Sudden withdrawal of carbamazepine increases cardiac sympathetic activity in sleep

Objective: To evaluate the cardiac autonomic effects of abrupt withdrawal o f carbamazepine (CBZ) during sleep in patients with epilepsy. Background: T he pathophysiology of sudden unexpected death in epilepsy (SUDEP) is uncert ain, with ictal or peri-ictal cardiorespiratory compromise appearing probab le. Risk factors for SUDEP include multiple antiepileptic drugs (AED), poor compliance, and abrupt AED withdrawal. The spectral analysis of the beat-t o-beat heart rate variability (HRV) displays two main components: low frequ ency (LF), representing sympathetic and parasympathetic influence and high frequency (HF), representing parasympathetic influence. The LF/HF ratio is commonly regarded as an indicator of sympathovagal balance. Methods: Twelve patients with medically intractable seizures underwent abrupt withdrawal o f CBZ to facilitate seizure recording during controlled circuit TV-EEG moni toring. Continuous EKG recording was begun 24 hours before CBZ reduction. S pectral analysis of the HRV was performed during selected samples of non-RE M sleep before and after CBZ reduction. Analyses were made at least 6 hours after from (complex) partial and 12 hours from generalized seizures. Resul ts: The mean LF/HF ratio before withdrawal of CBZ was 2.15 compared with a ratio of 2.65 on day 4 after withdrawal, an increase of 19% (geometric mean ; 95% CI, 2% to 34%; Wilcoxon test, z = 2.36; p = 0.018). The ratio increas ed in 10 patients compared with a decrease in only one patient. Conclusion: Abrupt withdrawal of CBZ leads to enhanced sympathetic activity in sleep a s evidenced by increased LF/HF ratios. Increased sympathetic activity in th e setting of seizure-induced hypoxia could predispose to SUDEP.