In a recent 26-week placebo-controlled, crossover trial (n=52) we found significant positive effects on verbal and visual memory, and negative symptoms in clozapine-treated patients with refractory schizophrenia.

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

To evaluate the persistence of improvements in cognitive functioning and symptoms of memantine add-on therapy to clozapine in schizophrenia.

Completers of the first trial who experienced a beneficial effect of memantine after 12 weeks continued memantine for one year. Primary endpoints were change from baseline to 26 weeks treatment and 26 weeks to 52 weeks treatment on memory and executive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression Severity Scale (CGI-S). Secondary endpoints were change on the Health of the Nation Outcome Scales (HoNOS) and Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS).

Of 32 completers who experienced a beneficial effect of memantine 23 patients continued memantine for one year. Memory improvement was sustained, verbal recognition memory improved even further between t=26 weeks and t=52 weeks. Continued treatment with memantine add-on to clozapine was associated with significantly improved PANSS positive, negative and overall score, CGI-S and HoNOS scores.

In the extension phase the positive effect of memantine add-on therapy on verbal memory sustained and positive, negative and overall symptoms of schizophrenia, clinical global status and psychosocial functioning significantly improved. Memantine was well tolerated without serious adverse effects.