The Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST): the efficacy of glutamatergic agents for negative symptoms and cognitive impairments
Abstract
OBJECTIVE: Patients with schizophrenia frequently present with negative symptoms and cognitive impairments for which no effective treatments are known. Agents that act at the glycine site of the N-methyl-D-aspartic acid (NMDA) glutamatergic receptor have been suggested as promising treatments for moderate to severe negative symptoms and cognitive impairments. METHOD: The Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST) was a 16-week double-blind, double-dummy, parallel group, randomized clinical trial of adjunctive glycine, D-cycloserine, or placebo conducted at four sites in the United States and one site in Israel. The participants were 157 inpatients and outpatients who met DSM-IV criteria for schizophrenia or schizoaffective disorder and retrospective and prospective criteria for moderate to severe negative symptoms without marked positive, depressive, or extrapyramidal symptoms. The primary outcome measures were the average "rate of change" of Scale for the Assessment of Negative Symptoms (SANS) total scores and change in the average cognitive domain z scores. RESULTS: There were no significant differences in change in the SANS total score between glycine and placebo subjects or D-cycloserine and placebo subjects. A prespecified test for the site-by-treatment-by-time interaction was significant in post hoc tests. One site had greater reduction in the SANS total score for patients receiving D-cycloserine relative to patients receiving placebo. A second site had greater reduction in the SANS total score for placebo patients compared with glycine patients. There were no significant differences between glycine and placebo or D-cycloserine and placebo subjects on the average cognition z score. CONCLUSIONS: The study results suggest that neither glycine nor D-cycloserine is a generally effective therapeutic option for treating negative symptoms or cognitive impairments.
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In the Buchanan et al trial, there was no difference between D-cycloserine vs placebo or glycine vs placebo in changes from baseline on the SANS.
“• No difference between D-cycloserine vs placebo or glycine vs placebo in changes from baseline on the SANS”
From Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? (2013) · cites this paper as [37]
In the Buchanan et al trial, there was no difference between D-cycloserine vs placebo or glycine vs placebo in changes from baseline on the cognitive domain z score.
“• No difference between D-cycloserine vs placebo or glycine vs placebo in changes from baseline on the cognitive domain z score”
From Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? (2013) · cites this paper as [37]
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- Authors
- Buchanan, R. W., Javitt, D. C., Marder, S. R., Schooler, N. R., Gold, J. M., McMahon, R. P., Heresco-Levy, U., & Carpenter, W. T.
- Affiliations
- University of Maryland, Baltimore (US)
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2007-10
- Volume
- 164
- Issue
- 10
- Pages
- 1593-1602
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2129116806
- Cited by
- 419
- References
- 47
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 11 · 2023: 7 · 2022: 12 · 2021: 16 · 2020: 14 · 2019: 22 · 2018: 23 · 2017: 24 · 2016: 21 · 2015: 27 · 2014: 31 · 2013: 32 · 2012: 38
- FWCI
- 17.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01mh059687-04, 5r01mh059750-04, 6r01mh059784-04)
- National Institute of Mental Health (5 R01 MH69807, P30 MH06850, 5 R01 MH59750, 5 R01 MH59687, 5 R01 MH59784)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- schizophrenia, negative symptoms, cognitive impairment, glycine, D-cycloserine, NMDA receptor, glutamatergic agents, adjunctive therapy, Scale for the Assessment of Negative Symptoms, schizoaffective disorder
- MeSH terms
- Adolescent, Adult, Cognition Disorders, Cycloserine, Double-Blind Method, Female, Follow-Up Studies, Glycine, Humans, Male, Middle Aged, Neuropsychological Tests, Placebos, Psychiatric Status Rating Scales, Psychotic Disorders, Schizophrenia, Schizophrenic Psychology, Severity of Illness Index, Receptors, N-Methyl-D-Aspartate, Treatment Outcome, Excitatory Amino Acid Agents
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