Delirium that causes injury to the patient or others should be treated with medications. The most common medications used are antipsychotic medications. While this is a common and seemingly useful strategy, the literature is still mixed. A 2015 meta-analysis of 15 studies found that second-generation antipsychotics (SGAs) may treat delirium better than placebo, usual care, or haloperidol.  A 2016 meta-analysis of 19 studies found that antipsychotic use was not associated with change in delirium duration, severity, or hospital or ICU length of stay. 
Benzodiazepines often are used for alcohol and benzodiazepine withdrawal states.
Since decreased anticholinergic activity may be associated with delirium, anticholinesterase inhibitors have been tried. Even though case reports showed evidence that cholinesterase inhibitors may play a role in the management of delirium, larger trials and systematic review did not support this use.  A randomized, double-blinded, placebo-controlled, multicenter trial in intensive care unit patients showed rivastigmine did not decrease duration of delirium and increased mortality in these patients. In this trial, the study group had more sicker patients with emergency admissions to the ICU, and this trial had used IV haloperidol, lorazepam, or propofol, in addition to rivastigmine, which might also have contributed to the delirium and increased mortality.  A review of 7 trials of anticholinesterase inhibitors found that in 5 of the studies there was no benefit from the medications in either the prevention or management of delirium. 
Recent clinical trials showed that the melatonin supplement and its receptor agonist ramelteon may be useful in the prevention and management of delirium. Melatonin levels were found to be altered in delirium subjects.  Melatonin is available over the counter in North America. Ramelteon has been approved by the FDA for the treatment of insomnia. 
This class of drugs are the medication of choice in the treatment of psychotic symptoms of delirium. Older antipsychotics such as haloperidol, a high-potency antipsychotic, are useful but have adverse neurological effects. Newer neuroleptics such as risperidone, olanzapine, and quetiapine relieve symptoms while minimizing adverse effects. Initial doses may need to be higher than maintenance doses. Use lower doses in patients who are elderly. Discontinue these medications as soon as possible. Attempt a trial of tapering the medication once symptoms are in control. Antipsychotics can be associated with adverse neurological effects such as extrapyramidal symptoms, neuroleptic malignant syndrome, and tardive dyskinesia. Longer term use is also associated with metabolic syndrome. Doses should be kept as low as possible to minimize adverse effects. Paradoxical and hypersensitivity reactions may occur.
A butyrophenone high-potency antipsychotic. One of most effective antipsychotics for delirium. High-potency antipsychotic medications also cause less sedation than phenothiazines and reduce risks of exacerbating delirium.
A newer antipsychotic with fewer extrapyramidal adverse effects than Haldol. Binds to dopamine D2-receptor with 20 times lower affinity than for 5-HT2-receptor. Improves negative symptoms of psychoses and reduces incidence of adverse extrapyramidal effects.
Reserved for delirium resulting from seizures or withdrawal from alcohol or sedative hypnotics. Coadministration with antipsychotics is considered only in patients who tolerate lower doses of either medication or have prominent anxiety or agitation. Benzodiazepines are preferred over neuroleptics for treatment of delirium resulting from alcohol or sedative hypnotic withdrawal. They also may be used when unknown substances may have been ingested and may be helpful in delirium from hallucinogen, cocaine, stimulant, or PCP toxicity. Use special precaution when using benzodiazepines because they may cause respiratory depression, especially in patients who are elderly, those with pulmonary problems, or debilitated patients.
Preferable because it is short acting and has no active metabolites. In addition, can be used in both IM and IV forms. When patient needs to be sedated for longer than 24 h, this medication is excellent. Commonly used prophylactically to prevent delirium tremens.
Patients with alcoholism and patients with malnutrition are prone to thiamine and vitamin B-12 deficiency, which can cause delirium.
For alcohol withdrawal and in cases of Wernicke encephalopathy.
Vitamin B-12 deficiency can cause confusion or delirium in patients who are elderly. Deoxyadenosylcobalamin and hydroxocobalamin are active forms of vitamin B-12 in humans. Vitamin B-12 is synthesized by microbes but not by humans or plants. Vitamin B-12 deficiency may result from intrinsic factor deficiency (pernicious anemia), partial or total gastrectomy, or diseases of the distal ileum.
Agents in this class may be useful in the prevention and management of delirium.
Melatonin is a naturally occurring hormone secreted by the pineal gland. The concentration of melatonin is highest in the blood during normal times of sleep and lowest during normal times of wakefulness. The general consensus is that melatonin given during normal waking hours has hypnotic properties.
Ramelteon is a melatonin receptor agonist with high selectivity for human melatonin MT1 and MT2 receptors. MT1 and MT2 are thought to promote sleep and be involved in maintaining circadian rhythm and a normal sleep-wake cycle. Ramelteon does not cause rebound insomnia or withdrawal symptoms at discontinuation. It is approved for prolonged use. It is indicated for insomnia characterized by difficulty with sleep onset.
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