Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
CNS Drugs
Published in: CNS Drugs 8/2008

01-08-2008 | Review Article

Delirium and its Treatment

Authors: Azizah Attard, Gopinath Ranjith, Dr David Taylor

Published in: CNS Drugs | Issue 8/2008

Login to get access

Abstract

Delirium occurs at rates ranging from 10% to 30% of all hospital admissions. It is a negative prognostic indicator, often leading to longer hospital stays and higher mortality. The aetiology of delirium is multifactorial and many causes have been suggested. The stress-diathesis model, which posits an interaction between the underlying vulnerability and the nature of the precipitating factor, is useful in understanding delirium.
Preventing delirium is the most effective strategy for reducing its frequency and complications. Environmental strategies are valuable but are often underutilized, while remedial treatment is usually aimed at specific symptoms of delirium. Antipsychotics are the mainstay of pharmacological treatment and have been shown to be effective in treating symptoms of both hyperactive and hypoactive delirium, as well as generally improving cognition. Haloperidol is considered to be first-line treatment as it can be administered via many routes, has fewer active metabolites, limited anticholinergic effects and has a lower propensity for sedative or hypotensive effects compared with many other antipsychotics. Potential benefits of atypical compared with typical antipsychotics include the lower propensity to cause over-sedation and movement disorder. Of the second-generation antipsychotics investigated in delirium, most data support the use of risperidone and olanzapine. Other drugs (e.g. aripiprazole, quetiapine, donepezil and flumazenil) have been evaluated but data are limited.
Benzodiazepines are the drugs of choice (in addition to antipsychotics) for delirium that is not controlled with an antipsychotic (and can be used alone for the treatment of alcohol and sedative hypnotic withdrawal-related delirium). Lorazepam is the benzodiazepine of choice as it has a rapid onset and shorter duration of action, a low risk of accumulation, no major active metabolites and its bioavailability is more predictable when it is administered both orally and intramuscularly.
Literature
1.
Lipowski ZW. Delirium: acute confusional states. Oxford: Oxford University Press, 1990
2.
Siddiqi N, House AO, Holmes JD. Occurrence and outcome of delirium in medical in-patients: a systematic literature review. Age Ageing 2006; 35(4): 350–64PubMed
3.
Inouye SK. Delirium in older persons. N Engl J Med 2006; 354(11): 1157–65PubMed
4.
Inouye SK, Schlesinger MJ, Lydon TJ. Delirium: a symptom of how hospital care is failing older persons and a window to improve quality of hospital care. Am J Med 1999; 106(5): 565–73PubMed
5.
van Zyl LT, Seitz DP. Delirium concisely: condition is associated with increased morbidity, mortality, and length of hospitalization. Geriatrics 2006; 61(3): 18–21PubMed
6.
McAvay GJ, Van Ness PH, Bogardus Jr ST, et al. Older adults discharged from the hospital with delirium: 1-year outcomes. J Am Geriatr Soc 2006; 54(8): 1245–50PubMed
7.
McCusker J, Cole M, Dendukuri N, et al. The course of delirium in older medical inpatients: a prospective study. J Gen Intern Med 2003; 18(9): 696–704PubMed
8.
McCusker J, Cole M, Dendukuri N, et al. Delirium in older medical inpatients and subsequent cognitive and functional status: a prospective study. CMAJ 2001; 165(5): 575–83PubMed
9.
Adamis D, Treloar A, Martin FC, et al. Recovery and outcome of delirium in elderly medical inpatients. Arch Gerontol Geriatr 2006; 43(2): 289–98PubMed
10.
Inouye SK. Predisposing and precipitating factors for delirium in hospitalized older patients. Dement Geriatr Cogn Disord 1999; 10(5): 393–400PubMed
