Antidepressants and Road Safety: A Forensic Toxicological Perspective Based on Observational Data and Current Evidence

Background/Objectives: Antidepressants are widely prescribed medications that may affect psychomotor performance and driving ability depending on their pharmacological profile. This study investigated the prevalence and patterns of antidepressant use among drivers undergoing forensic toxicological evaluation and explored their potential implications for road safety. Methods: An observational study was conducted on n = 6316 drivers undergoing forensic toxicological assessment following licence suspension for driving under the influence (DUI) of alcohol and/or drugs between January 2023 and December 2025. Reported antidepressants were classified into selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), serotonin antagonist and reuptake inhibitors (SARIs), tricyclic antidepressants (TCAs), norepinephrine–dopamine reuptake inhibitors (NDRIs), noradrenergic and specific serotonergic antidepressants (NaSSAs), and monoamine oxidase inhibitors (MAOIs). Distribution patterns were analysed descriptively and discussed considering the available literature. Results: Antidepressant use was reported by n = 132 participants (2.1%). SSRIs were the most common class (44.0%), followed by SNRIs (26.5%) and SARIs (17.4%). TCAs (6.1%), NDRIs (3.7%), and NaSSAs (2.3%) were less common, while no MAOI use was reported. Among antidepressant users, n = 28 individuals (21.2%) tested positive for other psychoactive substances, including benzodiazepines, cocaine, and cannabinoids. Conclusions: The use of antidepressants was relatively uncommon in the study population. However, clinical evaluation remains important, particularly at the start of treatment and during dose adjustments to determine the potential for an increased risk while driving. Further studies integrating toxicological analyses and clinical data are needed to better define the relationship between antidepressant exposure, polysubstance use, and road safety.