Things We Do For No Reason: Use of Antipsychotic Medications in Patients with Delirium

While few studies have demonstrated positive effects of antipsychotics in delirium treatment, the overall evidence is not persuasive. The results of some studies have not been reproduced while only the positive effects rather than the adverse side effects of antipsychotic medications were highlighted in other articles. For instance, the 2005 hip fracture delirium prophylaxis trial found there was no difference in the incidence of delirium in patients on postoperative day one.⁷ Furthermore, the 2010 quetiapine study was underpowered for the primary outcome of lower DRS-R-98 scores. Importantly, there was no significant difference in severity of delirium between treatment (quetiapine) and placebo groups on days one, three, or 10.¹⁰ These studies show that antipsychotics were neither effective at preventing delirium or in reducing its severity compared to placebo. In 2016, a systemic review in the Journal of the American Geriatric Society included both of the above studies in addition to 17 other studies to assess the efficacy of antipsychotics in preventing and treating delirium. This analysis concluded that antipsychotics did not change the length of delirium or length of stay.¹¹ In addition, the absence of convincing evidence of antipsychotics benefits in postoperative delirium has led the American Geriatrics Society to recommend: “The prescribing practitioner should not prescribe antipsychotic… medications for the treatment of older adults with postoperative delirium who are not agitated and threatening substantial harm to self or others.”¹²

There is a paucity of data speaking directly to whether antipsychotics reduce patient distress. A recent randomized controlled study compared haloperidol, risperidone, and placebo for delirium treatment in palliative care and hospice patients. With treatment, the patients in the antipsychotic arms demonstrated slightly more severe delirium and a significantly higher incidence of extrapyramidal symptoms (EPS) than the patients receiving placebo.¹³

Side effects such as EPS, aspiration pneumonia, and arrhythmia are concerns when using antipsychotics for delirium treatment.¹⁴ A systematic review and meta-analysis found the difference in EPS incidence between patients treated for delirium with antipsychotics versus no intervention ranged from no difference to over 10%.¹¹ In addition to EPS, patients receiving antipsychotics in a cohort study were at increased risk for aspiration pneumonia compared to patients who did not receive antipsychotics (adjusted odds ratio = 1.5, 95% CI, 1.2-1.9).¹⁵ These serious side effects led the Food and Drug Administration (FDA) to issue a black box warning for antipsychotic treatment in dementia-related psychosis. Most importantly, the FDA warns that there is an increased risk of death.¹⁶

In the first line management of delirium, hospitalists should address underlying modifiable contributions to the condition with attention to medications, pain, electrolytes, ischemia, infection, alcohol withdrawal, and reducing invasive lines. For example, two studies demonstrated a decrease in delirium severity and duration of palliative care in patients by treating delirium triggers, such as dehydration, electrolyte abnormalities, or infection, rather than using antipsychotics.^13,17 Furthermore, hospitalists should review the medication list carefully and look for opportunities to deprescribe sedative/hypnotics and anticholinergics.