Once-weekly D-cycloserine effects on negative symptoms and cognition in schizophrenia: an exploratory study.
BACKGROUND
Daily dosing with d-cycloserine has inconsistently improved negative symptoms in schizophrenia patients, whereas intermittent dosing significantly facilitated exposure-based therapy in two studies of patients with phobic anxiety. In animal models, single-dose administration enhances memory consolidation, but tachyphylaxis develops with repeated dosing. The objective of this exploratory study was to assess whether once-weekly dosing with d-cycloserine will produce persistent improvements in negative symptoms and cognition.


METHODS
Fifty stable adult schizophrenia outpatients treated with any antipsychotic except clozapine were enrolled and 38 were randomized, double-blind, in a parallel-group, eight-week add-on trial of d-cycloserine 50 mg or placebo administered once-weekly. Symptom rating scales and a cognitive battery were administered at baseline and week 8 before the dose of study drug. As an exploratory analysis of memory consolidation, the Logical Memory Test, modified to measure recall after 7 days, was administered at baseline and after the first weekly dose of d-cycloserine. The primary outcome measures were change from baseline to week 8 on the SANS total score and on a composite cognitive score.


RESULTS
Thirty-three subjects (87%) completed the trial. d-cycloserine significantly improved SANS total scores compared to placebo at week 8. Cognitive performance did not improve with d-cycloserine at 8 weeks. Delayed thematic recall on the Logical Memory Test was significantly improved with the first dose of d-cycloserine compared to placebo. Performance on immediate thematic recall and item recall on the Logical Memory Test did not differ between treatments.


CONCLUSIONS
Once-weekly dosing with d-cycloserine for 8 weeks produced persistent improvement of negative symptoms compared to placebo, although statistical significance was, in part, the result of worsening of negative symptoms with placebo. Consistent with animal models, a single dose of d-cycloserine facilitated memory consolidation tested after 7 days on a test of thematic recall. These results must be considered preliminary since a number of outcomes were examined without correction for multiple tests. These findings suggest that once-weekly dosing with d-cycloserine for the treatment of negative symptoms merits further study, as do d-cycloserine effects on memory consolidation.
Goff
Donald C
DC
Massachusetts General Hospital, Psychiatry Department, Freedom Trail Clinic, 25 Staniford St., 2nd Floor, Boston, MA 02114, USA. goff@psych.mgh.harvard.edu
Cather
Corinne
C
Gottlieb
Jennifer D
JD
Evins
A Eden
AE
Walsh
Jared
J
Raeke
Lisa
L
Otto
Michael W
MW
Schoenfeld
David
D
Green
Michael F
MF
D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000523:psychology; D003523:Cycloserine / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology
D014150:Antipsychotic Agents; D010919:Placebos; D003523:Cycloserine
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