A Randomized, Placebo-Controlled Study of Memantine as Adjunctive Treatment in Patients with Schizophrenia

Lieberman, Jeffrey A.; Papadakis, Kelly; Csernansky, John G.; Litman, Robert E.; Volavka, Jan; Jia, Xinwei D.; Gage, Allyson

doi:10.1038/npp.2008.200

Cited by 150 publications

(109 citation statements)

References 43 publications

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“…The present findings do not address the potential therapeutic value of memantine in daily dosing regimens in CPD (the evidence of which is mixed: de Lucena et al, 2009;Lieberman et al, 2009;Krivoy et al, 2007;Zdanys & Tampi, 2008), but do suggest the value for some CPD patients of adding an acute pharmacologic challenge with memantine to augment cognitive therapies that would benefit from gains in pre-attentive information processing (Swerdlow, 2011a,b,). Of course, memantine may not be the optimal drug for such a strategy: newer analogs of this compound have been developed, and our ongoing studies are assessing other drug classes Swerdlow et al, 2014).…”

Section: Discussionmentioning

confidence: 90%

Memantine Effects On Sensorimotor Gating and Mismatch Negativity in Patients with Chronic Psychosis

Swerdlow

Bhakta

Chou

et al. 2015

Neuropsychopharmacol

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Patients with chronic psychotic disorders (CPD) exhibit deficient sensorimotor gating (measured by prepulse inhibition (PPI) of startle) and mismatch negativity (MMN). In healthy subjects (HS), N-methyl-D-aspartate (NMDA) antagonists like memantine and ketamine increase PPI, and under some conditions, memantine enhances MMN; these findings present a challenge to understanding the basis for deficient PPI and MMN in psychotic disorders, as reduced NMDA activity is implicated in the pathogenesis of these disorders. Here we assessed for the first time the effects of memantine on PPI and MMN in CPD subjects. Baseline PPI was measured in HS and patients with a diagnosis of schizophrenia or schizoaffective disorder, depressed type. Subjects (total n = 84) were then tested twice, in a double-blind crossover design, comparing either: (1) placebo vs 10 mg of memantine or (2) placebo vs 20 mg memantine. Tests included measures of acoustic startle magnitude and habituation, PPI, MMN, autonomic indices, and subjective self-rating scales. Memantine (20 mg) significantly enhanced PPI in CPD subjects, and enhanced MMN across subject groups. These effects on PPI were age dependent and most evident in older CPD patients, whereas those on MMN were most evident in younger subjects. The lower dose (10 mg) either had no detectable effect or tended to degrade these measures. The NMDA antagonist, memantine, has dose-dependent effects on preconscious, automatic measures of sensorimotor gating and auditory sensory processing that are associated with enhanced cognition and function in CPD patients. Ongoing studies will determine whether these memantine-induced changes predict acute pro-cognitive or otherwise clinically beneficial effects in CPD patients.

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Section: Discussionmentioning

confidence: 90%

Memantine Effects On Sensorimotor Gating and Mismatch Negativity in Patients with Chronic Psychosis

Swerdlow

Bhakta

Chou

et al. 2015

Neuropsychopharmacol

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“…It has been reported that Zn serves as an endogenous neuromodulator of several important transmitters (19) and this role can be used for explaining its mechanism of action in the improvement of schizophrenia. There is growing the body of evidence implicating glutamatergic system in the pathophysiology of schizophrenia (4,17,18,38). Along with the studies reporting the efficacy of NMDA receptor allosteric agonists at the glycinB site in schizophrenia (4) some scientists have hypothesized the possible efficacy of NMDA antagonists in this disorder (4,39).…”

Section: Discussionmentioning

confidence: 99%

“…There is growing the body of evidence implicating glutamatergic system in the pathophysiology of schizophrenia (4,17,18,38). Along with the studies reporting the efficacy of NMDA receptor allosteric agonists at the glycinB site in schizophrenia (4) some scientists have hypothesized the possible efficacy of NMDA antagonists in this disorder (4,39). A preliminary study has even shown the probable efficacy of memantine as a noncompetitive NMDA antagonist in improvement of schizophrenia (39).…”

Section: Discussionmentioning

confidence: 99%

“…The characteristic onset of schizophrenia in early adulthood, its lifelong course, and debilitating symptoms, plus its high burden on caregivers and the society make it one of the most disabling and economically catastrophic disorders (1). Despite the improvement of antipsychotic medications, as the main-stay of treatment for patients with schizophrenia, the symptom response is not always optimal, side-effects are frequent, and treatment adherence is often poor (2)(3)(4). Therefore, still a large number of studies are ongoing for identifying new drugs of different classes that may be effective in the treatment of schizophrenia (2).…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of Zinc Sulfate as an Add-on Therapy to Risperidone versus Risperidone Alone in Patients With Schizophrenia: A Double-Blind Randomized Placebo-Controlled Trial

