Editorial – October 2013

Abstract

Clozapine was first synthesized more than 50 years ago but we are still using it, discussing it and finding out more about it. It is famously effective in refractory schizophrenia, for which it is both widely used and underused. It is also effective in bipolar disorder and psychosis associated with Parkinson’s disease, amongst other conditions. In this issue, Zarzar and McEvoy report on four compelling cases of clozapine reducing suicidal thoughts and self-harming activities in hospitalized patients with borderline personality disorder. In each case, the patient was highly suicidal and aggressive but after a few weeks of clozapine treatment (at what would normally be considered ‘subtherapeutic’ plasma concentrations) each patient was well enough to be discharged. Of course, clozapine’s beneficial effect on suicidality is well known in schizophrenia. These four cases suggest its antisuicidal effect is rather broader than previously thought. Clozapine treatment is often delayed because of fears about the drug’s wide range of potentially fatal adverse effects. The best known of these is neutropenia/agranulocytosis. When agranulocytosis occurs and is thought to be caused by clozapine, re-challenge is not often attempted. Granulocyte colony-stimulating factor (G-CSF) has occasionally been used for neutropenia occurring in patients taking clozapine, although only rarely when clozapine was thought to be the causative agent. Khan and colleagues describe three successful uses of G-CSF in patients in a secure setting with probable clozapine-induced neutropenia. That re-challenge was even considered (and then found to be effective) is perfect testament to clozapine’s efficacy. Three other case reports in this issue describe the resolution of difficulties associated with the use of clozapine. In one, the testosterone-suppressing drug goserelin was used to treat recurrent clozapine-induced priapism (a rare adverse effect of clozapine). In another, three metabolic inhibitors were used in turn to increase clozapine plasma concentrations: fluoxetine was too weak, fluvoxamine too strong, and cimetidine just right. In the third, a description of haematemesis related to clozapine-induced oesophagitis, resolution was achieved only by permanent discontinuation of clozapine. Also in this issue, a team from eastern England report on their very successful programme aimed at improving lithium monitoring, and workers and students from Iowa, USA review mechanisms involved in the effects of antipsychotics on the skeletons of young people.