D-cycloserine for Alzheimer's disease.
BACKGROUND
Evidence supports a role for the 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.


OBJECTIVE
To assess the efficacy and safety of D-cycloserine in patients with Alzheimer's disease.


METHODS
The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 14 June 2001 using the terms: cycloserine, D-cycloserine, Alzheimer*.


METHODS
Randomized, double-blinded and unconfounded trials comparing D-cycloserine with a control treatment.


METHODS
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.


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.


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.
Laake
K
K
Department of Geriatric Medicine, Ullevaal Hospital, Kirkevn. 166, Oslo, Norway. Knut.Laake@ioks.uio.no
Oeksengaard
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AR
D000544:Alzheimer Disease / Q000188:drug therapy*; D000892:Anti-Infective Agents, Urinary / Q000009:adverse effects / Q000627:therapeutic use*; D000904:Antibiotics, Antitubercular / Q000009:adverse effects / Q000627:therapeutic use*; D003523:Cycloserine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D016032:Randomized Controlled Trials as Topic
D000892:Anti-Infective Agents, Urinary; D000904:Antibiotics, Antitubercular; D003523:Cycloserine