A case-control study of antipsychotic use and pneumonia-related mortality in the United Kingdom

There is increasing evidence linking antipsychotic use with pneumonia, but limited evidence of an effect on pneumonia-related outcomes such as mortality. In this study, we aimed to examine the association of pneumonia-related death with specific antipsychotic exposure.

Deaths analysed were those reported to a UK-based drug-related deaths database, the National Programme on Substance Abuse Deaths (NPSAD), between 1997 and September 2020. We conducted a case-control study with cases defined as pneumonia-related deaths and controls as cases with alternative causes of death. Cases were analysed by considering drugs detected at post-mortem (PM) and by drugs prescribed to the deceased at the time of their death with calculated odds ratios (ORs) adjusted to account for confounders.

There were 2467 PM cases and 40,128 controls; 1818 prescribed cases and 28,018 controls. Second generation antipsychotics (SGAs) were robustly associated with an increased risk of pneumonia-related death compared with those not prescribed or taking antipsychotics (PM detection adjusted OR [AOR] 1·34 [95% CI 1·15-1·55]; prescribed AOR 1·28 [95% CI 1·11-1·49]). First generation antipsychotics had no clear association with death from pneumonia (PM detection AOR 1·06 [95% CI 0·77-1·47]; prescribed AOR 0·91 [95% CI 0·71-1·17]). Amongst SGAs, olanzapine was associated with an increased risk of death due to pneumonia (PM detection AOR 1·49 [95% CI 1·22-1·82]; prescribed AOR 1·44 [95% CI 1·18-1·76]) as was quetiapine (PM detection AOR 1·34 [95% CI 1·07-1·66]; prescribed AOR 1·28 [95% CI 1·01-1·64]).

Olanzapine and quetiapine were found to increase the risk of pneumonia-related death in this NPSAD sample to a clinically important extent.