Table 1.

Open-Label and RCTs of Antipsychotics in Treatment of Delirium in Patients With Cancer

Trial Type	Intervention	Mean Dose (SD) and Duration	Results	Comments
Open-label
Breitbart et al26	Open-label trial of hospitalized patients (n = 79) with advanced cancer with delirium who were treated with olanzapine.	Average starting dose was in the 2.5-5 mg range, and patients were given up to 20 mg/d olanzapine.	Olanzapine was effective in resolving delirium in 76% of patients with no incidence of extrapyramidal adverse effects. The mean MDAS scores declined from 19.85 to 10.78 in 7 days.	Sedation was the most common adverse effect. Factors found to be significantly associated with poorer response to olanzapine for treatment of delirium were age older than 70 years, history of dementia, and hypoactive delirium.
Kim et al42	Open-label trial of patients (n = 12; most with leukemia) with delirium who were treated with quetiapine.	Average dose was 93.75 mg. Mean duration for stabilization was 5.91 days. Quetiapine dose was tapered down about 1 month after discharge from the hospital.	The DRS scores declined from 18.25 to 8.00.	None of the patients experienced any Parkinsonian adverse effects; sedation and vivid dreaming were the only reported adverse effects.
Elsayem et al40	Open-label trial of patients (n = 24) with advanced cancer with delirium who were treated with subcutaneous olanzapine.	Patients received olanzapine 5 mg subcutaneously every 8 hours for 3 days and continued with haloperidol for breakthrough agitation.	Efficacy was achieved in nine patients (37.5%). Subcutaneous olanzapine was well tolerated in the treatment of delirium.	No injection site toxicity was observed after 167 injections. Probable adverse effects were observed in four patients (severe hypotension [blood pressure < 90/50 mmHg], paradoxical agitation, diabetes insipidus, and seizure).
Boettger et al25	Prospective, case-matched control comparison trial of patients with cancer who had delirium and were treated with aripiprazole (n = 21) v haloperidol (n = 21).	Mean aripiprazole dose was 15.2 mg at study entry and 18.3 mg at the end. Mean haloperidol dose was 4.9 mg at study entry and 5.5 mg at the end.	Over the course of treatment, MDAS scores improved from 18.1 to 8.3 for aripiprazole and 19.9 to 6.8 for haloperidol. The delirium resolution rate was 76.2% for aripiprazole and 76.2% for haloperidol.	There were no significant differences in treatment results between aripiprazole and haloperidol for patients with cancer with either hypoactive or hyperactive subtypes of delirium. However, there was a trend for poor response to aripiprazole among patients with hyperactive delirium. Treatment with haloperidol resulted in more extrapyramidal adverse effects.
Randomized controlled
Breitbart et al27	Double-blind RCT of terminally ill patients with AIDS with delirium who were treated with haloperidol (n = 11), chlorpromazine (n = 13), or lorazepam (n = 6).	1.4 (1.2) mg/d haloperidol, 36 (18.4) mg/d chlorpromazine, 4.6 (4.7) mg/d lorazepam for up to 6 days.	DRS scores significantly improved in haloperidol and chlorpromazine groups (P < .05). No significant extrapyramidal symptoms were observed.	Lorazepam group was discontinued early because of worsening of delirium symptoms.
Hu et al35	Double-blind RCT of hospitalized patients with delirium who were treated with olanzapine (n = 75), intramuscular haloperidol (n = 72), or oral placebo (n = 29).	4.5 (4) mg/d olanzapine, 7 (2.3) mg/d haloperidol, and placebo for 7 days.	The improvement in DRS scores was significantly higher in the olanzapine (72%) and haloperidol (70%) groups v placebo (29.7%; P < .01). Increased rates of extrapyramidal symptoms were observed in the haloperidol group.	Comparison of oral olanzapine and oral placebo with intramuscular haloperidol hinders the quality of double-blind study design.
Kim et al41	A randomized, single-blind clinical trial of mostly oncology patients with delirium comparing the effectiveness of treatment with risperidone (n = 17) and olanzapine (n = 15).	Study period: 7 days. Mean starting dose was 0.6 (0.2) mg/d risperidone and 1.8 (0.6) mg/d olanzapine. Mean dose at last observation was 0.9 (0.6) mg/d risperidone and 2.4 (1.7) mg/d olanzapine.	Significant within-group improvements in the DRS-R-98 scores over time were observed in both treatment groups; the response (defined as a 50% reduction in the DRS-R-98 scores) rates did not differ significantly between the two groups (risperidone group: 64.7%; olanzapine group: 73.3%).	The response to risperidone was significantly poorer in patients age 70 years or older compared with those younger than age 70 years. There was no significant difference in the safety profiles, including extrapyramidal symptoms, between the two groups.

Abbreviations: DRS, Delirium Rating Scale; DRS-R-98, DRS-Revised 98; MDAS, Memorial Delirium Assessment Scale; RCT, randomized controlled trial; SD, standard deviation.