertreated in the community and no medication has FDA approval for this indication. People with BPD experience chronic mood disturbances with depressed mood, suicidal ideation, and severe social difficulties. In this double-blind, randomized controlled pilot study, we tested the effects of one infusion of ketamine (0.5 mg/kg, n = 10) or the psychoactive comparator drug midazolam (0.04 mg/kg, n = 12) in adults with BPD. Infusions were well tolerated in both groups. Dissociative symptoms during infusion were more intense with ketamine than midazolam (t(12.3) = 3.61, p = 0.01), but they resolved by 40 min after infusion in both groups. Post-infusion adverse events were at the expected low levels in both groups. For our primary outcome measure of suicidal ideation and our secondary outcome measure of depression, we found numerical reduction but not significant group or group x timepoint difference (p > 0.05). For our secondary outcome measures of anxiety and BPD symptoms, we did not observe group or group x timepoint differences. There was a group x timepoint effect for socio-occupational functioning (F(1,20.12) = 5.16, p = 0.03, at Day 14, ketamine group showed more improvement than midazolam group). An exploratory analysis revealed that improvement in socio-occupational functioning was correlated with improvement in depression in the ketamine group (r(8) = 0.65, p = 0.04) but not midazolam group (r(9) = 0.41, p = 0.216). This pilot study provides the first randomized controlled evidence of the effects of antidepressant-dosed ketamine in people with BPD. Our results provide reason for optimism that antidepressant-dosed ketamine will be well-tolerated in larger studies and may provide clinical benefit for mood symptoms and related impairments in people with BPD.
这项研究是首个测试氯胺酮在边缘型人格障碍（BPD）中的作用的随机对照试验。BPD 在社区中仍未得到充分治疗，没有药物获得 FDA 对此适应症的批准。BPD 患者会出现慢性情绪障碍，表现为情绪低落、自杀意念和严重的社交困难。在这项双盲、随机对照的初步研究中，我们测试了单次氯胺酮（0.5mg/kg，n=10）或精神活性对照药物咪达唑仑（0.04mg/kg，n=12）输注在 BPD 成人中的作用。两组患者对输注均耐受良好。输注过程中，氯胺酮引起的分离症状比咪达唑仑更强烈（t(12.3)=3.61，p=0.01），但两组患者在输注后 40 分钟内症状均缓解。两组患者的输注后不良事件发生率均处于预期的低水平。对于我们自杀意念的主要结果测量和抑郁的次要结果测量，我们发现数值有所减少，但组间或组间 x 时间点差异无统计学意义（p>0.05）。对于我们的焦虑和 BPD 症状的次要结果测量，我们没有观察到组间或组间 x 时间点差异。社会职业功能的组间 x 时间点效应（F(1,20.12)=5.16，p=0.03，在第 14 天，氯胺酮组比咪达唑仑组改善更明显）。一项探索性分析显示，社会职业功能的改善与氯胺酮组的抑郁改善相关（r(8)=0.65，p=0.04），但与咪达唑仑组无关（r(9)=0.41，p=0.216）。这项初步研究提供了氯胺酮在 BPD 患者中具有抗抑郁作用的首个随机对照证据。我们的结果提供了令人乐观的理由，即更大规模的研究中，抗抑郁剂量的氯胺酮将具有良好的耐受性，并可能为 BPD 患者的情绪症状和相关障碍提供临床益处。
