Electrocardiographic Abnormalities in Patients Treated With Clozapine

Background: Cardiovascular side effects ofclozapine are not uncommon, but few systematic studies of theseeffects have been performed. In this study, we reviewed data onthe electrocardiographic (ECG) abnormalities in patients treatedwith clozapine.

Method: Sixty-one patients treated withclozapine were selected from the Seoul National UniversityHospital Treatment-Resistant Schizophrenia Clinic. A retrospective chart review was conducted to identify ECGabnormalities and cardiovascular side effects.

Results: The prevalence of ECG abnormalities inpatients who had been using antipsychotics other than clozapinewas 13.6% at baseline, which increased significantly to 31.1%after commencement of clozapine treatment. Among the 53 patientswithout baseline ECG abnormalities, 13 showed new-onset ECGabnormalities after using clozapine. Normal ECG under previousantipsychotic medication reduced the risk of new-onset ECGabnormalities, whereas increased age was found to increase therisk. The occurrence of orthostatic hypotension or tachycardiawas not related to the development of ECG abnormalities. Most ofthe newly developed abnormalities had little clinicalsignificance, and they tended to occur during the initial phaseof treatment. In 10 patients, ECGs normalized despite thecontinued use of clozapine. Clozapine increased corrected QTinterval (QTc) in a dose-dependent fashion; however, the clinicalsignificance of this observation is uncertain. Pathologicprolongation of QTc was found to be rare.

Conclusion: Although a substantial portion ofpatients treated with clozapine developed ECG abnormalities, mostof the abnormalities were benign and did not hinder furthertreatment.