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: 1.15). 06/2012; 9(2):166-73. DOI: 10.4306/pi.2012.9.2.166
Source: PubMed

ABSTRACT 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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Memantine, an uncompetitive N-methyl D-aspartate receptor (NMDAR) open-channel blocker holds great promise for its potential clinical effectiveness as add-on therapy to on-going treatment with antipsychotics. Methods: We report here the results of a chart review-based retrospective case series study that examined the effectiveness of off-label use of memantine in patients with schizophrenia when used as adjunctive therapy to standard neuroleptic therapy. Results: 17 of the 26 patients, whose case files were reviewed using a study-specific proforma showed clinical improvement in positive and/or negative psychopathology as well as in cognitive and/or functional domains. The doses of on-going antipsychotic medications could be reduced in a sizeable number of responders. None of the subjects reported serious adverse events. Discussion: Memantine holds great promise as adjunctive therapy for treatment of schizophrenia. Randomized controlled trials, wherein memantine is administered at adequate doses for an adequate period of time to ongoing antipsychotic treatment are required to confirm its efficacy in alleviating symptoms of schizophrenia.
    Pharmacopsychiatry 09/2014; 47(6):202-209. · 2.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) and Treatment Units for Research on Neurocognition and Schizophrenia projects were designed to facilitate the development of new drugs for the treatment of cognitive impairments in people with schizophrenia. The MATRICS project identified three drug mechanisms of particular interest: dopaminergic, cholinergic, and glutamatergic. As a group, while people with schizophrenia have moderate cognitive impairment, it is the best predictor of long-term outcome. Unfortunately, there are no approved medications for cognitive impairment in this population. Hence, the development of new pharmacological approaches is critical for reducing illness-related disability. The combination of an acetylcholinesterase inhibitor (AChEI) and memantine is more effective than either medication alone to improve cognition in Alzheimer's dementia. Galantamine is not only an AChEI, but also a positive allosteric modulator of the α4β2 and α7 nicotinic receptors. Hypofunction of N-methyl-d-aspartate (NMDA) receptors has been implicated in the pathophysiology of cognitive symptoms in schizophrenia and hence memantine may positively impact cognition. Memantine decreases the tonic NMDA current and galantamine enhances the action potential mediated by a postsynaptic NMDA current. This results in an increased signal transmission; therefore, a greater signal-to-noise ratio occurs with the combination than memantine alone. Galantamine improves the α-amino-3-hydroxy-5-methyl-4-isoxazol-propionate (AMPA)-mediated signaling which could be neuroprotective and may improve memory coding. The combination of galantamine and memantine may be particularly effective in schizophrenia in order to increase the selective cognition enhancement produced by either medication alone. In the future, multitarget-directed ligands may play a role in the treatment of complex diseases like schizophrenia.
    Schizophrenia Research 05/2014; · 4.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We discuss the relevance of the glutamate hypothesis in explaining cognitive disturbances and negative symptoms in schizophrenia. 4 lines of evidence support the hypothesis that glutamate deregulation, mainly through dysfunction of the N-methyl-D-aspartate (NMDA) receptor, is an important underlying mechanism of schizophrenia. Glutamate pathways are promising sites for intervention. Glutamate agonists combined with non-clozapine antipsychotics and glutamate antagonists augmented to clozapine show interesting clinical benefits in refractory schizophrenia. We illustrate how unique properties of the NMDA receptor antagonist memantine in addition to clozapine, may cause improvement of positive, negative and cognitive symptoms of schizophrenia.
    Pharmacopsychiatry 07/2014; · 2.17 Impact Factor

Full-text (2 Sources)

Available from
May 31, 2014