Krivoy Amir, Weizman Abraham, Laor Lucian, Hellinger Nurit, Zemishlany Zvi, Fischel Tsvi
Geha Mental Health Center, Petach-Tikva, Israel.
Eur Neuropsychopharmacol. 2008 Feb;18(2):117-21. doi: 10.1016/j.euroneuro.2007.07.008. Epub 2007 Aug 28.
Schizophrenia is comprised of several debilitating symptoms. Antipsychotics offer an effective treatment for positive symptoms, while the negative signs and cognitive deficits are usually treatment-resistant. It was suggested that glutamate dysregulation may be involved in the neuropathology of schizophrenia, mainly through NMDA dysfunction. We hypothesized that addition of memantine, a weak non-selective NMDA receptor antagonist approved for dementia, to antipsychotics would improve the clinical status of un-remitted schizophrenia patients, notably the negative signs and cognitive deficits.
Seven schizophrenia patients, were included in a six-week open-label study, with weekly increasing dosage (5, 10, 15, 20 mg) of memantine added to their on-going antipsychotic treatment.
We found a significant improvement of the PANSS score (baseline 116.28+/-21.9 vs. 97.86+/-24.48 after six weeks, t=5.98, p<0.001) with the most prominent improvement (21%) in negative signs sub-scale (baseline 40+/-6.38 vs. 31.71+/-7.76 after six weeks, t=5.87, p<0.001). Cognitive status, measured with the Neurobehavioral Cognitive Examination (NCSE) and Clock Drawing Test (CDT) showed no improvement.
Memantine addition to antipsychotic treatment, in schizophrenia patients might improve their clinical status, primarily the negative signs, but not their cognitive deficits. Further research is needed to replicate these observations.
精神分裂症由多种使人衰弱的症状组成。抗精神病药物对阳性症状提供了有效的治疗,而阴性症状和认知缺陷通常对治疗有抵抗性。有人提出谷氨酸调节异常可能参与精神分裂症的神经病理学,主要是通过N-甲基-D-天冬氨酸(NMDA)功能障碍。我们假设,在抗精神病药物中添加美金刚(一种被批准用于治疗痴呆的弱非选择性NMDA受体拮抗剂)将改善未缓解的精神分裂症患者的临床状况,特别是阴性症状和认知缺陷。
七名精神分裂症患者纳入一项为期六周的开放标签研究,在他们正在进行的抗精神病治疗基础上每周增加美金刚剂量(5、10、15、20毫克)。
我们发现阳性和阴性症状量表(PANSS)评分有显著改善(基线116.28±21.9 vs六周后97.86±24.48,t = 5.98,p < 0.001),其中阴性症状子量表改善最为显著(21%)(基线40±6.38 vs六周后31.71±7.76,t = 5.87,p < 0.001)。用神经行为认知检查(NCSE)和画钟试验(CDT)测量认知状态未显示改善。
在精神分裂症患者的抗精神病治疗中添加美金刚可能改善其临床状况,主要是阴性症状,但不能改善其认知缺陷。需要进一步研究来重复这些观察结果。