Greenberg William M, Benedict Melissa M, Doerfer Joanna, Perrin Megan, Panek Laura, Cleveland W Louis, Javitt Daniel C
New York University School of Medicine, Department of Psychiatry, 550 First Avenue, New York, NY 10016-6481, USA.
J Psychiatr Res. 2009 Mar;43(6):664-70. doi: 10.1016/j.jpsychires.2008.10.007. Epub 2008 Nov 30.
Recent preclinical findings, case reports and non-blinded studies have suggested that glutamatergic interventions may be efficacious for Obsessive-Compulsive Disorder (OCD).
We enrolled 24 adult outpatients with OCD on stabilized treatment regimens in a double-blind trial of adjunctive glycine, an NMDA glutamate receptor agonist. Participants were randomly assigned 1:1 to either placebo or glycine titrated to 60g/day, with follow-up visits scheduled at 4, 8 and 12 weeks. Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was the principal outcome measure.
Regimen non-adherence, principally related to complaints about the taste and/or nausea, resulted in only 14 individuals who were evaluable by predetermined criteria. Those receiving glycine (n=5) experienced a mean decrease of 6.04 points in Y-BOCS score, compared with a 1.00 point decrease for those receiving placebo (n=9). Using a hierarchical linear model, compared with placebo, individuals who received glycine had an average 0.82 decrease in Y-BOCS score for each week they remained in the study, not quite reaching statistical significance (p=0.053). Two of those receiving glycine were responders, versus none receiving placebo (p=0.11, ns, Fisher exact). Despite the dropouts, two participants were known to have subsequently continued taking glycine through their regular treating psychiatrist for over a year.
The glycine condition approached efficacy for treatment of OCD in this study, with the high dropout rate related to problems with palatability and small sample size the principal caveats. This may indicate a new strategy for treatment of OCD, although confirmatory studies are clearly needed. (ClinicalTrials.gov NCT00405535.).
近期的临床前研究结果、病例报告和非盲法研究表明,谷氨酸能干预可能对强迫症(OCD)有效。
我们招募了24名接受稳定治疗方案的成年强迫症门诊患者,进行辅助性甘氨酸(一种NMDA谷氨酸受体激动剂)的双盲试验。参与者按1:1随机分配至安慰剂组或滴定至60克/天的甘氨酸组,计划在第4、8和12周进行随访。耶鲁-布朗强迫症量表(Y-BOCS)是主要结局指标。
治疗方案不依从主要与味觉和/或恶心的主诉有关,导致只有14名个体可根据预定标准进行评估。接受甘氨酸治疗的患者(n = 5)Y-BOCS评分平均下降6.04分,而接受安慰剂治疗的患者(n = 9)下降1.00分。使用分层线性模型,与安慰剂相比,接受甘氨酸治疗的个体在留在研究中的每周Y-BOCS评分平均下降0.82分,未达到统计学显著性(p = 0.053)。接受甘氨酸治疗的患者中有2例有反应,而接受安慰剂治疗的患者中无反应(p = 0.11,无统计学意义,Fisher精确检验)。尽管有退出者,但已知有两名参与者随后通过其常规治疗精神科医生继续服用甘氨酸超过一年。
在本研究中,甘氨酸治疗组接近治疗强迫症的疗效,高退出率与适口性问题和小样本量是主要注意事项。这可能表明一种治疗强迫症的新策略,尽管显然需要进行验证性研究。(ClinicalTrials.gov NCT00405535.)