TY - JOUR
T1 - A randomized, placebo-controlled study of memantine as adjunctive treatment in patients with schizophrenia
AU - Lieberman, Jeffrey A.
AU - Papadakis, Kelly
AU - Csernansky, John
AU - Litman, Robert
AU - Volavka, Jan
AU - Jia, Xinwei Daniel
AU - Gage, Allyson
N1 - Funding Information:
John Csernansky has received research grants from the NIMH, NIA, and the Schizophrenia Trials Network (University of North Carolina). In addition, he has been a consultant for Sanofi-Aventis, Eli Lilly, Solvay, and Wyeth Pharmaceuticals, and has received honoraria for lectures from Eli Lilly and Janssen Pharmaceuticals.
PY - 2009/4
Y1 - 2009/4
N2 - 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.
AB - 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.
KW - Adjunctive therapy
KW - Clinical trial
KW - Glutamate
KW - Memantine
KW - NMDA receptor antagonist
KW - Schizophrenia
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U2 - 10.1038/npp.2008.200
DO - 10.1038/npp.2008.200
M3 - Article
C2 - 19005465
AN - SCOPUS:62349116484
SN - 0893-133X
VL - 34
SP - 1322
EP - 1329
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 5
ER -