Mortazavi

Farzin

Zarhghami

et al. 2015

Iran J Psychiatry Behav Sci

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Background: Zinc can modulate fast-excitatory transmission, facilitate the release of amino butyric acid and potentiate nicotinic acetylcholine receptors. There are also emerging evidences discussing the implication of these neurotransmitters in pathophysiology of schizophrenia. Objectives: The purpose of this study was to evaluate the efficacy of Zn sulfate as an add-on therapy in the treatment of schizophrenia in a 6-week, double-blind and placebo-controlled trial. Patients and Methods: Eligible participants were 30 inpatients with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Patients were randomly allocated into two equal groups; one group of patients received risperidone 6 mg/day plus capsules of Zn sulfate (each containing 50 mg elemental Zn) three times a day and another group received risperidone 6 mg/day plus placebo. The Positive and Negative Syndrome Scale (PANSS) was applied to assess the psychotic symptoms and aggression risk at baseline, week 2, 4, and 6 of the study. Results:The results of this study showed that both protocols significantly decreased the scores on all subscales of the PANSS and supplemental aggression risk subscale as well as PANSS total score over the study. However, this improvement was significantly higher in Zn sulfate receiving group compared to the placebo group. No major clinical side-effects were detected. Conclusions: It may be concluded that Zn is an effective adjuvant agent in the management of patients with schizophrenia.

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“…As ampaquinas, moduladoras glutamatérgicas, são as principais substâncias em estudo 43 . Dois pequenos ensaios clínicos não mostraram efi cácia da memantina como terapêutica adjuvante ao emprego de antipsicóticos para reduzir prejuízos cognitivos em pacientes com esquizofrenia 44,45 . Entretanto, quando associada à clozapina, foi observada melhora signifi cativa da cognição, avaliada pelo MiniExame do Estado Mental 46 .…”

Section: Sistema Glutamatérgicounclassified

Alterações cognitivas na esquizofrenia: atualização

Ferreira¹,

Barbosa

Barbosa³

et al. 2010

Rev. psiquiatr. Rio Gd. Sul

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ResumoAs alterações cognitivas são características centrais na esquizofrenia. Elas permanecem relativamente estáveis durante todo o curso da doença, não sendo secundárias a outros sintomas ou a efeitos colaterais de psicofármacos. Estão diretamente ligadas a prejuízo funcional e a pior qualidade de vida dos pacientes. Diversos estudos vêm sendo realizados no sentido de caracterizar as principais alterações cognitivas na esquizofrenia, identifi car suas bases neurobiológicas e padronizar instrumentos de pesquisa, fundamentais para o advento de novos alvos para intervenções farmacológicas na esquizofrenia. O objetivo deste trabalho foi fazer uma atualização sobre o assunto. Descritores: Esquizofrenia, cognição, avaliação, escalas. AbstractCognitive dysfunctions are among the core features of schizophrenia. They remain relatively stable throughout the course of the disease, and are secondary neither to other symptoms nor to side effects of psychotropic drugs. Cognitive defi cits are directly associated with functional impairment and poor quality of life. Many studies have been conducted to describe the main cognitive abnormalities observed in schizophrenia, to identify their neurobiological bases, and to standardize research instruments, which are of paramount importance for the identifi cation of new targets for pharmacological interventions in schizophrenia. The main objective of this paper was to provide an updated review of the subject. Keywords: Schizophrenia, cognition, evaluation, scales. Artigo de revisão IntroduçãoPrejuízos cognitivos são alterações primárias da esquizofrenia. Historicamente, Emil Kraepelin, na primeira sistematização conceitual da esquizofrenia, em 1896, descreveu diversos sintomas cognitivos na demência precoce (distúr-bios da atenção, da compreensão, do fl uxo e associação do pensamento e alterações do julgamento), assim como também sua evolução para a deterioração cognitiva e da personalidade. Eugen Bleuler, em 1911, considerou a avolição como uma característica central da doença. Esse sintoma está associado a défi cits executivos relacionados à disfunção do lobo frontal 1 . Apesar de a disfunção cognitiva não ser um critério de inclusão para o diagnóstico de esquizofrenia nas classificações atuais, a conceituação atual menciona as alterações cognitivas entre os sintomas característicos da doença 1,2 .As alterações cognitivas na esquizofrenia são evidentes durante todo o curso evolutivo da doença, inclusive no seu período prodrômico. Essas alterações não são secundárias a outros sintomas e não são resultantes de tratamentos com psicofármacos ou de hospitalizações 3,4 . Também são identifi cáveis, com menor gravidade, nos pais e irmãos saudáveis dos pacientes 5 . Estudos têm sido realizados buscando esclarecer quais seriam os défi cits cognitivos específi cos da esquizofrenia, suas ligações com disfunções de regiões cerebrais e certos circuitos neuronais, suas repercussões sobre a funcionalidade dos pacientes e as possibilidades terapêuticas 6 . O objetivo deste estudo foi apresentar, ...

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A Randomized, Placebo-Controlled Study of Memantine as Adjunctive Treatment in Patients with Schizophrenia

Cited by 150 publications

References 43 publications

Memantine Effects On Sensorimotor Gating and Mismatch Negativity in Patients with Chronic Psychosis

Memantine Effects On Sensorimotor Gating and Mismatch Negativity in Patients with Chronic Psychosis

Efficacy of Zinc Sulfate as an Add-on Therapy to Risperidone versus Risperidone Alone in Patients With Schizophrenia: A Double-Blind Randomized Placebo-Controlled Trial

Alterações cognitivas na esquizofrenia: atualização

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