Adjunctive Memantine Therapy for Cognitive Impairment in Chronic Schizophrenia: A Placebo-Controlled Pilot Study

Department of Psychiatry, Haeundae Paik Hospital, College of Medicine and Paik Institute for Clinical Research, Inje University, Busan, Korea.
Psychiatry investigation (Impact Factor: 1.28). 06/2012; 9(2):166-73. DOI: 10.4306/pi.2012.9.2.166
Source: PubMed


To investigate the effects of memantine, an N-methyl-d-aspartate (NMDA) receptor antagonist, on cognitive impairments in patients with chronic schizophrenia.
A 12-week, placebo-controlled trial was conducted to determine the effectiveness of memantine as an adjunctive treatment with conventional antipsychotic medications in 26 patients with chronic schizophrenia. The subjects were evaluated with the Korean version of the Mini-Mental State Examination (K-MMSE), the Positive and Negative Syndrome Scale (PANSS), the Hamilton Rating Scale for Depression (HAM-D), and a standard neuropsychological screening test.
Memantine treatment was not associated with significantly improved cognitive test scores compared with the placebo control treatment. An improvement in the scores on the PANSS negative subscale was noted with memantine, but it was not significant.
Adjunctive memantine treatment did not improve cognitive functioning or affect psychopathology in patients with chronic schizophrenia in the present study. Memantine, however, was tolerated well and did not exacerbate positive symptoms in patients with chronic schizophrenia.

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    • "Memantine has shown to improve agitation and delusions in patients with Alzheimer's dementia [11]. Furthermore, it does not seem to worsen the positive symptoms of patients with schizophrenia [6]. Therefore, memantine could possibly help in maintaining—and, in any case, not worsening—the improvement of positive symptoms achieved with the antipsychotic therapy. "
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    ABSTRACT: We present a case of a 52-year-old male patient suffering from chronic schizophrenia stabilized on risperidone long-acting injection (37,5 mg/2 weeks) and biperiden 4 mg/day. Residual symptoms are affective flattening, alogia, avolition, and asociality. Memantine 10 mg/day was added. After 1.5 months, the patient spontaneously referred to "feel better being in company of my relatives." The following scales have been completed: the Scale for the Assessment of Negative Symptoms (96), the Scale for the Assessment of Positive Symptoms (3), the Mini Mental Scale Examination (26), and the Calgary Depression for Schizophrenia Scale (2). Memantine was increased to 20 mg/day and biperiden was decreased to 2 mg/day. Two months later, apathy and asociality considerably improved and affective flattening, alogia, and attention slightly got better (SANS 76, SAPS 1, MMSE 26, and CDSS 1). After two more months, the improvement continued in the same domains (SANS: 70, SAPS: 1 MMSE: 27, and CDSS: 1). Positive symptoms remained in full remission. It has been hypothesized that one of the causes of schizophrenia is glutamate excitotoxicity. Memantine, a glutamate receptor antagonist, could possibly ameliorate schizophrenia symptoms, the negative ones among them, used as add-on therapy to atypical antipsychotics. Memantine could be of potential help in schizophrenia patients with severe residual negative symptoms.
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