The Effects of SSRIs and Antipsychotics on Long COVID Development in a Large Veteran Population

The development of Long COVID is a complex disease process that may be partially driven by neuroinflammation. Antipsychotics have been shown to exert neuroprotective effects under certain conditions. Our study aimed to determine if veterans treated with antipsychotics and/or selective serotonin reuptake inhibitors (SSRIs) for a psychiatric condition had a reduced risk of developing long-term COVID. We conducted a retrospective cohort study with two cohorts of patients based on the COVID-19 wave in which the patient’s initial infection occurred (Cohort 1: alpha/beta waves, and Cohort 2: delta/omicron waves) with stratification by age. A multivariate logistic regression model was used to evaluate the association between the use of antipsychotics and Long COVID diagnosis. In Cohort 1, antipsychotic use was associated with 43% and 34% reductions in the odds of developing Long COVID in patients aged <65 and >65 years, respectively. This association was reduced in the second cohort to 11% in patients aged <65 years and without an association over 65 years of age. SSRIs showed no benefit in either age group or cohort. Our results show that antipsychotic use for the treatment of a mental health condition was associated with a reduction in the risk of developing Long COVID, and the magnitude of this reduction varied between COVID-19 cohorts.