Elsevier

Epilepsy Research

Volume 57, Issue 1, November 2003, Pages 69-75
Epilepsy Research

Carbamazepine affects autonomic cardiac control in patients with newly diagnosed epilepsy

https://doi.org/10.1016/j.eplepsyres.2003.10.012Get rights and content

Abstract

Previous studies indicate that epilepsy patients may have impaired autonomic cardiovascular control in the interictal state although it is unclear whether the observed reduction in cardiovascular responses is due to the epilepsy and the interictal epileptogenic discharges, or to the treatment with antiepileptic drugs. Spectral analysis of heart rate variability makes it possible to partly separate the sympathetic components, low frequency (LF), from the vagal components, high frequency (HF) of autonomic cardiac control. We used spectral analysis of heart rate variability to assess the effect of carbamazepine (CBZ) on autonomic cardiac control in patients with newly diagnosed epilepsy. Fifteen adult outpatients with newly diagnosed seizures/epilepsy underwent 24 h ambulatory EKG recordings before and after commencement of CBZ treatment. Total power as well as low frequency (LF), very low frequency (VLF) and high frequency (HF) power in heart rate variability was calculated. When analysing the full 24 h recordings, patients had significantly lower standard deviation of RR-intervals (P=0.0015), total power (P=0.0010), LF (P=0.0002), VLF (P=0.0025) and HF (P=0.0139) during treatment with CBZ than before. The results were very similar for daytime and night time recordings. Our observations demonstrate that CBZ may suppress both parasympathetic and sympathetic functions in newly diagnosed patients with epilepsy. The possible implications of our results for sudden unexpected death in epilepsy are discussed.

Introduction

Epileptic seizures are frequently associated with changes in cardiac function (Buren, 1958, Buren and Ajmone-Marsan, 1960) including tacky- as well as brady-arrhythmia (Blumhardt et al., 1986, Keilson et al., 1989, Smith et al., 1989). The proposed mechanism for these changes is the spread of seizure discharges to autonomic centres in the cortical, limbic and hypothalamic structures (Wannamaker, 1985). Animal models of epilepsy suggests that even interictal epileptogenic activity may induce changes in the autonomic nervous system, which could result in cardiac arrhythmia (Lathers and Schraeder, 1982, Lathers et al., 1987). Clinical studies indicate that also patients with epilepsy may have impaired autonomic cardiovascular regulation in the interictal state, although it is unclear whether the observed reduction in cardiovascular responses is due to the epilepsy and the interictal discharges, or the treatment with antiepileptic drugs (AEDs) (Frysinger et al., 1993, Massetani et al., 1997, Isojarvi et al., 1998, Tomson et al., 1998, Ansakorpi et al., 2000, Ansakorpi et al., 2002). These observations are of particular interest considering the increased risk of sudden unexpected death among people with epilepsy (SUDEP) (Ficker et al., 1998) and the potential role for autonomic dysfunction in this context.

A recent study of heart rate variability demonstrated increased sympathetic activity in sleep after abrupt reduction of carbamazepine (CBZ) (Hennessy et al., 2001). Although these results suggest important effects of abrupt withdrawal of CBZ on autonomic cardiac control in patients with refractory epilepsy, the results cannot immediately be extrapolated to the general epilepsy population.The present study was therefore designed to assess directly the effect of CBZ on autonomic cardiac control by application of spectral analysis of heart rate variability to patients with newly diagnosed epilepsy before and after initiation of treatment with CBZ.

Section snippets

Patients

Adult patients with newly diagnosed epilepsy attending the Department of Neurology at the Karolinska Hospital in Stockholm, Sweden, were eligible for inclusion in the study. Only patients planned for CBZ treatment but without other AEDs were included. Patients with a history of heart failure, coronary heart disease, diabetes, uraemia or any other known disease that might affect the autonomic nervous system were excluded, as were patients with brain tumours and those for which immediate

Results

All patients had been seizure free at least 24 h before the EKG-recordings and none reported any seizures during the recordings. When analysing the full 24 h recording, patients had significantly lower standard deviation of RR-intervals, TP, VLF, LF and HF during treatment with CBZ than before, but there was no significant change in the LF/HF ratio (Table 2). The results were very similar when daytime (Table 3) and night time (Table 4) recordings were analysed separately.

Discussion

We used spectral analysis of heart rate variability to assess autonomic cardiac control in the present study. With this method, it is possible to partly separate the sympathetic components from the vagal components of the power spectrum (van Ravenswaaij-Arts et al., 1993). HF reflects respiratory sinus arrhythmia and is mainly related to parasympathetic activity (Katona and Jih, 1975, Akselrod et al., 1981, Pomeranz et al., 1985). LF oscillations are associated with baroreflexor control of

Acknowledgements

This study was supported by grants from the Karolinska Institute and by the Follin Foundation.

References (43)

  • S. Akselrod et al.

    Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control

    Science

    (1981)
  • H. Ansakorpi et al.

    Heart rate dynamics in refractory and well controlled temporal lobe epilepsy

    J. Neurol. Neurosurg. Psychiatry

    (2002)
  • H. Ansakorpi et al.

    Interictal cardiovascular autonomic responses in patients with temporal lobe epilepsy

    Epilepsia

    (2000)
  • J.T. Bigger et al.

    Frequency domain measures of heart period variability and mortality after myocardial infarction

    Circulation

    (1992)
  • T. Binder et al.

    Prognostic value of heart rate variability in patients awaiting cardiac transplantation

    Pacing Clin. Electrophysiol.

    (1992)
  • J.v. Buren

    Some autonomic concomitants of ictal automatism

    Brain

    (1958)
  • J.v. Buren et al.

    A correlation of autonomic and EEG components in temporal lobe epilepsy

    Arch. Neurol.

    (1960)
  • Burg JP, 1967. Maximum entropy spectral analysis. In: Proceedings of the 37th Meeting of the Society of Exploration...
  • H. Cohen et al.

    Association of autonomic dysfunction and clozapine. Heart rate variability and risk for sudden death in patients with schizophrenia on long-term psychotropic medication

    Br. J. Psychiatry

    (2001)
  • Danielsson, B., Lansdell, K., Patmore, L., Tomson, T., in press. Phenytoin and phenobarbital inhibit human HERG...
  • D.M. Ficker et al.

    Population-based study of the incidence of sudden unexplained death in epilepsy

    Neurology

    (1998)
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