Haloperidol versus placebo for delirium prevention in acutely hospitalised older at risk patients: A multi-centre double-blind randomised controlled clinical trial

Background: because the few randomised placebo-controlled trials investigating the potential role for prophylactic haloperidol in delirium prevention have focused on specific surgical populations, we investigated its efficacy and safety in acutely hospitalised older patients.Methods: this multi-centre, double-blind, stratified, block randomised, placebo-controlled trial was conducted at six Dutch hospitals. Patients age ≥ 70 years, acutely admitted through the emergency department for general medicine or surgical specialties and at risk for delirium were randomised (n = 245) to haloperidol or placebo 1 mg orally twice-daily (maximum of 14 doses) on top of standard nonpharmacological prevention strategies. The primary outcome was delirium incidence. Other endpoints included delirium severity and duration, drug safety and clinical outcomes.Results: intention-to-treat analysis included 242 participants (calculated sample size n = 390, statistical power of current sample 59%) allocated to haloperidol (n = 118) or placebo (n = 124). In the haloperidol and placebo group, delirium incidence was 19.5 versus 14.5% (OR 1.43, 95% CI 0.72 to 2.78); median (IQR) delirium duration 4 (2, 5) versus 3 (1, 6) days (P = 0.366); maximum DRS-R-98 score 16 (9.8, 19.5) versus 10 (5.5, 22.5) (P = 0.549; 53.7% missing data); hospital LOS 7 (4, 10.3) versus 7 (5, 11.8) days (P = 0.343); 3-month mortality 9.9 versus 12.5% (OR 0.77, 95% CI 0.34 to 1.75), respectively. No treatment-limiting side effects were noted.Conclusions: prophylactic low-dose oral haloperidol did not reduce delirium incidence in acutely hospitalised older patients. Therefore, prophylactic use of haloperidol in this population is not recommended.