QTc Prolongation in Patients with AN

The QT interval is the time taken for the cardiac ventricles to depolarize and repolarize, and is measured on the electrocardiogram (ECG) 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 can be corrected (QTc).

Drs. Blair Ritchie and Mark L. Norris recently reported a case of  QTc prolongation after a 15-year-old AN patient was treated with an atypical antipsychotic (J Can Acad Child Adolesc Psychiatry 2009; 18:60). The patient had restricting-type AN and had been transferred from a tertiary treatment center to an inpatient eating disorders treatment program at the authors’ hospital. Her body mass index (kg/M2) was 18, and she weighed 105 lb (48 kg). She was receiving fluoxetine, 20 mg daily, and olanzapine, 5 mg nightly. There was no history of substance abuse and, aside from low weight, her physical examination and laboratory test results were normal. An ECG taken at the time she was transferred showed a prolonged QTc interval of 457 msec (normal is generally <440 msec).

During the next few weeks, the two clinicians struggled to find a dosage that would help control her anxiety while avoiding QTc prolongation. Finally, on day 30, the patient and her family were counseled about and agreed to a trial of risperidone; a dose of 0.25 mg was started and the total daily dose was increased to 0.5 mg 7 days later, then to 0.75 mg. On day 55, the QTc was 473 msec, but it normalized within one week of discontinuing the risperidone. The patient tolerated a 25-mg dose of quetiapine and it was increased to 50 mg nightly without any changes in QTc.

Guidelines for patients receiving atypical antipsychotics

The authors stress that given the inherent cardiac risks associated with treating low-weight AN patients, care should be taken when atypical antipsychotic medication is being considered. Special attention should be paid to pre-existing cardiac history, clinical symptoms and ongoing monitoring. In addition, when measuring QTc, the timing of drug delivery and potential drug reactions should be considered.  Ideally, ECGs should be recorded at peak serum concentrations of the suspect drug. However, timing predicted pharmacokinetic effects based upon drug administration to completion of ECGs is not realistic.

Drs. Ritchie and Norris note that at their hospital baseline ECGs are completed on all patients at the beginning of treatment, and whenever medications are introduced that are known to affect QTc intervals. The interval is monitored over the course of drug therapy and after incremental changes are made in doses. They advise that ECGs be repeated whenever a patient has any other risk factor that might alter QTc while on antipsychotic medication. This may be the case when patients develop electrolyte disturbances. Patients who purge are especially at risk for electrolyte abnormalities and should be monitored very closely. When patients have prolonged QTcs  >450 msec, suspect medications should be halted and ECGs repeated until the interval is normal. When baseline values increase significantly (by more than 60 msec), the authors advise either stopping or tapering the medication while closely watching QTc intervals; once a week is usually adequate.