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

Clozapine has a range of serious adverse effects that may give rise to an increased risk of death.

To 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.

Comparison of patients receiving clozapine and an age-matched control group receiving risperidone injection.

We 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 Clozapine was less likely to be withdrawn because of ineffectiveness than was risperidone (OR=0.034, 95% CI 0.01-0.14).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.

Clozapine 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.