Bergman Joseph, Brettholz Izidor, Shneidman Michael, Lerner Vladimir
Mental Health Center Tirat Carmel, Haifa, Israel.
Clin Neuropharmacol. 2003 Mar-Apr;26(2):88-92. doi: 10.1097/00002826-200303000-00008.
Traditionally, the neuropsychiatric symptoms of Alzheimer's disease (AD) have been managed with neuroleptics or benzodiazepines, which have serious side effects. Preliminary observations suggest the possible value of cholinesterase inhibitors in the amelioration of psychotic symptoms in patients with dementia of the Alzheimer's type, dementia with Lewy bodies, and in patients with Parkinson's disease. Twelve inpatients with AD with psychotic symptoms and lack of improvement of their delusions/hallucinations during perphenazine treatment (8 mg/day) for 3 weeks received random open-label donepezil 5 mg daily in addition to an ongoing treatment of 8 mg/day perphenazine or 16 mg/day perphenazine. Assessments conducted at baseline and after weeks 2 and 4 included the Mini-Mental State Examination, the Global Deterioration Scale, the Positive and Negative Symptoms Scale, and the Clinical Global Impressions scale. Frequency of extrapyramidal symptoms was measured according to the Abnormal Involuntary Movement Scale. The donepezil-perphenazine group exhibited substantially greater and clinical improvements in mental state. At the end of the trial (4 weeks), Positive and Negative Symptoms Scale scores revealed significant differences between both groups (p = 0.006). The Clinical Global Impressions scale and the Mini-Mental State Examination scores also showed significant differences between the donepezil-perphenazine group and the perphenazine group (p = 0.028 and p = 0.027 respectively). No significant differences were found in the Global Deterioration Scale scores. Abnormal Involuntary Movement Scale scores showed a significant deterioration in extrapyramidal symptoms in the perphenazine group compared with the donepezil-perphenazine group (p = 0.016). Donepezil augmentation of neuroleptics may be appropriate for those patients for whom neuroleptic monotherapy either does not lead to symptom remission or is associated with intolerable adverse effects. This was an open-label study and there is need for larger studies with double-blind control and a long-term study design to define the efficacy of donepezil for patients with AD and psychotic symptoms.
传统上，阿尔茨海默病（AD）的神经精神症状一直使用抗精神病药物或苯二氮䓬类药物进行治疗，而这些药物具有严重的副作用。初步观察表明，胆碱酯酶抑制剂对于改善阿尔茨海默型痴呆、路易体痴呆患者以及帕金森病患者的精神病性症状可能具有一定价值。12名患有AD且伴有精神病性症状的住院患者，在接受奋乃静治疗（8毫克/天）3周后妄想/幻觉症状未改善，这些患者除了继续接受8毫克/天或16毫克/天的奋乃静治疗外，还随机接受开放标签的多奈哌齐治疗，剂量为每日5毫克。在基线以及第2周和第4周后进行的评估包括简易精神状态检查表、总体衰退量表、阳性与阴性症状量表以及临床总体印象量表。根据异常不自主运动量表来测量锥体外系症状的发生频率。多奈哌齐-奋乃静组在精神状态方面表现出显著更大且具有临床意义的改善。在试验结束时（4周），阳性与阴性症状量表评分显示两组之间存在显著差异（p = 0.006）。临床总体印象量表和简易精神状态检查表评分在多奈哌齐-奋乃静组与奋乃静组之间也显示出显著差异（分别为p = 0.028和p = 0.027）。总体衰退量表评分未发现显著差异。与多奈哌齐-奋乃静组相比，奋乃静组的异常不自主运动量表评分显示锥体外系症状有显著恶化（p = 0.016）。对于那些使用抗精神病药物单一疗法既不能使症状缓解又伴有无法耐受的不良反应的患者，多奈哌齐增强抗精神病药物治疗可能是合适的。这是一项开放标签研究，需要进行更大规模的双盲对照研究以及长期研究设计，以确定多奈哌齐对患有AD和精神病性症状患者的疗效。
