A randomized, placebo-controlled study of memantine as adjunctive treatment in patients with schizophrenia
Abstract
Memantine, an uncompetitive antagonist of glutamate receptors of the N-methyl-D-aspartate type is approved for the treatment of moderate to severe Alzheimer's disease. A growing body of evidence supports a link between the glutamatergic neurotransmission and schizophrenia. The purpose of this study (MEM-MD-29) was to examine the efficacy and safety of memantine as an adjunctive treatment to atypical antipsychotics in patients with persistent residual psychopathology of schizophrenia. In this double-blind, placebo-controlled study, participants were assigned to receive 20 mg/day memantine (n=70) or placebo (n=68), in addition to continuing treatment with atypical antipsychotics, for 8 weeks. The primary efficacy measure was the total score on the Positive and Negative Symptom Scale (PANSS). Secondary measures were positive and negative PANSS scores, PANSS responders, Calgary Depression Scale for Schizophrenia (CDSS), Clinical Global Impression of Severity (CGI-S), Clinical Global Impression of Improvement (CGI-I), and Brief Assessment of Cognition in Schizophrenia (BACS). Missing data were imputed using the last observation carried forward (LOCF) approach. Safety was assessed by means of physical examination, clinical laboratory evaluation, recording of adverse events (AEs), and measures of extrapyramidal symptoms. At end point, total PANSS scores did not differ between the memantine and the placebo group (p=0.570, LOCF). A similar outcome was observed for all secondary measures. The frequency of serious AEs in the memantine vs placebo group was 8.7 vs 6.0%; treatment discontinuations because of AEs occurred in 11.6 and 3.0% of patients in these groups, respectively. Memantine showed no efficacy as an adjunctive therapy in schizophrenia patients with residual psychopathology and was associated with a higher incidence of AEs than placebo.
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In the Lieberman et al memantine trial, a similar outcome was observed for all secondary measures.
“• A similar outcome was observed for all secondary measures.”
From Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? (2013) · cites this paper as [41]
Memantine was associated with a higher incidence of adverse events than placebo in the Lieberman et al trial.
“• Memantine showed no efficacy as an adjunctive therapy in schizophrenia patients with residual psychopathology and was associated with a higher incidence of AEs than placebo.”
From Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? (2013) · cites this paper as [41]
In the Lieberman et al memantine trial, at endpoint total PANSS scores did not differ between the memantine and the placebo group.
“• At endpoint, total PANSS scores did not differ between the memantine and the placebo group”
From Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? (2013) · cites this paper as [41]
Memantine showed no efficacy as an adjunctive therapy in schizophrenia patients with residual psychopathology.
“• Memantine showed no efficacy as an adjunctive therapy in schizophrenia patients with residual psychopathology and was associated with a higher incidence of AEs than placebo.”
From Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? (2013) · cites this paper as [41]
In the Lieberman et al memantine trial, the required sample size was determined using the assumption that a clinically meaningful difference between the 2 treatment groups would be 8.5 points in total PANSS score with a pooled SD of 14.7.
“The required sample size was determined using the assumption that a clinically meaningful difference between the 2 treatment groups would be 8.5 points in total PANSS score with a pooled SD of 14.7.”
From Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? (2013) · cites this paper as [41]
In the Lieberman et al memantine trial, an incorrect calculation of the BACS composite score made the primary cognition analysis uninterpretable.
“• Incorrect calculation of BACS composite score made primary cognition analysis uninterpretable”
From Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? (2013) · cites this paper as [41]
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- Authors
- for the MEM-MD-29 Study Group, Lieberman, J. A., Papadakis, K., Csernansky, J., Litman, R., Volavka, J., Jia, X. D., & Gage, A.
- Affiliations
- New York State Psychiatric Institute (US)
- Forest Laboratories (United States) (US)
- Washington University in St. Louis (US)
- NYU Langone Health (US)
- Corresponding author
- Lieberman, Jeffrey A
- Venue
- Neuropsychopharmacology
- Published
- 2008-11-12
- Volume
- 34
- Issue
- 5
- Pages
- 1322-1329
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- OpenAlex
- W2031792414
- Cited by
- 162
- References
- 47
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2 · 2023: 7 · 2022: 9 · 2021: 10 · 2020: 6 · 2019: 26 · 2018: 9 · 2017: 8 · 2016: 6 · 2015: 10 · 2014: 6 · 2013: 13 · 2012: 10
- FWCI
- 7.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Keywords
- memantine, schizophrenia, adjunctive therapy, atypical antipsychotics, NMDA receptor antagonists, glutamatergic neurotransmission, PANSS, adverse events, extrapyramidal symptoms, treatment efficacy
- MeSH terms
- Adolescent, Adult, Aged, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Male, Memantine, Middle Aged, Psychiatric Status Rating Scales, Schizophrenia, Antipsychotic Agents, Treatment Outcome, Excitatory Amino Acid Antagonists, Young Adult
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