Proarrhythmic Risk with Antipsychotic and Antidepressant Drugs

Abstract

The quinidine-like effects of some antidepressant drugs (particularly tricyclic antidepressants) and many antipsychotic drugs (particularly the phenothiazines) confound treatment of psychosis and depression in patients with major mental illness. This is especially true among elderly patients with existing risk factors for corrected QT (QTc) interval prolongation. We used PubMed, previously reported review articles and the extensive personal files of the authors to identify cases of subjects aged>or=60 years who developed QTc interval prolongation, polymorphic ventricular tachycardia (PVT)/torsade de pointes (TdP) and/or sudden cardiac death while taking antipsychotic or antidepressant drugs or a combination of these medications. We identified 37 patients who had taken, in total, 46 antipsychotic or antidepressant drugs. Our most striking finding was that almost four-fifths of our cases involved women. When the 14 critically ill subjects receiving haloperidol intravenously were excluded, 91.3% of our subjects were women. Almost three-quarters of our study subjects had cardiovascular disease. Intravenous administration of haloperidol in the critically ill and profoundly agitated elderly warrants particular comment. Of the 14 subjects in this category identified, six were men and eight were women. In 13 cases, the drug dose far exceeded the 2 mg necessary to produce an antipsychotic effect. These clinicians were using an agent to achieve sedation that usually requires very high doses in the critically ill and profoundly agitated elderly to achieve this effect. Inclusion criteria for our literature review required antipsychotic and/or antidepressant drug-induced QTc interval prolongation. Even so, our finding that 31 of our 37 subjects developed PVT is sobering. However, the reader should not conclude that drug-induced QTc interval prolongation is highly predictive of PVT or its TdP subtype. All of our study subjects had at least two risk factors for TdP, with age and sex being the most common. We included the rare case of a patient with congenital long QT syndrome who developed further lengthening of the QTc interval and TdP when prescribed an antidepressant drug well known to produce QTc interval prolongation. We conclude with recommendations for clinicians not expert in the specialty of cardiology to deal with the many questions raised in this review. Specifically, such clinicians treating elderly patients with antipsychotic and antidepressant drugs that may prolong the QTc interval should aggressively obtain a baseline ECG for elderly female patients with additional risk factors such as personal or family history of pre-syncope or syncope, electrolyte disturbances or cardiovascular disease. Elderly male patients are also subject to QTc interval prolongation when such risk factors are present. It is important that the clinicians themselves inspect ECGs. If the QT interval is more than half the RR interval, QTc interval prolongation is likely to be present. In such cases, a cardiology colleague interested in QTc in...

Antipsychotic Drug Administration Does Not Correlate with Prolonged Rate-Corrected QT Interval in Children and Adolescents: Results from a Nested Case–Control Study

“…The low prevalence of QTc prolongation in our pediatric cohort stands in stark contrast to the much higher prevalence of QT interval disturbance in older age groups (Lubart et al 2009;Vieweg et al 2009). Depending on sample selection and type correction for heart rate, the QTc was found to be to prolonged in 27%-75% of hospitalized patients older than 60 years (Lubart et al 2009).…”

Potential drug–drug interactions in a medical intensive care unit of a university hospital

“…Physicians of the ICU were informed about this possible X risk category DDI and warned for possible symptoms such as hyperthermia, tachycardia, hyperreflexia, agitation, or confusion. Combination of antipsychotics and antidepressants can cause QT prolongation and result in a life-threatening ventricular arrhythmia, torsades de pointes, a well-known cause of ventricular fibrillation and sudden cardiac death (18). Although it has been suggested that antipsychotics and antidepressants, particularly serotonin reuptake inhibitors or tricyclic antidepressants, prolong QT interval independently, combination therapy has been reported to influence QT interval significantly compared to monotherapy with antipsychotics in female patients.…”

Untreated preoperative depression is not associated with postoperative arrhythmias in CABG patients

“…Both tricyclic antidepressants and selective serotonin reuptake inhibitors may prolong the QT interval, affect heart rate variability, and cause arrhythmias. [35][36][37][38] In addition, nonpharmacological modalities, such as ECT and vagus nerve stimulation, can trigger arrhythmias by affecting the QT interval or causing heart block. 39,40 To avoid this confounding factor, patients who were treated for depression were excluded from our study.…”

“…34 Each option or their combination can potentially affect the incidence of arrhythmia in rather unpredictable ways. Antidepressants, ECT, and vagus nerve stimulation have possible arrhythmogenic effects, [35][36][37][38][39][40] yet, psychotherapy, such as biofeedback 41 and cognitive behaviour therapy, 42 can decrease the incidence of arrhythmia in cardiac patients.…”