Efficacy and safety of guanfacine in hospitalized patients with delirium: A scoping review

Objective: To assess current evidence regarding guanfacine use in hospitalized patients with delirium. Introduction: Delirium is a common and important complication of critical illness. Central alpha-2 agonists are often used for symptomatic management. Guanfacine is an enteral central alpha-2 agonist approved for the treatment of attention deficit hyperactivity disorders. However, its use for delirium treatment has not been systematically assessed. Inclusion criteria: All studies of guanfacine to treat patients with delirium during hospitalization. We excluded reviews, letters, commentaries, correspondence, conference abstracts, expert opinions or editorials. Methods: We performed a systematic search of the literature using: MEDLINE (Ovid), Embase (Ovid), CENTRAL and SCOPUS (Elsevier) from inception until 29 February, 2024. Two independent reviewers assessed the identified citations and abstracts. Data on study and patient characteristics, as well as efficacy and safety outcomes, were extracted. Efficacy was defined by guanfacine's ability to relieve delirium and improve clinical outcomes, including intensive care unit (ICU) length of stay (LOS), hospital LOS, and mortality. Safety was assessed for hemodynamic stability or other reported side effects. Results: We screened 908 articles and included two case reports, one case series, two retrospective descriptive cohorts, and one retrospective analytic cohort. Guanfacine therapy was associated with delirium attenuation and a reduction in the use of sedative agents. Median dosage was 1.5 mg daily, with a median time to delirium improvement of 3 days. However, guanfacine therapy was not associated with decreased ICU or hospital LOS. The most frequently reported adverse events were mild hypotension and bradycardia. Conclusion: There is limited data on the efficacy of guanfacine for the treatment of delirium. However, given its pharmacologic properties and its available safety data, controlled investigations may be justified.