Correspondence

Overdose of Cyclic Antidepressants and the Brugada Syndrome

N Engl J Med 2002; 346:1591-1592May 16, 2002

Article

To the Editor:

The Brugada syndrome is a rare clinical and electrocardiographic entity consisting of sudden death from cardiac causes associated with right bundle-branch block and unusual ST-segment elevation in the right precordial leads (V₁ to V₃).1 A Brugada electrocardiographic pattern mimicked by overdose of cyclic antidepressants has been reported in rare instances.2 To assess the prevalence of the Brugada electrocardiographic pattern and its relation to death during overdose of cyclic antidepressants, a retrospective study was carried out in our intensive care unit.

We studied 98 consecutive cases of intoxication with cyclic antidepressants in 95 patients (mean [±SD] age, 41±13 years) that occurred between January 1998 and December 2001 (Table 1Table 1Characteristics of Patients with Cyclic-Antidepressant Poisoning.). No patient had a personal or familial history of cardiac disease, and none had ingested antiarrhythmic drugs. Intoxication with cyclic antidepressants was defined by a plasma concentration greater than 1 μM per liter. All 12-lead electrocardiograms obtained at admission, during the hospital stay, and at discharge were examined.

A Brugada electrocardiographic pattern was present in 15 of 98 cases of overdose of cyclic antidepressants (15.3 percent). The Brugada electrocardiographic pattern was definite in 12 (Figure 1Figure 1Electrocardiograms Recorded in a Single Patient Admitted with Cyclic-Antidepressant Poisoning.) and equivocal in 3 patients. One woman admitted three times for poisoning with cyclic antidepressants and one time for poisoning with another drug had a Brugada electrocardiographic pattern during each overdose of cyclic antidepressants. The overall mortality rate was 3 percent, with one patient with the Brugada electrocardiographic pattern and one patient without it dying from refractory ventricular fibrillation. The mortality rate was 6.7 percent among patients with the Brugada electrocardiographic pattern and 2.4 percent among patients without it (P=0.39). The Brugada electrocardiographic pattern disappeared when plasma concentrations of cyclic antidepressants were less than 1 μM per liter. No antiarrhythmic-drug assays or electrophysiologic or genotyping studies were performed.

The Brugada syndrome is a cardiac disorder related to a genetically determined sodium-channel dysfunction (blockade of inward sodium current) without evidence of structural heart disease. This disease is associated with a high mortality rate in middle-aged men, resulting from ventricular fibrillation whose pathophysiology remains incompletely understood. Drugs that block sodium channels such as class IA or IC antiarrhythmic drugs are usually used to aggravate or unmask the Brugada electrocardiographic pattern in order to confirm the diagnosis.1 Cyclic antidepressants have the ability to block cardiac sodium channels.3

In our study, the prevalence of the Brugada electrocardiographic pattern in patients with overdose of cyclic antidepressants exceeds the prevalence in the general population (0.05 to 0.1 percent).1 A functional or organic disease exacerbated by cyclic antidepressants cannot be ruled out, but there was no statistically significant increase in the risk of death from cardiac causes related to the Brugada electrocardiographic pattern in the patients we studied. The Brugada electrocardiographic pattern has also been reported in cases of poisoning with neuroleptic agents, which likewise have blocking effects on sodium channels.3 Information on the dose of neuroleptic agents is not commonly requested. Thus, combined poisoning with neuroleptic agents cannot be ruled out and renders our conclusions questionable with respect to the relation between overdose of cyclic antidepressants alone and the Brugada electrocardiographic pattern.

Every physician in charge of patients with cyclic-antidepressant poisoning should be aware of the Brugada electrocardiographic pattern, which may be a marker of a high risk of death.

Dany Goldgran-Toledano, M.D.
Georgios Sideris, M.D.
Jean-Philippe Kevorkian, M.D.
Lariboisière Teaching Hospital, 75475 Paris, France
jean-philippe.kevorkian@lrb.ap-hop-paris.fr

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