Adjunctive Memantine Treatment of Schizophrenia

Abstract

Purpose/Background This double-blind, placebo-controlled clinical trial was designed to assess the efficacy and safety of memantine augmentation to standard regimen of antipsychotic treatment on psychotic symptoms and cognitive function in individuals with chronic schizophrenia for 8 weeks. Methods/Procedures Forty stabilized individuals with chronic schizophrenia were randomized in a 1:1 ratio to memantine (20 mg/d) and control (placebo) groups, along with their antipsychotic regimen for 8 weeks. The efficacy of treatment was assessed by the Positive and Negative Syndrome Scale (PANSS) and Brief Assessment of Cognition Scale, and the safety was measured by the Abnormal Involuntary Movement Scale and Barnes Akathisia Rating Scale at baseline and at weeks 4 and 8. Findings/Results No significant differences were observed in demographic or clinical variables between both groups at baseline. During the study, all subscales and total scores of PANSS decreased significantly within both groups, except the subscale score in memantine, which was found to be positive. Reduction in general subscale and total scores of PANSS was significantly higher in the control group compared with the memantine group. All subscale scores of the Brief Assessment of Cognition Scale increased significantly only in the memantine group. The increase in the Verbal Memory, Working Memory, Verbal Fluency Letter, and Verbal Fluency Total subscale scores was significantly higher in the memantine group than in the control group. There was no significant difference in the Abnormal Involuntary Movement Scale and Barnes Akathisia Rating Scale scores between the 2 groups during the study. Implications/Conclusions This study showed that adjunctive memantine to antipsychotic regimen improved the verbal memory, learning, verbal letter fluency, and working memory without improvement on psychotic symptoms in individuals with chronic schizophrenia.

Pharmacological management of neurocognitive impairment in schizophrenia: A narrative review

“…27 Another study that investigated add-on treatment of memantine (20 mg/ day) in 40 patients on a stable antipsychotic regimen saw all subscale scores of the BACS increase significantly in the memantine group only. 29 These studies are in line with recent discussions postulating that memantine as a NMDA receptor modulator may have neuroprotective properties to improve long-term outcome and cognition in patients with schizophrenia. However, it is important to note that major limitations were present in the above studies.…”

“…Similarly, in a proof‐of‐concept study with 24 patients with schizophrenia, adjunctive memantine (10 mg twice daily) on top of stable risperidone showed significantly higher performance in attention intensity, problem‐solving, verbal learning, flexibility, and immediate memory when compared to the placebo group 27 . Another study that investigated add‐on treatment of memantine (20 mg/day) in 40 patients on a stable antipsychotic regimen saw all subscale scores of the BACS increase significantly in the memantine group only 29 . These studies are in line with recent discussions postulating that memantine as a NMDA receptor modulator may have neuroprotective properties to improve long‐term outcome and cognition in patients with schizophrenia.…”

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

“…Memantine is useful for the treatment of both cognitive deterioration and BDs in AD and other forms of dementia [172,173]. AD patients treated with memantine plus citalopram show improvement in BDs [174]; in combination with antipsychotics, it may improve verbal memory, learning, verbal letter fluency, and working memory with no effect on psychotic symptoms in patients with chronic schizophrenia [175,176]; at a dose of 20 mg/day, it may be effective in patients with obsessive-compulsive disorder [177]; at 10 mg/day, it may be helpful in migraine [178]; and, in combination with naltrexone, it enhances the efficacy of naltrexone in reducing alcohol drinking and craving [179]. Memantine might also be useful in the treatment of punctate and dynamic allodynia by the blockade of the microglia Kir2.1 channel to suppress microglia activation [180], and in combination with dextromethorphan, it may be beneficial in neuropathic pain [181].…”

Más allá de lo habitual: Nuevos enfoques en la terapia de la esquizofrenia resistente

“…Otro estudio evaluó la eficacia de la memantina más otro antipsicótico contra solamente usar antipsicótico durante 8 semanas medido con la Escala para el Síndrome Positivo y Negativo de la Esquizofrenia (PANSS, por sus siglas en inglés) y la Escala de Evaluación Breve de la Cognición (BACS). Este estudio demostró una mejoría significativa en la memoria verbal, memoria de trabajo y fluidez verbal en el grupo de la memantina (Hassanpour et al, 2019). Por otro lado, existe evidencia creciente de que la combinación de galantamina-memantina mejora los síntomas positivos, cognitivos y negativos de la esquizofrenia con un mejor perfil de seguridad (Koola, 2018).…”