Purpose/Background This double-blind, placebo-controlled clinical trial was designed to assess the efficacy and safety of memantine augmentation to standard regimen of antipsychotic treatment on psychotic symptoms and cognitive function in individuals with chronic schizophrenia for 8 weeks. Methods/Procedures Forty stabilized individuals with chronic schizophrenia were randomized in a 1:1 ratio to memantine (20 mg/d) and control (placebo) groups, along with their antipsychotic regimen for 8 weeks. The efficacy of treatment was assessed by the Positive and Negative Syndrome Scale (PANSS) and Brief Assessment of Cognition Scale, and the safety was measured by the Abnormal Involuntary Movement Scale and Barnes Akathisia Rating Scale at baseline and at weeks 4 and 8. Findings/Results No significant differences were observed in demographic or clinical variables between both groups at baseline. During the study, all subscales and total scores of PANSS decreased significantly within both groups, except the subscale score in memantine, which was found to be positive. Reduction in general subscale and total scores of PANSS was significantly higher in the control group compared with the memantine group. All subscale scores of the Brief Assessment of Cognition Scale increased significantly only in the memantine group. The increase in the Verbal Memory, Working Memory, Verbal Fluency Letter, and Verbal Fluency Total subscale scores was significantly higher in the memantine group than in the control group. There was no significant difference in the Abnormal Involuntary Movement Scale and Barnes Akathisia Rating Scale scores between the 2 groups during the study. Implications/Conclusions This study showed that adjunctive memantine to antipsychotic regimen improved the verbal memory, learning, verbal letter fluency, and working memory without improvement on psychotic symptoms in individuals with chronic schizophrenia.

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