Possible Medications for Treatment of Delirium

Olanzapine

  • Least QTc prolongation
  • Antiemetic effects
  • Risk of orthostatic hypotension or sedation
  • Concomitant administration of IM olanzapine and
  • IV benzodiazepines should be avoided due to risk of orthostatic hypotension and cardiorespiratory depression
    • Separate by ≥2 hours

DOSE:
2.5–5 mg PO (onset 40–60 minutes); available SL
2.5–5 mg IM (onset 15–30 minutes)

Risperidone

  • Older patients at risk of orthostatic hypotension.

DOSE:
0.25–1 mg PO (onset 45–60 minutes)

Ziprasidone

  • Risk of orthostatic hypotension and sedation
  • Greatest QTc prolongation
    • Caution in QTc prolongation, recent myocardial infarction, or uncompensated heart failure

DOSE:
10–20 mg IM (onset 30–45 minutes)
Not to exceed 40 mg in 24-hour period

Quetiapine

Currently do not support the use of quetiapine

  • Understudied for acute agitation
  • Risk of orthostatic hypotension and sedation
  • Risk of anticholinergic side effects, especially at high doses

DOSE:
12.5–25 mg PO (onset 30–90 minutes)

Haloperidol

  • IV administration not FDA approved due to risk of hypotension and QTc prolongation/torsades de pointes
  • More extrapyramidal side effects than SGAs
  • Do not administer with promethazine or benztropine
    due to anticholinergic side effects

DOSE:
0.25–0.5 mg PO (onset 90–120 minutes)
0.5–1 mg IM (onset 15–30 minutes)

Benzodiazepines

  • AVOID if possible
  • Prolonged sedation, paradoxical agitation, respiratory depression, and worsening delirium
  • If chronically on benzodiazepines, do not stop them
  • Preferred in alcohol or benzodiazepine withdrawal

DOSE:
0.25–0.5 mg lorazepam PO, IV, or IM

Melatonin

  • Sleep-wake disturbance
  • May improve sundowning or agitated behavior
  • Good safety profile

DOSE:
3–6 mg

References

Olanzapine

ZYPREXA [prescribing information]. Indianapolis, IN: Eli Lilly & Co; 2018

Zacher JL, Roche-Desilets J. Hypotension secondary to the combination of intramuscular olanzapine and intramuscular lorazepam. J Clin Psychiatry. 2005;66(12):1614–1615

Marder SR, Sorsaburu S, Dunayevich E, et al. Case reports of postmarketing adverse event experiences with olanzapine intramuscular treatment in patients with agitation. J Clin Psychiatry. 2010;71(4):433–441

Risperidone

Wilson MP, Nordstrom K, Hopper A, Porter A, Castillo EM, Vilke GM. Risperidone in the emergency setting is associated with more hypotension in elderly patients. J Emerg Med. 2017;53(5):735-–739

Ziprasidone

Rais AR, Williams K, Rais T, Singh T, Tamburrino M. Use of intramuscular ziprasidone for the control of acute psychosis or agitation in an inpatient geriatric population: an open-label study. Psychiatry (Edgmont). 2010;7(1):17–24

Kohen I, Preval H, Southard R, Francis A. Naturalistic study of intramuscular ziprasidone versus conventional agents in agitated elderly patients: retrospective findings from a psychiatric emergency service. Am J Geriatr Pharmacother. 2005;3(4):240–245

Quetiapine

Mullinax S, Shokraneh F, Wilson MP, Adams CE. Oral medication for agitation of psychiatric origin: a scoping review of randomized controlled trials. J Emerg Med. 2017;53(4):524–529

Currier GW, Trenton AJ, Walsh PG, van Wijngaarden E. A pilot, open-label safety study of quetiapine for treatment of moderate psychotic agitation in the emergency setting. J Psychiatr Pract. 2006;12(4):223–228

Villari V, Rocca P, Fonzo V, Montemagni C, Pandullo P, Bogetto F. Oral risperidone, olanzapine and quetiapine versus haloperidol in psychotic agitation. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(2):405–413

Benzodiazepines

Lonergan E, Luxenberg J, Areosa Sastre A. Benzodiazepines for delirium. Cochrane Database Syst Rev. 2009(4):CD006379

Melatonin

de Jonghe A, Korevaar JC, van Munster BC, de Rooij SE. Effectiveness of melatonin treatment on circadian rhythm disturbances in dementia. Are there implications for delirium? A systematic review. Int J Geriatr Psychiatry. 2010;25(12):1201–1208