https://doi.org/10.4081/ahr.2025.28

Drug-associated delirium: basic pharmacologic principles and clinical considerations. A narrative review

Vol. 2 (2025)
Published: February 25, 2025
BEERs criteria, drug-induced delirium, anticholinergic, antimuscarinic, adverse drug reaction
Abstract Views: 66
PDF: 32
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

Phat H. Le
School of Medicine, American University of the Caribbean, Miramar, FL, United States.
William C. Upshaw
School of Medicine, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA, United States.
Tyler A. Le
School of Medicine, American University of the Caribbean, Miramar, FL, United States.
Horace Townsend
School of Medicine, American University of the Caribbean, Miramar, FL, United States.
Thanh P.D. Vu
School of Medicine, American University of the Caribbean, Miramar, FL, United States.
Jill M. Salonga
School of Medicine, American University of the Caribbean, Miramar, FL, United States.
Taylor Moss
Department of Anesthesiology, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA, United States.
Sridhar Tirumala
Department of Anesthesiology, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA, United States.
Sahar Shekoohi
Sahar.shekoohi@lsuhs.edu
https://orcid.org/0009-0007-4545-4523
Department of Anesthesiology, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA, United States.
Adam M. Kaye
Clinical Professor of Pharmacy, Department of Pharmacy Practice, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, CA, United States.
Alan D. Kaye
Professor, Vice Chairman of Research, Pain Fellowship Director, Departments of Anesthesiology and Pharmacology, Toxicology, and Neurosciences, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, United States.

Delirium is an acute state of impaired awareness and cognition with significant implications for patient outcomes, particularly in the elderly. Its clinical features include fluctuating consciousness, disorientation, hallucinations, agitation, psychomotor changes, and speech disturbances. While delirium has a broad differential diagnosis—including dementia, acute intoxication, metabolic encephalopathies, infections, and withdrawal syndromes-drug-induced delirium warrants specific attention due to its high prevalence and reversible nature. Certain drug classes are commonly associated with delirium, including anticholinergics, benzodiazepines, opioids, corticosteroids, and anticonvulsants. These drugs precipitate delirium through mechanisms such as disrupting neurotransmitter systems, including acetylcholine, dopamine, and serotonin pathways. For instance, anticholinergics impair cognition by blocking acetylcholine, while benzodiazepines and opioids can induce sedation and confusion, especially in vulnerable populations. The pathophysiology of drug-induced delirium is multifactorial, involving neurotransmitter disruptions, inflammation, and metabolic disturbances. Preventing and managing drug-induced delirium requires a detailed review of a patient’s medication list, with a focus on minimizing high-risk drugs, identifying vulnerable patients (e.g., the elderly or those with polypharmacy), and monitoring for early symptoms. Treatment of delirium includes pharmacological and non-pharmacological strategies. Antipsychotics, such as haloperidol or atypical agents, are the primary pharmacological treatment, while non-pharmacological approaches involve environmental modifications, such as creating a calm, well-lit setting and involving family members for reassurance. Early recognition and prompt identification of the underlying cause are essential to improving outcomes.

