Memantine add-on to antipsychotic treatment for residual negative and cognitive symptoms of schizophrenia: a meta-analysis.

Abstract

We examined whether memantine add-on to antipsychotic treatment is beneficial in schizophrenia treatment. This systematic review and meta-analysis aimed to achieve stronger evidence on the efficacy and safety of memantine add-on for treating schizophrenia. We analyzed double-blind, randomized, placebo-controlled trials of memantine add-on treatment in schizophrenia patients receiving antipsychotics. The primary outcomes were amelioration of negative symptoms and all-cause discontinuation. Dichotomous outcomes are presented as risk ratios (RRs), and continuous outcomes are presented as mean differences (MDs) or standardized mean differences (SMDs). Eight studies (n=448) were included. Although memantine add-on treatment was superior to placebo for ameliorating negative symptoms (SMD=-0.96, p=0.006, I 2=88%; N=7, n=367) in the Positive and Negative Syndrome Scale general subscale (MD=-1.62, p=0.002, I 2=0%; N=4, n=151) and Mini-Mental Status Examination score (MD=-3.07, p<0.0001, I 2=21%; N=3, n=83), there were no statistically significant differences in the amelioration of overall (SMD=-0.75, p=0.06, I 2 =86%; N=5, n=271), positive (SMD=-0.46, p=0.07, I 2=80%; N=7, n=367), and depressive symptoms (SMD=-0.127, p=0.326, I 2=0%; N=4, n=201); all-cause discontinuation (RR=1.34, p=0.31, I 2=0%; N=8, n=448); and individual adverse events (fatigue, dizziness, headache, nausea, constipation) between the groups. For negative symptoms, the significant heterogeneity disappeared when risperidone studies alone were considered (I 2=0%). However, memantine add-on treatment remained superior to placebo (SMD=-1.29, p=0.00001). Meta-regression analysis showed that patient age was associated with memantine-associated amelioration of negative symptoms (slope=0.171, p=0.0206). Memantine add-on treatment may be beneficial for treating psychopathological symptoms (especially negative symptoms) in schizophrenia patients. The negative-symptom effect size may be associated with younger adult schizophrenia patients.