Mortality in children and adolescents prescribed antipsychotic medication: a retrospective cohort study using the UK general practice research database.

BACKGROUND: Antipsychotic prescribing in children has risen in many countries; however, the safety of these agents in the young has not yet been fully established. Potentially fatal antipsychotic-related adverse events include cardiac complications and neuroleptic malignant syndrome.
OBJECTIVE: The objective of this study was to investigate mortality in children and adolescents taking antipsychotic medication.
METHODS: The General Practice Research Database (GPRD) was used as a data source for this study. Cases were identified from a cohort of patients previously studied. The study population encompassed all patients aged 18 years and under who received at least one prescription for an antipsychotic from 1 January 1992 to 31 December 2005. Patients were followed from the date of the first antipsychotic drug prescription until the earliest occurrence of a code of death, age >18 years or the end of the study period. Cases of death were identified by screening patients' medical records for clinical or referral events with events indicating death, or if a transferred-out patient has a 'transfer out reason' specified as 'death'. Confirmation of cases was carried out by examining individual patient profiles and from questionnaires sent to GPs. If necessary, the death certificates and/or post mortem reports were obtained by the source data verification service the GPRD provide. Once cases of death were identified, crude mortality rate (CMR) and standardized mortality ratio (SMR) were calculated. Baseline mortality rates were obtained from the Office for National Statistics. A modified WHO causality assessment was conducted to determine the likelihood of a relationship between the drug and an event of death.
RESULTS: The cohort contained 2767 patients who received at least one antipsychotic prescription. There were 30 deceased cases in the cohort. The GP questionnaire response rate was 97%. Of the 30 cases, 24 were related to pre-existing medical conditions, including neoplastic diseases and HIV. After excluding these patients, six cases of death from 5963 person-years and 1958 treatment-years remained. The median age of death was 17 years (interquartile range 14-17.75). The overall CMR was 1.01 per 1000 person-years at risk (95% CI 0.20, 1.81) and SMR was 4.03 (95% CI 1.48, 8.76). Of the six cases, only one was deemed possibly associated with antipsychotic therapy, based on the causality assessment analysis conducted; CMR based on this case was 0.51 per 1000 treatment-years (95% CI 0.09, 2.89). The remaining five cases of death were unlikely to be associated with antipsychotic therapy.
CONCLUSIONS: Our study demonstrated an elevated SMR in patients exposed to antipsychotics. However, the elevated SMR was unlikely caused by antipsychotic treatment, but would suggest the possibility of inadequate management or poor control of patients' underlying medical conditions prior to death.