Understanding the Risks: What are the two types of common medications that could cause delirium?

October 11, 2025 •

3 min read

Delirium affects as many as 50% of older adults during a hospital stay, and certain medications are a major modifiable risk factor for this serious medical condition. Understanding what are the two types of common medications that could cause delirium is crucial for patient safety, especially in vulnerable populations such as the elderly or those with pre-existing cognitive issues. These drug classes can disrupt brain function and lead to acute confusion.

Quick Summary

Delirium is often precipitated or worsened by certain drugs. Anticholinergic medications block key neurotransmitters, while benzodiazepines and other sedatives depress the central nervous system, leading to confusion. Polypharmacy, age, and renal function increase the risk. Careful prescribing and monitoring are essential for prevention and management.

Key Points

Anticholinergics Block Acetylcholine: These drugs interfere with the neurotransmitter acetylcholine, which is critical for cognitive function, memory, and attention.
Benzodiazepines Depress the CNS: These medications enhance the inhibitory effects of GABA, causing sedation and a high risk of confusion and delirium, especially in older adults.
Polypharmacy is a Major Risk: Taking multiple medications, particularly in combination with other risk factors like older age and pre-existing cognitive issues, drastically increases the likelihood of delirium.
Opioids and Sedatives are Also Culprits: Beyond the two main classes, drugs like opioids and certain hypnotics are also known to cause or prolong delirium.
Prevention Involves Careful Prescribing: To prevent medication-induced delirium, healthcare providers should conduct regular medication reviews, minimize polypharmacy, and use the lowest effective dose of any necessary high-risk drug.
Non-Pharmacological Strategies are Key: Environmental and supportive measures like maintaining hydration, ensuring proper sleep, and providing orientation cues are crucial for preventing and managing delirium.
Elderly are Especially Vulnerable: Due to age-related changes in metabolism and lower acetylcholine levels, older adults are highly susceptible to the delirious effects of these medications.

Delirium is a serious and potentially preventable condition characterized by an acute, fluctuating disturbance in attention, awareness, and cognition. While it can have many causes, a significant portion of cases are triggered or worsened by medications, especially in high-risk individuals like older adults. Among the numerous culprits, two types of common medications are particularly notorious for inducing delirium: anticholinergics and benzodiazepines. Understanding why these drug classes are so problematic is the first step toward effective prevention and management.

Anticholinergic Medications: Blocking Key Neurotransmitters

Anticholinergic drugs block the action of acetylcholine, a neurotransmitter important for cognitive functions like learning, memory, and attention. In the central nervous system, decreased acetylcholine can lead to significant cognitive impairment and delirium, particularly in older individuals who already have lower levels. A high cumulative effect from multiple anticholinergic medications increases the risk of delirium. Common examples include certain antihistamines, tricyclic antidepressants, and medications for overactive bladder or muscle spasms.

Benzodiazepines and Other Sedative-Hypnotics

Benzodiazepines are CNS depressants that enhance the effect of GABA, an inhibitory neurotransmitter. While useful for sedation and anxiety, their depressive effects on the CNS can cause confusion and delirium, especially in older or vulnerable patients. Longer-acting benzodiazepines and withdrawal after prolonged use carry a higher risk. Common benzodiazepines include lorazepam and diazepam. Non-benzodiazepine hypnotics like zolpidem can also cause confusion.

Other Contributing Factors and High-Risk Situations

Delirium risk from medication is often multifactorial. Polypharmacy is a key contributor, as taking multiple medications increases the likelihood of interactions and cumulative effects. Dehydration, infection, and pre-existing cognitive impairment also significantly raise susceptibility. The use of three or more medications in older patients is linked to a higher risk. Opioid analgesics, particularly in surgical and critically ill patients, are also commonly associated with delirium. Some opioids, like meperidine, have a higher risk due to toxic metabolites.

