Cytidinediphosphocholine (CDP choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly

Abstract

Background: 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.

Objectives: 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.

Search strategy: 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.

Selection criteria: 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.

Data collection and analysis: 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.

Main results: 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.