Abstract
Dysfunction of neuroplasticity due to N-methyl-d-aspartate (NMDA) receptor hypofunction may be a causal factor for memory and executive dysfunctioning in schizophrenia. Deregulation of NMDA transmission in the prefrontal cortex may also explain negative and positive symptoms. Clozapine augmentation with memantine targets altered NMDA receptor-mediated neurotransmission in schizophrenia and showed substantial beneficial effects on several symptom domains in a small proof-of-concept study. We evaluate effects of memantine add-on treatment to clozapine for memory and executive function, and negative and positive symptoms in schizophrenia. Clozapine-treated patients with refractory schizophrenia were randomly assigned to 12 weeks of double-blind adjunctive treatment with memantine (n = 26) or placebo (n = 26). Crossover occurred after a 2-week placebo wash-out period. Primary endpoints were change from baseline to 12 weeks treatment and 14 weeks to 26 weeks treatment on memory and executive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression Severity Scale (CGI-S). Side effects were assessed using the Liverpool University Neuroleptic Side-Effect Rating Scale. When compared with placebo, memantine improved a composite memory score comprising verbal recognition memory and paired associates learning task scores on the CANTAB (effect size = 0.30) and PANSS negative subscale score (effect size = 0.29). Side effects were mild and transient. In patients with clozapine-treated refractory schizophrenia, memantine addition significantly improved verbal and visual memory and negative symptoms without serious adverse effects. These results justify further investigations on long-term memantine augmentation to clozapine in treatment-resistant schizophrenia.
Highlights
Clozapine is efficacious for treatmentresistant schizophrenia patients, as many as 70% of patients show only a partial response (Hasan et al 2012)
On the basis of the glutamate hypothesis, with hypofunction of the glutamate N-methyl-D-aspartate (NMDA) receptor as an underlying mechanism for schizophrenia (Stone et al 2007; Kantrowitz & Javitt, 2010), glutamate modulators can be seen as promising antipsychotic agents (Veerman et al 2014c)
Positive symptoms may develop through disinhibition of prefrontal cortical γ-amino butyric acid (GABA) interneurons, which are responsible for recurrent inhibition of pyramidal neurons (Homayoun & Moghaddam, 2007)
Summary
Clozapine is efficacious for treatmentresistant schizophrenia patients, as many as 70% of patients show only a partial response (Hasan et al 2012). The glutamate hypothesis of schizophrenia stipulates that hypofunction of the NMDA receptor is responsible for excitotoxic neurodegeneration, dysfunction of neuroplasticity and dysregulation of downstream neurons in response to glutamate release, resulting in cognitive. Dysfunction of neuroplasticity due to N-methyl-D-aspartate (NMDA) receptor hypofunction may be a causal factor for memory and executive dysfunctioning in schizophrenia. We evaluate effects of memantine add-on treatment to clozapine for memory and executive function, and negative and positive symptoms in schizophrenia
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
