What are the risks of vascular events with olanzapine (Olanzapine) Long-Acting Injection (LAI) and how can they be managed?

From the Guidelines

Olanzapine Long-Acting Injection (LAI) poses a significant risk of vascular events, particularly post-injection delirium/sedation syndrome (PDSS), which can lead to sedation, confusion, and potentially life-threatening cardiovascular complications, as evidenced by a study published in the European Heart Journal in 2015 1. The risk of vascular events with olanzapine LAI is a critical concern, especially in patients with pre-existing cardiovascular disease. According to the study, the use of antipsychotics, including olanzapine, is associated with an increased risk of ventricular arrhythmia and/or sudden cardiac death, with an adjusted odds ratio of 1.64 for olanzapine 1. To manage these risks, healthcare providers should:

• Administer olanzapine LAI only in facilities with emergency response capabilities
• Follow proper deep gluteal injection technique to minimize the risk of accidental intravascular injection
• Observe patients for at least 3 hours after each injection to monitor for signs of PDSS
• Advise patients not to drive or operate machinery on injection days and to report symptoms like excessive drowsiness, dizziness, or confusion immediately
• Regularly assess cardiovascular risk factors, including blood pressure and ECGs, throughout treatment, as suggested by a study published in Circulation in 2016 1. The mechanism behind these vascular events involves olanzapine's strong affinity for multiple neurotransmitter receptors, which contribute to its sedative effects when blood levels rise rapidly. Key considerations for managing vascular risks with olanzapine LAI include:
• Patient education on recognizing and reporting symptoms of PDSS
• Close monitoring of patients with pre-existing cardiovascular disease
• Regular cardiovascular assessments to minimize the risk of vascular events.

From the FDA Drug Label

Patients and caregivers should be advised that elderly patients with dementia-related psychosis treated with olanzapine for injection had a significantly higher incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack) compared with placebo.

The risk of vascular events, including stroke and transient ischemic attack, is increased in elderly patients with dementia-related psychosis treated with olanzapine LAI. To manage these risks, patients should be:

• Monitored regularly for signs and symptoms of cerebrovascular adverse events
• Advised to report any concerns or changes in their condition to their prescriber
• Counseled on the importance of maintaining a healthy lifestyle to reduce the risk of vascular events
• Considered for alternative treatments if they have a history of vascular events or are at high risk for these events 2

From the Research

Vascular Events with Olanzapine LAI

• The risk of vascular events with olanzapine Long-Acting Injection (LAI) is a concern, as evidenced by studies such as 3, which found a significantly higher rate of cardiac mortality in olanzapine users relative to psychiatric nonusers.
• Another study, 4, found that the risk of acute major cardiovascular events was similar with use of olanzapine, quetiapine, and risperidone in young and middle-aged adults.
• However, 5 reported that high-dose olanzapine therapy was associated with adverse effects such as extrapyramidal symptoms, sedation, and corrected QT-interval (QTc) prolongation, which may increase the risk of vascular events.

Management of Vascular Events

• To manage vascular events associated with olanzapine LAI, clinicians should be aware of the potential risks and monitor patients closely for signs of adverse events, as recommended by 5.
• In cases of olanzapine overdose, lipid emulsion has been shown to be effective in relieving toxicity, as reported in 6.
• Additionally, 7 suggests that olanzapine may have a positive effect on angiogenesis, which could potentially reduce the risk of vascular events, although more research is needed to confirm this finding.

Key Findings

• Olanzapine LAI is associated with an increased risk of cardiac mortality and other vascular events, as evidenced by 3 and 4.
• High-dose olanzapine therapy can lead to adverse effects that may increase the risk of vascular events, according to 5.
• Lipid emulsion may be effective in relieving olanzapine toxicity, as reported in 6.
• Olanzapine may have a positive effect on angiogenesis, which could potentially reduce the risk of vascular events, as suggested by 7.