Introduction

Affecting more than 21 million people worldwide, schizophrenia is associated with considerable health, societal and economic costs.1–3 Approximately, one-third of people with schizophrenia fail to respond to first-line antipsychotic medication, with a similar proportion only partially responding.3,4 It has been estimated that treatment resistance constitutes about 60%–80% of the total annual cost associated with schizophrenia.5,6

Clozapine is the only antipsychotic drug licensed for use in treatment-refractory schizophrenia. The authors of one systematic review (40 studies, 5172 participants) reported that there was insufficient evidence to determine which antipsychotic is more efficacious for patients with treatment-resistant schizophrenia, while randomised controlled trials, including three large effectiveness studies, and one systematic review (21 studies, 2364 participants) concluded that clozapine was superior to other antipsychotics for positive symptoms.7–11 Some studies also suggest short-term advantages in managing negative symptoms and suicidality.11,12 In a recent retrospective study involving a small number of participants, 75% of people suffering first-onset treatment-refractory schizophrenia responded to clozapine.13

Despite a recommendation from the National Institute for Health and Care Excellence (NICE) to offer clozapine to people who have treatment-refractory schizophrenia, there is often a prolonged delay before clozapine is introduced, and the use of high doses and more than two non-clozapine antipsychotic drugs is common.14–17 Clinical inexperience and the need for routine haematological monitoring, as well as concerns …