Altmetrics

Downloads

Download data is not yet available.
1. Ramírez Echeverría M de L, Schoo C, Paul M. Delirium. StatPearls [Internet]. Treasure Island, StatPearls Publishing; 2024.
2. Mart MF, Williams Roberson S, Salas B, et al. Prevention and management of delirium in the intensive care unit. Semin Respir Crit Care Med 2021;42:112-26. DOI: https://doi.org/10.1055/s-0040-1710572
3. Cole MG, Bailey R, Bonnycastle M, et al. Partial and no recovery from delirium in older hospitalized adults: frequency and baseline risk factors. J Am Geriatr Soc 2015;63:2340-8. DOI: https://doi.org/10.1111/jgs.13791
4. Jin Z, Hu J, Ma D. Postoperative delirium: perioperative assessment, risk reduction, and management. Br J Anaesth 2020;125:492-504. DOI: https://doi.org/10.1016/j.bja.2020.06.063
5. Velayati A, Vahdat Shariatpanahi M, Shahbazi E, et al. Association between preoperative nutritional status and postoperative delirium in individuals with coronary artery bypass graft surgery: A prospective cohort study. Nutrition 2019;66:227-32. DOI: https://doi.org/10.1016/j.nut.2019.06.006
6. Nitchingham A, Kumar V, Shenkin S, et al. A systematic review of neuroimaging in delirium: predictors, correlates and consequences. Int J Geriatr Psychiatry 2018;33:1458-78. DOI: https://doi.org/10.1002/gps.4724
7. Silver G, Traube C, Gerber LM, et al. Pediatric delirium and associated risk factors: a single-center prospective observational study. Pediatr Crit Care Med 2015;16:303-9. DOI: https://doi.org/10.1097/PCC.0000000000000356
8. McNicoll L, Pisani MA, Zhang Y, et al. Delirium in the intensive care unit: occurrence and clinical course in older patients. J Am Geriatr Soc 2003;51:591-8. DOI: https://doi.org/10.1034/j.1600-0579.2003.00201.x
9. Trzepacz PT, Teague GB, Lipowski ZJ. Delirium and other organic mental disorders in a general hospital. Gen Hosp Psychiatry 1985;7:101-6. DOI: https://doi.org/10.1016/0163-8343(85)90018-0
10. Ryan DJ, O’Regan NA, Caoimh RÓ, et al. Delirium in an adult acute hospital population: predictors, prevalence and detection. BMJ Open 2013;3:e001772. DOI: https://doi.org/10.1136/bmjopen-2012-001772
11. van der Mast RC, Fekkes D. Serotonin and amino acids: partners in delirium pathophysiology? Semin Clin Neuropsychiatry 2000;5:125-31.
12. Sadlonova M, von Arnim CAF. [Update on the diagnosis and treatment of delirium].[Article in German]. Inn Med (Heidelb) 2023;64:855-63. DOI: https://doi.org/10.1007/s00108-023-01561-7
13. Kalish VB, Gillham JE, Unwin BK. Delirium in older persons: Evaluation and management. Am Fam Physician. 2014;90(3):150-158.
14. Chan S-L, Lam J-C, Chan J-W, et al. Cytochrome P450 polymorphisms and susceptibility to drug-induced delirium: A case study. Clin Drug Investig 2015;35:537-43.
15. Alagiakrishnan K, Wiens CA. An approach to drug induced delirium in the elderly. Postgrad Med J 2004;80:388-93. DOI: https://doi.org/10.1136/pgmj.2003.017236
16. Gupta N, de Jonghe J, Schieveld J, Leonard M, Meagher D. Delirium phenomenology: what can we learn from the symptoms of delirium? J Psychosom Res 2008;65:215-22. DOI: https://doi.org/10.1016/j.jpsychores.2008.05.020
17. Carter GL, Dawson AH, Lopert R. Drug-induced delirium. Incidence, management and prevention. Drug Saf 1996;15:29-301. DOI: https://doi.org/10.2165/00002018-199615040-00007
18. Francis J. Drug-induced delirium. CNS Drugs 1996;5:103-14. DOI: https://doi.org/10.2165/00023210-199605020-00003
19. Thom RP, Levy-Carrick NC, Bui M, Silbersweig D. Delirium. Am J Psychiatry 2019;176:785-93. DOI: https://doi.org/10.1176/appi.ajp.2018.18070893
20. Moore AR, O’Keeffe ST. Drug-induced cognitive impairment in the elderly. Drugs Aging 1999;15:15-28. DOI: https://doi.org/10.2165/00002512-199915010-00002
21. Vilke GM, Bozeman WP, Dawes DM, et al. Excited delirium syndrome (ExDS): treatment options and considerations. J Forensic Leg Med 2012;19:117-21. DOI: https://doi.org/10.1016/j.jflm.2011.12.009
22. Gleason OC. Delirium. Am Fam Physician 2003;67:1027-34.
23. Marcantonio ER, Flacker JM, Wright RJ, Resnick NM. Reducing delirium after hip fracture: a randomized trial. J Am Geriatr Soc 2001;49:51-22. DOI: https://doi.org/10.1046/j.1532-5415.2001.49108.x
24. McCusker J, Cole M, Abrahamowicz M, et al. Environmental risk factors for delirium in hospitalized older people. J Am Geriatr Soc 2001;49:1327-34. DOI: https://doi.org/10.1046/j.1532-5415.2001.49260.x
