Clinical Research Directory

Inclusion Criteria: 1. \>=18-years-old 2. Admitted to the surgical ICU for \>24 hours 3. Written informed consent obtained from the patient or their surrogate decision maker. 4. Diagnosis of ICU delirium defined by positive CAM-ICU score AND exhibiting symptomatic delirium (i.e., combative, pulling at lines, a danger to self or others, inability to sleep, hallucinations, etc.), thus, requiring the need for pharmacologic intervention as determined by the attending intensivist Exclusion Criteria: 1. Acute alcohol or substance abuse withdrawal symptoms/syndrome (i.e., delirium tremens) requiring treatment/intervention (i.e., implementation of the Clinical Institute Withdrawal Assessment for Alcohol (CIWA) protocol, benzodiazepines, alpha-2 agonist, etc.) 2. Recent torsade de pointes or ventricular arrhythmia 3. Prolonged QTc syndrome AND/OR prolonged QT-interval (QTc\>500 ms on baseline EKG, performed on the day of randomization) 4. Active psychosis 5. Patients taking medications with known interactions with either trazodone and/or quetiapine 6. Acute encephalopathy (i.e., hepatic, uremic, etc.) 7. Seizure disorder 8. myocardial infarction (MI) within the past 30 days 9. Tardive dyskinesia 10. Hyponatremia 11. Terminal state 12. Diagnosis of liver disease 13. Patients who are strict NPO, are a high aspiration risk (defined as frequent nausea/vomiting, ileus, gastric dysmotility disorder, uncontrolled GERD, weakness/deconditioning, diabetes with gastroparesis, not tolerating full tube feeds if being enterally fed (high residual gastric volume \>500 cc), elderly patients with waxing/waning mental status), have dysphagia, and/or have difficulty swallowing capsules as determined by speech therapist 14. Patients who have enteral access such as a small-bore feeding tube, nasogastric or orogastric tube, or gastrostomy/gastrojejunostomy tube (as these patients will need medications crushed in order to administer via the tube, and the capsules used in this study cannot be crushed) 15. Presence of an acute neurologic condition (i.e., acute cerebrovascular accident, intracranial tumor, traumatic brain injury, etc.) on ICU admission. History of stroke or other neurological condition(s) without cognitive impairment is not an exclusion criterion. 16. Pregnancy/lactation 17. History of ventricular arrhythmia including torsade de pointes 18. Allergy/hypersensitivity reaction to trazodone and/or quetiapine 19. Diagnosis of dementia 20. History of neuroleptic malignant syndrome and/or serotonin syndrome 21. Diagnosis of Parkinson's disease or parkinsonism (also referred to as hypokinetic rigidity syndrome) 22. Schizophrenia or other psychotic disorder 23. Patients in whom CAM-ICU cannot be performed to screen for delirium (i.e., acute encephalopathy, mental retardation, vegetative state/coma, deaf, blind, etc.) 24. Inability to speak or understand English 25. Expected to die or transfer out of the ICU within 24 hours 26. Currently enrolled and participating in another interventional study 27. No signed written informed consent by patient or their surrogate decision maker.