Pharmacotherapeutic approaches for the effective treatment of postoperative delirium: the state of play.

Introduction: Post-operative delirium (POD) is a common neuropsychiatric complication that is associated with increased morbidity, prolonged hospital stays, and persistent cognitive deficits. Despite its clinical relevance, pharmacologic treatment options remain limited and inconsistently supported by evidence.

Areas covered: In this review, the authors synthesize the current understanding of pathophysiological mechanisms underlying POD then critically evaluate the evidence around pharmacotherapeutic interventions, focusing on the use of antipsychotics, cholinesterase inhibitors, sleep-wake cycle modulators, and dexmedetomidine, in the treatment of established delirium. Relevant articles were identified using PubMed, EMBASE, and Cochrane databases.

Expert opinion: There remains insufficient evidence to support the routine use of pharmacologic interventions in the treatment of POD. While the evidence supporting dexmedetomidine seems most promising, its clinical significance is questionable and therefore its impact is likely in prevention rather than treatment. Various methodological challenges, including heterogeneity in trial design and insufficient stratification by delirium subtype, hinder generalizability of study results and advancements in how delirium is understood. Future progress will depend on reconceptualizing delirium away from a purely descriptive condition and toward a heterogenous, biologically driven disorder.