title: Adjunctive memantine in clozapine-treated refractory schizophrenia: an open-label 1-year extension study.
abstract: 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.
authors: Mental Health Service Noord-Holland Noord,Community Mental Health Division,Flexible Assertive Community Treatment,Alkmaar,The Netherlands.
authors: S R T
authors: SR
authors: Veerman
authors: Mental Health Service Noord-Holland Noord,Division for Specialized Treatment,Treatment Centre for Bipolar Disorders,Alkmaar,The Netherlands.
authors: P F J
authors: PF
authors: Schulte
authors: Vrije Universiteit,Faculty of Behavioural and Movement Sciences,Section Clinical Neuropsychology,Amsterdam,The Netherlands.
authors: J B
authors: JB
authors: Deijen
authors: Early Psychosis Department,Academic Medical Centre,University of Amsterdam,Academic Psychiatric Centre,Arkin,Amsterdam,The Netherlands.
authors: L
authors: L
authors: de Haan
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000209:etiology; D004351:Drug Resistance; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D056344:Executive Function / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008559:Memantine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology; D008875:Middle Aged; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D003024:Clozapine; D008559:Memantine
keywords: Clozapine; cognitive functioning; glutamate antagonists; memantine; therapy-resistant schizophrenia