Ventricular repolarization
Lithium concentration correlates with QTc in patients with psychosis

https://doi.org/10.1016/j.jelectrocard.2004.10.004Get rights and content

Abstract

QT prolongation induced by antipsychotics has been reported to be a determinant for the development of torsade de pointes and sudden death. However, the effect of lithium on QT interval has not been fully clarified. The aim of the present study was to elucidate the relationship between serum lithium concentration and QT interval in patients treated with lithium. We examined serum lithium concentrations and electrocardiographic features in 39 inpatients with bipolar affective disorder or schizophrenia. The longest QT interval in the 12 electrocardiographic leads was measured using GE Marquette QT guard System Software, and Bazett formula was used for heart rate correction. The longest QTc was positively correlated with lithium concentration (r = 0.46, P = .003). Multiple regression analysis revealed that sex (female, P = .037), lower serum K+ concentration (P = .029), and especially, higher serum lithium concentration (P = .009) were determinants for the prolongation of the QTc.

Introduction

Lithium salts are widely used in psychiatric therapy and prophylaxis as mood stabilizers. The mechanism of lithium as a mood-stabilizing agent remains unknown, although effects on biologic membranes are speculated. It is well recognized that lithium may induce various electrocardiographic (ECG) changes including nonspecific T-wave flattening, dysfunction of sinus node (eg, irregular sinus bradycardia with sinus arrest or sinoatrial block) [1], [2], [3], atrioventricular conduction disturbances, and reversible premature ventricular contractions [4], [5]. However, the effect of lithium on QT interval has not been fully elucidated. QT interval prolongation has been identified as a determinant for the development of torsade de pointes and sudden death [6]. The known determinants of QT prolongation include presence of congenital long QT syndromes, heart failure, bradycardia, electrolyte imbalance, overdose of a QTc-prolonging drug, sex (female), restraint, old age, and hepatic or renal impairment [7]. Among many psychotropic drugs, antipsychotics (especially thioridazine, pimozide, and sertindole) and antidepressants (especially tricyclic antidepressants) have proved to be determinants of QT prolongation [8]. The efficacy and toxicity of lithium are closely related to serum lithium concentration, with its therapeutic range reported to be 0.6 to 1.2 mEq/L [9], [10]. The aim of the present study was to examine the relationship between serum lithium concentration and QT interval in patients treated with lithium.

Section snippets

Patients and methods

This study was carried out at the Hizen Psychiatric Center at Saga prefecture in Japan and was approved by the local ethics committee. All participants gave their informed consent to the attending psychiatrists. A total of 46 inpatients with bipolar affective disorder or schizophrenia were investigated in this study. We designed to exclude patients with heart rates being more than 100 per minute or less than 50 per minute, complete bundle-branch block, or atrial fibrillation and patients

Results

Serum lithium concentration in this study population (0.20-1.08 mEq/L) was within the therapeutic range. ECG parameters are shown in Table 2. PQ interval exceeded 200 milliseconds in one patient. QRSmax exceeded 100 milliseconds in 12 patients. Although there is no clear definition of the normal upper limits for QTc (Bazett formula), it was reported to be 430 milliseconds for men and 450 milliseconds for women [17]. QTcmax of 7 male patients exceeded 430 milliseconds and QTcmax of 2 female

Discussions

Our results showed that 3 determinants (Li+ concentration, K+ concentration, and sex) significantly affected QTc interval. Hypopotassemia and sex (female) [18] are well-known determinants of QTc prolongation. We found that higher serum lithium concentration was also a determinant of QTc prolongation in this study, although there were not any patients with marked QTc prolongation within lithium therapeutic concentration.

Few reports have described the relationship between lithium administration

Acknowledgments

The authors thank Dr M Hirano, the director of the Hizen Psychiatric Center, for giving us the opportunity to perform this study.

References (22)

  • P.J. Goodnich et al.

    Psychotropic drugs and the EEG: focus on the QTc interval

    Expert Opin. Pharmacother.

    (2002)
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