Clozapine-Related Tachycardia: An Analysis of Incidence

Sinus tachycardia commonly occurs at the start of clozapine treatment, often leading to discontinuation owing to perceived adverse cardiovascular effects. However, little evidence exists on its natural course after clozapine initiation. We aimed to determine the frequency and course of clozapine-induced tachycardia over the first month of treatment and to identify possible risk factors METHODS: In this cross-sectional study, we serially monitored heart rates (HRs) and other clinical variables of psychiatric inpatients commencing clozapine over the first 28 days. HRs were plotted over time and modelled by explanatory variables, including age group, sex, body mass index (BMI), smoking status and prescribed medications for HR.

In total, 123 consecutive inpatients undergoing clozapine titration were assessed daily, with 2901 HR measures collected. After starting clozapine, mean HR increased from 83.7 to 99.5 beats per minute (bpm). Almost all participants (93.5%) had at least one recorded HR > 100 bpm, and 68% had three consecutive days with HR > 100 bpm (being then defined as tachycardic). At least one HR > 120 bpm was recorded in 35.8%, and 8% had persistent HRs > 120 bpm. Tachycardia occurred early during clozapine titration, with a dose response effect at lower doses, which plateaued between 150 and 350 mg daily. Tachycardia spontaneously resolved for some but 44% remained tachycardic at day 28. Female sex was associated with early tachycardia at day 14 (p = 0.008) but not at day 28, while age, smoking status, and BMI were not significantly associated with tachycardia.

Sinus tachycardia occurred in over two thirds of participants during the first month of clozapine titration. Spontaneous resolution of tachycardia in some suggests watchful monitoring may be appropriate prior to treatment with rate-controlling agents such as β-blockers or ivabradine. Long term follow-up is required to determine the effects of sinus tachycardia on cardiovascular outcomes in patients treated with clozapine.