Effect of atenolol versus ivabradine on heart rate variability in patients of schizophrenia with clozapine-induced tachycardia: a randomized controlled trial.

Amit Bahmania; Manisha Kar; Tathagata Biswas; Rituparna Maiti; Debadatta Mohapatra; Srikanta Behera; Archana Mishra; Biswa Ranjan Mishra

doi:10.1016/j.psychres.2026.117341

PubMed · 42567080

Effect of atenolol versus ivabradine on heart rate variability in patients of schizophrenia with clozapine-induced tachycardia: a randomized controlled trial.

Amit Bahmania·Manisha Kar·Tathagata Biswas·Rituparna Maiti·Debadatta Mohapatra·Srikanta Behera·Archana Mishra·Biswa Ranjan Mishra

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Abstract

BACKGROUND: A third of schizophrenia cases are resistant to antipsychotics, where clozapine is the only FDA-approved medication. Clozapine use is often limited by intolerable adverse effects. Persistent tachycardia occurs in approximately 25-54% patients receiving clozapine. Heart rate variability (HRV) is a non-invasive, clinically relevant marker of autonomic nervous system functioning. Atenolol and Ivabradine are usually prescribed for clozapine-induced tachycardia (CIT), although evidence guiding their optimal use remains limited. AIM: This study aimed to compare the effects of atenolol versus ivabradine on HRV in patients with treatment-resistant schizophrenia (TRS) receiving clozapine. METHODS: This open-label randomised clinical trial, conducted at a tertiary-care center over 20 months, involved TRS patients on clozapine for more than three months and having persistent tachycardia. Twenty patients received atenolol 25mg once-daily, while twenty received ivabradine 5mg twice-daily for two months. The primary outcome was the change in the frequency domain of HRV, while the secondary outcomes were time-domains, central and peripheral blood pressure, pulse rate and treatment-emergent adverse events (TEAE). RESULTS: While both drugs significantly reduced pulse-rates (atenolol: -20.56±13.00, p<0.001; ivabradine: -21.855±12.873, p<0.001). Within-group analysis showed that, the atenolol group had significant improvements in high-frequency [HF] power (p=0.048) and LF/HF ratio (p=0.044), along with a non-significant trend towards increased total power (p=0.053); no significant within-group changes were observed in the ivabradine group. CONCLUSION: No significant between-group differences in HRV parameters were established between atenolol and ivabradine. Ivabradine could be a viable option in patients where atenolol is either contraindicated or not tolerated. Future larger multicentric studies are needed for greater generalisability. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06505668.

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Humans Atenolol Ivabradine Heart Rate Female Antipsychotic Agents Clozapine Male Adult Schizophrenia Tachycardia Benzazepines Middle Aged Schizophrenia, Treatment-Resistant Heart rate variability Journal Article Randomized Controlled Trial

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Amit Bahmania, Manisha Kar, Tathagata Biswas, Rituparna Maiti, Debadatta Mohapatra, Srikanta Behera, Archana Mishra, Biswa Ranjan Mishra. 2026-07-28. Effect of atenolol versus ivabradine on heart rate variability in patients of schizophrenia with clozapine-induced tachycardia: a randomized controlled trial.. https://doi.org/10.1016/j.psychres.2026.117341

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Journal Article; Randomized Controlled Trial resource Adult subject Antipsychotic Agents subject Female subject Heart Rate subject Humans subject Journal Article subject Male subject Middle Aged subject Randomized controlled trials study heart rate variability subject

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