CNS Drugs

Delirium occurs at rates ranging from 10% to 30% of all hospital admissions. It is a negative prognostic indicator, often leading to longer hospital stays and higher mortality. The aetiology of delirium is multifactorial and many causes have been suggested. The stress-diathesis model, which posits an interaction between the underlying vulnerability and the nature of the precipitating factor, is useful in understanding delirium.

Preventing delirium is the most effective strategy for reducing its frequency and complications. Environmental strategies are valuable but are often underutilized, while remedial treatment is usually aimed at specific symptoms of delirium. Antipsychotics are the mainstay of pharmacological treatment and have been shown to be effective in treating symptoms of both hyperactive and hypoactive delirium, as well as generally improving cognition. Haloperidol is considered to be first-line treatment as it can be administered via many routes, has fewer active metabolites, limited anticholinergic effects and has a lower propensity for sedative or hypotensive effects compared with many other antipsychotics. Potential benefits of atypical compared with typical antipsychotics include the lower propensity to cause over-sedation and movement disorder. Of the second-generation antipsychotics investigated in delirium, most data support the use of risperidone and olanzapine. Other drugs (e.g. aripiprazole, quetiapine, donepezil and flumazenil) have been evaluated but data are limited.

Benzodiazepines are the drugs of choice (in addition to antipsychotics) for delirium that is not controlled with an antipsychotic (and can be used alone for the treatment of alcohol and sedative hypnotic withdrawal-related delirium). Lorazepam is the benzodiazepine of choice as it has a rapid onset and shorter duration of action, a low risk of accumulation, no major active metabolites and its bioavailability is more predictable when it is administered both orally and intramuscularly.