Journal Article Annotations
2023, 2nd Quarter
Annotations by O. Joseph Bienvenu, MD, PhD and Jon Sole, MD MSc
The authors used a large database to address whether SSRIs initiated prior to ICU-level care influenced mortality risk, adjusting for a variety of potential confounding factors. SSRIs were independently associated with increased risk of mortality (between 24% and 43%, depending on the statistical model). The authors found that the mortality risk was enhanced in elderly, females, those admitted to medical orsurgical ICUs, and those with a depression diagnosis. The risk of death was reduced when SSRIs were held, thought his may increase the risk of uncomfortable – but not lethal – withdrawal effects.
Strength and weaknesses:
Strengths include a large sample size, several statistical models to control for potential confounders, allowing severity of organ failure (SOFA score) into the model as a time-varying factor, and assessing delirium and/or coma as potential mediators of the primary outcome. As with any observational study, the authors acknowledged potential unmeasured confounders (i.e., patients were not randomized to SSRI exposure). Additionally, they could have included more variables as potential time-varying confounders (including markers of brain dysfunction).
Though one recent analysis suggested a protective effect of SSRIs on in-ICU delirium, another found no such effect. The current study suggests that C-L psychiatrists should consider discontinuing SSRIs, perhaps particularly in elderly female patients with depression admitted to medical or surgical ICUs.
This is a multicentre, blinded, parallel group, placebo-controlled clinical trial with central randomization of 1000 critically ill patients with delirium. The study assesses the use of haloperidol on the number of days alive and out of the hospital at 90 days. The findings suggest that haloperidol does not significantly improve this primary endpoint. The study does show that use of up to 20 mg of intravenous haloperidol per day in critically ill patients was not associated with increased morbidity or mortality. There may be an all-cause mortality benefit with use of haloperidol in critically ill patients with delirium.
Strength and weaknesses:
Strengths include a large sample size, multicenter randomization, and placebo control with little loss to follow up. Interestingly, no primary or secondary outcomes in this study relate to complications of delirium, such as psychomotor agitation or frightening psychotic symptoms, which haloperidol is generally used to manage in clinical settings. Limitations of the study include under-reporting of medical comorbidities and use of other pharmacologic medications in study participants that may confound the results. Lastly, the study could have been better powered given the composite endpoints.
The use of haloperidol remains a staple in the management of delirium complications. The findings of this large study and those of MIND-USA (DOI: 10.1056/NEJMoa1808217) suggest haloperidol does not reduce length of stay nor increase the number of days alive and out of the ICU as it relates to delirium. Importantly however, both studies demonstrate that use of haloperidol in these populations, up to 20 mg per day in the case of AID-ICU, did not result in increased morbidity or mortality and may provide an all-cause mortality benefit in critically ill patients with delirium.