Memantine Add-On to Risperidone for Treatment of Negative Symptoms in Patients With Stable Schizophrenia

Abstract

We aimed to evaluate the efficacy of memantine add-on in the treatment of primary negative symptoms of patients with stable schizophrenia. In a double-blind placebo-controlled clinical trial, 40 patients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) who were stabilized on risperidone for a minimum of 8 weeks were randomized to either memantine (20 mg) or placebo in addition to risperidone, 6 mg/d, for eight weeks. Assessment was done using the Positive and Negative Syndrome Scale at baseline, week 4, and week 8. The Hamilton Depression Rating Scale and the Extrapyramidal Symptom Rating Scale at baseline and week 8 were used to assess depression and extrapyramidal symptoms, respectively. All 40 patients had at least one postbaseline measurement, and 38 patients completed the trial. Patients in the memantine group showed a significantly greater improvement on negative subscale than the placebo group at end point (P < 0.001). The same effect was observed for the total score (P < 0.001) and the general psychopathology subscale score (P = 0.002). There was no significant difference in reduction of positive symptoms score between the 2 groups (P = 0.757). Changes in the Hamilton Depression Rating Scale and the Extrapyramidal Symptom Rating Scale scores and frequency of adverse effects did not differ between the 2 groups. Our study showed that memantine is a tolerable and efficacious add-on treatment for primary negative symptoms of schizophrenia.

Memantine protects thalamocortical hyper‐glutamatergic transmission induced by NMDA receptor antagonism via activation of system xc−

“…A meta‐analysis of NMDAR agonists as adjunctive therapies for schizophrenia accordingly showed that NMDAR agonists are superior to placebo in terms of overall and negative symptoms . In contrast with NMDAR agonists, the NMDAR antagonists amantadine and memantine (MEM) improved cognitive impairments of schizophrenia according to another meta‐analysis, and adjuvant medication with MEM and antipsychotics was effective on positive, negative, and cognitive symptoms in schizophrenia . Other clinical studies demonstrate clinical benefits of MEM against several psychiatric disorders, including mood and anxiety disorders and schizophrenia …”

Tackling Negative Symptoms of Schizophrenia with Memantine

“…Rezaei et al [16] in their study used the same combination of medications as we did—risperidone + memantine—for tackling the negative symptoms in their sample. The authors suggested that, in order to evaluate improvement in primary negative symptoms, it is essential that the patient should be depression-free and without positive or extrapyramidal symptoms.…”

Off-label Use of Memantine as Adjunctive Treatment in Schizophrenia: A Retrospective Case Series Study

“…However, the few randomized double-blind placebo controlled studies that have evaluated the effi cacy of add-on memantine have shown mixed results. Memantine, when used as add-on therapy to on-going treatment with atypical antipsychotics in patients with schizophrenia having residual symptoms showed signifi cant benefi t in improving residual symptoms when assessed at 8 weeks posttreatment in one study [ 18 ] while another study reported negative fi ndings [ 19 ] . In another double-blind placebo-controlled trial in patients with chronic schizophrenia, 12 weeks of adjunctive therapy with memantine did not improve psychopathology or cognitive functioning; however, memantine was tolerated well and did not exacerbate positive symptoms [ 20 ] .…”