Massachusetts General Hospital, Schizophrenia Clinical and Research Program, Boston, MA, USA.
Expert Opin Investig Drugs. 2013 Feb;22(2):259-65. doi: 10.1517/13543784.2013.750650. Epub 2012 Dec 9.
Even though cognitive impairment is manifested in almost all patients with schizophrenia, the Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE) study showed no significant difference between first- and second-generation psychotropic drugs in improving cognitive abilities. Discovering new drugs that can improve impaired cognition, thus, is an attractive treatment target for patients with schizophrenia.
This article briefly reviews about donepezil, a highly selective (IC(50) = 6.7 nM) centrally acting reversible acetylcholinesterase inhibitor that has been approved by FDA for treating cognitive deficit states such as in Alzheimer's disease and its uses in clinical trials for the treatment of schizophrenia. The literature search included PubMed and Cochrane library with the following words: donepezil, schizophrenia and cognitive impairments.
The results of several clinical trials utilizing donepezil as an adjunct to second-generation antipsychotic drugs targeting cognitive deficits in schizophrenia subjects have been disappointing and would not lead clinicians to consider this as a potential treatment option. While longer randomized controlled trials, increase dosage and selected groups of patients at different stage of cognitive impairment may provide a better understanding of the potential for this drug in addressing cognitive deficits, results to date have not been encouraging.
尽管认知障碍几乎在所有精神分裂症患者中都有表现，但临床抗精神病药物干预有效性试验（CATIE）表明，第一代和第二代精神药物在改善认知能力方面并无显著差异。因此，发现能够改善认知障碍的新药是精神分裂症患者极具吸引力的治疗靶点。
本文简要回顾了多奈哌齐，一种高度选择性（IC50 = 6.7 nM）的中枢作用可逆乙酰胆碱酯酶抑制剂，已被 FDA 批准用于治疗阿尔茨海默病等认知功能障碍状态，并在治疗精神分裂症的临床试验中得到应用。文献检索包括 PubMed 和 Cochrane 图书馆，使用的关键词为：多奈哌齐、精神分裂症和认知障碍。
将多奈哌齐作为辅助治疗精神分裂症患者认知缺陷的第二代抗精神病药物的几项临床试验结果令人失望，不会促使临床医生将其视为一种潜在的治疗选择。虽然更长时间的随机对照试验、增加剂量以及在认知障碍不同阶段选择特定患者群体可能会更好地了解该药物在解决认知缺陷方面的潜力，但迄今为止的结果并不令人鼓舞。
