Background Delirium is common in those with serious medical illness. There may be underlying physiologic causes to delirium and it can be categorized as hyperactive, hypoactive, or mixed. Common reversible etiologies include infections, constipation, urinary retention, medications, electrolyte abnormalities, and sleep deprivation. Initial management strategies should include identifying and treating the underlying cause, as well as non-pharmacological treatment. However, when these strategies are not effective, pharmacological interventions may be necessary to ensure patient and staff safety. This Fast Fact identifies pharmacologic pearls regarding the management of a reversible, hyperactive delirium. See Fast Fact #1 for more information on terminal delirium.
1st Generation Antipsychotics
- Haloperidol (Haldol) Although no medication has been FDA approved for the treatment of delirium, haloperidol is most commonly used since it can be administered safely through oral, subcutaneous, and parenteral routes. Starting doses are 0.5 – 1 mg PO/SC/IV. Titration can occur by 2 – 5 mg every 1 hour as needed until a total daily requirement is established, which is then administered in daily or twice daily doses. Recommended maximum dose is 100 mg/day. IV or SC haloperidol may cause less extrapyramidal symptoms than oral but may cause more significant QTc prolongation.
- Chlorpromazine (Thorazine) has more sedative effects than haloperidol for patients in whom sedation is desired. The starting dose is 25 – 50 mg PO or IV. Titration can occur by 25 – 50 mg every 1 hour until a total daily requirement is established, which is then administered in daily or twice daily doses. Slow titration is recommended for IV doing. Maximum dose is 2000 mg/day.
2nd Generation Antipsychotics Also known as atypical antipsychotics, no evidence currently exists for improved efficacy with 2nd generation antipsychotics, so they are not considered to be first-line treatment. Still, these agents are associated with fewer extrapyramidal side effects than 1st generation antipsychotics, hence, in patients with a history of extrapyramidal reactions from 1st generation antipsychotics this class of agents may be preferred. For acutely agitated patients requiring onset of action within minutes, providers should know that these agents do not work as fast as conventional antipsychotics.
- Olanzapine (Zyprexa) The starting daily dose is 2.5-5 mg PO. It is often given at night. After one week, the dose can be raised to 10 mg a day; then 20 mg a day. Orally disintegrating tablets (Zydis) are available. It has shown effectiveness for chemotherapy-induced nausea (see Fast Fact #315).
- Quetiapine (Seroquel) is initially given 25 mg PO once or twice a day which can be raised by 25 – 50 mg per dose every 2 – 3 days. Compared to the atypical neuroleptics, it has the least extrapyramidal side effects, but has more orthostasis and sedative potentials. It is the antipsychotic of choice for patient with Parkinson’s Disease or Lewy Body Dementia.
- Risperidone (Resperidal) is given 1 – 2 mg PO at night and is gradually raised 1 mg every 2 – 3 days until an effective dose (usually 4 – 6 mg PO) is reached. It has minimal anticholinergic effects and does not cause orthostasis. It is the least sedating of this class of antipsychotics
- Aripiprazole (Abilify) initially 2 mg daily PO (tablet, solution, disintegrating), repeat dosing every 4-6 hours as needed to a maximum of 15 mg/day. Least likely to prolong QTc in retrospective studies. It has less sedation and extrapyramidal side effects but may cause orthostasis. It does not need dose adjustments in renal or hepatic failure.
Risks The FDA has issued a black-box warning about the increased risk of death and stroke when first- or second-generation antipsychotics are used to treat dementia-related psychosis in elderly patients. This warning is based on limited studies which have not been replicated and do not address the short-term use of antipsychotics to manage delirium especially in terminally ill patients. Since, delirium is a poor prognostic marker, goals of care and values must be discussed and taken into account regarding the medical management of delirium.
Benzodiazepines Benzodiazepines can make delirium worse and precipitate withdrawal syndromes. Hence, unless the patient is acutely dying, and sedation is preferred; the patient’s agitation is severe and uncontrolled; the patient is withdrawing from benzodiazepines or alcohol; or suffering from anticholinergic excess, benzodiazepines should be avoided for potentially reversible forms of delirium.
Melatonin This hormone is produced naturally in the pineal gland and can help regulate the sleep-wake rhythm cycle. Randomized placebo-controlled trials have validated the use of melatonin and a melatonin analog (ramelteon) in the prevention of delirium for at-risk, hospitalized patients. See Fast Fact #306.
Discharge Prior to discharge it is important to reconcile medications and discontinue antipsychotics once delirium has resolved.
- Breitbart W, Bruera E, Chochinov H, Lynch M. Neuropsychiatric syndromes and psychological symptoms in patients with advanced cancer. J Pain Symptom Manage. 1995; 10:131-41.
