Antidepressants and the risk of traumatic brain injury in the elderly: differences between individual agents

To determine the association of individual antidepressants (ADs) with the risk of traumatic brain injury (TBI) in the elderly.

We conducted a case-control study nested in a cohort of new users of ADs aged ≥65 years, identified in the German Pharmacoepidemiological Research Database during 2005-2014. Cases were patients first hospitalized for TBI. Up to 100 controls per case were selected using incidence density sampling. AD use was ascertained at the index date based on the supply of last dispensing (adding 150% of the defined daily doses [DDDs]; in sensitivity analysis, no additional DDDs were considered). We estimated adjusted ORs (aORs) and 95% CIs using conditional logistic regression.

Among 701,309 cohort members, 16,750 cases were identified and matched to 1,673,320 controls (in both groups: 70.4% women; median age 80 years). Compared with remote users of the same AD, current users had an aOR (95% CI) of 1.87 (1.56-2.24) for duloxetine, 1.74 (1.41-2.15) for escitalopram, 1.70 (1.58-1.83) for citalopram, 1.66 (1.40-1.97) for sertraline, 1.64 (1.24-2.15) for fluoxetine and 1.57 (1.20-2.06) for paroxetine. The aOR was lower for amitriptyline (1.45; 1.32-1.58), trimipramine (1.17; 0.99-1.38) and opipramol (1.11; 0.99-1.25). Mirtazapine had an aOR of 1.03 (0.94-1.12). Sensitivity analysis confirmed the findings.

The large variability between individual ADs shows the importance of considering the safety of individual agents rather than focusing on class alone.