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An Approach to Drug Induced Delirium in the Elderly K Alagiakrishnan, C a Wiens

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An Approach to Drug Induced Delirium in the Elderly K Alagiakrishnan, C a Wiens 388 REVIEW Postgrad Med J: first published as 10.1136/pgmj.2003.017236 on 14 July 2004. Downloaded from An approach to drug induced delirium in the elderly K Alagiakrishnan, C A Wiens ............................................................................................................................... Postgrad Med J 2004;80:388–393. doi: 10.1136/pgmj.2003.017236 Drugs have been associated with the development of with, for example, infections, structural, meta- bolic, or environmental causes. Sometimes drugs delirium in the elderly. Successful treatment of delirium may be the sole cause of delirium. Clinicians depends on identifying the reversible contributing factors, should be aware of medications with a signifi- and drugs are the most common reversible cause of cant anticholinergic effect. They should also be cautioned that the addition of medications with delirium. Anticholinergic medications, benzodiazepines, mild to moderate anticholinergic levels to an and narcotics in high doses are common causes of drug already complicated medical regimen carries induced delirium. This article provides an approach for with it the potential risk of negatively affecting the patient’s cognition. In patients who develop clinicians to prevent, recognise, and manage drug induced delirium a record of all medications and supple- delirium. It also reviews the mechanisms for this condition, ments given within the past few weeks should be especially the neurotransmitter imbalances involving carefully obtained. The most effective initial step is to review the medication list and attention acetylcholine, dopamine, and gamma aminobutyric acid should be given to the delirogenic drugs, the and discusses the age related changes that may contribute anticholinergic load of these medications, and to altered pharmacological effects which have a role in possible drug interactions. Sometimes it is clear which drug is responsible for an episode of delirium. Specific interventions for high risk elderly with the delirium because of a temporal relationship. If goal of preventing drug induced delirium are discussed. not, the clinician should carefully analyse the ........................................................................... patient’s history and look for a characteristic constellation of drug related findings. Any recent addition of a new medication or increase in dose should be verified. In situations where an elderly rugs are one of the common risk factors patient is likely to combat anticholinergic effects for delirium and may be considered the of multiple medications, the patient should often Dmost easily reversible trigger. Drug induced be examined for signs of anticholinergic toxicity.8 delirium is commonly seen in medical practice, Specific syndromes such as serotonin syndrome especially in hospital settings. The risk of anti- and neuroleptic malignant syndrome caused by cholinergic toxicity is greater in the elderly, and medications can also present as delirium with http://pmj.bmj.com/ the risk of inducing delirium by medications other features seen. is high in the frail elderly, and those with Drugs can cause any of the three types of dementia. In addition to polypharmacy, altered delirium: hyperactive, hypoactive, and mixed pharmacokinetics and pharmacodynamics seen delirium. Both hyperactive and mixed delirium with aging, and associated co-morbid diseases, are commonly seen in cholinergic toxicity, have an additive or synergistic role with drugs in alcohol intoxication, certain illicit drug (stimu- causing delirium. lant) intoxication, serotonin syndrome, alcohol on September 30, 2021 by guest. Protected copyright. Many drugs have been associated with delir- and benzodiazepine withdrawal. By contrast, ium, but certain classes of drugs (deliriants) (box hypoactive delirium is often due to benzodiaze- 1) are more commonly viewed as causative pines, narcotic overdose, or sedative hypnotic or agents for delirium. alcohol intoxication. The most common deliriants include high dose narcotics, benzodiazepines, and anticholinergic medications. Anticholinergic activity is also asso- MEDICATIONS ASSOCIATED WITH ciated with the occurrence and severity of deli- DELIRIUM 12 rium. A number of studies have shown that Many groups of drugs can cause delirium. This anticholinergic medication use is a common pre- includes prescription, over the counter, comple- See end of article for 34 authors’ affiliations cipitating risk factor. While delirium is a mentary/alternative, or illicit products. Obser- ....................... multifactorial process, it is estimated that med- vational studies show that the most common ications alone