Previous studies have suggested that use of antidepressant medications may reduce the risk of developing infections. One possible reason for this may be that there is something in the medication that inhibits the production of certain enzymes that affect the death of important immune cells. Thus, antidepressants may prevent the death of immune cells which may, in turn, help the body fight infections. In laboratory studies, many antidepressants have been shown to inhibit this enzyme, but it remains unknown whether use of antidepressants may actually translate into the prevention of infections in the general population.
The potential association between antidepressants and infections is currently of particular importance given the COVID-19 pandemic and the subsequent search for drugs that may prevent infections. We plan to use data from the Clinical Practice Research Datalink (CPRD) GOLD to examine the risk of infection among patients who newly started a treatment with commonly used antidepressants in the UK.
Antidepressants interact with the immune system, but the exact mechanism of this interaction is not yet fully understood. Amongst other mechanisms of action, antidepressants inhibit acid sphingomyelinase (ASM), thereby reducing the concentration of ceramide, and consequently reducing apoptosis of important immune cells. However, the extent of a potentially beneficial effect of antidepressants on immune function in the general population has not yet been investigated.
We aim to conduct a retrospective cohort study using CPRD GOLD data to assess the incidence of acute infections (respiratory, genitourinary, gastrointestinal, septicemia and SARS-CoV-2) in patients with a new prescription of one of the five most frequently prescribed antidepressants in the UK. These five cohorts will include female and male patients above the age of 18 years with first-time antidepressant prescriptions, who meet certain inclusion and exclusion criteria. We will compare the risk of acute infection between users of different antidepressants (fluoxetine, sertraline, paroxetine, and venlafaxine) in pairwise comparisons to users of the antidepressant citalopram (which showed the least inhibitory effect on ASM in prior in vitro studies).
We will calculate incidence rate ratios (IRRs) with 95% confidence intervals (CIs) to quantify the risk of acute infections in new users of different antidepressants. We will control for multiple baseline covariates by weighting comparison patients by fine strata of the propensity score of the exposed group.
This study will generate new information for the public on whether certain antidepressants, compared with citalopram, may protect against acute infections, including COVID-19.
The number of recorded diagnoses of either one of the following acute infections (Read codes will be counted as separate episodes of infections if they are recorded at least 14 days apart, in Appendix):
- Respiratory infections
- Urogenital infections
- Gastrointestinal infections
- Septicemia
- SARS-CoV-2 infections
Susan Jick - Chief Investigator - BCDSP - Boston Collaborative Drug Surveillance Program
Noah Aebi - Corresponding Applicant - University of Basel
- Collaborator -
Christoph Meier - Collaborator - University of Basel
Johannes Kornhuber - Collaborator - Friedrich-Alexander Universitat Erlangen-Nurnberg
Undine Lang - Collaborator - University of Basel