General Management Approach to Delirium
Symptomatic Management: The Role of Pharmacologic Agents
The pathogenesis of delirium is complex and is poorly understood. Abnormalities of various neurotransmitter and other endogenous agents have been postulated, including reduced cerebral cholinergic transmission (or excess dopaminergic transmission relative to cholinergic transmission), altered gamma aminobutyric acid transmission, altered serotonin transmission, cytokine production, and altered cortisol levels. The mainstay of pharmacological management has been the use of powerful antidopaminergic neuroleptics such as haloperidol  and the newer atypical antipsychotic agents such as olanzapine, risperidone, and quetiapine.[16,17];[Level of evidence: I]
Some authors have tentatively suggested that the different subtypes of delirium (hypoactive, hyperactive, and mixed) reflect different underlying pathophysiologies and therefore have differing treatment requirements, treatment responsiveness, and outcomes.[Level of evidence: II] One study suggests that the hypoactive subtype is as distressing for patients as the hyperactive or mixed subtypes.[Level of evidence: II] Some preliminary evidence suggests that the hypoactive subtype is less responsive to neuroleptic treatment. Evidence would therefore suggest that all three subtypes warrant symptomatic treatment but that the hyperactive or agitated subtype requires more sedating agents. Although psychostimulants have been proposed for the treatment of hypoactive delirium,[Level of evidence: III];[Level of evidence: II] little empirical evidence attests to their benefit. In a prospective clinical study of 14 patients with advanced cancer and hypoactive delirium, patients demonstrated improvement in cognitive function after receiving 20 to 50 mg of methylphenidate hydrochloride per day.[Level of evidence: III] Relatively higher doses of stimulants (>10 mg of methylphenidate) should be used with caution in delirious patients because such doses can contribute to the unmasking of paranoia and confusion and can lead to agitation. Clinical experience suggests that psychostimulants should be avoided in the presence of hallucinations or delusions.
Haloperidol, a neuroleptic agent with potent antidopaminergic properties, is still considered the drug of choice for the treatment of delirium in the patient with cancer.[1,7] Haloperidol has a low incidence of cardiovascular and anticholinergic effects. Although there is no high-level evidence to substantiate the use of haloperidol in patients with cancer, a double-blind trial of haloperidol, chlorpromazine, and lorazepam in the treatment of hospitalized patients with delirium and acquired immunodeficiency syndrome suggested that haloperidol and chlorpromazine were equivalent in efficacy, and both were associated with a very low prevalence of extrapyramidal side effects. Lorazepam, however, was ineffective and associated with adverse effects, resulting in early closure of this arm of the protocol.[Level of evidence: I] The optimal dose range of haloperidol for patients with delirium has not been determined. Consensus guidelines recommended initial doses in the range of 1 to 2 mg every 2 to 4 hours as needed and lower starting doses, such as 0.5 mg every 4 hours as needed, in elderly patients.