A Randomized, 8-Week Study of the Effects of Extended-Release Paliperidone and Olanzapine on Heart Rate Variability in Patients With Schizophrenia

Abstract

Purpose This study aimed to explore the effect of extended-release paliperidone (paliperidone ER) and olanzapine on heart rate variability (HRV) in patients with schizophrenia. Methods A total of 106 patients with schizophrenia diagnosed by the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) were randomly divided into the paliperidone ER group or the olanzapine group for an 8-week clinical trial, with 53 patients in each group. The time domain and frequency domain analyses including the SD of all the R-R intervals in 24 hours (SDNN), the SD of the mean value of all the normal R-R intervals in every 5-minute interval within 24 hours (SDANN index), the mean value of the SD of all the normal R-R intervals in every 5-minute interval within 24 hours (SDNN index), the root mean square of successive R-R differences, the percentage of adjacent R-R intervals that differ by more than 50 milliseconds, high-frequency power (HF), low-frequency power (LF), and LF/HF were adopted to assess the HRV of patients at baseline and after treatment for 8 weeks in each group. The Positive and Negative Symptom Scale was used to evaluate the clinical efficacy. The incidence rates of adverse reactions were also calculated. Results In total, 48 patients in the paliperidone ER group and 45 patients in the olanzapine group completed the entire 8-week treatment. The SDNN, SDNN index, and SDANN index in the olanzapine group were significantly lower than those in the paliperidone ER group (P < 0.05) after treatment for 8 weeks, whereas their mean LF level was higher than that in the paliperidone ER group (P < 0.05) after completion of treatment. Patients in the olanzapine group showed a significant decrease in the SDNN, SDANN index, and SDNN index as well as a statistical increase in the LF and LF/HF in comparison with the pretreatment values (P < 0.05), whereas patients in the paliperidone ER group showed a decrease in the SDANN index and a statistical increase in the LF in comparison with the pretreatment values (P < 0.05). Conclusion The HRV of patients with schizophrenia changes when they are administered with paliperidone ER or olanzapine, and more attention should be paid to their cardiac autonomic function when using these 2 antipsychotics.

Samidorphan/olanzapine combination therapy for schizophrenia: Efficacy, tolerance and adverse outcomes of regimen, evidence-based review of clinical trials

“…In view of the adverse effects of olanzapine which are evident from various studies, such as weight gain, obesity, dyslipidemia, diabetes mellitus, and metabolic syndrome; U.S. FDA approved a combination dose of OLZ/SAM (LYBALVI™) to mitigate the effects of weight gain by olanzapine for the treatment of schizophrenia and bipolar I disorder [ [26] , [27] , [28] , [29] , [30] ]. It received its first approval on May 28, 2021 in the USA for treating not only schizophrenia but also bipolar I disorder (including acute treatment of manic or mixed episodes as monotherapy and as an adjunct to lithium or valproate, and maintenance monotherapy treatment) in adults [ 30 ].…”

“…The purpose of reviewing the evidence-based clinical trials is to provide a comprehensive elucidation of the benefits and side effects of the intervention for clinicians to better understand its efficacy as a therapeutic agent. Numerous studies have associated olanzapine with various side effects including obesity, dyslipidemia, metabolic syndrome, diabetes mellitus and Heart Rate Variability (HRV) [ 26 , 27 ]. This new combined regimen although, superior to olanzapine monotherapy, is not without its adverse effects which have been weighed against its efficacy in alleviating the symptoms of schizophrenia.…”

“…Olanzapine has also been linked with a negative influence on Heart Rate Variability (HRV) and the autonomic nervous system [ 27 ]. This is due to its mechanism of action on cardiac cholinergic receptors which increases K+ delivery suppressing the vagal system.…”

“…This is due to its mechanism of action on cardiac cholinergic receptors which increases K+ delivery suppressing the vagal system. It also blocks alpha 1 adrenergic receptors leading to vasodilation as well as hypertension [ 27 ]. Olanzapine's continued use as a monotherapy has been linked with cardiomyopathy affecting the function of cardiac autonomous systems [ 27 ].…”

“…It also blocks alpha 1 adrenergic receptors leading to vasodilation as well as hypertension [ 27 ]. Olanzapine's continued use as a monotherapy has been linked with cardiomyopathy affecting the function of cardiac autonomous systems [ 27 ]. The renin-angiotensin system also comes into action as an increased level of catecholamines excites the sympathetic functions [ 27 ].…”