11.
Inouye SK, Viscoli CM, Horwitz RI, et al. A predictive model for delirium in hospitalized elderly medical patients based on admission characteristics. Ann Intern Med 1993; 119(6): 474–81PubMed
12.
Inouye SK, Charpentier PA. Precipitating factors for delirium in hospitalized elderly persons: predictive model and interrelationship with baseline vulnerability. JAMA 1996; 275(11): 852–7PubMed
13.
Lindesay J, Rockwood K, Rolfson D. The epidemiology of delirium. In: Lindesay J, Rockwood K, Macdonald A, editors. Delirium in old age. Oxford: Oxford University Press, 2002: 27–50
14.
Rockwood K, Hogan DB, MacKnight C. Conceptualisation and measurement of frailty in elderly people. Drugs Aging 2000: 17(4): 295–302PubMed
15.
Rolfson D. The causes of delirium. In: Lindesay J. Rockwood K, Macdonald A, editors. Delirium in old age. Oxford: Oxford University Press, 2002: 101–19
16.
Mach Jr JR, Dysken MW, Kuskowski M, et al. Serum anticholinergic activity in hospitalized older persons with delirium: a preliminary study. J Am Geriatr Soc 1995; 43(5): 491–5PubMed
17.
Han L, McCusker J, Cole M, et al. Use of medications with anticholinergic effect predicts clinical severity of delirium symptoms in older medical inpatients. Arch Intern Med 2001; 161(8): 1099–105PubMed
18.
Pandharipande P, Shintani A, Peterson J, et al. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology 2006; 104(1): 21–6PubMed
19.
World Health Organisation. The ICD-10 classification of mental and behavioural disorders. Geneva: World Health Organisation, 2003
20.
Caine E, Fann J. Delirium, dementia and other cognitive disorders. In: American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC; American Psychiatric Association, 1994: 124–7
21.
de Rooij SE, Schuurmans MJ, van der Mast RC, et al. Clinical subtypes of delirium and their relevance for daily clinical practice: a systematic review. Int J Geriatr Psychiatry 2005; 20(7): 609–15PubMed
22.
Meagher DJ, O’Hanlon D, O’Mahony E, et al. Relationship between etiology and phenomenologic profile in delirium. J Geriatr Psychiatry Neurol 1998; 11(3): 146–9PubMed
23.
O’Keeffe ST, Lavan JN. Clinical significance of delirium subtypes in older people. Age Ageing 1999; 28(2): 115–9PubMed
24.
Marcantonio E, Ta T, Duthie E, et al. Delirium severity and psychomotor types: their relationship with outcomes after hip fracture repair. J Am Geriatr Soc 2002; 50(5): 850–7PubMed
25.
Liptzin B, Levkoff SE. An empirical study of delirium subtypes. Br J Psychiatry 1992; 161: 843–5PubMed
26.
Adamis D, Morrison C, Treloar A, et al. The performance of the Clock Drawing Test in elderly medical inpatients: does it have utility in the identification of delirium? J Geriatr Psychiatry Neurol 2005; 18(3): 129–33PubMed
27.
Tune L, Carr S, Hoag E, et al. Anticholinergic effects of drugs commonly prescribed for the elderly: potential means for assessing risk of delirium. Am J Psychiatry 1992; 149(10): 1393–4PubMed
28.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd ed. Washington, DC: American Psychiatric Association, 1980
29.
Albert MS, Levkoff SE, Reilly C, et al. The delirium symptom interview: an interview for the detection of delirium symptoms in hospitalized patients. J Geriatr Psychiatry Neurol 1992; 5(1): 14–21PubMed
30.
Trzepacz PT, Baker RW, Greenhouse J. A symptom rating scale for delirium. Psychiatry Res 1988; 23(1): 89–97PubMed
31.
Trzepacz PT, Mittal D, Torres R, et al. Validation of the Delirium Rating Scale-revised-98: comparison with the delirium rating scale and the cognitive test for delirium. J Neuropsychiatry Clin Neurosci 2001; 13(2): 229–42PubMed
32.
Inouye SK, van Dyck CH, Alessi CA, et al. Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med 1990; 113(12): 941–8PubMed
