Fioravanti M, Yanagi M
Department of Psychiatric Science and Psychological Medicine, University of Rome "La Sapienza", P.le A. Moro, 5, Rome, Italy, 00185.
Cochrane Database Syst Rev. 2000(2):CD000269. doi: 10.1002/14651858.CD000269.
The prevalent use of this compound in the treatment of disorders of a cerebrovascular nature does not mean that a homogeneous and consistent application of this therapy has been applied. Dosage, method of administration, and selection criteria of patients have varied. The modalities of the studies, including length of observation, severity of disturbance, and methodology of the evaluation of the results were also heterogeneous. In spite of uncertainties about its efficacy, CDP-choline is a frequently prescribed drug for cognitive impairment in several European countries, especially when the clinical picture is predominantly one of cerebrovascular disease, hence the need for this review.
The objective is to assess the efficacy of CDP-choline (cytidinediphosphocholine) in the treatment of cognitive, emotional, and behavioural deficits associated with chronic cerebral disorders of the elderly.
The CDCIG register of trials was searched for all relevant, non-animal randomised controlled trials using the terms CDP-choline/CDP, Citicoline, Cytidine Diphosphate Choline and Diphosphocholine. The Psychlit (1974-1996), Psychiatry (1980-1996) and MEDLINE electronic databases have been searched independently by the reviewers. The reviewers have also contacted manufacturers of CDP-choline.
All relevant, non-animal, unconfounded, double-blind, placebo-controlled, randomised trials of CDP-choline in cognitive impairment due to chronic cerebral disorders will be considered for inclusion in the review.
Two reviewers independently reviewed the included studies, extracted the data, and pooled it when appropriate and possible. The pooled odd ratios (95% CI) or the average differences (95% CI) were estimated. No intention-to-treat data were available from the studies included.
Seven of the included studies observed the subjects for a period between 20 to 30 days, one study was of 6 weeks duration, 2 studies used cycles extending over 2 and 3 months and one study observed continuous administration over 3 months. The studies were heterogeneous in dose, inclusion criteria for subjects, and outcome measures. Results are reported for the domains of attention, memory testing, behavioural rating scales, global clinical impression and tolerability. There was no significant evidence of a beneficial effect of CDP-choline on attention. There were modest, but significant, beneficial effects of CDP-choline on memory function and behaviour. For the outcome of clinical global impression, the odds ratio for improvement in the subjects treated with CDP-Choline as opposed to the subjects treated with placebo was 8.89 [5.19, 15.22]. The drug was well tolerated.
REVIEWER'S CONCLUSIONS: There is some evidence that CDP Choline has a positive effect on memory and behaviour in at least the short term. The evidence of benefit from global impression is stronger, but is still limited by the duration of the studies. There is evidence that the effect of treatment is more homogeneous for patients with cognitive impairment secondary to cerebrovascular disorder. Other studies with a more appropriate length of treatment are recommended owing to the chronic and irreversible nature of the disorders for which this treatment is indicated.
这种化合物在治疗脑血管疾病方面的广泛应用并不意味着该疗法得到了统一且一致的应用。剂量、给药方法以及患者的选择标准各不相同。研究方式,包括观察时长、障碍严重程度以及结果评估方法也存在差异。尽管其疗效存在不确定性,但在几个欧洲国家,胞磷胆碱是治疗认知障碍的常用药物,尤其是当临床表现主要为脑血管疾病时,因此有必要进行此次综述。
评估胞磷胆碱在治疗与老年人慢性脑部疾病相关的认知、情感和行为缺陷方面的疗效。
使用胞磷胆碱/CDP、西吡氯铵、胞苷二磷酸胆碱和二磷酸胆碱等术语,在CDCIG试验注册库中检索所有相关的非动物随机对照试验。评审人员独立检索了Psychlit(1974 - 1996年)、Psychiatry(1980 - 1996年)和MEDLINE电子数据库。评审人员还联系了胞磷胆碱的制造商。
所有关于胞磷胆碱治疗慢性脑部疾病所致认知障碍的相关、非动物、无混淆、双盲、安慰剂对照、随机试验均将被纳入此次综述。
两名评审人员独立审查纳入的研究,提取数据,并在适当且可行的情况下进行汇总。估计汇总的优势比(95%置信区间)或平均差异(95%置信区间)。纳入的研究均未提供意向性治疗数据。
纳入的七项研究对受试者观察了20至30天,一项研究为期6周,两项研究采用了持续2至3个月的周期,一项研究观察了3个月的持续给药情况。这些研究在剂量、受试者纳入标准和结局指标方面存在差异。报告了注意力、记忆测试行为评定量表、整体临床印象和耐受性等方面的结果。没有显著证据表明胞磷胆碱对注意力有有益影响。胞磷胆碱对记忆功能和行为有适度但显著的有益影响。对于临床整体印象的结果,与接受安慰剂治疗的受试者相比,接受胞磷胆碱治疗的受试者改善的优势比为8.89[5.19, 15.22]。该药物耐受性良好。
有证据表明,至少在短期内,胞磷胆碱对记忆和行为有积极影响。来自整体印象的获益证据更强,但仍受研究时长的限制。有证据表明,对于脑血管疾病继发认知障碍的患者,治疗效果更具同质性。鉴于该治疗所针对疾病的慢性和不可逆性质,建议进行其他治疗时长更合适的研究。