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Adjunctive Memantine in Clozapine-Treated Refractory Schizophrenia: An Open-Label One-Year Extension Study

Published online by Cambridge University Press:  23 March 2020

P. Schulte ,
S. Veerman ,
J.B. Deijen  and
L. De Haan
P. Schulte
Affiliation:
Mental Health Service North-Holland-North, Department for Specialized Treatments, Treatment Center for Bipolar Disorder, Alkmaar, Netherlands
S. Veerman
Affiliation:
Mental Health Service North-Holland-North, Community Mental Health Division, Alkmaar, Netherlands
J.B. Deijen
Affiliation:
Vrije Universiteit, Faculty of Behavioural and Movement Sciences, Section Clinical Neuropsychology, Amsterdam, Netherlands
L. De Haan
Affiliation:
Academic Medical Centre, University of Amsterdam, Academic Psychiatric Center, Early Psychosis Department, Arkin, Amsterdam, Netherlands

Abstract

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Introduction

In a recent placebo-controlled, double blind crossover trial (n = 52), we found significant beneficial effects on memory (d = 0.30) and negative symptoms (d = 0.29) after 12 weeks memantine augmentation in patients with clozapine-refractory schizophrenia.

Aims

In this open-label 1 year extension study, we report the long-term effects and tolerability of memantine add-on therapy to clozapine.

Methods

Completers of the first trial who experienced beneficial effects during 12 weeks of memantine treatment received memantine for one year. Primary endpoints were memory and executive function using the Cambridge neuropsychological test automated battery (CANTAB), the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impression Severity Scale (CGI-S).

Results

Of 31 RCT completers who experienced beneficial effects from memantine, 24 received memantine for one year. The small improvement in memory found in the memantine condition in the placebo-controlled trial remained stable in the extension study. Executive function did not improve. After 26 weeks of memantine add-on therapy to clozapine, PANSS negative symptoms (r = 0.53), PANSS positive symptoms (r = 0.50), and PANSS total symptoms (r = 0.54) significantly improved. Even further significant improvement in all these measures was observed between 26 weeks and 52 weeks memantine, with effect sizes varying from 0.39 to 0.51. CGI-S showed a non-significant moderate improvement at 26 weeks (r = 0.36) and 52 weeks (r = 0.34). Memantine was well tolerated without serious adverse effects.

Conclusions

In the one-year extension phase, the favorable effect of adjunctive memantine on memory was sustained and we observed further improvement of positive, negative and overall symptoms of schizophrenia.

Disclosure of interest

P.F.J.S. reports personal fees from H. Lundbeck A/S, outside the submitted work and he is a board member of the Dutch Clozapine Collaboration Group. L.d.H., has received investigator-led research grants or recompense for presenting his research from Eli Lilly, Bristol-Myers Squibb, Janssen-Cilag and AstraZeneca.

Type
e-Poster Walk: Schizophrenia and Other Psychotic Disorders–Part 4
Information
European Psychiatry , Volume 41 , Issue S1: Abstract of the 25th European Congress of Psychiatry , April 2017 , pp. S279 - S280
Copyright
Copyright © European Psychiatric Association 2017
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