Comparison of Delirium-Inducing Drug Classes


Feature	Anticholinergic Medications	Benzodiazepines	Opioid Analgesics
Mechanism	Block the neurotransmitter acetylcholine, impairing cognitive function.	Enhance the inhibitory effects of GABA, depressing the central nervous system.	Act on opioid receptors in the brain, leading to sedation and neurotoxicity.
Common Examples	Diphenhydramine, Amitriptyline, Oxybutynin.	Lorazepam, Diazepam, Zolpidem.	Morphine, Oxycodone, Meperidine.
Primary Indication	Allergies, depression, overactive bladder.	Anxiety, insomnia, seizures.	Pain management.
Onset of Action	Varies, but effects can accumulate over time.	Rapid onset, especially with high doses or IV administration.	Varies by drug and route; toxicity can occur with metabolite buildup.
Reversal Options	Effects can be mitigated by reducing or stopping the medication; physostigmine may be used in specific cases.	Often managed by reducing the dose or discontinuing the drug; flumazenil can be used to reverse effects in an overdose scenario.	Reducing dose or rotating to a different opioid; naloxone can be used for overdose.
Risk in Elderly	High due to lower baseline acetylcholine levels and slower metabolism.	High risk, as metabolism slows and can cause paradoxical excitation or sedation.	Higher risk due to altered metabolism and dehydration.

Prevention and Management Strategies

Preventing medication-induced delirium involves careful prescribing practices. This includes regular medication reviews, prioritizing lower-risk alternatives, minimizing the number of medications used, and using the lowest effective doses. Non-pharmacological interventions are also crucial, such as ensuring proper hydration, nutrition, sleep hygiene, early mobilization, and maintaining patient orientation. If delirium occurs, management focuses on identifying and treating the underlying cause, which may involve adjusting or stopping the offending medication. Caution is needed with medications to manage agitation, as they can sometimes worsen delirium.

Conclusion

Delirium is a serious condition often linked to medication use, particularly anticholinergics and benzodiazepines. These drug classes disrupt brain function and increase risk, especially in vulnerable individuals like older adults and those with polypharmacy. By understanding these risks, healthcare providers can implement preventive strategies such as careful prescribing, medication reviews, and non-pharmacological interventions. A proactive and comprehensive approach is essential for reducing the incidence and improving outcomes of medication-induced delirium. For additional information, the National Institutes of Health is a valuable resource {Link: NIH https://www.nia.nih.gov/health/delirium/delirium-what-it-all-about}.

Disclaimer: This article is for informational purposes only and does not constitute medical advice. Always consult with a healthcare professional before making any changes to your medication regimen.

Frequently Asked Questions

First-generation antihistamines, such as diphenhydramine (found in products like Benadryl), are common over-the-counter medications with strong anticholinergic properties that can cause confusion and delirium.

Benzodiazepines are typically not recommended for general delirium management and can worsen symptoms. However, they have a specific role in treating delirium caused by alcohol or sedative-hypnotic withdrawal, where they are considered the treatment of choice.

Delirium symptoms typically have a sudden onset and fluctuate throughout the day. If you notice a change in a person's mental state, such as increased confusion, disorientation, or agitation, shortly after starting a new medication or increasing a dose, it could be the cause.

No, delirium and dementia are different, though they can co-exist. Delirium is an acute and often temporary state of fluctuating confusion, while dementia is a chronic, progressive decline in cognitive function. Delirium often has a clear trigger, like medication, that can be treated.

Polypharmacy refers to the use of multiple medications. It increases delirium risk because it raises the likelihood of drug-drug interactions and increases the cumulative anticholinergic burden on the central nervous system, overwhelming the brain's ability to function normally.

Opioids, particularly in higher doses or in susceptible patients, can cause neurotoxicity and sedation that leads to delirium. Certain opioids, especially those with active metabolites, are more prone to causing this effect.

You should immediately contact their healthcare provider. They will conduct a medication review to determine if a drug is the likely cause and may adjust the dosage or switch to a different, safer medication.