Effects of D-cycloserine on negative symptoms in schizophrenia.
BACKGROUND
The negative and cognitive symptoms of schizophrenia are poorly responsive to neuroleptic treatment. Glutamatergic dysfunction may mediate some of these symptoms. Low dose D-cycloserine (DCS) is a partial agonist at the glycine site of the NMDA-associated receptor complex, noncompetitively enhancing NMDA neurotransmission. Prior studies suggest a beneficial effect of DCS on negative symptoms and cognition. This treatment trial was initiated to confirm and extend these findings.


METHODS
Twenty-two male schizophrenic subjects displaying prominent negative symptoms who were stabilized on typical neuroleptics completed the study. A randomized double-blind parallel group design was used to compare the effects of 50 mg p.o. QD of DCS to placebo over 4 weeks. The two subject groups did not differ significantly in age, age of onset of illness or time on current neuroleptic treatment. Symptoms were rated by means of the SANS, BPRS and Abrams and Taylor rating scale. Cognition was assessed with the Sternberg Memory Test and the Continuous Performance Test.


RESULTS
Both medication groups improved over the 4 weeks of treatment. However, there were no significant differences between the DCS and placebo group on any symptom rating. DCS effects on cognition did not differ from placebo.


CONCLUSIONS
This study did not detect improvement in negative symptoms or cognitive performance with DCS treatment that has been found in some prior studies. This negative finding may be attributed to small sample size, relatively short duration of treatment and the overall modest effect of DCS. Future studies of DCS should be adequately powered to detect a small to medium effect size and should provide for a longer treatment phase than was used in this study in order to avoid a type II error.
Duncan
Erica J
EJ
Atlanta Veterans Affairs Medical Center/Emory University School of Medicine, Atlanta, GA 30033, USA. erica.duncan2@med.va.gov
Szilagyi
Sandor
S
Schwartz
Marion P
MP
Bugarski-Kirola
Dragana
D
Kunzova
Alena
A
Negi
Shobhit
S
Stephanides
Myrsini
M
Efferen
Toby R
TR
Angrist
Burt
B
Peselow
Eric
E
Corwin
June
J
Gonzenbach
Stephen
S
Rotrosen
John P
JP
D000339:Affect / Q000187:drug effects*; D000963:Antimetabolites / Q000008:administration & dosage / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000097:blood / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000175:diagnosis*; D003523:Cycloserine / Q000008:administration & dosage / Q000494:pharmacology*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005998:Glycine / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012720:Severity of Illness Index
D000963:Antimetabolites; D014150:Antipsychotic Agents; D016194:Receptors, N-Methyl-D-Aspartate; D003523:Cycloserine; D005998:Glycine