Mortality and adverse events associated with statin use in primary care patients with depression: a real-world, population-based cohort study.

Background: New National Institute for Health and Care Excellence (NICE) guidance endorses the prescription of statins in larger population groups for the prevention of cardiovascular and cerebrovascular morbidity and mortality, especially in people with severe mental illness. However, the evidence base for their safety and risk/benefit balance in depression is not established.
Objectives: This study aims to assess the real-world mortality and adverse events of statins in depressive disorders.
Methods: Population-based, nationwide (England), between-subject, cohort study. We used electronic health records (QResearch database) of people aged 18-100 years with first-episode depression, registered with English primary care practices over January 1998-August 2020 for 12(+) months, divided into statin users versus non-users.Primary safety outcomes included all-cause mortality and any adverse event measured at 2, 6 and 12 months. Multivariable logistic regression was employed to control for several potential confounders and calculate adjusted ORs (aORs) with 99% CIs.
Findings: From over 1 050 105 patients with depression (42.64% males, mean age 43.23±18.32 years), 21 384 (2.04%) died, while 707 111 (67.34%) experienced at least one adverse event during the 12-month follow-up. Statin use was associated with lower mortality over 12 months (range aOR _2-12months 0.66-0.67, range 99% CI 0.60 to 0.73) and with lower adverse events over 6 months (range aOR _2-6months 0.90-0.96, range 99% CI 0.91 to 0.99), but not at 1 year (aOR _12months 0.99, 99% CI 0.96 to 1.03). No association with any other individual outcome measure (ie, any other neuropsychiatric symptoms) was identified.
Conclusions: We found no evidence that statin use among people with depression increases mortality or other adverse events.
Clinical Implications: Our findings support the safety of updated NICE guidelines for prescribing statins in people with depressive disorders.
Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/ and declare the following: RDG is supported by the Wellcome Trust (award 102176/Z/13/Z, grant 216452/Z/19/Z, title 'The effects of anti-inflammatory drugs on emotional and reward processing'). FDC is supported by the National Institute for Health Research (NIHR) Research Professorship to AC (grant RP-2017-08-ST2-006) and by the NIHR Oxford Health Biomedical Research Centre (grant BRC-1215-20005). EGO is supported by the NIHR Research Professorship to AC (grant RP-2017-08-ST2-006). PC is supported by the Medical Research Council (MRC) (grant MR/S003037/1, title 'Clinical Psychopharmacology of Depression'). CJH is supported by the NIHR Oxford Health Biomedical Research Centre. SF is supported by the NIHR Oxford Health Biomedical Research Centre. AC is supported by the NIHR Oxford Cognitive Health Clinical Research Facility, by an NIHR Research Professorship (grant RP-2017-08-ST2-006), by the NIHR Oxford and Thames Valley Applied Research Collaboration, by the NIHR Oxford Health Biomedical Research Centre (grant BRC-1215-20005) and by Wellcome Trust (GALENOS Project). CJH has received consultancy fees from P1vital, Lundbeck, Servier, UCB, Zogenix, J&J and Syndesi outside of the current work. AC has received research and consultancy fees from INCiPiT (Italian Network for Paediatric Trials), CARIPLO, Lundbeck and Angelini Pharma outside of the current work. The other authors declare that they have no conflict of interest.
(© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)