• DOI:10.4088/JCP.08m04935gry
• Corpus ID: 26374475

Improvement of negative and positive symptoms in treatment-refractory schizophrenia: a double-blind, randomized, placebo-controlled trial with memantine as add-on therapy to clozapine.

@article{DeLucena2009ImprovementON,
  title={Improvement of negative and positive symptoms in treatment-refractory schizophrenia: a double-blind, randomized, placebo-controlled trial with memantine as add-on therapy to clozapine.},
  author={David De Lucena and Brisa Fernandes and Michael Berk and Seetal Dodd and Dalton Wiggers Medeiros and Mariana Pedrini and Maur{\'i}cio Kunz and Fabiano Alves Gomes and L Giglio and Maria Ines R. Lobato and Paulo S Belmonte-de-Abreu and Clarissa Severino Gama},
  journal={The Journal of clinical psychiatry},
  year={2009},
  volume={70 10},
  pages={
          1416-23
        }
}

• David De Lucena, Brisa Fernandes, +9 authors C. Gama
• Published 15 October 2009
• Psychology, Medicine
• The Journal of clinical psychiatry

BACKGROUND
Glutamate deregulation may be involved in the neuropathology of schizophrenia, mainly through N-methyl-d-aspartate (NMDA) receptor dysfunction. Memantine, a drug approved by the FDA for the treatment of moderate to severe Alzheimer's disease, acts as a weak nonselective NMDA receptor antagonist. The aim of this study was to examine the efficacy of memantine as an adjunctive treatment to clozapine in patients with refractory schizophrenia.

METHOD
In this double-blind, placebo-controlled study, outpatients with refractory schizophrenia according to DSM-IV clinical criteria were randomly assigned, from March 2005 to February 2008, to receive either 20 mg/d memantine (n = 10) or placebo (n = 11), in addition to clozapine, for 12 weeks. The primary outcome measure was the total score on the 18-item Brief Psychiatry Rating Scale (BPRS) and BPRS subscales of positive and negative symptoms. Secondary outcomes were global severity of disease as measured by the Clinical Global Impressions scale (CGI), cognition as assessed by the Mini-Mental State Examination (MMSE), and extrapyramidal symptoms as assessed by the Simpson-Angus Scale (SAS).

RESULTS
Twenty-one participants completed the study and were used in the analysis. Significant improvement (P < .01) on the total BPRS score, its subscales of positive (effect size [ES] = -1.38) and negative (ES = -3.33) symptoms, the CGI score (ES = 1.56), and the MMSE score was observed with memantine as compared with placebo. No significant changes in extrapyramidal symptoms were observed.

CONCLUSIONS
Memantine add-on to clozapine therapy was associated with improvement in negative and positive symptoms in refractory schizophrenia patients.

TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT00757978.