Cardiovascular Drugs and Therapy

, Volume 16, Issue 2, pp 161–165

Acute Delirium Induced by Metoprolol

  • Alexander A. Fisher
  • Michael Davis
  • Ian Jeffery


Objective: To describe a case of delirium associated with use of metoprolol and to analyse 24 such cases including 22 cases reported to Australian Adverse Drug Reaction Advisory Committee and one case previously published (S. Ahmad, Am Fam Physician, 1991;44:1142, 1144).

Case Summary: An 89 year old caucasian man with an acute coronary syndrome who had no psychiatric history and no infections, brain injury, stroke, metabolic nor neoplastic disease developed delirium after two small doses of metoprolol (25 mg). The delirium disappeared within 20 hours after metoprolol was ceased, despite continuing all other medications.

The Combined Series: Of 24 patients (12 women, mean age 71.8 years), 83% were older than 60 years. The duration of therapy before onset of delirium in 14 (58%) subjects was within one week; 23 of 24 patients were receiving therapeutic amounts of the drug (25–200 mg/day). Clinical features included confusion/disorientation in all subjects, agitation in 13, aggression in 6, visual hallucinations in 7, auditory hallucinations in 1, paranoid delusions in 3, vivid dreams in 2 and language disturbances in 3 persons. Bradycardia was reported in 4 cases, hypotension in 2, fatigue/tiredness in 3, Raynaud's phenomenon in 1 and skin rash in 1 patient.

Discussion: The mechanism of metoprolol-induced delirium is unclear. It could be due to impairment of hepatic metabolism (especially in the ageing liver) and complex neurotransmitter-related effects on brain beta-adrenoceptors and serotonin (5-HT) receptors.

Conclusions: Physicians should be aware that metoprolol, a widely used beta-blocker, may rarely cause delirium, especially in the elderly population.

