From the Guidelines
Drug-induced delirium in elderly patients with pre-existing cognitive impairment can be caused by several medication classes, including anticholinergic medications, benzodiazepines, opioid analgesics, sedative-hypnotics, antipsychotics, anticonvulsants, corticosteroids, and histamine-2 blockers. The most common culprits are anticholinergic medications like diphenhydramine, oxybutynin, and tricyclic antidepressants, which block acetylcholine, already deficient in patients with dementia 1. Other contributors include:
- Benzodiazepines such as lorazepam, diazepam, and alprazolam, which can cause paradoxical excitation and confusion, especially with long-acting formulations
- Opioid analgesics including morphine, hydrocodone, and oxycodone, which frequently cause delirium through multiple mechanisms including dopamine modulation
- Sedative-hypnotics like zolpidem and eszopiclone, which can worsen confusion, particularly at higher doses
- Certain antipsychotics (especially first-generation), anticonvulsants, corticosteroids, histamine-2 blockers (ranitidine, famotidine), and medications with strong anticholinergic properties like some antihistamines and antispasmodics Polypharmacy itself increases risk, as does dehydration, infection, or electrolyte abnormalities that may enhance medication sensitivity 1. When managing these patients, consider medication reconciliation, using lower starting doses, choosing medications with fewer anticholinergic properties, and monitoring closely for early signs of delirium. Some key strategies for delirium prevention include:
- Orienting communication
- Therapeutic activities
- Early mobilization and walking
- Nonpharmacologic approaches to sleep
- Maintaining nutrition and hydration
- Adaptive equipment for vision and hearing impairment
- Medication review
- Infection control
- Preventing falls and injuries 1.
From the Research
Causes of Drug-Induced Delirium
- Delirium can be caused by almost any drug, especially in vulnerable patients, such as the elderly with pre-existing cognitive impairment 2
- Anticholinergic medications are important causes of acute and chronic confusional states, and polypharmacy with anticholinergic compounds is common, especially in nursing home residents 2
- Psychoactive drugs, such as narcotic agents, long-acting benzodiazepines, and tricyclic antidepressants, are also important causes of delirium 2, 3
- Nonpsychoactive drugs, such as histamine H2 receptor antagonists, cardiac medications, corticosteroids, non-steroidal anti-inflammatory agents, and antibiotics, can also cause acute and chronic confusion 2
Drug Classes Associated with Delirium
- Antiseizure medications, antidepressants, antiparkinsonian drugs, antipsychotics, lithium, benzodiazepines/Z-drugs, opioids, first-generation antihistamines, and drugs for urinary incontinence have been associated with delirium 4
- Proton pump inhibitors, glucocorticoids, NSAIDs, statins, antihypertensives, and chemotherapeutic agents have also been linked to delirium 4
- Sedatives, such as benzodiazepines, have a high risk of cognitive impairment, and centrally acting sympathetic antihypertensive agents, sedating antipsychotic drugs, opioids, digitalis, anti-Parkinsonian drugs, antidepressants, and corticosteroids are also associated with greater risk 5
Prevention and Management
- Rationalization of drug therapy is key to preventing cognitive impairment and delirium, and most causative drugs are contained in negative lists, such as the Beers list 3
- Avoidance or optimization of psychotropic drug prescriptions is crucial in preventing cognitive impairment in the elderly 3
- Strategies to minimize the risk of drug-induced impairment include optimizing overall health, avoiding unnecessary medications, and selecting medications least likely to cause delirium 5