Antipsychotics do not improve outcomes in hospitalized patients with delirium
Routine use of haloperidol or second-generation antipsychotics to treat delirium in hospitalized adults does not lead to improved patient outcomes, with little evidence of neurologic harms but a tendency for more frequent potentially harmful cardiac effects, a study has shown.
“We found no differences for haloperidol and second-generation antipsychotics, compared with placebo, in hospital length of stay, sedation status, delirium duration and mortality, and insufficient or no evidence regarding the effect on cognitive functioning and delirium severity,” the researchers said.
The databases of PubMed, Embase, Central, Cinahl and PsychINFO were accessed from inception to July 2019 to identify randomized controlled trials (RCTs) of antipsychotic vs placebo or another antipsychotic and prospective observational studies reporting harms.
One reviewer extracted data and evaluated the strength of evidence (SOE) for critical outcomes, while another reviewer confirmed these findings. Two reviewers independently assessed risk of bias.
Sixteen RCTs and 10 observational studies of adult inpatients were included. No difference was observed in sedation status (low and moderate SOE), delirium duration, hospital length of stay (moderate SOE) or mortality between haloperidol and second-generation antipsychotics vs placebo. [Ann Intern Med 2019;doi:10.7326/M19-1860]
Haloperidol vs second-generation antipsychotics showed no difference in delirium severity (moderate SOE) and cognitive functioning (low SOE), with insufficient or no evidence for antipsychotics vs placebo. Direct comparisons of different second-generation antipsychotics also showed no difference in mortality and insufficient or no evidence for several other outcomes.
Evidence showing neurologic harms related to short-term use of antipsychotics for treating delirium in hospitalized adults was little. However, potentially harmful cardiac effects tended to occur more frequently.
These findings support those of a recent Cochrane review focusing on RCTs on noncritically ill inpatients, in which no beneficial effect was also seen for antipsychotics in reducing the delirium severity or resolving delirium-related symptoms, and no differences were observed in extrapyramidal symptoms or mortality. [Cochrane Database Syst Rev 2018;6:CD005594]
There was also no difference reported in delirium incidence, length of stay, delirium- and coma-free days, short-term mortality, risk for QT interval prolongation, or extrapyramidal symptoms in another systematic review of RCTs that compared haloperidol with placebo solely in critically ill patients. [J Crit Care 2019;50:280-286]
“Our findings are also consistent with recent clinical practice guidelines that do not recommend routine use of antipsychotics for treating delirium,” the researchers said. “These include the 2018 Society of Critical Care Medicine guidelines for critically ill patients (conditional recommendation with low quality of evidence) and the 2019 Scottish Intercollegiate Guidelines Network guideline for inpatients with and those without critical illness (insufficient evidence).” [Crit Care Med 2018;46:e825-e873]
The current study was limited by the presence of heterogeneity in terms of dose and administration route of antipsychotics, outcomes and measurement instruments, as well as insufficient or no evidence regarding multiple clinically important outcomes.
“For some clinically important outcomes and specific patient subgroups (such as older adults and palliative care patients), there was insufficient or no evidence, emphasizing the need for continued future research in the field,” the researchers noted.