02. Deprescribing Antipsychotics Post-Delirium: Why It Matters

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Deprescribing Antipsychotics After Delirium

Deprescribing is being talked about a lot these days in psychiatry and in medicine more broadly. Most commonly, I hear it discussed in the context of taking older patients off longstanding medications that could potentially be harmful from a cognitive or fall risk standpoint—like benzodiazepines or anticholinergic agents. It can also be a useful strategy in a patient who ends up of five different psychiatric medications without a clear indication.

Today, we’re going to consider another situation in which deprescribing may be tremendously helpful to patients. When patients experience an episode of delirium in the hospital setting, they are often prescribed antipsychotics to help mitigate the sequelae of delirium including agitation and perceptual disturbances.

Many Patients Continue Antipsychotics Indefinitely

In the best of scenarios, these medications are stopped once the delirium has resolved and the patient is nearing discharge. In many cases, however, patients remain on these medications through discharge either because they are still exhibiting some features of delirium or because it’s not made clear to the patient’s family or the primary team that the medication was meant to be a short-term treatment strategy.

For patients who are discharged on antipsychotics after an episode of delirium, chances are that those medications might continue to be prescribed for months to years afterwards without a clear indication.

First Large-Scale Discontinuation Study Results

A new study shed some light on the dangers of continuing these agents indefinitely. It was recently published in JAMA Psychiatry and is the first large-scale trial using nationwide US databases to look at what happens when antipsychotics prescribed for delirium are either continued or discontinued after discharge. The authors used 5½ years of US Medicare claims as well as data from a US commercial healthcare database to examine outcomes among older adults without psychiatric disorders or prior usage of antipsychotics who filled a prescription for an antipsychotic within 30 days of hospital discharge.

Those who discontinued the antipsychotics were matched with those who continued the medication based on factors like type of antipsychotic, time since their first prescription and ICU admission

Discontinuation Reduces Multiple Adverse Outcomes

Outcomes included a variety of indications for rehospitalization as well as all-cause mortality. The overall sample included more than 27,000 individuals with an average age of about 82 years. Approximately 54% of the sample was female.

The study found that discontinuing antipsychotics was associated with significantly lower risks of:

• Rehospitalization
• Inpatient delirium
• Fall-related ED visits
• Hospitalizations for UTI
• All-cause mortality

No differences were seen in terms of hospitalizations for pneumonia or stroke.

Antipsychotic Use During Delirium: Benefits and Limitations

We’ve talked before about the benefits of using antipsychotics in patients with delirium. Although studies have consistently shown that antipsychotics don’t treat delirium—that is, they don’t shorten the length of delirium or reverse the underlying cause—when used judiciously, they can be tremendously beneficial in keeping patients and staff safe in the setting of hyperactive delirium. They can also reduce the risk of post-ICU syndrome or post-delirium PTSD when perceptual disturbances are prominent and distressing.

Approximately 5%-10% of hospitalized older adults receive antipsychotics during admission, rising to 30%-40% for patients with premorbid dementia.

Reasons for Prolonged Antipsychotic Use

When used for delirium, antipsychotics are intended to be short-term medications used during the acute period when patients are actively delirious. Concerningly though, prior evidence suggests that at least one-third of patients who are prescribed an antipsychotic during a delirious episode remain on the medication at the time of discharge.

Two primary factors contribute to extended antipsychotic use:

1. Communication gaps:
   • Consultants may inadequately inform primary teams and families that antipsychotics are short-term hospital medications.
   • Consultants may start an antipsychotic for delirium, follow up a few times to see how the patient is doing but then not see the patient again prior to discharge if no further issues are reported.
   • In some cases, consultants may not even be aware that a patient is nearing discharge and often aren’t thinking about the goal of deprescribing prior to discharge.
   This scenarios seem largely preventable but require consultants to communicate clearly with primary teams up front and to track the progress of patients during their stay even if they’re not being actively followed.
2. Persistent delirium at discharge:

• Increasingly, at least in our system, patients with delirium are being discharged to rehab or skilled nursing facilities before the delirium and its sequelae fully resolve.
• This is especially true of patients who have a delirium that lasts for a few weeks and don’t have obvious lab abnormalities—a scenario we commonly see after a major surgery like a AAA repair or in patients who have a major neurocognitive disorder at baseline and don’t recover from their new insult as quickly. In those cases, it may be more difficult for inpatient providers to mitigate against the antipsychotics remaining on board indefinitely

Unpacking the Adverse Outcomes

Getting back to the study, many of the adverse outcomes observed at higher rates in patients who continued on antipsychotics for longer periods make sense when you think about the side effects of commonly used medications like quetiapine and olanzapine.

• Falls result from orthostatic hypotension (alpha-blocking effects) and sedation (anticholinergic and antihistaminergic effects).
• UTIs arise from urinary retention associated with low-potency antipsychotics’ anticholinergic burden.

The association of prolonged antipsychotic use with increased hospitalizations and all-cause mortality is a bit harder to unpack. On the one hand, antipsychotics are associated with an increased risk of sudden death in older patients with dementia, which could explain the findings. Another possibility though is that the relationship between these outcomes is not causal but that patients who have a more persistent or more severe delirium are more likely to remain on these agents for longer periods.

