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

Abstract

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 cancerregistries 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.

Risk of Breast Cancer With Prolactin Elevating Antipsychotic Drugs

“…Mentally ill patients face disparities in screening/prevention of common cancers and are more likely to die from breast cancer, and women with psychotic disorders are about half as likely as the general population to receive mammography screening 35 . Our data and the other publications 36–43 reviewed previously suggest that the use of antipsychotic drugs that elevate prolactin may contribute to incident cases of breast cancer. We also report a surprisingly elevated association of breast cancer risk with category 2 drugs, particularly in younger women, aged 18 to 50 years.…”

Antipsychotic exposure is an independent risk factor for breast cancer: A systematic review of epidemiological evidence

“…Moreover, we examined all-cause mortality in the available studies. Data from the study by Hicks ( 30 ) suggested higher all-cause mortality in patients with cancer who were exposed to antipsychotics (OR, 1.54; 95% CI, 1.29–1.82). A summary of our findings is provided in Table 2 .…”

Association between prolactin increasing antipsychotic use and the risk of breast cancer: a retrospective observational cohort study in a United States Medicaid population

“…Numerous observational studies have been conducted examining the relationship between antipsychotic use and breast cancer outcomes. In a dozen such studies that were reviewed, findings were mixed (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Many studies found no evidence of association between exposure to prolactin increasing antipsychotics and breast cancer, while others, reported positive associations, including recent publications by Taipale et al and Rahman et al (10,11).…”