Review 10.1517/14740330802257442 © 2008 Informa UK Ltd ISSN 1474-0338 525 All rights reserved: reproduction in whole or in part not permitted The safety of clozapine in the elderly Pietro Gareri † , Pasquale De Fazio, Emilio Russo, Norma Marigliano, Salvatore De Fazio & Giovambattista De Sarro † University “Magna Græcia” of Catanzaro, Mater Domini University Hospital, School of Medicine, Clinical Pharmacology Unit, Department of Experimental and Clinical Medicine, via Tommaso Campanella, 115, 88100 Catanzaro, Italy Background: Clozapine was the first atypical ‘broad spectrum’ antipsychotic drug to be marketed and the first agent approved for the treatment of schizophrenia refractory to other medications. It is also effective for the treatment of aggressive behaviour in schizophrenic and demented patients and in the management of psychosis and aggression in Parkinson’s disease and Lewy body dementia. Objective: The aim of this review is to study the safety of clozapine for use in elderly patients. Methods: An extensive Medline search was made. Some studies that were referenced in reports from our pharmacovigilance centre and from regulatory agencies such as the FDA, EMEA and WHO were included. Conclusions: Clozapine treatment in the elderly requires a careful geriatric assessment. However, its use is strongly limited by the possibility of onset of severe adverse effects such as potentially fatal agranulocytosis, myocarditis and others such as seizures, weight gain and metabolic adverse effects. Keywords: adverse effects, agranulocytosis, clozapine, cytochromes, elderly, genetic polymorphism, safety Expert Opin. Drug Saf. (2008) 7(5):525-538 1. Introduction Antipsychotic drugs are now used in the elderly for treatment of psychoses, schizophrenia, behavioural and psychological symptoms of dementia, agitation, insomnia and so on. In recent years, second-generation antipsychotics such as clozapine, also named ‘atypical’ antipsychotics, were introduced; they have new receptor binding profiles by interacting with both dopamine and serotonin receptors. They have reduced extrapyramidal symptoms (EPS) and a good efficacy with respect to the negative symptoms of psychosis [1]; however, their use in elderly patients to treat behavioural and psychological symptoms of dementia is restricted because of recent observations of increased cardiovascular events in patients taking risperidone and olanzapine [1,2]. Atypical antipsychotics include serotonin-dopamine antagonists (SDA), such as risperidone, ziprasidone and sertindole, and multiple acting receptors targeted antipsychotics (MARTA); the latter are antipsychotic drugs whose receptor binding profile is wide, involving also muscarinic, adrenergic and histamine receptors including clozapine, olanzapine, quetiapine and zotepine [3]. The aim of the present work is to study the safety of clozapine for use in elderly patients. Talking about safety in the elderly is a remarkable matter requiring a review on pharmacology of clozapine, its age-dependent pharmacokinetic and pharmacodynamic changes and its adverse effects. An extensive Medline search was made using clozapine and its combination with cytochromes, elderly, safety and adverse effects as keywords. We also included some studies referenced in reports from our pharmacovigilance centre. Furthermore, 1. Introduction 2. Clozapine 3. Adverse effects of clozapine 4. Conclusions 5. Expert opinion Copia ad esclusivo uso personale da non lasciare a terzi