D-cycloserine is a broad-spectrum antibiotic formerly used at high doses (500-1000 mg/day) for the treatment of tuberculosis (TB). It has been suggested that D-cycloserine might improve memory and other cognitive processes through its desired effects on N-methyl-D-aspartate (NMDA) receptor function. It was not possible to extract the results from the first phases of two included crossover studies of D-cycloserine for Alzheimer's disease and therefore the meta-analyses are based on the included two parallel group 6-month studies. The lack of a positive effect of D-cycloserine on cognitive outcomes in controlled clinical trials with statistical power high enough to detect a clinically meaningful effect means that D-cycloserine has no place in the treatment of patients with Alzheimer's disease.
Read the full abstract
Evidence supports a role for NMDA receptors in learning and memory. These can be modulated by the antibiotic D-cycloserine in such a way that the effect of the excitatory transmitter substance glutamate is enhanced. A study on healthy subjects pretreated with scopolamine to mimic Alzheimer's disease showed a positive effect of D-cycloserine at low doses.
Objectives
To assess the efficacy and safety of D-cycloserine in patients with Alzheimer's disease.
Search strategy
The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 2 January 2004 using the terms: cycloserine, D-cycloserine. The Register contains records from all major health care databases and is updated regularly.
Selection criteria
Randomized, double-blinded and unconfounded trials comparing D-cycloserine with a control treatment.
Data collection and analysis
Two larger and two smaller randomized controlled trials were identified. The Clinical Global Impression scale was used in all studies and was a primary outcome measure.
Main results
It was not possible to extract the results from the first phases of the two crossover studies and therefore the meta-analyses are based on the two parallel group 6-month studies. There was no indication of a positive effect favouring D-cycloserine for the numbers showing improvement at 6 months as assessed by the Clinical Global Impression for any dose. The number of withdrawals for any reason before end of treatment at 6 months was significantly in favour of placebo (fewer withdrawals) compared with D-cycloserine for dose levels of 30 mg/day (OR 2.94, 95% CI 1.52, 5.70) and 100 mg/day (OR 3.23, 95% CI 1.67, 6.25). There was no significant difference between treatment, (2, 10, 30, 100, or 200 mg/day) and placebo for the number of withdrawals due to adverse events by six months.
Authors' conclusions
The lack of a positive effect of D-cycloserine on cognitive outcomes in controlled clinical trials with statistical power high enough to detect a clinically meaningful effect means that D-cycloserine has no place in the treatment of patients with Alzheimer's disease.