- Breitbart W, Marotta R, Platt MM, et al. A double-blind trial of haloperidol, chlorpromazine, and lorazepam in the treatment of delirium in hospitalized AIDS patients. Am J Psych. 1996; 153:231-7.
- Jackson KC, Lipman AG. Drug therapy for delirium in terminally ill patients. Cochrane Database 2004; Syst Rev 2: CD004770.
- Inouye SK, Bogardus ST Jr, Charpentier PA, et al. A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med. 1999; 4:340:669-76.
- Lawlor PG, Gagnon B, Mancini IL, et al. Occurrence, causes, and outcome of delirium in patients with advanced cancer: a prospective study. Arch Intern Med. 2000; 160:786-94.
- McIver B, Walsh D, Nelson K. The use of chlorpromazine for symptom control in dying cancer patients. J Pain Symptom Manage. 1994; 9:341-5.
- Menza MA, Murray GB, Holmes VF, Rafuls WA. Decreased extrapyramidal symptoms with intravenous haloperidol. J Clin Psych. 1987; 48:278-280.
- Sadock B, Sadock V. Kaplan and Sadock’s Pocket Handbook of Psychiatric Drug Treatment. 3rd Edition. Philadelphia, PA: Lippincott Williams and Williams; 2001.
- Stahl S. Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 2nd Edition. New York, NY: Cambridge University Press; 2000.
- Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia. Meta-analysis of randomized placebo controlled trials. JAMA 2005; 294:1934-1943.
- Breitbart W, Alici Y. Evidence-based treatment of delirium in patients with cancer. Journal of Clinical Oncology 2012; 30: 1206-1214.
- Navari RM, Einhorn LH, et al. A phase II trial for the prevention of chemotherapy induced nausea and vomiting: a Hoosier Oncology Group Study. Support Care Cancer 2005; 13: 529-34.
- Prommer, Eric. “Aripiprazole: a new option in delirium.” American Journal of Hospice and Palliative Medicine® 34.2 (2017): 180-185.
- Hategan A, Bourgeois JA. Aripiprazole-associated qtc prolongation in a geriatric patient. J Clin Psychopharmacol. 2014;34(6): 766-768.
- Hatta K, Kishi Y, et al. Preventive Effects of Ramelteon on Delirium A Randomized Placebo-Controlled Trial. JAMA Psychiatry. 2014;71(4):397-403.
- Al-Aama T, Brymer C, Gutmanis I, Woolmore-Goodwin SM, Esbaugh J, Dasgupta M. Melatonin decreases delirium in elderly patients: a randomized, placebo-controlled trial. Int J Geriatr Psychiatry. 2011;26(7):687-694.
- Irwin SA, Pirrelo RD, et al. Clarifying delirium management: practical, evidence-based expert recommendations for clinical practice. Journal of Pall Med 2013; 16: 423-435.
- Hui, David, et al. “Effect of lorazepam with haloperidol vs haloperidol alone on agitated delirium in patients with advanced cancer receiving palliative care: a randomized clinical trial.” Jama 318.11 (2017): 1047-1056.
- Thom, Robyn Pauline, Clare Kelleher Mock, and Polina Teslyar. “Delirium in hospitalized patients: risks and benefits of antipsychotics.” Cleve Clin J Med 84.8 (2017): 616-622.
Version History: This Fast Fact was originally edited by David E Weissman MD. 2nd Edition published September 2006; 3rd Edition May 2015; 4th Edition March 2019.
Conflicts of Interest: None to report
Fast Facts and Concepts are edited by Sean Marks MD (Medical College of Wisconsin) and associate editor Drew A Rosielle MD (University of Minnesota Medical School), with the generous support of a volunteer peer-review editorial board, and are made available online by the Palliative Care Network of Wisconsin (PCNOW); the authors of each individual Fast Fact are solely responsible for that Fast Fact’s content. The full set of Fast Facts are available at Palliative Care Network of Wisconsin with contact information, and how to reference Fast Facts.
Copyright: All Fast Facts and Concepts are published under a Creative Commons Attribution-NonCommercial 4.0 International Copyright (http://creativecommons.org/licenses/by-nc/4.0/). Fast Facts can only be copied and distributed for non-commercial, educational purposes. If you adapt or distribute a Fast Fact, let us know!
Disclaimer: Fast Facts and Concepts provide educational information for health care professionals. This information is not medical advice. Fast Facts are not continually updated, and new safety information may emerge after a Fast Fact is published. Health care providers should always exercise their own independent clinical judgment and consult other relevant and up-to-date experts and resources. Some Fast Facts cite the use of a product in a dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.