Journal Article

Post-diagnostic antipsychotic use and cancer mortality: a population based cohort study

Cardwell, Chris R., Busby, John, O’Neil, Francis A., Zhang, Shu-Dong, Hicks, Blánaid M., Mills, Ken, McIntosh, Stuart A., Liberante, Fabio Giuseppe

2020

Overview

Background Many antipsychotics elevate prolactin, a hormone implicated in breast cancer aetiology however no studies have investigated antipsychotic use in patients with breast cancer. This study investigated if antipsychotic use is associated with an increased risk of cancer-specific mortality among breast cancer patients. Methods A cohort of 23,695 women newly diagnosed with a primary breast cancer between 1st January 1998 and 31st December 2012 was identified from the UK Clinical Practice Research Datalink linked to English cancer-registries and followed for until 30th September 2015. Time-dependent Cox proportional hazards models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer-specific mortality comparing use of antipsychotics with non-use, overall, and by prolactin elevating activitiy. Analyses were repeated restricting to patients with a history of severe mental illness to control for potential confounding by indication. Results In total 848 patients were prescribed an antipsychotic and of which 162 died due to their breast cancer. Compared with non-use, antipsychotic use was associated with an increased risk of breast-cancer specific mortality (HR 2.25, 95%CI 1.90–2.67), but this did not follow a dose response relation. Restricting the cohort to patients with severe mental illness attenuated the association between antipsychotic use and breast cancer-specific mortality (HR 1.11, 95%CI 0.58–2.14). Conclusions In this population-based cohort of breast cancer patients, while the use of antipsychotics was associated with increased breast cancer-specific mortality, there was a lack of a dose response, and importantly null associations were observed in patients with severe mental illness, suggesting the observed association is likely a result of confounding by indication. This study provides an exemplar of confounding by indication, highlighting the importance of consideration of this important bias in studies of drug effects in cancer patients.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Aged / Antipsychotic Agents - adverse effects / Antipsychotics / Bias / Biomedical and Life Sciences / Biomedicine / Bipolar disorder / Breast cancer / Breast Neoplasms - diagnosis / Breast Neoplasms - mortality / Breast Neoplasms - therapy / Cancer / Cancer Research / Cancer therapies / Cohort analysis / Confounding Factors, Epidemiologic / Droperidol / Drug dosages / Drug Prescriptions - statistics & numerical data / Epidemiology / Female / Follow-Up Studies / Health Promotion and Disease Prevention / Hormone replacement therapy / Humans / Medical diagnosis / Medical screening / Medicine/Public Health / Mental disorders / Mental Disorders - diagnosis / Mental Disorders - drug therapy / Mental Disorders - epidemiology / Mentally ill persons / Middle Aged / Mortality / Oncology / Patient outcomes / Patients / Population / Population studies / Population-based studies / prevention and public health / Prolactin / Proportional Hazards Models / Psychosis / Psychotropic drugs / Registration / Registries - statistics & numerical data / Research Article / Risk Factors / Schizophrenia / Severity of Illness Index / Surgical Oncology / Survival / Survival Analysis / United Kingdom - epidemiology