Adjunctive memantine in clozapine-treated refractory schizophrenia: an open-label 1-year extension study. Issue 2 (25th October 2016)

• Record Type: Journal Article
• Authors: Veerman, S. R. T.; Schulte, P. F. J.; Deijen, J. B.; de Haan, L.
• Is Part Of: Psychological medicine. Volume 47:Issue 2(2017)
• Page Start: 363
• Page End: 375
• Publication Date: 2016-10-25
• Subjects: Clozapine, -- cognitive functioning, -- glutamate antagonists, -- memantine, -- therapy-resistant schizophrenia; Psychiatry -- Periodicals; Medicine and psychology -- Periodicals; Clinical psychology -- Periodicals; 616.89
• DOI: 10.1017/S0033291716002476
• Languages: English
• ISSNs: 0033-2917

Abstract

Abstract : Background: 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. Method: 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). Results: 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. Conclusions: 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.