Does olanzapine (Zyprexa) affect the QTc interval?

From the Guidelines

Zyprexa (olanzapine) can affect QTc intervals, but it generally has a lower risk of QTc prolongation compared to many other antipsychotic medications, with a mean QT prolongation of 2 ms, as reported in a study published in Pediatrics 1. The effect is typically modest and dose-dependent, with higher doses potentially causing more significant QTc prolongation. For most patients without pre-existing cardiac conditions, this effect is not clinically significant. However, caution should be exercised in patients with risk factors for QTc prolongation such as:

• Congenital long QT syndrome
• Heart disease
• Electrolyte abnormalities
• Those taking other medications that prolong QTc In these high-risk patients, baseline ECG monitoring and periodic follow-up ECGs may be warranted, especially after dose increases. The mechanism behind QTc prolongation with antipsychotics like Zyprexa involves blockade of cardiac potassium channels that affect cardiac repolarization. If significant QTc prolongation occurs (generally considered >500 ms or an increase of >60 ms from baseline), dose reduction or switching to an antipsychotic with even lower QTc risk might be necessary, as suggested by guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death 2. Some key points to consider when evaluating the risk of QTc prolongation with Zyprexa include:
• The patient's underlying cardiac condition
• The presence of other risk factors for QTc prolongation
• The dose and duration of Zyprexa treatment
• The use of other medications that may interact with Zyprexa and increase the risk of QTc prolongation.

From the FDA Drug Label

ECG Changes — In pooled studies of adults as well as pooled studies of adolescents, there were no significant differences between olanzapine and placebo in the proportions of patients experiencing potentially important changes in ECG parameters, including QT, QTc (Fridericia corrected), and PR intervals.

Olanzapine's effect on QTc: The FDA drug label states that there were no significant differences between olanzapine and placebo in the proportions of patients experiencing potentially important changes in ECG parameters, including QTc.

• Key finding: No significant effect on QTc interval was observed.
• Clinical decision: Based on the available data, olanzapine is not expected to have a significant impact on the QTc interval 3.

From the Research

Zyprexa and QTc Interval

• Zyprexa, also known as olanzapine, is an atypical antipsychotic medication used to treat schizophrenia and related psychoses.
• The effect of Zyprexa on the QTc interval has been studied in several clinical trials, with results indicating that it does not significantly prolong the QTc interval 4, 5.
• In one study, electrocardiogram recordings from 2,700 patients with schizophrenia and related psychoses were analyzed, and the results showed that olanzapine did not contribute to QTc prolongation resulting in potentially fatal ventricular arrhythmias 4.
• Another study compared the cardiac safety parameters of olanzapine with other atypical and typical antipsychotics, and found that olanzapine did not significantly prolong the QTc interval 5.

Comparison with Other Antipsychotics

• Other antipsychotic medications, such as ziprasidone, have been shown to prolong the QTc interval to a moderate degree 6.
• The QTc prolonging effects of antipsychotics can increase the risk of torsade de pointes, a potentially fatal ventricular tachycardia arrhythmia 7, 8.
• However, the overall risk of torsade de pointes and sudden death associated with antipsychotics is low, and routine ECG monitoring is not recommended in the absence of cardiac risk factors 7.

Risk Factors and Monitoring

• Certain risk factors, such as hypokalemia, female sex, and drug-drug interactions, can increase the risk of QTc interval prolongation and torsade de pointes 8.
• Patients at risk for QT interval prolongation should be educated to seek medical attention if they experience symptoms such as palpitations, lightheadedness, or syncope 8.
• Close monitoring of electrocardiography and electrolytes is necessary to prevent torsade de pointes, especially in patients with pre-existing cardiac risk factors 8.