Efficacy and Safety of Risperidone and Trazodone Monotherapy and Combination Therapy in Critically Ill Patients With Delirium

Delirium is defined as a disturbance of consciousness characterized by an acute onset of
impaired cognitive function. Although delirium is thought to be common in the Intensive Care
Unit (ICU) there are few studies that have evaluated its incidences, risks and outcomes. It
has been associated with increased morbidity, and mortality and increased cost to the
healthcare system. In addition to the uncertainty of the incidence of ICU delirium, there is
a lack of information about the effects that certain pharmacological treatments have on
delirious patients.

The rationale for this study is to evaluate the efficacy and safety of risperidone alone,
trazodone alone, and risperidone plus trazodone for the treatment of delirium in critically
ill patients when compared to placebo.

Inclusion Criteria:

- Age greater than 18 years old who are admitted for more than 24 hours in the MICU or
SICU

- Patients diagnosed with delirium by primary team (screened positive for delirium
using the CAM-ICU or with clinical manifestations of delirium)

- Patients have an order for as-needed haloperidol or have received a one-time dose of
haloperidol within 24 hours of randomization

- Patients must be tolerating enteral feeding (greater than 20 mL/hour for more than 12
hours)

Exclusion Criteria:

- Patients who are unlikely to survive 24 hours after admission to the ICU

- Patients who are admitted with a primary neurological condition or injury (i.e.
stroke, active seizures, prolonged coma, overdose)

- Patients who can not actively participate in delirium assessment

- Patients actively withdrawing from alcohol or narcotics

- Patients who were treated with any antipsychotic or trazodone within 30 days prior to
ICU admission

- Patients with a marked baseline prolongation of the QTc interval (repeated
demonstration of QTc interval greater 500 milliseconds (msec))

- Patients with a history of Torsades de Pointes

- Patients with current treatment with an agent having either the potential to affect
or increase the risk of QTc prolongation (e.g. erythromycin, any class Ia, Ic, or III
antiarrhythmics)

- Patients being treated with a neuromuscular blocker

- Patients in whom haloperidol, risperidone, or trazodone is contraindicated

- Pregnant patients or patients who are breast-feeding

- Patients with a modified Blessed dementia rating scale score ≥4 or an Informant
Questionnaire of Cognitive Dysfunction in the Elderly Score ≥4

- Patients in which informed consent can not be obtained from the legally authorized
representative