What is the evidence for using long-acting antipsychotic (LAA) depots in patients with neurocognitive disorders or dementia?

From the Guidelines

The use of long-acting antipsychotic (LAA) depots in patients with neurocognitive disorders or dementia is not recommended as first-line treatment due to limited evidence and significant concerns about increased mortality and cerebrovascular events. The American Psychiatric Association practice guideline recommends that antipsychotic medications should only be used for the treatment of agitation or psychosis in patients with dementia when symptoms are severe, dangerous, and/or cause significant distress to the patient 1. When antipsychotics are necessary, oral formulations like risperidone (0.25-1mg daily), quetiapine (25-200mg daily), or aripiprazole (2.5-10mg daily) at the lowest effective dose are typically preferred 1. LAA depots such as risperidone Consta, paliperidone palmitate, or aripiprazole monohydrate might only be considered in very specific circumstances where adherence is a major concern and the patient has demonstrated a positive response to the oral form without significant adverse effects. Key considerations include:

• Initiating treatment at a low dose and titrating up to the minimum effective dose as tolerated 1
• Regularly reviewing treatment every 4-12 weeks, with attempts to discontinue or reduce the dose when possible, as the risk-benefit ratio often becomes less favorable over time
• Non-pharmacological approaches focusing on identifying and addressing underlying causes of behavioral symptoms should always be the initial management strategy
• If a patient with dementia experiences a clinically significant side effect of antipsychotic treatment, the potential risks and benefits of antipsychotic medication should be reviewed by the clinician to determine if tapering and discontinuing of the medication is indicated 1.

From the FDA Drug Label

WARNINGS AND PRECAUTIONS SECTION 5. 1 Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1. 7 times the risk of death in placebo-treated patients.

The evidence suggests that antipsychotic drugs, including long-acting antipsychotic (LAA) depots, may be associated with an increased risk of mortality in elderly patients with dementia-related psychosis.

• The drug label does not provide direct evidence for the use of LAA depots in patients with neurocognitive disorders or dementia.
• However, it warns of the increased risk of death and cerebrovascular adverse reactions associated with antipsychotic drugs in this population 2. The use of LAA depots in patients with neurocognitive disorders or dementia should be approached with caution, considering the potential risks and benefits.

From the Research

Evidence for Long-Acting Antipsychotic Depots in Neurocognitive Disorders or Dementia

The use of long-acting antipsychotic (LAA) depots in patients with neurocognitive disorders or dementia is a topic of significant interest and debate. The evidence regarding their efficacy and safety is crucial for guiding clinical practice.

Efficacy of Atypical Antipsychotics

• A meta-analysis of randomized, placebo-controlled trials 3 found that atypical antipsychotics, such as aripiprazole and risperidone, showed efficacy on rating scales for treating dementia symptoms, although the effect sizes were small.
• The study also noted that the quality of reporting of trials varied, and adverse events, including somnolence, urinary tract infection, and extrapyramidal symptoms, were common across drugs.

Safety Concerns and Recommendations

• Antipsychotics, when used to treat neuropsychological symptoms associated with dementia, are associated with low effectiveness but a high risk of side effects, including an increased rate of cerebrovascular events and mortality 4.
• It is recommended that antipsychotics should be used only when all non-pharmacological strategies have failed, and a clear definition of the treatment target and continuous monitoring of therapy are mandatory 4.
• A comprehensive assessment should be performed before starting an atypical antipsychotic to rule out medical causes of neuropsychiatric symptoms and to identify contributing environmental or caregiver factors 5.

Guidelines for Long-Acting Injectable Antipsychotics

• Guidelines for the use and management of long-acting injectable antipsychotics in serious mental illness suggest that LAI antipsychotics should be considered and systematically proposed to any patients for whom maintenance antipsychotic treatment is indicated 6.
• However, these guidelines do not specifically address the use of LAI antipsychotics in patients with neurocognitive disorders or dementia.

Alternatives to Antipsychotic Medications

• An evidence-based practice protocol has been developed to guide clinicians away from prescribing antipsychotic medications in the treatment of dementia behaviors and toward the use of potentially safer and more efficacious psychotropic medications 7.
• This protocol establishes a hierarchy of psychotropic medications based on risk and efficacy and offers flexibility for clinical judgment.

Key Points

• The evidence for using LAA depots in patients with neurocognitive disorders or dementia is limited, and more research is needed to fully understand their efficacy and safety in this population.
• Atypical antipsychotics may be effective for treating dementia symptoms, but their use is associated with significant safety concerns, including an increased risk of cerebrovascular events and mortality.
• Non-pharmacological strategies should be tried first, and antipsychotics should be used only when necessary, with careful monitoring and a clear definition of the treatment target.