QTc prolongation associated with atypical antipsychotic use in the treatment of adolescent-onset anorexia nervosa.

Abstract

Anorexia nervosa (AN) is a chronic illness that is associated with significant morbidity and mortality. Large scale prospective placebo-controlled studies supporting the use of psychotropic medications, including atypical antipsychotics, for the treatment of AN are currently limited. A recent double-blind placebo-controlled trial in an adult population provided evidence for efficacy in olanzapine-treated patients as indicated by greater rates of weight gain, earlier achievement of target body mass index (BMI), and a greater rate of decrease in obsessive symptoms (Bissada et al., 2008). To date, prospective controlled studies examining the use of atypical antipsychotics in paediatric AN populations are non-existent. As a result, little has been published on the side effects of these medications in this population (Fairburn et al., 2003). Herein, we describe a case of corrected QT (QTc) prolongation associated with atypical antipsychotic use in an adolescent patient with AN and discuss safety and medical monitoring issues as it pertains to antipsychotic use in this population. The QT interval is the time taken for the ventricle to depolarize and repolarize and is measured from the beginning of the Q wave to the end of the T wave on an electrocardiogram (ECG). The QT interval can vary with heart rate, and as such can be corrected (QTc) using various methods, including the Fridericia, Hodges, and Framingham formulas. The Bazett formula (QTc=RR/QT1/2) is most often cited in Canadian clinical practice and is used by cardiologists within our pediatric center. Risk factors for QT prolongation include female sex, bradycardia, hypokalemia, and cardiac disease (Roden, 2004). A number of medications, including various antiarrhythmic drugs (class IA and III), antibiotics, antihistamines, methadone, and psychotropic medication have also been associated with QTc prolongation (Harrigan et al, 2004). Given the prevalence of these risk factors in patients with AN, care should be taken in the cardiac monitoring of low weight medically compromised patients, as baseline QTc have been shown to be longer than those of healthy controls (Cooke et al., 1994). Acute risk associated with prolongation of the QTc includes torsade de pointes, a potentially fatal type of arrhythmia (Al-Khatib, 2003). There are few studies that comment on the safety of atypical antipsychotics in the child and adolescent population. In one non-eating disorder (ED) paediatric study involving 20 subjects, use of ziprasidone was associated with an average QTc prolongation of 28 msec (p = 0.07) (Blair et al., 2005). McConville’s 2000 open-label study of quetiapine in adolescents with psychotic disorders also commented specifically on tolerability relating to medical effects of the drug. No significant changes in QTc were observed. QTc prolongation has been reported in adolescents who have overdosed on quetiapine and on ziprasidone in combination with bupropion (Biswas et al., 2003; Kurth & Maguire, 2004).