Letters to the Editor
Lorazepam-Induced Prolongation of the QT Interval in a Patient With Schizoaffective Disorder and Complete AV Block
Dear Editor:
A wide range of noncardiovascular therapeutic agents have been shown to prolong the QT interval. The large scope of this problem has created an issue for drug developers and health authorities and is of critical importance for attending physicians (1). The noncardiac agents associated with QT prolongation belong to many different pharmacologic classes, including psychotropic drugs, prokinetic medicines, antimalarial medicines, antibiotics belonging to several different chemical classes, antifungal agents, and nonsedating antihistamines (2). In many cases, psychotropic drugs, particularly tricyclic antidepressants and antipsychotic agents, are correlated with iatrogenic prolongation of the QT interval of the ECG (3). This is associated with dangerous polymorphic ventricular tachyarrhythmia torsades de pointes and sudden death. In addition to ventricular conduction time, the QT interval of the ECG reflects the duration of the ventricular action potential (AP) at the cellular level. Thus, the prolongation of the QT interval may reflect effects on ion channels involved in ventricular AP generation. However, the QT interval also depends on the heart rate, and therefore, the determination of QT prolongation in patients is usually measured using the heart rate corrected QT interval. Vulnerability to medication-induced prolongation of the QT interval may also reside in the patient, with respect to the underlying psychiatric diagnosis, any underlying medical illness (especially cardiovascular disease), genetic predisposition to drug-induced QT prolongation (4), and patient age. The interactions between different psychotropic drugs used in combination or used with other medications that have known effects on the cardiovascular system may also lead to QT prolongation and risk of arrhythmia.
QT prolongation during lorazepam therapy has not been documented in the literature. We present a case of lorazepam-induced severe QT prolongation.
Case report
A woman, aged 40 years, with an acute schizomanic episode, a third-degree atrioventricular (AV) block, and cardiovascular disease meeting ICD-10 criteria was admitted to our psychiatric hospital. The ECG showed the complete AV block (heart rate 45 bpm, QT interval 394 ms), and the blood tests revealed abnormal findings (elevated creatine kinase and creatine kinase-MB isoenzyme, normal troponin T, and elevated liver enzymes). The electro-encephalogram and the brain CT revealed no abnormal findings. Because of the severe symptoms, psychopharmacotherapy with 12.5 mg quetiapine, 100 mg trimipramine, 40 mg pipamperone, and 5 mg diazepam daily was started. The psychopharmacotherapy had no influence on the QT interval. At day 6, 0.5 mg lorazepam was given 3 times, inducing QT prolongation up to 580 ms. Psychopharmacotherapy was discontinued, and the patient was admitted to the medical department for 1 day. The QT prolongation persisted for 7 days, and according to the international treatment criteria, the insertion of a cardiac pacemaker was mandatory. On day 16, a permanent cardiac pacemaker with dual-chamber pacing (that is, DDD mode) was implanted. Afterwards, a sophisticated psychopharmacotherapeutic regimen was established, and the patient responded to the therapy.
In this case, we found a constellation of putative risk factors for the development of QT prolongation. We hypothesize that lorazepam induced the QT prolongation. For a given medication, arrhythmogenic risk must be understood to be partially mechanistically dependent on vulnerability intrinsic to the individual patient with regard to the particular drug. We suggest cautious use of psychotropic drugs in patients with risk factors.
References
1. Crumb W, Cavero I. QT interval prolongation by non-cardiovascular drugs: issues and solutions for novel drug development. Pharm Sci Technol Today 1999;2:270–80.
2. Witchel HJ, Hancox JC. Familial and acquired long QT syndrome and the cardiac rapid delayed rectifier potassium current. Clin Exp Pharm Physiol 2000;27:753–66.
3. Reilly JG, Ayis SA, Ferrier IN, Jones SJ, Thomas SH. QTC-interval abnormalities and psychotropic drug therapy in psychiatric patients. Lancet 2000;355:615–40.
4. Warmke JW, Ganetzky B. A family of potassium channel genes related to eag in drosophila and mammals. Proc Natl Acad Sci USA 1994;91:3438–44.
Marc Ziegenbein, MD
Stefan Kropp, MD
Hanover, Germany
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