Table 2. Prospective Parallel-Arm Comparative Trials of Pharmacologic Treatment for Delirium.

Year	First Author	Study Design	Patient Population	Study Size	Study Intervention	Primary Outcome	Main Study Finding
2012	Tagarakis61	RCT	Postcardiac surgery	80	Haloperidol vs. ondansetron	Resolution of delirium symptoms assessed 10 minutes after single dose of the study drug	No difference in efficacy between haloperidol and ondansetron but fewer side effects with ondansetron.
2012	Hakim62	RCT	Postcardiac surgery with subsyndromal delirium	101	Risperidone vs. placebo	Proportion of patients transitioning from subsyndromal delirium to clinical delirium	Early administration of risperidone was associated with significantly less clinical delirium compared with placebo.
2011	Devlin63	Post hoc analysis of RCT	ICU	29	Quetiapine vs. placebo	Time to resolution of delirium symptoms	Quetiapine associated with faster resolution of delirium symptoms compared with placebo despite the use of as needed haloperidol.
2011	Grover64	Single blind RCT	Mixed medical/surgical patients	64	Haloperidol vs. olanzapine vs. risperidone	Efficacy (Delirium Rating Scale-Revised-98) and safety.	All patients showed improvement in delirium severity over the six day study period, but no difference between drugs was found.
2010	van Eijk65	RCT	ICU	104	Rivastigmine vs. placebo	Efficacy (duration of delirium) and safety	This study, originally planned to enroll 440 patients, was stopped early after 104 patients were enrolled because of increased mortality in the rivastigmine arm compared with placebo (22% vs. 8%, P = 0.07).
2010	Tahir66	RCT	Mixed medical, surgical, and orthopedic patients	42	Quetiapine vs. placebo	Efficacy (Delirium Rating Scale-Revised-98) and safety.	Quetiapine was associated with faster resolution of some non-noncognitive symptoms of delirium when compared to compared with placebo.
2010	Overshott67	RCT	Hospitalized medical patients	15	Rivastigmine vs. placebo	Feasibility of a larger trial	Described as a pilot study. No meaningful inferences about delirium treatment made.
2010	Kim68	RCT	Hospitalized patients (72% with malignant cancer)	32	Risperidone vs. olanzapine	Efficacy (Delirium Rating Scale-Revised-98) and safety	Risperidone and olanzapine were both effective in reducing symptoms of delirium, but no difference in efficacy or safety between groups was found. Response to olanzapine was better in patients over 70 years of age.
2010	Girard69	RCT	ICU	101	Haloperidol vs. ziprasidone vs. placebo	Feasibility of a larger trial	Described as a pilot study. No difference in clinical outcomes (efficacy or safety).
2010	Devlin70	RCT	ICU	36	Quetiapine vs. placebo	Time to resolution of delirium	All patients received haloperidol as needed. Quetiapine was associated with faster resolution and shorter durations of delirium compared with the placebo group.
2009	Reade71	RCT	ICU	20	Dexmedetomidine vs. haloperidol	Time to extubation	The α2 agonist dexmedetomidine was associated with a significantly shorter time to extubation in mechanically ventilated critically ill patients and ICU length of stay compared with haloperidol.
2005	Lee72	RCT	Hospitalized medical patients	31	Quetiapine vs. amisulpride	Efficacy (Delirium Rating Scale-Revised-98) and safety	Both agents were shown to improve symptoms of delirium, but no difference between groups was found.
2004	Han73	RCT	Hospitalized medical patients	28	Risperidone vs. haloperidol	Efficacy (Memorial Delirium Assessment Scale) and safety	Both agents were shown to improve symptoms of delirium over the seven day study period, but no between-group differences were found.
2004	Skrobik74	RCT	ICU	73	Olanzapine vs. haloperidol	Efficacy (Delirium Index) and safety	Clinical improvement over the five day study period in both groups. No differences in efficacy were identified between groups. Extrapyramidal symptoms were noted more frequently among patients randomized to haloperidol.
2004	Kim75	RCT	Hospitalized medical and surgical patients	42	Risperidone vs. haloperidol	Describe the relationship between treatment response and dopamine transporter genetic polymorphisms	Both drugs were shown to be effective, but no differences in efficacy between groups were found.
1996	Breitbart76	RCT	Hospitalized AIDS patients	30	Haloperidol vs. chlorpromazine vs. lorazepam	Efficacy (Delirium Rating Scale) and safety	Patients randomized to haloperidol or chlorpromazine exhibited symptomatic improvement over the course of the study, whereas the lorazepam arm of the study was terminated prematurely because of treatment-limiting adverse effects.

RCT = randomized controlled trial; ICU = intensive care unit