Evidence-Based Reviews

Treatment of delirium: A review of 3 studies

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Delirium is defined as a disturbance in attention, awareness, and cognition that develops over hours to days as a direct physiological consequence of an underlying medical condition and is not better explained by another neurocognitive disorder.1 This condition is found in up to 31% of general medical patients and up to 87% of critically ill medical patients. Delirium is commonly seen in patients who have undergone surgery, those who are in palliative care, and patients with cancer.2 It is associated with increased morbidity and mortality. Compared with those who do not develop delirium, patients who are hospitalized who develop delirium have a higher risk of longer hospital stays, post-hospitalization nursing facility placement, persistent cognitive dysfunction, and death.3

Thus far, the management and treatment of delirium have been complicated by an incomplete understanding of the pathophysiology of this condition. However, prevailing theories suggest a dysregulation of neurotransmitter synthesis, function, or availability.2 Recent literature reflects this theory; researchers have investigated agents that target dopamine or acetylcholine. Below we review some of this recent literature on treating delirium; these studies are summarized in the Table.4-6

Treatment of delirium: 3 studies

1. Burry L, Mehta S, Perreault MM, et al. Antipsychotics for treatment of delirium in hospitalized non-ICU patients. Cochrane Database Syst Rev. 2018;6:CD005594.

An extensive literature review identified randomized or quasi-randomized trials on the treatment of delirium among non-critically ill hospitalized patients in which antipsychotics were compared with nonantipsychotic medications or placebo, or in which a first-generation antipsychotic (FGA) was compared with a second-generation antipsychotic (SGA).4

Study design

  • Researchers conducted a literature review of 9 trials that included 727 hospitalized but not critically ill patients (ie, they were not in an ICU) who developed delirium.
  • Four trials compared an antipsychotic with a medication from another drug class or with placebo.
  • Seven trials compared a FGA with an SGA.


  • Although the intended primary outcome was the duration of delirium, none of the included studies reported on duration of delirium. Secondary outcomes were delirium severity and resolution, mortality, hospital length of stay, discharge disposition, health-related quality of life, and adverse effects.
  • Among the secondary outcomes, no statistical difference was observed between delirium severity, delirium resolution, or mortality.
  • None of the included studies reported on hospital length of stay, discharge disposition, or health-related quality of life.
  • Evidence related to adverse effects was determined to be very low quality due to potential bias, inconsistency, and imprecision.


  • A review of 9 randomized trials did not find any evidence supporting the use of antipsychotics for treating delirium. However, most of the studies included were of lower quality because they were single-center trials with insufficient sample sizes, heterogeneous study populations, and risk of bias.

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