Quetiapine-Induced Bradycardia Without QT Interval Prolongation in an Elderly Woman

Abstract

To the Editor: Bradycardia has recently been reported as a rare but severe adverse effect of atypical antipsychotics like risperidone,1,2 olanzapine,3 and clozapine.4 Most case reports describe bradycardia with QT interval prolongation.1–5 Until now, the mechanism of this bradyarrhythmogenic character of atypical antipsychotics has not fully been understood. Interference with K+ transport inward ventricular cells was suggested by Magyar et al.6 Quetiapine is increasingly used in the treatment of elderly patients and those with relevant comorbidity because of its apparently lower incidence of side effects. Among others, Gareri et al7 stated in their review article on adverse effects of atypical antipsychotics that no electrocardiogram (ECG) monitoring was required, because of infrequent QTc time alterations on using quetiapine. Here, however, we present a case of an elderly woman with paranoid schizophrenia treated with quetiapine who suffered from asymptomatic bradycardia without QT interval prolongation that resolved after withdrawal. Case report. Ms A, a 63-year-old woman diagnosed with paranoid schizophrenia according to DSM-IV criteria, was admitted in November 2006 to the gerontopsychiatric unit of De Gelderse Roos Mental Health Care. She had previously received several antipsychotics, both classical and atypical, and at admission was receiving quetiapine at a daily dose of 1,000 mg. Despite this high dose, the psychosis persisted, but she did not experience any physical complaints except fatigue. At physical examination, we found a slow irregular pulse rate (52 bpm) and a blood pressure of 115/77 mm Hg without orthostasis. In the following days, the bradycardia persisted with pulse rates varying from 40 to 55 bpm. The ECG showed a sinus bradycardia with normal conduction times (PQ interval = 123 ms, QT interval = 440 ms) and some ventricular extrasystoles. During exercise, the bradycardia persisted, and at laboratory examination no abnormalities were found, with findings including a plasma quetiapine concentration (160 mg/mL) within normal limits. The bradycardia and the lack of antipsychotic effect forced us to reduce the quetiapine dose. During a 6-week taper, the bradycardia persisted but completely disappeared 6 days after full cessation with the pulse rate increasing to over 60 bpm. On prescription of clozapine, the bradycardia did not return. The Holter ECG showed only a few 3- to 4-second pauses during the night. No tachycardias were registered. The echocardiography showed normal left ventricular function and normal aortic valve dimensions. Therefore, a sick-sinus syndrome or atrioventricular node dysfunction as a cause of the bradycardia—although not fully ruled out—is less likely. To our knowledge, this is the first case of quetiapine-induced bradycardia unrelated to the QT interval. According to the criteria proposed by Naranjo et al,8 it is a probable cause. Although quetiapine is assumed to be safe in elderly patients and patients with comorbidity, this report indicates that it needs to be prescribed with the same precautions as other antipsychotics. Since it is still unknown which patients are at risk for developing bradycardia, we support the advice of Stollberger et al5 of routinely monitoring the ECG when prescribing atypical antipsychotics. At least at baseline and after the introduction of the drug, both QT interval and heart rate need to be documented.