33.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd ed, revised. Washington, DC: American Psychiatric Association, 1987
34.
Ely EW, Margolin R, Francis J, et al. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med 2001; 29(7): 1370–9PubMed
35.
Breitbart W, Rosenfeld B, Roth A, et al. The Memorial Delirium Assessment Scale. J Pain Symptom Manage 1997; 13(3): 128–37PubMed
36.
Lonergan E, Britton AM, Luxenberg J, et al. Antipsychotics for delirium. Cochrane Database Syst Rev 2007; (3): CD005594
37.
Tune L, Carr S, Hoag E, et al. Anticholinergic effects of drugs commonly prescribed for the elderly: potential means for assessing risk of delirium. Am J Psychiatry 1992; 149(10): 1393–4PubMed
38.
Meagher DJ. Delirium: optimising management. BMJ 2001; 322(7279): 144–9PubMed
39.
Chan D, Brennan NJ. Delirium: making the diagnosis, improving the prognosis. Geriatrics 1999; 54(3): 28–42PubMed
40.
Young J, Inouye SK. Delirium in older people. BMJ 2007; 334(7598): 842–6PubMed
41.
Meagher DJ, O’Hanlon D, O’Mahony E, et al. The use of environmental strategies and psychotropic medication in the management of delirium. Br J Psychiatry 1996; 168(4): 512–5PubMed
42.
43.
Casarett DJ, Inouye SK. Diagnosis and management of delirium near the end of life. Ann Intern Med 2001; 135(1): 32–40PubMed
44.
Gaudreau JD, Gagnon P, Roy MA, et al. Association between psychoactive medications and delirium in hospitalized patients: a critical review. Psychosomatics 2005; 46(4): 302–16PubMed
45.
Anthony JC, LeResche L, Niaz U, et al. Limits of the ‘minimental state’ as a screening test for dementia and delirium among hospital patients. Psychol Med 1982; 12(2): 397–408PubMed
46.
Patten SB, Williams JV, Petcu R, et al. Delirium in psychiatric inpatients: a case-control study. Can J Psychiatry 2001; 46(2): 162–6PubMed
47.
Moran JA, Dorevitch MI. Delirium in the hospitalised elderly. Aust J Hosp Pharm 2001; 31(1): 35–40
48.
Kalisvaart KJ, de Jonghe JF, Bogaards MJ, et al. Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study. J Am Geriatr Soc 2005; 53(10): 1658–66PubMed
49.
Vaurio LE, Sands LP, Wang Y, et al. Postoperative delirium: the importance of pain and pain management. Anesth Analg 2006; 102(4): 1267–73PubMed
50.
51.
Tauscher J, Tauscher-Wisniewski S, Kasper S. Treatment of patients with delirium [letter]. Am J Psychiatry 2000; 157(10): 1711PubMed
52.
Potter J, George J. The prevention, diagnosis and management of delirium in older people: concise guidelines. Clin Med 2006; 6(3): 303–8PubMed
53.
Schwartz TL, Masand PS. The role of atypical antipsychotics in the treatment of delirium. Psychosomatics 2002; 43(3): 171–4PubMed
54.
Meagher D. Delirium: the role of psychiatry. Adv Psychiatr Treat 2001; 7(6): 433–42
55.
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 Psychiatry 1996; 153(2): 231–7PubMed
56.
Platt MM, Breitbart W, Smith M, et al. Efficacy of neuroleptics for hypoactive delirium. J Neuropsychiatry Clin Neurosci 1994; 6(1): 66–7PubMed
57.
Leentjens AF, van der Mast RC. Delirium in elderly people: an update. Curr Opin Psychiatry 2005; 18(3): 325–30PubMed
58.
American Psychiatric Association. Practice guideline for the treatment of patients with delirium. Am J Psychiatry 1999; 156(5 Suppl.): 1–20
59.
Ely EW, Stephens RK, Jackson J, et al. Current opinions regarding the importance, diagnosis, and management of delirium in the intensive care unit: a survey of 912 healthcare professionals. Crit Care Med 2004; 32(1): 106–12PubMed
60.
Centeno C, Sanz A, Bruera E. Delirium in advanced cancer patients. Palliat Med 2004; 18(3): 184–94PubMed
61.
Bourgeois JA, Seritan A. Diagnosis and management of delirium. Continuum 2006; 12(5): 15–32
62.
Boettger S, Breitbart W. Atypical antipsychotics in the management of delirium: a review of the empirical literature. Palliat Support Care 2005; 3(3): 227–37PubMed
