Hematopoetic, hepatic and dermatological toxicity of Carbamazepine is well-known, but cardiac side-effects are not that widely recognized. Its use has rarely been reported to cause conduction abnormalities, predominantly in elderly women, with therapeutic (or moderately elevated) plasma concentrations of the drug [1]. We herein report a child with syncopal attacks following carbamazepine use.

An 8-year-old child presented with history of fainting attacks while playing, which lasted for a few seconds, followed by spontaneous recovery. He had two such witnessed episodes in the preceding week, which prompted the present consultation. He was developing normally, studied in class III, and never had any previous episodes of dizziness, syncope, breathlessness or cyanosis. He did not report any other associated cardiac symptoms. He was on regular treatment with carbamazepine (15 mg/kg/d) for Idiopathic generalized epilepsy from another institution since past one year, with no non-compliance, or missing a dose in the last 24-hours. Contrast-enhanced CT head done at that time was normal.

On detailed history, these episodes of fainting did not resemble the seizures that he had experienced in the past, and during this episode he did not have any other neurologic symptoms. The fainting attacks were transient and the child recovered immediately after the fall. On examination, the patient was alert and cooperative with blood pressure of 98/76 mmHg. He was noted to have an irregularly irregular pulse, and ectopic heart beats after every 8 to 10 beats, with a heart rate of 70 to 80 beats per minute. A 12-lead electrocardiogram showed ventricular premature beats (Fig. 1). Child was admitted and started on tablet atenolol, 25 mg daily . An echocardiogram ruled out structural heart disease. Holter monitoring for 24 hours showed frequent ventricular ectopic beats though the child did not have further fainting episodes during the hospital stay.

Fig. 1 Ventricular premature beats seen in the child’s electrocardiogram on admission.

In the background of reports of carbamazepine causing conduction disturbances, it was replaced with tablet valproate 15 mg/kg/day. Atenolol was stopped. Serum carbamazepine level six hour after the last dose of the drug was 10.6 µg/mL (therapeutic range 8-12 µg/mL). The patient was discharged on day 5, after documenting a normal ECG. Repeat holter study at 3 months of follow-up, did not show any abnormality. On follow-up at one year, he was asymptomatic without any complaints of fainting attacks or giddiness.

Carbamazepine exerts its effect by acting as a sodium channel blocker, and is known to produce negative chronotropic and dromotropic effects on the heart; thus, it may sometimes lead to conduction disturbances, including Sinus bradycardias, sinus pauses, junctional bradycardias, and AV blocks, ranging from first degree to complete [2]. A recent review of these reports showed that elderly women, particularly those with a pre-existing conduction abnormality, were mostly involved [1], though reports in young also exist. Usually brady-arrhythmias occur at therapeutic doses, whereas sinus tachycardia is the main arrhythmia in massive CBZ overdose [3]. An increase in ventricular premature beats over next five days has also been reported in patients who abruptly discontinued CBZ because of cardiac side-effects [4]. Our patient, however, did not have any history of discontinuation of the drug prior to presentation. Another possibility could have been arrhythmia-related seizures [5]; however, there was no recurrence of the ECG abnormality after stopping carbamazepine. Using the Naranjo Adverse Drug Reaction Probability Scale classified the event as a ‘possible’ adverse drug reaction.

We wish to highlight that cardiac side-effects may sometimes occur after prolonged carbamazepine therapy, and may be associated with normal or slightly high serum levels. As seen in this child, rapid resolution of symptoms occurs on discontinuing the drug.

Acknowledgement: Dr Priyanka Solanki, Department of Pediatrics, Lok Nayak Hospital; and Dr. Sanjiv Kathuria DM, Department of Cardiology, GB Pant Hospital.

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2. Tomson T, Kenneback G. Arrhythmia, heart rate variability, and antiepileptic drugs. Epilepsia. 1997; 38:S48-51.

3. Kasarskis EJ, Berger R, Nelson KR. Carbamazepine-induced cardiac dysfunction. Characterization of two distinct syndromes. Arch Intern Med. 1992;152:186-91.

4. Kennebäck G, Ericson M, Tomson T, Bergfeldt L. Changes in arrhythmia profile and heart rate variability during abrupt withdrawal of antiepileptic drugs. Implications for sudden death. Seizure. 1997;6:369-75.