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document
A placebo-controlled trial of D-cycloserine added to conventional neuroleptics in patients with schizophrenia . BACKGROUND In a preliminary dose-finding study , D-cycloserine , a partial agonist at the glycine modulatory site of the glutamatergic N-methyl-D-aspartate ( NMDA ) receptor , improved negative symptoms and cognitive function when added to conventional neuroleptics at a dose of 50 mg/d . METHODS Forty-seven patients with schizophrenia meeting criteria for deficit syndrome were randomized to D-cycloserine , 50 mg/d ( n=23 ) or placebo ( n=24 ) added to their conventional neuroleptic for an 8-week , double-blind trial . Clinical assessments were performed at baseline and at weeks 1 , 2 , 4 , 6 , and 8 . Serum concentrations of D-cycloserine , relevant amino acids , and homovanillic acid were assayed at baseline and at weeks 4 and 8 . A cognitive battery was performed at baseline and at week 8 . RESULTS Thirty-nine patients completed the 8-week trial . Seven dropouts occurred in the D-cycloserine group and 1 in the placebo group . The mean reduction in negative symptoms with D-cycloserine ( 23 % ) was significantly greater than with placebo ( 7 % ) as calculated by slopes representing Scale for the Assessment of Negative Symptoms ( SANS ) total scores . Improvement of negative symptoms was predicted by low neuroleptic dose and low baseline SANS total score . No differences were found in performance on any cognitive test between groups or in changes in any other clinical measure . Clinical response did not correlate significantly with serum amino acid concentrations at baseline or with concentrations of D-cycloserine at weeks 4 and 8 . CONCLUSION These results support the hypothesis that agents acting at the glycine modulatory site of the NMDA receptor improve primary negative symptoms .
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Intervention_Control
placebo-controlled
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Intervention_Pharmacological
D-cycloserine
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Intervention_Pharmacological
D-cycloserine
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Intervention_Pharmacological
D-cycloserine
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Intervention_Control
placebo
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Intervention_Pharmacological
D-cycloserine
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Intervention_Pharmacological
D-cycloserine
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Intervention_Control
placebo
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Intervention_Pharmacological
D-cycloserine
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Intervention_Control
placebo
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Intervention_Pharmacological
D-cycloserine
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Outcome_Physical
Serum concentrations of D-cycloserine , relevant amino acids , and homovanillic acid
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Outcome_Mental
cognitive battery
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Outcome_Mortality
performance on any cognitive test
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Participant_Condition
schizophrenia
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Participant_Sample-size
Forty-seven
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Participant_Condition
schizophrenia
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Participant_Condition
deficit syndrome
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Participant_Sample-size
Thirty-nine