Pain, Agitation/Sedation, Delirium, Immobility, Sleep Disruption, and Neuromuscular Blockade
Drug
CYP Substrate
(major)
Usual
Starting Dose
Significant Adverse Effectsb
Formulations
Haloperidol
3A4, 2D6
1–2 mg older adults;
2–4 mg if history of
psychiatric disorders
Anticholinergic: *
Sedation: *
EPS: **
NMS: *
Olanzapine
1A2
5 mg
Anticholinergic: **
Sedation: **
EPS: *
NMS: *
Neuromuscular weakness
PO, disintegrating
tablet, IV, IM
Quetiapine
3A4
12.5–25 mg
Anticholinergic: **
Sedation: **
NMS: *
Orthostatic hypotension: **
PO
Risperidone
2D6
0.5–1 mg
Anticholinergic: *
Sedation *
EPS: **
NMS: *
Orthostatic hypotension: **
Cardiac conduction abnormalities
PO, disintegrating
tablet
Ziprasidone
1A2 (minor)
3A4 (minor)
20 mg PO;
10 mg IM
Anticholinergic: *
Sedation: *
EPS: *
NMS: *
Oral,
IM
NOTE: * = lower risk; ** = medium-higher risk
aNot all medications listed are FDA label approved for use in delirium; not all are recommended by SCCM for the treatment of delirium in the ICU.
bAdverse effects other than QTc prolongation. Documented QTc prolongation incidence: IV haloperidol = ziprasidone > risperidone > olanzapine = quetiapine.
EPS = extrapyramidal symptoms; IM = intramuscular(ly); IV = intravenous(ly); NMS = neuroleptic malignant syndrome; PO = oral(ly)
Haloperidol (Haldol): Available in oral, intravenous, and intramuscular injection dosage forms
Pharmacokinetics: Hepatically metabolized to inactive metabolites, renally cleared. Many drug
CYP3A4 and 2D6 substrate. Peak plasma concentrations for oral about 6 hours for oral and 20
minutes for intramuscular.
Suggested starting dose for ICU delirium: 2–5 mg as needed
Adverse effects (early onset): Cardiac arrhythmias, anticholinergic effects, extrapyramidal symptoms
of scheduled quetiapine with placebo for the treatment of delirium in ICU patients during a 10-day
liver disease, those with alcohol withdrawal, those with a QTc greater than 500, and those receiving
concomitant QTc-prolonging agents. This small pilot study (n=36), in which the placebo group was
administered as-needed intravenous haloperidol, found that quetiapine was associated with a shorter time
to first resolution of delirium, reduced duration of delirium, and less agitation than placebo. Mortality
and ICU length of stay were not different from placebo.
Pharmacokinetics: Hepatically metabolized to one active and two inactive metabolites. Metabolites
renally cleared. Many drug interactions, CYP3A4 (major) and CYP2D6 (minor) substrates. Peak
plasma concentrations for oral about 1½ hours (immediate release).