Olanzapine and Prolonged PR Interval

Dear Editor:

Considerable interest has been expressed concerning the possible role of psychotropic medications in inducing conduction deficits. Though QT interval has always received more attention, it should not be forgotten that other aspects of cardiac conduction like PR interval can also be adversely affected by psychotropic medications.

We report a case of first-degree heart block (prolonged PR interval) induced by olanzapine (Zyprexa®) in a young patient.

Mr. A is 12-year-old Caucasian boy referred to child psychiatry outpatient clinic with diagnosis of bipolar disorder, attention deficit hyperactive disorder, and obsessive compulsive disorder. His medications at the time of referral included lithium 300mg p.o. three times daily, pemoline (Cylert^®) 150mg in the morning and 75mg in the evening, and citalopram (Celexa^®) 30mg once daily. There was no past history of medical problems or any heart problems in family. The lithium level was 0.7. The patient remained stable on these medications for one year but then he become increasingly irritable, impulsive, and aggressive. He had numerous suspensions from school for disruptive and unruly behavior, and even attempted to steal a kitchen knife from his grandparents. The treatment team decided to start risperidone (Risperdal^®) 0.5mg twice daily and later added 1mg at bed time. Though the patient's aggression improved significantly, he complained of severe abdominal bloating after starting the risperidone. The treatment team decided to discontinue the risperidone. But a month later, the patient again started to become aggressive. He became uncontrollable, destroying property and making physical threats to others. At that time, the treatment team decided to start olanzapine (Zyprexa^®) 5mg at bed time which was increased to 10mg at bed time after one week.

A week later, the patient showed significant improvement in his aggressive behavior. There was no report of any out of control or threatening behavior. After a month on olanzapine 10mg, patient had one episode of mild to moderately intense chest pain that lasted an hour. An EKG was obtained, which showed first-degree atrioventricular block with PR interval of 0.206. A pediatric cardiology consult was called. The cardiologist suspected the role of olanzapine, since this medication was added recently and there were no previous reports of any such concerns. The treatment team decided to replace olanzapine with thiothixene (Navane®) at 5mg bid. Repeat EKGs after one month and three months showed no evidence of atrioventricular block and showed a PR interval of 0.170. Patient had no other episodes of chest pain. Among his other medications, lithium¹ has also been reported to cause heart block. However, because the EKG returned to normal after the olanzapine was discontinued and no other changes in medications were made, this suggests that patient's first-degree heart block (prolonged PR interval) was induced by the olanzapine.

A PubMed search was performed with the key words “olanzapine” and “olanzapine and prolonged PR interval,” which revealed only two previous cases of first-degree heart block related to olanzapine. On both occasions, the subjects were adults and it occurred on relatively high doses of 50mg and 20mg, respectively. In both cases, the symptoms and EKG abnormalities resolved when doses were decreased to 40mg and 17.5mg.²

Chest pain or prolonged PR interval are not listed as side effects of olanzapine³ by the manufacturers, but this data is based on trials performed using adult populations.

We do not recommend any overgeneralization of findings from this single case report. Nevertheless, since off label use of olanzapine is common in the pediatric population, we recommend careful monitoring of EKG in children who are on even normal doses of olanzapine, especially when they complain of chest pain.

With regards,
Muhammad I. Rajput, MD
Tanvir Singh, MD
Theodore Rais, MD
Medical University of Ohio Department of Psychiatry Toledo, Ohio