Is poor dose selection undermining the translational validity of antidepressant research involving animal models?
bioRxiv (Cold Spring Harbor Laboratory) November 1, 2025 Dasha Anderson, Justyna Hinchcliffe, Megan Jackson et al. 1 citation preprint
Antidepressant doses used in conventional rodent models of depression often exceed those used in clinical practice by 1.5 to 25 times, potentially engaging mechanisms irrelevant to human therapeutic effects. A review of forced swim test studies found median doses of 10 mg/kg across antidepressants, while the more recently developed affective bias test showed doses closer to clinical levels. In a separate analysis of 232 ketamine and 202 fluoxetine rodent studies, median doses were also 10 mg/kg, exceeding animal equivalent doses by 1.6–6.5 times. This mismatch may explain why positive preclinical results often fail to translate into clinical efficacy.