Augmentation of Antipsychotic Treatment with Memantine in Patients with Schizophrenia: A Systematic Review and Meta-Analysis

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Many patients with schizophrenia respond partially to treatment with antipsychotic medications. A wide range of pharmaceutical agents are utilized as augmentation therapy in order to increase the efficacy of antipsychotic medication treatment. Memantine which is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist is one such agent among these. In this study, by conducting a systematic review and meta-analysis we aimed to assess the efficacy of memantine augmentation on psychopathology in patients with schizophrenia receiving antipsychotic medication. We analyzed double-blind, randomized, placebo-controlled trials of memantine add-on treatment in schizophrenia patients receiving antipsychotic medications. The primary outcome measure was amelioration of negative symptoms and the secondary outcome measures were amelioration of positive, total and general psychopathology symptoms. Publication bias was evaluated by Funnel plot and Egger test. Eleven studies (n=570) were included. Although memantine add-on treatment was superior to placebo for ameliorating negative symptoms (SMD=0.596, 95% CI=0.075-1.118, p=0.025), there were no statistically significant differences in the amelioration of general psychopathology (SMD=0.034, 95% CI=0.419-0.488, p=0.883), positive (SMD=-0.041, 95% CI=0.217-0.135, p=0.650) and overall (SMD=0.315, 95% CI=0.256-0.887, p=0.280) symptoms. No publication bias was observed between studies according to Funnel plots and Egger test results. Memantine augmentation treatment seems to be beneficial for particularly treating negative symptoms in schizophrenia patients. Further studies with larger sample size and longer follow-up durations are needed.