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

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.

journal_name

Psychol Med

journal_title

Psychological medicine

authors

Veerman SR,Schulte PF,Deijen JB,de Haan L

doi

10.1017/S0033291716002476

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

363-375

issue

eissn

0033-2917

issn

1469-8978

pii

S0033291716002476

journal_volume

pub_type

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