Delirium is common in those with serious medical illness. Initial management strategies include identifying and treating the underlying cause, as well as non-pharmacological treatment. When these strategies are not effective, pharmacological interventions may be necessary. The pharmacological interventions below are for potentially reversible, hyperactive delirium.

1st generation antipsychotics
Haloperidol. It is the best studied antipsychotic, and the agent of choice for the treatment of delirium. Starting doses are 0.5-1 mg PO or IV. Titration can occur by 2-5 mg every 1 hour until a total daily requirement is established, which is then administered in daily or twice daily doses. Recommended maximum dose is 100 mg/day. Intravenous haloperidol may cause less extrapyramidal symptoms than oral haloperidol.
Chlorpromazine. It has more sedative effects than haloperidol for patients in whom sedation is desired. The starting dose is 25-50 mg PO. Titration can occur by 25-50 mg every 1 hour until a total daily requirement is established, which is then administered in daily or twice daily doses. Recommended maximum dose is 2000 mg/day.

2nd generation antipsychotics
Known as "atypical antipsychotics"; as no evidence exists for improved efficacy with them, they are not considered to be first-line treatment. They are associated with fewer extrapyramidal side effects than 1st generation antipsychotics, hence, in Parkinson’s disease and related neuromuscular disorders and in patients with a history of extrapyramidal reactions from 1st generation antipsychotics this class of agents may be preferred. For acutely agitated patients requiring onset of action within minutes, providers should know that these agents do not work as fast as conventional antipsychotics.
Olanzapine. The starting dose is 5 mg PO every day; after one week, the dose can be raised to 10 mg a day; then to 20 mg a day.
Quetiapine. It is initially given 25 mg PO twice a day which can be raised by 25-50 mg per dose every 2 to 3 days up to a target of 300-400 mg a day, divided into 2 or 3 doses. Compared to the atypical neuroleptics, it is the most sedating and causes the least extrapyramidal side effects. It has more orthostasis than olanzapine and risperidone.
Risperidone. It is given 1-2 mg PO at night and is gradually raised 1 mg every 2 to 3 days until an effective dose (usually 4-6 mg PO hs) is reached. It has minimal anticholinergic effects and does not cause orthostasis. It is the least sedating of this class of antipsychotics
Newer antipsychotics include ziprasidone and aripiprazole; their role in the management of delirium is not firmly established.

Side effects include:
- extrapyramidal effects
- anticholinergic effects (dry mouth, constipation)
- anti-adrenergic effects (postural hypotension)
- antihistaminic effects (drowsiness)

Benzodiazepines. With the exception of treating delirium due to drug withdrawal or anticholinergic excess, benzodiazepines should be avoided for potentially reversible, hyperactive delirium unless the agitation is severe and uncontrolled by the neuroleptic. Benzodiazepines can make delirium worse and precipitate withdrawal syndromes.

Melatonin. This hormone is produced naturally in the pineal gland and can help regulate the sleep-wake rhythm cycle. Randomized placebo-controlled trials have validated the use of both melatonin and a melatonin analog (ramelteon) in the prevention of delirium in at-risk, hospitalized patients.

Adapted from Quijada E and Billings A. Palliative Care Network of Wisconsin. Fast facts and concepts #60. Pharmacologic management of delirium: update on newer agents. Internet. Accessed on October 5, 2016.