Transient,asymptomatic,fluctuating bradycardia with oral ziprasidone in an older woman

To the Editor

Ziprasidone, an atypical antipsychotic, has many pharmacokinetic properties including a low propensity for extrapyramidal symptoms and a favourable metabolic profile that render it an attractive choice for managing psychotic symptoms in older people. However, concerns remain about its cardiac side effects with most reports centred on the engendering of potentially fatal conduction disturbances (Taylor, 2003; Witsil et al., 2012). We report the case of an older woman who developed transient, asymptomatic, fluctuating bradycardia after the initiation of oral ziprasidone.

An 80-year-old woman, a known diabetic and hypertensive on specific treatment for 30 years, presented with a 20-year history of schizophrenia and current exacerbation of symptoms for 4 months. A chart review revealed that she had not tolerated risperidone and quetiapine trials and had failed a complete trial with aripiprazole. We decided to initiate ziprasidone to manage her psychotic symptoms. Baseline biochemical and metabolic investigations were unremarkable. The baseline electrocardiogram (ECG) was in the normal range with a corrected QT interval of 430 ms. The patient’s resting pulse rate was 80 bpm and her blood pressure was 130/80 mmHg. Oral ziprasidone was introduced at 40 mg/day in divided doses. On the second day, the heart rate dropped to 58–64 bpm. No ECG changes apart from bradycardia were noted and no symptoms were reported by the patient. The heart rate picked up over the next few days, and at the end of the week it had reached 84 bpm. When ziprasidone was increased to 60 mg/day, again a drop in heart rate to 60 bpm was noted. This time, it was also fluctuating from day to day. The patient continued to be asymptomatic, and daily monitoring of her ECG was negative. Over the course of 1–2 weeks, her heart rate stabilized and a further drug hike to 80 mg/day, necessitated by psychopathology, did not provoke any further change in cardiac activity. Currently, she is responding to 80 mg/day of ziprasidone and her pulse rate is stable (80 bpm).

Based on the Naranjo Adverse Drug Reaction Probability Scale (Naranjo et al., 1981), the reaction we have described is classified as probable. Previously, clinicians reported similarly on bradycardia with ziprasidone (Menon et al., 2011; Snarr et al., 2010). This report differs from earlier ones in two ways. First, the adverse event was in an older patient, an age group which is assumed to be vulnerable to such effects, but not previously reported. Second, and perhaps more pertinently for clinicians, the adverse reaction did not necessitate a discontinuation of the drug but just watchful waiting. The side effects eventually resolved and the patient was avoided a potentially risky cross-tapering of antipsychotics. Longitudinal observations may identify electrocardiographic markers of cardiac damage in at-risk patients, which may be useful in screening for these important adverse outcomes. Alternatively, a comparison between those who develop adverse events and those who do not would help to identify at-risk individuals. In the wider interests of time and resources, a policy of judicious watchful waiting could be adopted in the case of minor side effects and if the patient is otherwise asymptomatic.