Impact of Antidepressant Use and Serotonergic Profile on Short-Term Outcome of Traumatic Brain Injury: Retrospective Nationwide Cohort Study.

Abstract

Concerns have been raised that the use of serotonergic antidepressants may increase the risk of intracranial hemorrhage and worsen outcomes following traumatic brain injury (TBI). However, large-scale evidence on their impact on TBI outcomes remains limited. Our aim was to investigate the association between preinjury antidepressant use, antidepressant type and serotonergic profile, and the short-term outcome of TBI, focusing on mortality, acute neurosurgical operations (ANOs), and length of hospitalization. This nationwide, retrospective cohort study included all patients aged ≥16 years admitted with TBI (ICD-10 S06.*) in Finland between 2005 and 2018. Preinjury antidepressant (Anatomical Therapeutic Chemical codes N06A* and N06CA*) use was identified from national prescription records using daily pill counting method and categorized by serotonergic profile (weak, intermediate, strong). The primary outcome was 30-day mortality, while secondary outcomes included ANOs and length of hospitalization. Cox proportional hazards models were used for mortality analysis, modified Poisson regression models for ANOs, and linear regression models for hospitalization, adjusting for age, sex, comorbidities, vitamin K antagonists (VKAs) use, admission location, and study year. Of 54,876 patients with TBI, 7,845 (14.3%) were taking antidepressants at the time of injury. Adjusted models showed no significant association between antidepressant use and 30-day mortality (adjusted hazard ratio 0.98; 95% CI 0.90-1.07; <i>p</i> = 0.696). Serotonergic profile or type of antidepressant was not associated with mortality. Antidepressant users had a lower likelihood of ANOs (adjusted relative risk 0.89; 95% CI 0.82-0.97; <i>p</i> = 0.007). Length of hospitalization did not differ between groups. Antidepressant use, profile, or type did not modify the association of VKA use with increased mortality or ANOs in the interaction analyses. Preinjury antidepressant use, regardless of antidepressant type or serotonergic profile, was not associated with increased mortality, increased need for ANOs, or prolonged hospitalization in TBI patients. No interaction was found between VKA use and antidepressant use, serotonergic class, or type of antidepressant, suggesting that antidepressants do not exacerbate the adverse impact of VKA on these outcomes. Overall, our results suggest that preinjury antidepressant use does not worsen early clinical outcomes after TBI.