Antipsychotics for the Prevention and Treatment of Delirium

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Purpose of Review

To assess the benefits and harms of antipsychotics for the prevention and treatment of delirium among adult patients.

Key Messages

Haloperidol or second-generation antipsychotics used to prevent or treat delirium did not decrease length of stay in hospital.
There was little or no evidence to determine the effect of antipsychotics on cognitive function, delirium severity, or caregiver burden, or for sedation when used for prevention.
Second-generation antipsychotics may lower the occurrence of delirium in postoperative patients.
Haloperidol or second-generation antipsychotics used to prevent or treat delirium may lead to little or no difference in cardiac arrhythmias, electrocardiogram changes (problems with rate or rhythm of heart) or extrapyramidal side effects (problems with muscles like spasms or restlessness) or sedation when used for treatment.
Future studies are needed to assess the effects of using antipsychotics on patient agitation and distress, subsequent memories of delirium, caregiver burden and distress, inappropriate continuation of antipsychotic therapy, and long-term cognitive and functional outcomes.

Structured Abstract

Objectives. To assess benefits and harms of antipsychotics for the prevention and treatment of delirium in adult patient populations.

Data sources. We searched PubMed, Embase™, the Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL®), and PsycINFO® through June 2018. We also handsearched the reference lists of included articles, relevant reviews and delirium-specific bibliographic repositories.

Review methods. We included randomized controlled trials (RCTs) of antipsychotics that evaluated benefits or harms, and also observational studies that reported harms. Two reviewers independently screened search results for eligibility, serially abstracted data, and independently assessed the risk of bias of the studies and graded the strength of evidence (SOE) for pre-specified critical outcomes: delirium severity, cognitive functioning, length of stay in hospital, inappropriate continuation of antipsychotic drugs, falls, sedation, and caregiver burden/strain.

Results. We identified 13 RCTs and 1 observational study evaluating the use of antipsychotics in prevention of delirium. For the treatment of delirium, we identified 18 RCTs and 28 observational studies. Two RCTs were classified as both a prevention and treatment trial. In trials of the prevention of delirium across all populations, there was no difference in delirium incidence for haloperidol versus placebo (relative risk [RR], 0.96; 95% confidence interval [CI], 0.77 to 1.19). Second-generation antipsychotics, compared with placebo, may decrease delirium incidence in postoperative patients at risk for delirium (RR, 0.36; 95% CI, 0.26 to 0.50). Antipsychotics (both haloperidol and second-generation), compared to placebo, demonstrated no differences for length of stay in hospital (low SOE for second-generation antipsychotics and high SOE for haloperidol). We were unable to draw conclusions regarding the effect of antipsychotics on sedation, falls, and delirium severity (insufficient SOE). We found no studies evaluating cognitive functioning, inappropriate continuation of antipsychotic drugs, or caregiver burden/strain. For treatment of delirium, effects of antipsychotics were not significantly different compared with placebo for delirium severity (moderate SOE), cognitive functioning (low SOE), length of stay in hospital (moderate SOE), and sedation (low SOE). We found no studies reporting inappropriate continuation of antipsychotic drugs, falls, or caregiver burden/strain. We did not find differences for haloperidol or second-generation antipsychotics in cardiac and neurologic harms, including cardiac arrhythmias, prolongation of the corrected QT interval on electrocardiogram, hypotension, extrapyramidal side effects, including akathisia and dystonia, and neuroleptic malignant syndrome.

Conclusions. Haloperidol or second-generation antipsychotics, compared to placebo, used for the prevention or treatment of delirium did not improve length of stay in hospital. We found little or no evidence to determine the effect of antipsychotics on cognitive function, delirium severity, or caregiver burden. Second-generation antipsychotics may decrease delirium incidence in postoperative patients. We did not detect cardiac or neurological harms associated with haloperidol or second-generation antipsychotics used for the prevention or treatment of delirium. Future studies should include standardized, clinically meaningful measures of patient agitation and distress, subsequent memories of delirium, caregiver burden and distress, inappropriate continuation of antipsychotic therapy, and long-term cognitive and functional outcomes.