Haloperidol Versus Placebo for Delirium Prevention in Acutely Hospitalised Older at Risk Patients

A Multi-centre Double-blind Randomised Controlled Clinical Trial

Edmée J.M. Schrijver; Oscar J. De Vries; Peter M. Van De Ven; Pierre M. Bet; AD M. Kamper; Sabine H.A. Diepeveen; Rob J. Van Marum; Astrid M. Van Strien; Sander Anten; Anne M. Lagaay; Leo Boelaarts; Frank W. Bloemers; Mark H.H. Kramer; Prabath W.B. Nanayakkara


Age Ageing. 2018;47(1):48-55. 

In This Article

Abstract and Introduction


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.


Delirium[1] is a frequent problem in acute clinical settings and may occur in up to 37% and 51% of older acute medical[2] and hip-fracture[3] admissions, respectively. Older patients who develop delirium experience more functional dependency and are at greater risk for institutionalisation and death,[2,4,5] underlying the importance of adequate delirium prevention.

Although multicomponent delirium prevention strategies that target orientation, circadian rhythm, early mobilisation, maintaining optimal fluid and nutritional status are effective in reducing delirium incidence,[6,7] implementation and adherence challenges remain.[8] Studies examining the efficacy of pharmacological interventions to prevent delirium have demonstrated contradicting results.[9] Haloperidol is currently the drug of choice for treatment of delirium symptoms.[10,11] Although there is a growing interest in the use of haloperidol for delirium prevention, evidence is limited and on the basis of current studies no definite conclusions can be drawn on its effectivity in general in-hospital older patients.[12]

We therefore aimed to assess the efficacy of prophylactic haloperidol in lowering delirium incidence in a population of older, acutely admitted, medical and surgical patients. Secondary aims were to assess its safety and impact on clinical outcomes.