may account for 12%–39% of all drugs associated with delirium are sedative Correspondence to: 5–7 Dr Kannayiram cases of delirium. hypnotics (benzodiazepines), analgesics (narco- Alagiakrishnan, 1259, tics), and medications with an anticholinergic Glenrose Hospital, 10230, effect. Other medications in toxic doses can also 111Ave NW, Edmonton, CLINICAL RECOGNITION OF DRUG AB T5G OB7, Canada; INDUCED DELIRIUM cause delirium. Drugs may indirectly contribute [email protected] In the elderly who have acute confusion or acute on chronic confusion, delirium can be diagnosed Submitted 16 November 2003 by applying confusion assessment method cri- Abbreviations: GABA, gamma aminobutyric acid; Accepted 16 January 2004 teria. Since delirium is often multifactorial, NMDA, N-methyl-D-aspartate; NSAIDs, non-steroidal ....................... medications can be contributing in combination anti-inflammatory drugs www.postgradmedj.com Drug induced delirium in the elderly 389 of digoxin can accumulate and cause toxicity and delirium. Postgrad Med J: first published as 10.1136/pgmj.2003.017236 on 14 July 2004. Downloaded from Box 1: Deliriants (drugs causing delirium) Beta-blockers, especially propanolol, have been reported to cause delirium.9 Diuretics can induce delirium by dehydra- Prescription drugs tion and electrolyte disturbances. N Central acting agents: (B) Pulmonary drugs – Sedative hypnotics (for example, benzodiazepines). Theophylline and steroids in high doses may be contributors – Anticonvulsants (for example, barbiturates). to delirium. Often these medications are used in patients – Antiparkinsonian agents (for example, benztropine, with poor oxygenation, which in itself can increase the risk of trihexyphenidyl). delirium. N Analgesics: (C) Central nervous system drugs – Narcotics (NB. meperidine*). Benzodiazepines are lipid soluble medications that have a prolonged half life in the elderly because of accumulation – Non-steroidal anti-inflammatory drugs*. in lipid tissue. Because of the extended duration of action N Antihistamines (first generation—for example, and increased sensitivity to sedative hypnotics in the elderly, hydroxyzine). benzodiazepines can cause delirium. Benzodiazepines are independently associated as a risk factor for delirium.10 N Gastrointestinal agents: All antidepressants can contribute to delirium. The tricyclic – Antispasmodics. antidepressants have an anticholinergic effect and can induce –H2-blockers*. delirium. Of the selective serotonin uptake inhibitors, paro- xetine has the greatest affinity for muscaranic receptors, N Antinauseants: similar to nortriptyline.11 Dopaminergic medications such as – Scopolamine. levodopa or dopamine agonists can contribute to delirium in – Dimenhydrinate. a dose related manner. For these necessary medications, a dosage reduction or adjusting the dosage schedule may be N Antibiotics: helpful. If antiparkinsonism medications are suspected of causing confusion, anticholinergic medications (for example, – Fluoroquinolones*. trihexyphenidyl) should be the first to be discontinued, N Psychotropic medications: followed by selegiline, dopamine agonists and finally by tapering levodopa. Delirium occurs usually with end stage – Tricyclic antidepressants. Parkinson’s disease and with high doses of medications. In – Lithium*. elderly patients with dementia, lithium can cause delirium even at therapeutic serum levels.12 Narcotics are also inde- N Cardiac medications: pendent risk factors for delirium. Meperidine (demerol, – Antiarrhythmics. pethidine) is often avoided in seniors due to accumulation – Digitalis*. in decreased renal function. Meperidine is converted to an – Antihypertensives (b-blockers, methyldopa) anticholinergic metabolite that can cross the blood-brain barrier and lead to delirium. All other opioids can cause N Miscellaneous: delirium if excessive doses are used. http://pmj.bmj.com/ – Skeletal muscle relaxants. (D) Role of anaesthetic agents in postoperative – Steroids. delirium The incidence of postoperative delirium varies from 10%– Over the counter medications and complementary/ 26%. Ketamine is an intravenous anaesthetic agent and has alternative medications been associated with excitability, vivid unpleasant dreams, N Antihistamines (NB. first generation— for example, and delirium. Delirium has also been associated with diphenhydramine, chlorpheniramine). inhalational anaesthetics.13 on September 30, 2021 by guest. Protected copyright. N Antinauseants (for example, dimenhydrinate, scopolamine). (E) Miscellaneous drugs N Liquid medications containing alcohol. Non-steroidal anti-inflammatory drugs (NSAIDs) have been N reported to induce delirium. Some NSAIDs can cross the Mandrake. blood-brain barrier. In addition, older antihistamines (for N Henbane. example, diphenhydramine, dimenhydrinate, chlorphenira- N Jimson weed. mine) have potent anticholinergic
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