Reasons for discontinuing clozapine: matched, case–control comparison with risperidone long-acting injection

Abstract

BackgroundClozapine has a range of serious adverse effects that may give rise to an increased risk of death.AimsTo compare reasons for discontinuation of clozapine with reasons for discontinuation of risperidone long-acting injection in age-matched individuals treated in the same clinical environment.MethodComparison of patients receiving clozapine and an age-matched control group receiving risperidone injection.ResultsWe established outcome for 529 consecutive patients receiving clozapine and 250 receiving risperidone (161 discontinuers from each group were compared). Adverse effects (odds ratio OR=2.19, 95% CI 1.31–3.67) and death (OR=7.0, 95% CI 2.09–23.5) were more commonly observed as reasons for discontinuation of clozapine than of risperidone. Clozapine was less likely to be withdrawn because of ineffectiveness than was risperidone (OR=0.034, 95% CI 0.01–0.14). Standardised mortality ratio (SMR) was significantly raised for patients receiving clozapine (SMR=4.17, 95% CI 2.78–6.26). Pneumonia was the most common single cause of death.ConclusionsClozapine use in patients with severe mental illness was associated with a significantly increased risk of death compared with that for the general population. Causation could not be established. Adverse effects and death are common causes of clozapine discontinuation.