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Adjunctive memantine in clozapine-treated refractory schizophrenia: an open-label 1-year extension study

  • S. R. T. Veerman (a1), P. F. J. Schulte (a2), J. B. Deijen (a3) and L. de Haan (a4)



In a recent placebo-controlled, double-blind crossover trial (n = 52), significant beneficial effects on memory (d = 0.30) and negative symptoms (d = 0.29) were found after 12 weeks of memantine augmentation in patients with clozapine-refractory schizophrenia. In this open-label 1-year extension study we report the long-term effects and tolerability of memantine add-on therapy to clozapine.


Completers of the first trial who experienced beneficial effects during 12 weeks of memantine treatment received memantine for 1 year. Primary endpoints were memory and executive function using the Cambridge Neuropsychological Test Automated Battery, the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impression Severity Scale (CGI-S).


Of 31 randomized controlled trial completers who experienced beneficial effects from memantine, 24 received memantine for 1 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 of 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.


In the 1-year extension phase the favourable effect of adjunctive memantine on memory was sustained and we observed further improvement of negative, positive and overall symptoms in patients with clozapine-treated refractory schizophrenia.


Corresponding author

*Address for correspondence: S. R. T. Veerman, M.D., Mental Health Service Noord-Holland Noord, Community Mental Health Division, Flexible Assertive Community Treatment, Oude Hoeverweg 10, 1816 BT Alkmaar, The Netherlands. (Email:


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Adjunctive memantine in clozapine-treated refractory schizophrenia: an open-label 1-year extension study

  • S. R. T. Veerman (a1), P. F. J. Schulte (a2), J. B. Deijen (a3) and L. de Haan (a4)


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