Department of Psychiatry and Behavioral Sciences, Eastern Virginia Medical School, United States; Department of Psychiatry, Georgetown University School of Medicine, United States.
Schizophr Res. 2013 Aug;148(1-3):138-44. doi: 10.1016/j.schres.2013.05.023. Epub 2013 Jun 13.
Alpha7 nicotinic acetylcholine receptor (α7 nAChR) agonists may be valuable treatments for negative symptoms and cognitive impairment in schizophrenia. Unfortunately, chronic exposure to an agonist may reduce the receptor's sensitivity. Therefore, we combined CDP-choline, a dietary source of the direct agonist choline, with galantamine, a positive allosteric modulator (PAM) of nicotinic acetylcholine receptors, to improve the efficiency of transducing the choline signal and, possibly, preserve the receptor in a sensitive state. We conducted a single-site, double-blind randomized clinical trial comparing galantamine/CDP-choline to placebos in schizophrenia patients with negative symptoms who were receiving second generation antipsychotics. Forty-three subjects received galantamine and CDP-choline or matching placebos for 16weeks. The primary outcome measure was the 5-item Marder negative-symptoms factor of the Positive and Negative Syndrome Scale (PANSS). Cognition and functioning were also assessed. Trial completion was high; 79%. There was no significant treatment effect on negative symptoms, other PANSS symptom factors, or the MATRICS Cognitive Consensus Battery. There were significant treatment effects in overall functioning and a test of free verbal recall. Three subjects discontinued treatment in the active treatment group for gastro-intestinal adverse events (AE). The most common AE for galantamine/CDP-choline was abdominal pain; for placebo it was headache and sweating. Although there was no significant treatment effect on negative symptoms, the direction of effect mirrored the effects on a cognitive measure and overall functioning. Further study of α7 nAChR agonist/PAMs is warranted in larger studies that will have greater power.
α7 烟碱型乙酰胆碱受体 (α7 nAChR) 激动剂可能是治疗精神分裂症阴性症状和认知障碍的有效方法。不幸的是，长期暴露于激动剂可能会降低受体的敏感性。因此，我们将 CDP-胆碱（一种直接激动剂胆碱的膳食来源）与加兰他敏（烟碱型乙酰胆碱受体的正变构调节剂 (PAM)）结合使用，以提高胆碱信号转导的效率，并可能使受体保持敏感状态。我们进行了一项单中心、双盲随机临床试验，比较了加兰他敏/CDP-胆碱与安慰剂在接受第二代抗精神病药物治疗的伴有阴性症状的精神分裂症患者中的疗效。43 名受试者接受了加兰他敏和 CDP-胆碱或匹配的安慰剂治疗 16 周。主要结局指标是阳性和阴性综合征量表 (PANSS) 的 5 项 Marder 阴性症状因子。还评估了认知和功能。试验完成率很高；79%。阴性症状、其他 PANSS 症状因子或 MATRICS 认知共识电池均无显著治疗效果。在整体功能和自由言语回忆测试中存在显著的治疗效果。在活性治疗组中有 3 名受试者因胃肠不良事件 (AE) 停止治疗。加兰他敏/CDP-胆碱最常见的 AE 是腹痛；安慰剂组最常见的 AE 是头痛和出汗。尽管阴性症状无显著治疗效果，但效应方向与认知测量和整体功能的效应一致。在更大的研究中进一步研究 α7 nAChR 激动剂/PAMs 是必要的，因为这些研究将具有更大的效力。