delirium metoprolol beta-blockers 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Olsson G, Tuomilehto J, Berglund G, et al. Primary prevention of sudden cardiovascular death in hypertensive patients. Mortality results from the MAPHY Study. Am J Hypertens 1991;4:151–158.Google Scholar
  2. 2.
    Kendall MJ. Clinical trial data on the cardioprotective effects of beta-blockade. Basic Res Cardiol 2000;95:125–130.Google Scholar
  3. 3.
    Cruickshank JM. The clinical importance of cardioselectivity and lipophilicity in beta blockers. Am Heart J 1980;100:160–178.Google Scholar
  4. 4.
    Gengo FM, Gabos C. Central nervous system considerations in the use of beta-blockers, angiotensin-converting enzyme inhibitors, and thiazide diuretics in managing essential hypertension. Am Heart J1988;116:305–310.Google Scholar
  5. 5.
    Dimsdale JE, Newton RP, Joist T. Neuropsychological side effects of beta-blockers. Arch Intern Med 1989;149:514–525.Google Scholar
  6. 6.
    McAinsh J, Cruickshank JM. Beta-blockers and central nervous system side effects. Pharmacol Ther 1990;46:163–197.Google Scholar
  7. 7.
    Gleiter CH, Deckert J. Adverse CNS-effects of betaadrenoceptor blockers. Pharmacopsychiatry 1996;29:201–211.Google Scholar
  8. 8.
    Patel L, Turner P. Central actions of beta-adrenoceptor blocking drugs in man. Med Res Rev 1981;1:387–410.Google Scholar
  9. 9.
    Westerlund A. Central nervous system side-effects with hydrophilic and lipophilic beta-blockers.EurJ Clin Pharmacol 1985;28:73–76.Google Scholar
  10. 10.
    Cove-Smith JR, Kirk CA. CNS-related side-effects with metoprolol and atenolol. Eur J Clin Pharmacol 1985;28:69–72.Google Scholar
  11. 11.
    Kostis JB, Rosen RC. Central nervous system effects of beta-adrenergic-blocking drugs: The role of ancillary properties. Circulation1987;75:204–212.Google Scholar
  12. 12.
    Drayer DE.Lipophilicity, hydrophilicity, and the central nervous system side effects of beta blockers. Pharmacotherapy 1987;7:87–91.Google Scholar
  13. 13.
    Ahmad S. Metoprolol-induced delirium perpetuated by propafenone. Am Fam Physician 1991;44:1142, 1144.Google Scholar
  14. 14.
    White WB, Riotte K. Propranolol and white rabbits.NEngl J Med 1982;307:558–559.Google Scholar
  15. 15.
    Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239–245.Google Scholar
  16. 16.
    Parker DL, Hodge JR. Delirium in a coronary care unit. JAMA1967;201:702–703.Google Scholar
  17. 17.
    Gershon ES, Goldstein RE, Moss AJ, van Kammen DP. Psychosis with ordinary doses of propranolol. Ann Intern Med 1979;90:938–939.Google Scholar
  18. 18.
    Greenblatt DJ, Koch-Weser J. Adverse reactions to propranolol in hospitalized medical patients: A report from the Boston Collaborative Drug Surveillance Program. Am Heart J 1973;86:478–484.Google Scholar
  19. 19.
    Gengo FM, Huntoon L, McHugh WB. Lipid-soluble and water-soluble beta-blockers. Comparison of the central nervous system depressant effect. Arch Intern Med 1987;147:39–43.Google Scholar
  20. 20.
    Gengo FM, Ermer JC, Carey C, Kalonaros GC, McHugh WB. The relationship between serum concentrations and central nervous system actions of metoprolol. J Neurol Neurosurg Psychiatry 1985;48:101–106.Google Scholar
  21. 21.
    Le Couteur DG, McLean AJ. The aging liver. Drug clearance and an oxygen diffusion barrier hypothesis. Clin Pharmacokinet 1998;34:359–373.Google Scholar
  22. 22.
    Le Couteur DG, Cogger VC, Markus AM, et al. Pseudocapillarization and associated energy limitation in the aged rat liver. Hepatology 2001;33:537–543.Google Scholar
  23. 23.
    Hickey PL, McLean AJ, Angus PW, Choo EF, Morgan DJ. Increased sensitivity of propranolol clearance to reduced oxygen delivery in the isolated perfused cirrhotic rat liver. Gastroenterology1996;111:1039–1048.Google Scholar
  24. 24.
    Frohlich ED. Beta-blockers and mental performance. Arch Intern Med 1988;148:777–778.Google Scholar
  25. 25.
    Stephen SA. Unwanted effects of propranolol.AmJ Cardiol 1966;18:463–472.Google Scholar
  26. 26.
    Conway J, Greenwood DT, Middlemiss DN. Central nervous actions of beta-adrenoreceptor antagonists. Clin Sci Mol Med 1978;54:119–124.Google Scholar
  27. 27.
    Fleminger R. Visual hallucinations and illusions with propranolol. Br Med J1978;1:1182.Google Scholar
  28. 28.
    Fleming PD, Drachman DA. Propranolol, hallucinations, and sleep disturbance. Am J Psychiatry 1982;139:540–541.Google Scholar
  29. 29.
    Shore JH, Fraunfelder FT, Meyer SM. Psychiatric side effects from topical ocular timolol, a beta-adrenergic blocker. J Clin Psychopharmacol1987;7:264–267.Google Scholar
  30. 30.
    Inouye SK, Charpentier PA. Precipitating factors for delirium in hospitalized elderly persons. Predictive model and interrelationship with baseline vulnerability. JAMA 1996;275:852–857.Google Scholar
  31. 31.
    O'Keeffee ST. Delirium in the elderly. Age Ageing 1999;28(Suppl 2):5–8.Google Scholar
  32. 32.
    Gray SL, Lai KV, Larson EB. Drug-induced cognition disorders in the elderly: Incidence, prevention and management. Drug Saf1999;21:101–122.Google Scholar
  33. 33.
    Francis J, Martin D, Kapoor WN. A prospective study of delirium in hospitalized elderly. JAMA 1990;263:1097–1101.Google Scholar
  34. 34.
    Moore AR, O'Keeffe ST. Drug-induced cognitive impairment in the elderly. Drugs Aging 1999;15:15–28.Google Scholar
  35. 35.
    Trzepacz PT. Is there a final common neural pathway in delirium? Focus on acetylcholine and dopamine. Semin Clin Neuropsychiatry 2000;5:132–148.Google Scholar
  36. 36.
    Cruickshank JM, Neil-Dwyer G. Beta-blocker brain concentrations in man. Eur J Clin Pharmacol 1985;28:21–23.Google Scholar
  37. 37.
    McCaffrey PM,Riddell JG, Shanks RG.Anassessment of the partial agonist activity of Ro 31-1118, flusoxolol and pindolol in man. Br J Clin Pharmacol 1987;24:571–580.Google Scholar
  38. 38.
    Turner P. Beta-adrenoceptor blockers reduce blood pressure in normal subjects. Br J Clin Pharmacol 1983;15:128.Google Scholar
  39. 39.
    Brismar K, Mogensen L, Wetterberg L. Depressed melatonin secretion in patients with nightmares due to betaadrenoceptor blocking drugs. ActaMedScand 1987;221:155–158.Google Scholar
  40. 40.
    Brismar K, Hylander B, Eliasson K, Rossner S,Wetterberg L. Melatonin secretion related to side-effects of betablockers from the central nervous system. Acta Med Scand 1988;223:525–530.Google Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Alexander A. Fisher
    • 1
  • Michael Davis
    • 1
  • Ian Jeffery
    • 2
  1. 1.Department of Geriatric Medicine, The Canberra HospitalThe Canberra Clinical School of the University of SydneyAustralia
  2. 2.Department Cardiology, The Canberra HospitalThe Canberra Clinical School of the University of SydneyAustralia

Personalised recommendations