63.
Akiskal HS, Akiskal K, Allilaire JF, et al. Validating affective temperaments in their subaffective and socially positive attributes: psychometric, clinical and familial data from a French national study. J Affect Disord 2005; 85(1–2): 29–36PubMed
64.
Skrobik YK, Bergeron N, Dumont M, et al. Olanzapine vs haloperidol: treating delirium in a critical care setting. Intensive Care Med 2004; 30(3): 444–9PubMed
65.
Sipahimalani A, Sime RM, Masand PS. Treatment of delirium with risperidone. Int J Geriatr Psychopharmacol 1997; 1(1): 24–6
66.
Sipahimalani A, Masand PS. Olanzapine in the treatment of delirium. Psychosomatics 1998; 39(5): 422–30PubMed
67.
Liu CY, Juang YY, Liang HY, et al. Efficacy of risperidone in treating the hyperactive symptoms of delirium. Int Clin Psychopharmacol 2004; 19(3): 165–8PubMed
68.
Horikawa N, Yamazaki T, Miyamoto K, et al. Treatment for delirium with risperidone: results of a prospective open trial with 10 patients. Gen Hosp Psychiatry 2003; 25(4): 289–92PubMed
69.
Parellada E, Baeza I, de Pablo J, et al. Risperidone in the treatment of patients with delirium. J Clin Psychiatry 2004; 65(3): 348–53PubMed
70.
Lee KU, Won WY, Lee HK, et al. Amisulpride versus quetiapine for the treatment of delirium: a randomized, open prospective study. Int Clin Psychopharmacol 2005; 20(6): 311–4PubMed
71.
Straker DA, Shapiro PA, Muskin PR. Aripiprazole in the treatment of delirium. Psychosomatics 2006; 47(5): 385–91PubMed
72.
Alao AO, Soderberg M, Pohl EL, et al. Aripiprazole in the treatment of delirium. Int J Psychiatry Med 2005; 35(4): 429–33PubMed
73.
Young CC, Lujan E. Intravenous ziprasidone for treatment of delirium in the intensive care unit. Anesthesiology 2004; 101(3): 794–5PubMed
74.
Leso L, Schwartz TL. Ziprasidone treatment of delirium. Psychosomatics 2002; 43(1): 61–2PubMed
75.
Bostwick JM, Masterson BJ. Psychopharmacological treatment of delirium to restore mental capacity. Psychosomatics 1998; 39(2): 112–7PubMed
76.
Hanania M, Kitain E. Melatonin for treatment and prevention of postoperative delirium. Anesth Analg 2002; 94(2): 338–9PubMed
77.
Cronin AJ, Keifer JC, Davies MF, et al. Melatonin secretion after surgery. Lancet 2000; 356(9237): 1244–5PubMed
78.
Okamoto Y, Matsuoka Y, Sasaki T, et al. Trazodone in the treatment of delirium. J Clin Psychopharmacol 1999; 19(3): 280–2PubMed
79.
Gleason OC. Donepezil for postoperative delirium. Psychosomatics 2003; 44(5): 437–8PubMed
80.
Dautzenberg PL, Mulder LJ, Olde Rikkert MG, et al. Adding rivastigmine to antipsychotics in the treatment of a chronic delirium. Age Ageing 2004; 33(5): 516–7PubMed
81.
Dautzenberg PL, Mulder LJ, Olde Rikkert MG, et al. Delirium in elderly hospitalised patients: protective effects of chronic rivastigmine usage. Int J Geriatr Psychiatry 2004; 19(7): 641–4PubMed
82.
Bourgeois JA, Koike AK, Simmons JE, et al. Adjunctive valproic acid for delirium and/or agitation on a consultation-liaison service: a report of six cases. J Neuropsychiatry Clin Neurosci 2005; 17(2): 232–8PubMed
83.
Seitz DP, Gill SS, van Zyl LT. Antipsychotics in the treatment of delirium: a systematic review. J Clin Psychiatry 2007; 68(1): 11–21PubMed
84.
British national formulary. 52nd ed. London: British Medical Association and Royal Pharmaceutical Society of Great Britain, 2006
85.
Menza MA, Murray GB, Holmes VF, et al. Decreased extrapyramidal symptoms with intravenous haloperidol. J Clin Psychiatry 1987; 48(7): 278–80PubMed
86.
Sharma ND, Rosman HS, Padhi ID, et al. Torsades de pointes associated with intravenous haloperidol in critically ill patients. Am J Cardiol 1998; 81(2): 238–40PubMed
87.
Taylor D, Paton C, Kerwin R. The Maudsley prescribing guidelines. 9th ed. London: Informa Healthcare, 2007