25. Hshieh TT, Yue J, Oh E, et al. Effectiveness of multicomponent nonpharmacological delirium interventions: a meta-analysis. JAMA Intern Med 2015;175:512-20. DOI: https://doi.org/10.1001/jamainternmed.2014.7779
26. Safavynia SA, Arora S, Pryor KO, García PS. An update on postoperative delirium: Clinical features, neuropathogenesis, and perioperative management. Curr Anesthesiol Rep 2018;8:252-62. DOI: https://doi.org/10.1007/s40140-018-0282-5
27. White N, Bazo-Alvarez JC, Koopmans M, et al. Understanding the association between pain and delirium in older hospital inpatients: systematic review and meta-analysis. Age Ageing 2024;53:afae073. DOI: https://doi.org/10.1093/ageing/afae073
28. Fong TG, Tulebaev SR, Inouye SK. Delirium in elderly adults: diagnosis, prevention and treatment. Nat Rev Neurol 2009;5:210-20. DOI: https://doi.org/10.1038/nrneurol.2009.24
29. Richelson E. Treatment of acute depression. Psychiatr Clin North Am 1993;16:461-78. DOI: https://doi.org/10.1016/S0193-953X(18)30160-6
30. Karlsson I. Drugs that induce delirium. Dement Geriatr Cogn Disord 1999;10:412-5. DOI: https://doi.org/10.1159/000017180
31. Foy A, O’Connell D, Henry D, et al. Benzodiazepine use as a cause of cognitive impairment in elderly hospital inpatients. J Gerontol A Biol Sci Med Sci 1995;50:M99-106. DOI: https://doi.org/10.1093/gerona/50A.2.M99
32. Griffin CE, Kaye AM, Bueno FR, Kaye AD. Benzodiazepine pharmacology and central nervous system-mediated effects. Ochsner J 2013;13:214-23.
33. Greenblatt DJ, Shader RI, Harmatz JS. Implications of altered drug disposition in the elderly: studies of benzodiazepines. J Clin Pharmacol 1989;29:866-72. DOI: https://doi.org/10.1002/j.1552-4604.1989.tb03246.x
34. Cook PJ. Benzodiazepine hypnotics in the elderly. Acta Psychiatr Scand Suppl 1986;332:149-58. DOI: https://doi.org/10.1111/j.1600-0447.1986.tb08992.x
35. Gale L, McGill K, Twaddell S, et al. Hospital-treated deliberate self-poisoning patients: Drug-induced delirium and clinical outcomes. Aust N Z J Psychiatry 2022;56:154-63. DOI: https://doi.org/10.1177/00048674211009608
36. Friedrich ME, Grohmann R, Rabl U, et al. Incidence of drug-induced delirium during treatment with antidepressants or antipsychotics: a drug surveillance report of German-speaking countries between 1993 and 2016. Int J Neuropsychopharmacol 2022;25:556-66. DOI: https://doi.org/10.1093/ijnp/pyac005
37. Fick DM, Steis MR, Waller JL, et al. Delirium superimposed on dementia: A review of the literature and evidence-based guidelines for management. J Am Geriatr Soc 2013;61:914-22.
38. Hshieh T, Yang T, Oh E, et al. Association between polypharmacy and risk of delirium in older adults: A systematic review and meta-analysis. J Clin Psychiatry 2017;78:e1-e10.
39. Reisinger M, Reininghaus EZ, Biasi JD, et al. Delirium‐associated medication in people at risk: A systematic update review, meta‐analyses, and GRADE‐profiles. Acta Psychiatr Scand 2023;147:16-42. DOI: https://doi.org/10.1111/acps.13505
40. Chyou T-Y, Nishtala PS. Identifying frequent drug combinations associated with delirium in older adults: Application of association rules method to a case‐time‐control design. Pharmacoepidemiol Drug Saf 2021;30:1402-10. DOI: https://doi.org/10.1002/pds.5292
41. Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet 2014;383:911-22. DOI: https://doi.org/10.1016/S0140-6736(13)60688-1
42. Ebersbach G, Ip CW, Klebe S, et al. Management of delirium in Parkinson’s disease. J Neural Transm (Vienna) 2019;126:905-12. DOI: https://doi.org/10.1007/s00702-019-01980-7
43. Kalisvaart KJ, de Jonghe JF, van der Mast RC. Risk factors for delirium in intensive care patients: a systematic review. Intensive Care Med 2005;31:1227-33.
44. Grover S, Avasthi A. Clinical practice guidelines for management of delirium in elderly. Indian J Psychiatry 2018;60:S329-40. DOI: https://doi.org/10.4103/0019-5545.224473

How to Cite

1.
Le PH, Upshaw WC, Le TA, Townsend H, Vu TP, Salonga JM, et al. Drug-associated delirium: basic pharmacologic principles and clinical considerations. A narrative review. Adv Health Res [Internet]. 2025 Feb. 25 [cited 2025 Mar. 12];2. Available from: https://www.ahr-journal.org/site/article/view/28
Copyright (c) 2025 the Author(s) Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.