Tabriz University of Medical Sciences Pharmaceutical Sciences 1735-403X 32 4 2026 10 31 Antidepressants and Road Safety: A Systematic Review and Network Meta-Analysis of RCTs on Driving Impairment 520 535 10.34172/ps.43327 EN Homayoun Sadeghi-Bazargani https://orcid.org/0000-0002-0396-8709 Razieh Abdolrahmanzadeh https://orcid.org/0000-0002-0237-1396 Mahshad Narimani Melika Ahmadi Bonabi Sepita Taghizadeh Morteza Ghojazadeh https://orcid.org/0000-0002-9946-9452 REVIEW 10.34172/ps.43327 2025 10 02 2026 02 17 Introduction: 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 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: In conclusion, the effects of antidepressants on driving performance vary according to the type and dose of medication, with sedating antidepressants showing greater potential for driving impairment, particularly during acute administration. Clinicians should consider dose-dependent effects and individual responses when prescribing antidepressants to patients who drive. Further research using standardized driving assessments in real-world populations is needed to strengthen the evidence base.