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As a consultation–liaison (CL) psychiatrist working primarily on medical and surgical floors, I often find myself defending the safety of haloperidol more than any other medication. There are many myths and misconceptions about haloperidol, particularly its IV formulation. I was therefore thrilled when a recent article in the Annals of Internal Medicine reported that haloperidol is just as safe as atypical antipsychotics for older patients following surgery.
I’m Scott Beach from the Psychopharmacology Institute, and this is Quick Takes.
The study included over 17,000 patients aged 65 and older who received new oral antipsychotic medication postoperatively and during the first 7 days of admission. The authors compared those receiving oral haloperidol with those receiving olanzapine, quetiapine, or risperidone, examining in-hospital adverse events like cardiac arrhythmias, pneumonia, stroke, or TIA. Interestingly, patients treated with haloperidol were typically older, more medically complex, and on more medications. Despite low overall rates of death and adverse events, no significant differences were observed between haloperidol and other antipsychotics. The study, albeit retrospective and not controlling for delirium severity, suggests a solid conclusion. However, the authors unexpectedly advocate for reduced antipsychotic prescribing in general, a stance I find confusing given their findings.
Antipsychotics play a crucial role in managing delirium, not by treating it or shortening its duration but by reducing agitation and perceptual disturbances. This approach can prevent harm to patients and staff, minimize post-delirium PTSD or post-ICU syndrome, and in severe cases, be lifesaving. For agitated, delirious patients, physical restraints alone seem inhumane without also providing medication to alleviate distress and promote sleep. Antipsychotics should be used judiciously, primarily in hyperactive delirium and at the lowest effective doses, often as PRNs before considering standing doses.
Regarding the study’s findings, I’m cautious about advocating for widespread use of oral haloperidol in older, delirious patients. Personally, I prefer IV haloperidol for its rapid onset, longer duration, and safety profile. For more sedation, I might choose chlorpromazine or olanzapine. I’m less inclined to use risperidone due to its narrow dose range for delirium and generally avoid quetiapine for this indication because of its limited D2 blockade and antihistaminergic and anticholinergic effects at low doses.
Addressing the safety of haloperidol, the study’s findings on cardiac arrhythmias align with my understanding that haloperidol does not cause greater QTc prolongation than atypicals. In fact, it may be safer, with IV haloperidol showing no significant prolongation at doses under 20 mg. If QTc interval is a concern, then no antipsychotic should be used.
Finally, discussing haloperidol and extrapyramidal symptoms (EPS), it’s true that as a high-potency typical antipsychotic, it carries a higher risk of EPS. However, IV haloperidol appears to have a lower incidence of dystonic reactions and parkinsonism, even at high doses. This difference in EPS occurrence between IV and oral or IM forms is intriguing but not fully understood. Therefore, combining IV haloperidol with benzodiazepines or anticholinergics is unnecessary.
In summary, I will continue using IV haloperidol as my primary treatment for delirious patients, reassured by this study’s findings that oral haloperidol is no less safe than other antipsychotics in this population.
Abstract
Comparative Safety Analysis of Oral Antipsychotics for In-Hospital Adverse Clinical Events in Older Adults After Major Surgery: A Nationwide Cohort Study
Dae Hyun Kim, Su Been Lee, Chan Mi Park, Raisa Levin, Eran Metzger, Brian T Bateman, E Wesley Ely, Pratik P Pandharipande, Margaret A Pisani, Richard N Jones, Edward R Marcantonio, Sharon K Inouye
Background: Antipsychotics are commonly used to manage postoperative delirium. Recent studies reported that haloperidol use has declined, and atypical antipsychotic use has increased over time.
Objective: To compare the risk for in-hospital adverse events associated with oral haloperidol, olanzapine, quetiapine, and risperidone in older patients after major surgery.
Design: Retrospective cohort study.
Setting: U.S. hospitals in the Premier Healthcare Database.
Patients: 17 115 patients aged 65 years and older without psychiatric disorders who were prescribed an oral antipsychotic drug after major surgery from 2009 to 2018.
Interventions: Haloperidol (≤4 mg on the day of initiation), olanzapine (≤10 mg), quetiapine (≤150 mg), and risperidone (≤4 mg).
Measurements: The risk ratios (RRs) for in-hospital death, cardiac arrhythmia events, pneumonia, and stroke or transient ischemic attack (TIA) were estimated after propensity score overlap weighting.
Results: The weighted population had a mean age of 79.6 years, was 60.5% female, and had in-hospital death of 3.1%. Among the 4 antipsychotics, quetiapine was the most prescribed (53.0% of total exposure). There was no statistically significant difference in the risk for in-hospital death among patients treated with haloperidol (3.7%, reference group), olanzapine (2.8%; RR, 0.74 [95% CI, 0.42 to 1.27]), quetiapine (2.6%; RR, 0.70 [CI, 0.47 to 1.04]), and risperidone (3.3%; RR, 0.90 [CI, 0.53 to 1.41]). The risk for nonfatal clinical events ranged from 2.0% to 2.6% for a cardiac arrhythmia event, 4.2% to 4.6% for pneumonia, and 0.6% to 1.2% for stroke or TIA, with no statistically significant differences by treatment group.
Limitation: Residual confounding by delirium severity; lack of untreated group; restriction to oral low-to-moderate dose treatment.
Conclusion: These results suggest that atypical antipsychotics and haloperidol have similar rates of in-hospital adverse clinical events in older patients with postoperative delirium who receive an oral low-to-moderate dose antipsychotic drug.
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Reference
Kim, D. H., Lee, S. B., Park, C. M., Levin, R., Metzger, E., Bateman, B. T., Ely, E. W., Pandharipande, P. P., Pisani, M. A., Jones, R. N., Marcantonio, E. R., & Inouye, S. K. (2023).
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Annals of Internal Medicine, 176
(9), 1153–1162.
