Table 4.
High-Risk Drugs in Delirium and Potential Substitutes.*
| Drug | Mechanism of Adverse Effect | Substitutes or Alternative Strategies | Comments |
|---|---|---|---|
| Benzodiazepines | CNS sedation and withdrawal | Nonpharmacologic sleep protocol36 | Associated with delirium in hospitalized patients; if patient is already taking, maintain or lower dose, but do not discontinue abruptly |
| Opioid analgesics (especially meperidine) | Anticholinergic toxicity, CNS sedation, and fecal impaction | Local and regional analgesic measures; non-psychoactive pain medications (e.g., acetaminophen and NSAIDs) around the clock; reserve opioids for breakthrough and severe pain | Consider risks versus benefits, since uncontrolled pain can also cause delirium; patients with renal insufficiency are at elevated risk for adverse effects; naloxone can be used for severe overdoses |
| Nonbenzodiazepine sedative hypnotics (e.g., zolpidem) | CNS sedation and withdrawal | Nonpharmacologic sleep protocol36 | Like other sedatives, these agents can cause delirium |
| Antihistamines, especially first-generation sedating agents (e.g., doxylamine and diphenhydramine) | Anticholinergic toxicity | Nonpharmacologic sleep protocol,36 pseudoephedrine for upper respiratory congestion, and nonsedating antihistamines for allergies | Patients should be asked about the use of over-the-counter medications; many patients do not realize that drugs with names ending in “PM” contain diphenhydramine or other sedating antihistamines |
| Alcohol | CNS sedation and withdrawal | If patient has a history of heavy intake, monitor closely and use benzodiazepines for withdrawal symptoms | The history taking must include questions about alcohol intake |
| Anticholinergics (e.g., oxybutynin and benztropine) | Anticholinergic toxicity | Lower the dose or use behavioral approaches for urinary incontinence (e.g., scheduled toileting) | Delirium is unusual at low doses |
| Anticonvulsants (e.g., primidone, phenobarbital, and phenytoin) | CNS sedation | Use an alternative agent or consider stopping if patient is at low risk for seizures and has no recent history of them | Delirium can occur despite therapeutic drug concentrations |
| Tricyclic antidepressants, especially tertiary amines (e.g., amitriptyline, imipramine, and doxepin) | Anticholinergic toxicity | Serotonin-reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, and secondary amine tricyclics (e.g., nortriptyline and desipramine) | Newer agents (e.g., duloxetine) are as effective as tertiary amines for adjuvant treatment of chronic pain |
| Histamine H2–receptor blockers | Anticholinergic toxicity | Lower the dose or substitute antacids or proton-pump inhibitors | Anticholinergic toxic effects occur primarily with high-dose intravenous infusions |
| Antiparkinsonian agents (e.g., levodopa and amantadine) | Dopaminergic toxicity | Lower the dose or adjust dosing schedule | Dopaminergic toxic effects occur primarily in advanced disease and at high doses |
| Antipsychotics, especially low-potency typical antipsychotics (e.g., chlorpromazine and thioridazine) | Anticholinergic toxicity as well as CNS sedation | Discontinue entirely or, if necessary, use low doses of high-potency agents | Carefully consider risks vs. benefits of use in delirium |
| Barbiturates | CNS sedation and severe withdrawal syndrome | Gradual discontinuation or benzodiazepine substitution | In most cases, barbiturates should not be prescribed; avoid inadvertent or abrupt discontinuation |
*
In older adults, the risks and benefits of all medications should be considered carefully. Adverse effects should be monitored whenever any medication is started or the dose is adjusted. CNS denotes central nervous system, and NSAIDs nonsteroidal antiinflammatory drugs.