‘Hidden’ corrected QT interval prolongation induced by olanzapine

To the Editor

Prolongation of the corrected QT interval (QTc) is an important finding because QTc longer than 500 ms confers increased risk of torsade de pointes, which can cause sudden cardiac death (Morita et al., 2008). Olanzapine is known to increase the risk of QTc prolongation (Morissette et al., 2007). We report the first case of QTc prolongation induced by olanzapine that is only occurred after exercise and was not apparent in the resting electrocardiography (ECG).

A 45-year-old woman with schizophrenia treated with 6 mg per day of aripiprazole was attending our hospital. She had no history of cardiovascular disease. On April 2017, her auditory hallucinations were exacerbated, and 5 mg per day of olanzapine was initiated, while aripiprazole was decreased to 3 mg per day. After starting olanzapine, her auditory hallucinations improved. However she sometimes felt palpitations and was seen by the cardiology department. Her ECG showed no abnormalities, and the QTc was 434 ms. Her echocardiography showed no structural abnormalities. Treadmill exercise stress testing was performed in October 2018. The QTc increased from 400 ms before the exercise test to 540 ms. We suspected the adverse effect of olanzapine; hence, it was discontinued and aripiprazole was increased to 6 mg per day. After discontinuation of olanzapine, the treadmill exercise test was repeated in December 2018. The QTc returned to the normal range, increasing from 370 ms before the exercise test to 420 ms.

The QT interval is determined by repolarization that is caused by an outward flow of potassium through two delayed rectifier potassium currents, rapid component (IKr) and slow component (IKs). In congenital long QT syndrome (LQTS), mutations in the genes encoding for potassium channels cause malfunction of IKr or IKs. Drug-induced LQTS, including induction by antipsychotics, is generally ascribed to blockade of the IKr. In congenital LQTS, sympathetic stimulations such as exercise or emotional stress trigger QTc prolongation (Morita et al., 2008). A previous cohort study found that users of antipsychotics had an increased risk of sudden cardiac death compared with nonusers (Ray et al., 2009). We suppose that a proportion of patients taking antipsychotics (including olanzapine) died from sudden cardiac death might have such drug-induced QTc prolongation triggered by sympathetic stimulation during daily life. Although it is unclear whether only olanzapine or a combination of olanzapine with aripiprazole led to QTc prolongation in our patient, all clinicians should be cautious about such ‘hidden’ QTc prolongation induced by olanzapine.