Medicines Associated with Delirium

Delirium is an acute, fluctuating disturbance of attention and awareness with change in cognition, caused by a medical condition, substance or withdrawal. Medicines are among the commonest reversible causes in older adults, and hypoactive delirium with drowsiness is frequently missed. A validated bedside screen such as the 4AT should be applied on admission and with any acute change.

Recognition. List every drug started or increased in the previous 2 weeks and every drug stopped abruptly. Check alcohol, khat and benzodiazepine use, as withdrawal and intoxication both cause delirium.

Mechanism. Common mechanisms are cholinergic deficiency, dopaminergic excess, GABA-ergic disturbance and neurotoxic drug accumulation in renal impairment.

Culprit medicines.

• Anticholinergics: tricyclic antidepressants, oxybutynin, chlorphenamine, promethazine, hyoscine.
• Sedatives: benzodiazepines, zopiclone, zolpidem.
• Opioids: especially pethidine and tramadol, and any opioid accumulating in renal failure.
• Corticosteroids: particularly prednisolone 40 mg daily or more.
• Dopaminergic drugs: levodopa, dopamine agonists, amantadine.
• Anti-infectives: fluoroquinolones, high-dose metronidazole, cefepime in renal impairment, mefloquine.
• Others: histamine H2 blockers, metoclopramide, baclofen, gabapentinoids, digoxin toxicity, lithium toxicity, phenytoin toxicity.

Management of the cause. Stop or reduce the culprit, correct dehydration and infection, relieve pain, retention and constipation, and restore glasses, hearing aids and sleep routine.

Agitation. Use a drug only when there is severe distress or danger to self or others and non-drug measures have failed. Haloperidol 0.25 to 0.5 mg orally or intramuscularly as a single dose, repeated after at least 2 hours if needed, maximum 2 mg in 24 hours. Obtain an ECG first and avoid if QTc is over 500 ms. Review daily and stop once settled, usually within 3 days.

Parkinson disease or Lewy body dementia. Avoid haloperidol. Use quetiapine 12.5 to 25 mg orally as a single dose, maximum 50 mg in 24 hours.

Withdrawal states. Benzodiazepines are used only for alcohol or benzodiazepine withdrawal and seizures. Lorazepam 0.5 mg orally, repeated as needed, maximum 2 mg in 24 hours in older adults.

Special groups. People with dementia are at highest risk and recover slowest. Reduce all doses in renal impairment: creatinine clearance under 30 mL/min lowers the threshold for opioid and antibiotic neurotoxicity.

Monitoring. Screen daily for delirium, record vital signs, glucose, sodium, calcium, creatinine, and ECG when an antipsychotic is used. Check digoxin, lithium or phenytoin levels when these drugs are taken.

Bladder and bowel. Check for urinary retention and faecal loading, which are both precipitants and drug effects.

Stopping. Remove anticholinergics and sedatives where possible, tapering benzodiazepines if long-term use is established, to avoid withdrawal delirium and seizures.

Referral and escalation. Seek urgent senior review for delirium with fever and neck stiffness, head injury, focal signs, severe hyponatraemia (sodium under 125 mmol/L) or suspected serotonin or neuroleptic malignant syndrome. Refer to old-age psychiatry or geriatric services for delirium lasting over 7 days.