Reasons for discontinuing clozapine: matched, case-control comparison with risperidone long-acting injection.
BACKGROUND
Clozapine has a range of serious adverse effects that may give rise to an increased risk of death.


OBJECTIVE
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.


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


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 Clozapine was less likely to be withdrawn because of ineffectiveness than was risperidone (OR=0.034, 95% CI 0.01-0.14).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


CONCLUSIONS
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.
Taylor
David M
DM
Pharmacy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London SE5 8AZ, UK. David.Taylor@slam.nhs.uk
Douglas-Hall
Petrina
P
Olofinjana
Banke
B
Whiskey
Eromona
E
Thomas
Arwel
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D002423:Cause of Death; D003024:Clozapine / Q000009:adverse effects*; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D018967:Risperidone / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy* / Q000401:mortality; D016312:Treatment Refusal; D055815:Young Adult
D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D003024:Clozapine; D018967:Risperidone