Making clozapine safer: current perspectives on improving its tolerability

Abstract

ABSTRACT:  Clozapine is the gold standard treatment for refractory schizophrenia and its benefits are supported by an evidence base. Yet, it remains largely underused in clinical practice. This is because of low acceptability from patients and reluctance in initiating, and delays in prescribing by clinicians. A major deterrent is often the common adverse reactions, which clinicians are apt to disregard, focusing instead on the severe but rare complications of clozapine, such as agranulocytosis. We will review recent evidence on increasing the prescription of clozapine, focusing particularly on improving the safety and tolerability of the drug, by effective management of its adverse effects. The adverse effects considered in our review include sedation, seizures, myoclonus, hypersalivation, nausea, constipation, hypotension, hypertension, tachycardia, myocarditis, cardiomyopathy, weight gain, diabetes, dyslipidemia, neutropenia, agranulocytosis, fever, nocturnal enuresis and obsessive–compulsive symptoms. We will also discuss strategies to enable successful clozapine rechallenge after severe cardiac and hematological adverse reactions, thus aiming to offer patients their best chance at recovery.