Yale Child Study Center, Yale University School of Medicine, New Haven, Connecticut, USA.
Biol Psychiatry. 2012 Dec 1;72(11):964-70. doi: 10.1016/j.biopsych.2012.05.028. Epub 2012 Jul 10.
Treatments for obsessive-compulsive disorder (OCD) usually lead to incomplete symptom relief and take a long-time to reach full effect. Convergent evidence suggests that glutamate abnormalities contribute to the pathogenesis of OCD. Ketamine is a potent noncompetitive antagonist of the N-methyl-D-aspartate glutamate receptor. Trials have reported rapid antidepressant effects after low-dose ketamine infusion.
We conducted an open-label trial of ketamine (.5 mg/kg IV over 40 min) in 10 subjects with treatment-refractory OCD. Response was defined as >35% improvement in OCD symptoms and >50% improvement in depression symptoms from baseline at any time between 1 and 3 days after infusion.
None of 10 subjects experienced a response in OCD symptoms in the first 3 days after ketamine. Four of seven patients with comorbid depression experienced an antidepressant response to ketamine in the first 3 days after infusion. Both OCD and depression symptoms demonstrated a statistically significant improvement in the first 3 days after infusion compared with baseline, but the OCD response was <12%. The percentage reduction in depressive symptoms in the first 3 days after ketamine infusion was significantly greater than the reduction in OCD symptoms.
Ketamine effects on OCD symptoms, in contrast to depressive symptoms, did not seem to persist or progress after the acute effects of ketamine had dissipated.
强迫症(OCD)的治疗方法通常无法完全缓解症状,而且需要很长时间才能达到完全的效果。越来越多的证据表明谷氨酸异常与 OCD 的发病机制有关。氯胺酮是一种有效的 N-甲基-D-天冬氨酸谷氨酸受体非竞争性拮抗剂。试验报告称,低剂量氯胺酮输注后会迅速产生抗抑郁作用。
我们对 10 名治疗抵抗性 OCD 患者进行了氯胺酮(静脉注射 0.5mg/kg,持续 40 分钟)的开放性试验。反应定义为在输注后 1 至 3 天内,OCD 症状改善>35%,抑郁症状改善>50%,与基线相比。
在氯胺酮输注后的头 3 天内,没有 10 名受试者的 OCD 症状出现反应。在输注后前 3 天内,7 名合并抑郁的患者中有 4 名对氯胺酮有抗抑郁反应。与基线相比,OCD 和抑郁症状在输注后第 1 至 3 天均有明显改善,但 OCD 反应<12%。氯胺酮输注后前 3 天内抑郁症状的减轻百分比明显大于 OCD 症状的减轻百分比。
与抑郁症状相比,氯胺酮对 OCD 症状的作用似乎在氯胺酮的急性作用消退后并没有持续或进展。