Aboujaoude Elias, Barry John J, Gamel Nona
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
J Clin Psychopharmacol. 2009 Feb;29(1):51-5. doi: 10.1097/JCP.0b013e318192e9a4.
Data from the fields of genetics, neuroimaging, and animal studies, along with case reports and small clinical trials, point to a role for glutamatergic dysfunction in the pathophysiology of obsessive-compulsive disorder (OCD). We report on the first open-label study to test the hypothesis that memantine, a noncompetitive glutamate antagonist, will result in a clinically meaningful reduction in OCD symptoms in adults with treatment-resistant OCD.
We recruited 15 adult subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined OCD and a baseline Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) of 18 or higher, who had failed to respond to treatment with a serotonin reuptake inhibitor (SRI), given at an adequate and stable dose for at least 12 weeks. The duration of memantine treatment was 12 weeks, and the dose was gradually increased to a target of 20 mg/d. Response was defined as a 25% or greater reduction in the Y-BOCS score at study end and a Clinical Global Impression-Improvement scale rating of "much" or "very much" improved.
Data from 14 subjects were analyzable. Mean baseline Y-BOCS score was 27.4 (SD, 5.0). Subjects had failed an average of 2.8 (SD, 1.8) SRI trials; 6 subjects had failed augmentation with atypical antipsychotics. At study end, 6 subjects (42.9%) were responders, and response was achieved by EOW4. Responders had significantly lower baseline Y-BOCS scores (2-tailed t tests, P < 0.05, t = 2.2) and had failed fewer SRIs (P <or= 0.05, t = 2.2). Side effects to memantine were mild and transient, and no subject withdrew from the study for an adverse event.
In this open-label augmentation trial of memantine in treatment-resistant OCD, almost half the subjects had a meaningful improvement in symptoms. Our study was limited by its small size, presence of comorbidities, and lack of control. Large double-blind placebo-controlled trials are needed to further test our findings.
来自遗传学、神经影像学和动物研究领域的数据，以及病例报告和小型临床试验表明，谷氨酸能功能障碍在强迫症（OCD）的病理生理学中起作用。我们报告了第一项开放标签研究，以检验美金刚（一种非竞争性谷氨酸拮抗剂）能使难治性OCD成年患者的OCD症状在临床上得到有意义减轻这一假设。
我们招募了15名成年受试者，他们符合《精神障碍诊断与统计手册》第四版定义的OCD，且耶鲁-布朗强迫症量表（Y-BOCS）基线得分在18分及以上，这些受试者对血清素再摄取抑制剂（SRI）以足够且稳定的剂量治疗至少12周均无反应。美金刚治疗持续时间为12周，剂量逐渐增加至目标剂量20mg/d。反应定义为研究结束时Y-BOCS得分降低25%或更多，且临床总体印象改善量表评分为“明显”或“非常明显”改善。
14名受试者的数据可分析。Y-BOCS基线平均得分为27.4（标准差，5.0）。受试者平均进行了2.8（标准差，1.8）次SRI试验；6名受试者使用非典型抗精神病药物增效治疗失败。研究结束时，6名受试者（42.9%）有反应，且在第4周周末达到反应。有反应者的基线Y-BOCS得分显著更低（双侧t检验，P<0.05，t=2.2），且使用SRI治疗失败的次数更少（P≤0.05，t=2.2）。美金刚的副作用轻微且短暂，没有受试者因不良事件退出研究。
在这项美金刚治疗难治性OCD的开放标签增效试验中，近一半受试者的症状有显著改善。我们的研究因样本量小、存在共病以及缺乏对照而受到限制。需要进行大型双盲安慰剂对照试验来进一步检验我们的发现。