88.
Breitbart W, Tremblay A, Gibson C. An open trial of olanzapine for the treatment of delirium in hospitalized cancer patients. Psychosomatics 2002; 43(3): 175–82PubMed
89.
90.
Herrmann N, Mamdani M, Lanctot KL. Atypical antipsychotics and risk of cerebrovascular accidents. Am J Psychiatry 2004; 161(6): 1113–5PubMed
91.
Gill SS, Rochon PA, Herrmann N, et al. Atypical antipsychotic drugs and risk of ischaemic stroke: population based retrospective cohort study. BMJ 2005; 330(7489): 445–8PubMed
92.
Ananth J, Parameswaran S, Gunatilake S. Side effects of atypical antipsychotic drugs. Curr Pharm Des 2004; 10(18): 2219–29PubMed
93.
Broadhurst C, Wilson KC, Kinirons MT, et al. Clinical pharmacology of old age syndromes. Br J Clin Pharmacol 2003; 56(3): 261–72PubMed
94.
Gupta N, Sharma P, Prabhakar S. Olanzapine for delirium in parkinsonism: therapeutic benefits in lieu of adverse consequences. Neurol India 2004; 52(2): 274–5PubMed
95.
Pandharipande P, Jackson J, Ely EW. Delirium: acute cognitive dysfunction in the critically ill. Curr Opin Crit Care 2005; 11(4): 360–8PubMed
96.
Sasaki Y, Matsuyama T, Inoue S, et al. A prospective, open-label, flexible-dose study of quetiapine in the treatment of delirium. J Clin Psychiatry 2003; 64(11): 1316–21PubMed
97.
Shinno H, Matsuoka T, Yamamoto O, et al. Successful treatment with quetiapine for delirium in terminally ill cancer patients. Psychogeriatrics 2007; 7(2): 64–8
98.
Eli Lilly & Co. Important safety information reported serious adverse events following use of Zyprexa IM [letter to healthcare professionals]. Eli Lilly and Company Ltd, 2004
99.
Gupta N, Sharma P, Mattoo SK. Effectiveness of risperidone in delirium [letter]. Can J Psychiatry 2005; 50(1): 75PubMed
100.
Han CS, Kim YK. A double-blind trial of risperidone and haloperidol for the treatment of delirium. Psychosomatics 2004; 45(4): 297–301PubMed
101.
Miyaji S, Yamamoto K, Hoshino S, et al. Comparison of the risk of adverse events between risperidone and haloperidol in delirium patients. Psychiatry Clin Neurosci 2007; 61(3): 275–82PubMed
102.
Pae CU, Lee SJ, Lee CU, et al. A pilot trial of quetiapine for the treatment of patients with delirium. Hum Psychopharmacol 2004; 19(2): 125–7PubMed
103.
Nakamura J, Uchimura N, Yamada S, et al. Does plasma free-3-methoxy-4-hydroxyphenyl(ethylene)glycol increase in the delirious state? A comparison of the effects of mianserin and haloperidol on delirium. Int Clin Psychopharmacol 1997; 12(3): 147–52PubMed
104.
Sampson EL, Raven PR, Ndhlovu PN, et al. A randomized, double-blind, placebo-controlled trial of donepezil hydrochloride (Aricept) for reducing the incidence of postoperative delirium after elective total hip replacement. Int J Geriatr Psychiatry 2007; 22(4): 343–9PubMed
105.
Kaufer DI, Catt KE, Lopez OL, et al. Dementia with Lewy bodies: response of delirium-like features to donepezil [letter]. Neurology 1998; 51(5): 1512PubMed
Metadata
Title
Delirium and its Treatment
Authors
Azizah Attard
Gopinath Ranjith
Dr David Taylor
Publication date
01-08-2008
Publisher
Springer International Publishing
Published in
CNS Drugs / Issue 8/2008
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI
https://doi.org/10.2165/00023210-200822080-00002

Other articles of this Issue 8/2008

CNS Drugs 8/2008 Go to the issue

Review Article

Role of Cannabinoids in the Management of Neuropathic Pain

Leading Article

Novel Thrombolytic Drugs

Review Article

Efficacy and Tolerability of Pharmacotherapies for Borderline Personality Disorder

Review Article

Bipolar Disorder and the Metabolic Syndrome

Original Research Article

A Randomized, Double-Blind, Crossover Study of Once-Daily Dexmethylphenidate in Children with Attention-Deficit Hyperactivity Disorder