Pharmacological interventions in hypoactive delirium: mapping the evidence through a scoping review

Hypoactive delirium is a frequently underrecognized subtype associated with increased morbidity and mortality, yet it lacks clearly established pharmacologic treatment strategies. This scoping review aimed to map and critically examine the existing evidence on pharmacological interventions specifically evaluated for hypoactive delirium in hospitalized adults, focusing on symptom severity and clinical outcomes. The available literature is limited and heterogeneous. Identified studies included randomized controlled trials, observational studies, and recent systematic reviews evaluating agents such as antipsychotics, dexmedetomidine, melatonin, flumazenil, and methylphenidate. However, most trials were small, methodologically diverse, and not specifically powered for the hypoactive subtype. Evidence supporting atypical antipsychotics remains inconsistent, and no high-quality randomized trials demonstrate clear benefit for routine use in hypoactive delirium. Alternative agents such as flumazenil and methylphenidate have been explored in limited or exploratory contexts, without consistent improvement in clinically meaningful outcomes. Current evidence does not support the routine use of any pharmacologic agent as a standard treatment for hypoactive delirium. Existing studies are constrained by small sample sizes, heterogeneity in diagnostic criteria and outcome measures, and overlap across systematic reviews and primary trials. Further well-designed, subtype-specific randomized controlled trials are needed to determine whether targeted pharmacologic strategies can improve outcomes in this vulnerable population.