The increased rates of hospitalization and mortality in these individuals may therefore be representative of the fact that they are sicker—which drives the delirium, the decision to maintain antipsychotics for longer periods, and the adverse outcomes. In other words, the design of this particular study cannot answer the question of why patients who remain on antipsychotics for a longer time have these worse outcomes. For that, we need randomized controlled trials.

Antipsychotic Prescribing Patterns

Looking at specific antipsychotics, quetiapine was far and away the most commonly prescribed antipsychotic in the study, accounting for nearly 60% of all prescriptions, followed by risperidone at 21% and olanzapine at 12%. One interesting finding in sub-analysis was that patients with dementia benefited even more from discontinuation of antipsychotics.

This is worth highlighting given that we might imagine a scenario wherein these patients are more likely to be continued indefinitely on these agents, both because they may be more likely to reside in long-term care facilities and because they may have behavioral disturbances at baseline as part of their dementia.

A final point that is worth making explicitly is that the study didn’t even examine patients who had their antipsychotics stopped before discharge. In other words, significant differences were noted even with discontinuation of antipsychotics early after discharge. This suggests that stopping medications prior to discharge could yield even better outcomes.

Clinical Implications for Practice

As clinicians, we should:

• Be vigilant about discontinuing antipsychotics before discharge when possible.
• Create clear tapering plans at discharge if discontinuation isn’t feasible.
• Ask the primary team to note a clear stop date in the discharge summary or to add a line that says: “Antipsychotic started for delirium; discontinue if mental status improves.”

I find that patients whose delirium gets managed with IV haloperidol in the hospital are essentially guaranteed to stop their antipsychotics prior to discharge. Whereas patients for whom quetiapine or olanzapine are used are much more likely to still be on those medications at the time of discharge.

Finally, for outpatient providers and especially for psychiatrists working in long-term care settings, understanding the indication for new antipsychotic medication in recently hospitalized patients is essential. Making efforts to gradually taper these medications in the outpatient setting may lead to significant benefit for patients.

Abstract

Health Outcomes of Discontinuing Antipsychotics After Hospitalization in Older Adults

Chun-Ting Yang, Ph.D.; James M. Wilkins, M.D., DPhil; Elyse DiCesare, BS; et al

Importance: Among hospitalized older adults, prolonged use of antipsychotic medications (APMs) following hospital discharge may increase the risk of APM-associated adverse events. There are limited data on whether early discontinuation of APMs is associated with reduced adverse clinical outcomes compared with APM continuation after discharge.

Objective: To compare clinical outcomes between discontinuation vs continuation of APMs initiated to manage hospitalization-related delirium.

Design, Setting, and Participants: This population-based cohort study examining nationwide US Medicare claims data from July 1, 2013, through December 31, 2018, and data from a large deidentified US commercial health care database (Optum CDM) from July 1, 2004, through May 31, 2024, included adults aged 65 years and older without psychiatric disorders or previous use of APMs who filled an APM prescription within 30 days of hospital discharge. Using incidence density sampling, APM discontinuers (gap ≥45 days) were matched with continuers based on the type of APM prescribed, the time since their first APM prescription, and whether they had been admitted to intensive care units prior to the first APM prescription. Data analysis was performed from July 12, 2024, to December 25, 2024.

Exposure  Discontinuation vs continuation of APMs.

Main Outcomes and Measures: Propensity score matching was applied to adjust for 162 covariates. Study outcomes included rehospitalization, specific rehospitalization reasons, and all-cause mortality. Hazard ratios (HRs) were estimated using the Cox proportional hazards model; estimates from the 2 databases were further pooled using the fixed-effects meta-analysis model.

Results: A total of 13 712 propensity score–matched pairs were included, for an overall sample of 27 424 adults (discontinuers: mean [SD] age, 81.86 [7.26] years; 7400 [54.0%] female; continuers: mean [SD] age, 81.86 [7.27] years; 7360 [53.7%] female). During the median (IQR) follow-up of 180 (87-180) days, APM discontinuation vs continuation was associated with significantly lower risks of rehospitalization (HR, 0.89 [95% CI, 0.85-0.94]), inpatient delirium (HR, 0.87 [95% CI, 0.79-0.96]), fall-related emergency department visits or hospitalizations (HR, 0.77 [95% CI, 0.67-0.90]), hospitalization with urinary tract infection (HR, 0.79 [95% CI, 0.66-0.94]), and all-cause mortality (HR, 0.77 [95% CI, 0.69-0.86]). There was no statistical difference in the risks of pneumonia (HR, 0.88 [95% CI, 0.73-1.06]) or stroke (HR, 1.22 [95% CI, 0.97-1.53]) between discontinuers and continuers. Subgroups by dementia status, type and dose of APM prescribed, and duration of APM exposure showed consistent results.

Conclusions and Relevance  Based on 2 nationwide US cohorts including older adults without psychiatric disorders, APM discontinuation was associated with reduced risks of all-cause rehospitalization and mortality, suggesting the importance of minimizing the duration of APM use after acute hospitalization.

Reference

Ting Yang, C., Ph.D.; Wilkins, J., M.D., DPhil; DiCesare, E., BS & et al. (2025). Health Outcomes of Discontinuing Antipsychotics After Hospitalization in Older Adults. JAMA Psychiatry 82(7):671–680.