Pittenger Christopher, Bloch Michael H, Wasylink Suzanne, Billingslea Eileen, Simpson Ryan, Jakubovski Ewgeni, Kelmendi Ben, Sanacora Gerard, Coric Vladimir
34 Park St, W315, New Haven, CT 06519
J Clin Psychiatry. 2015 Aug;76(8):1075-84. doi: 10.4088/JCP.14m09123.
Obsessive-compulsive disorder (OCD) affects approximately 2.5% of the population and is associated with significant morbidity. Many patients receive little benefit from the best available treatments, and even those who do respond often suffer from significant residual symptoms. Convergent evidence suggests that abnormalities in glutamate homeostasis and neurotransmission may contribute to OCD and that glutamate-modulating medications may be of benefit in patients whose symptoms are refractory to standard interventions. Small open-label trials of augmentation of serotonin reuptake inhibitor (SRI) pharmacotherapy with the glutamate modulator riluzole have suggested benefit in adults with refractory symptoms. We report a pilot randomized placebo-controlled trial of riluzole augmentation of ongoing SRI treatment in SRI-refractory patients.
Outpatients (n = 27) and inpatients (n = 11) with DSM-IV OCD on stable SRI pharmacotherapy were randomized between November 2006 and December 2012 to receive riluzole 50 mg or placebo twice a day and followed for 12 weeks after a 2-week placebo lead-in phase.
Riluzole was well tolerated; 1 patient experienced moderate nausea, but none discontinued treatment due to side effects. While there was nominally greater Y-BOCS improvement in the riluzole group (our primary outcome) compared to placebo, it did not reach statistical significance. In the outpatient subsample, a trend suggesting benefit from riluzole augmentation for obsessions (P = .056, 2-tailed, uncorrected) was found in a secondary analysis. Among outpatients, more achieved at least a partial response (> 25% improvement) with riluzole than with placebo (P = .02 in a secondary analysis).
Riluzole may be of benefit to a subset of patients. Larger samples would be required to detect effects of the order suggested by the nominal improvement in our outpatient subsample.
ClinicalTrials.gov identifier: NCT00523718.
强迫症（OCD）影响约2.5%的人口，且与显著的发病率相关。许多患者从现有的最佳治疗中获益甚微，即使是那些有反应的患者也常常有明显的残留症状。越来越多的证据表明，谷氨酸稳态和神经传递异常可能导致强迫症，且谷氨酸调节药物可能对症状对标准干预无效的患者有益。用谷氨酸调节剂利鲁唑增强5-羟色胺再摄取抑制剂（SRI）药物治疗的小型开放标签试验表明，对有难治性症状的成年人有益。我们报告了一项针对SRI难治性患者进行的利鲁唑增强正在进行的SRI治疗的随机安慰剂对照试验。
2006年11月至2012年12月期间，将稳定接受SRI药物治疗的DSM-IV强迫症门诊患者（n = 27）和住院患者（n = 11）随机分组，分别接受每日两次50mg利鲁唑或安慰剂治疗，并在2周安慰剂导入期后随访12周。
利鲁唑耐受性良好；1例患者出现中度恶心，但无患者因副作用停药。虽然与安慰剂相比，利鲁唑组（我们的主要结局指标）的耶鲁布朗强迫症量表（Y-BOCS）改善名义上更大，但未达到统计学显著性。在门诊亚组的二次分析中，发现有一个趋势表明利鲁唑增强治疗对强迫观念有益（P = 0.056，双侧检验，未校正）。在门诊患者中，使用利鲁唑至少获得部分缓解（改善>25%）的患者比使用安慰剂的患者更多（二次分析中P = 0.02）。
利鲁唑可能对一部分患者有益。需要更大的样本量来检测我们门诊亚组中名义改善所提示的效应大小。
ClinicalTrials.gov标识符：NCT00523718。
