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This single-center, retrospective cohort study investigated the effects of timing of initiating home neuropsychiatric medications (NPMs) on sedation-related outcomes.Subjects included adult medical intensive care unit (MICU) patients who had an NPM on their admission medication list; intubated before or on arrival to the intensive care unit (ICU); and were on benzodiazepine-based sedation. The intervention assessed was the timing of the initiation of home NPMs: early (≤5 days) vs. late (>5 days) into the ICU stay.There were 56 and 53 patients in the early and late restart groups, respectively. Early cohort patients maintained a median daily RASS of −1.5, while late cohort patients had a median daily RASS of −2.0 (p = 0.02). The effect was driven by the subgroup of patients on home anti-depressant therapy who were restarted early on these agents. The early restart group had a higher percentage of days with RASS scores within goal (p = 0.01) and less delirium (p = 0.02). Early restarting of home NPMs was associated with a non-significant decrease in ventilator days compared with late restarting (p = 0.11).Restarting home NPMs was associated with lighter sedation levels and less delirium.