Letters to the Editor
QTc Prolongation: Chlorpromazine and High-Dosage Olanzapine
Dear Editor:
The electrocardiographic QT interval reflects ventricular depolarization (QRS complex) and repolarization (ST segment and T wave). It varies inversely with heart rate and is usually less than or equal to one-half the RR duration (1). The heart rate corrected interval (QTc) is normally less than or equal to 440 ms, and a QTc of over 500 ms characterizes an increased risk for developing dangerous cardiac dysrhythmias (for example, torsades de pointes) (2,3). This interval exhibits additional variability with sex, age, circadian variation, metabolic abnormalities, and exposure to selected pharmaceuticals. Antipsychotic agents are among the many medicines that can cause QTc prolongations: chlor- promazine, thioridazine, olanzapine, quetiapine, and ziprasidone can create this cardiac concern (3–7). Olanzapine is associated with such change in higher dosages but is generally better tolerated at conventional quantities (4,5). The following case report documents QTc prolongation in an elderly woman receiving chlorpromazine and quetiapine, which improved when she was taken off these drugs. Later, however, prolongation reoccurred while on high-dosage olanzapine, which was not evident on a lesser olanzapine dosage.
Case Report
A 66-year-old obese woman was hospitalized with diagnoses of schizoaffective disorder, hypertension, hypothyroidism, and hyperlipidemia. Chlorpromazine and quetiapine were among 13 medications that she had been prescribed. Initial laboratory reports evidenced normal serum chemistries, thyroid-stimulating hormone, and hemogram. Baseline electrocardiographic QTc prolongation at 450 ms was attributed to the antipsychotic medicines, which were discontinued.
Olanzapine 40 mg daily was prescribed, and 13 days later, the QTc was 416 ms. The next day, olanzapine was increased to 60 mg, owing to severe agitation. Four days later, the QTc interval was 436 ms (20 ms lengthening). New serum chemistries, including calcium, magnesium, sodium, and potassium concentrations were normal; electrolyte imbalance or hypothyroid etiologies for QTc prolongation were unlikely.
Olanzapine 60 mg daily was deemed as the cause of this cardiac finding, and the dosage was reduced to 40 mg. Follow-up electrocardiograms the next morning and afternoon evidenced intervals at 393, 396, and 415 ms. After the olanzapine dosage was decreased, however, the QTc returned to a safer value.
Several antipsychotic medicines have been reported to be associated with QTc interval prolongation (3–7). Drug combinations, as in our case with chlorpromazine and quetiapine, may be an additional risk factor. The electrocardiogram helped to detect the cardiac conduction delay. It provided a clinical guide for discontinuing chlorpromazine and quetiapine and for prescribing olanzapine. It was not surprising to observe QTc prolongation with chlorpromazine and quetiapine that normalized once these drugs were discontinued. The QT interval with olanzapine was unremarkable until the dosage was 60 mg daily. The literature documents that olanzapine can cause QTc prolongation in various amounts; high-dosage olanzapine induces greater risk, but as little as 2.5 mg daily can also extend this interval (5,6). Our case demonstrates QTc prolongation that was still in the acceptable range with initiation of higher-than-conventional dosages of olanzapine. After the dosage was decreased, the QTc shortened to a safer value.
Thus, it is prudent to provide careful electrocardiographic monitoring in patients taking chlorpromazine and high-dosage olanzapine, in cases of antipsychotic drug polypharmacies, and in older people.
References
1. Victor W, Vieweg R. Mechanisms and risks of electrocardiographic QT interval prolongation when using antipsychotic drugs. J Clin Psychiatry 2002;63 (Suppl 9):18–24.
2. Tan HL, Hou CJ, Lauer MR, and others. Electrophysiologic mechanisms of the long QT interval syndromes and torsades de pointes. Ann Intern Med 1995;122:701–14.
3. Glassman AH. Clinical management of cardiovascular risks during treatment with psychotropic drugs. J Clin Psychiatry 2002;63(Suppl 9):12–6.
4. Czekalla J, Beasley CM, Deelva MA, and others. Analysis of the QTc interval during olanzapine treatment of patients with schizophrenia and related psychosis. J Clin Psychiatry 2001;62:191–8.
5. Czekalla J, Kollack-Walker S, Beasley CM. Cardiac safety parameters of olanzapine: comparison with other atypical and typical antipsychotics. J Clin Psychiatry 2001;62 (Suppl 22):35–40.
6. Gupta N, Malhotra P. Olanzapine: a proarrhythmic drug? [letter]. Can J Psychiatry 2002;47:683–4.
7. Bouchard RH, Demers MF, Simoneau I, and others. Atypical antipsychotics and cardiovascular risk in schizophrenic patients [letter]. J Clin Psychopharmacol 2001;21:110–11.
Irina Gurovich, MD; Anitha Vempaty, BA
Steven Lippmann, MD
Louisville,Kentucky
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