Abstract
Background: Antidepressants are useful for treating mood disorders, but because of their cognitive and psychomotor adverse effects, they may make driving less safe. This study is the first network meta-analysis (NMA) comparing driving impairment across antidepressant classes using standardized measures.
Methods: We systematically searched five databases, including PubMed, Scopus, Embase, Cochrane CENTRAL, and Google Scholar, through June 2025. From 5285 screened records, we included 27 RCTs comprising 736 participants in this systematic review, with 13 studies eligible for network meta-analysis. We assessed driving performance using standardized mean differences with 95% credible intervals and ranked treatments by P-scores for treatment ranking.
Results: NMA revealed differential impairment patterns across antidepressant classes, with substantial heterogeneity observed. Paroxetine demonstrated dose-dependent effects, showing potential impairment at a 10 mg dosage but neutral effects at 20 mg. Mianserin 10 mg showed modest impairment, while most SSRIs, including fluoxetine and paroxetine 20mg, exhibited minimal driving effects. Sedating antidepressants such as amitriptyline and mirtazapine showed greater impairment, particularly during acute administration phases.
Conclusion: These findings demonstrate that clinicians should consider dose-dependent effects and monitor individual responses. Future research should employ standardized driving assessments in real-world populations to strengthen the evidence base.