Abstract
BackgroundClozapine is uniquely effective in the management of treatment-resistant schizophrenia (TRS). However, a substantial proportion of patients discontinue treatment and this carries a poor prognosis. MethodsWe investigated the risk factors, reasons and timing of clozapine discontinuation in a two-year retrospective cohort study of 316 patients with TRS receiving their first course of clozapine. Reasons for discontinuation of clozapine and duration of treatment were obtained from case notes and Cox regression was employed to test the association of baseline clinical factors with clozapine discontinuation. ResultsA total of 142 (45%) patients discontinued clozapine within two years. By studying the reasons for discontinuations due to a patient decision, we found that adverse drug reactions (ADRs) accounted for over half of clozapine discontinuations. Sedation was the most common ADR cited as a reason for discontinuation and the risk of discontinuation due to ADRs was highest in the first few months of clozapine treatment. High levels of deprivation in the neighbourhood where the patient lived were associated with increased risk of clozapine discontinuation (HR=2.12, 95% CI 1.30–3.47). ConclusionsLiving in a deprived neighbourhood was strongly associated with clozapine discontinuation. Clinical management to reduce the burden of ADRs in the first few months of treatment may have a significant impact and help more patients experience the benefits of clozapine treatment.
Highlights
Clozapine is uniquely effective in the management of treatment-resistant schizophrenia (TRS)
The majority of the 162 (51.3%) patients who were detained under the Mental Health Act at the time of clozapine initiation were under a section 3 or sections 37–49
We found that adverse drug reactions (ADRs) accounted for over half of clozapine discontinuations
Summary
Clozapine is uniquely effective in the management of treatment-resistant schizophrenia (TRS). By studying the reasons for discontinuations due to a patient decision, we found that adverse drug reactions (ADRs) accounted for over half of clozapine discontinuations. Given the benefits of clozapine treatment and the poor prognosis for those who discontinue, efforts have been made to identify patients that may be at increased risk of discontinuation and to understand the causes. The most common reasons for discontinuation identified in previous studies were patient decision, non-adherence and adverse drug reactions (Atkinson et al, 2007; Davis et al, 2014; Mustafa et al, 2015; Pai and Vella, 2012; Taylor et al, 2009). Patient decision and non-adherence have been identified as major reasons for discontinuation of clozapine, there has been no exploration of reasons behind this choice
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