Once-weekly D-cycloserine effects on negative symptoms and cognition in schizophrenia: an exploratory study.

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.
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.
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.
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.
AuthorsDonald C Goff, Corinne Cather, Jennifer D Gottlieb, A Eden Evins, Jared Walsh, Lisa Raeke, Michael W Otto, David Schoenfeld, Michael F Green
JournalSchizophrenia research (Schizophr Res) Vol. 106 Issue 2-3 Pg. 320-7 (Dec 2008) ISSN: 0920-9964 [Print] Netherlands
PMID18799288 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
Chemical References
  • Antipsychotic Agents
  • Placebos
  • Cycloserine
  • Adolescent
  • Adult
  • Aged
  • Antipsychotic Agents (therapeutic use)
  • Cognition Disorders (drug therapy, psychology)
  • Cycloserine (therapeutic use)
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Placebos
  • Psychiatric Status Rating Scales
  • Schizophrenia (diagnosis, drug therapy)
  • Schizophrenic Psychology

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