Both tricyclic antidepressants and some atypical antipsychotics, such as ziprasidone and quetiapine, used as augmentation agents in severe major depression, are known to increase QTc interval to a moderate extent (10-20 msec). Moreover, electroconvulsive therapy (ECT) also increases patients’ propensity to arrhythmias. Finally, females are more prone than males to both drug-induced QTc prolongation and torsades-de-pointes. Thus, the combination of all the above treatments raises serious safety concerns. We investigated the safety of the co-administration of ECT with a tricyclic-ziprasidone-quetiapine combination with respect to QTc interval in six female patients with severe major depression resistant to pharmacotherapy.

Each patient underwent a series of 10-11 sessions of bilateral ECT. QTc intervals were calculated at baseline and several times up to 10 min after seizures cessation in a total of 63 patients/ECT sessions.

A small initial decrease of QTc after the administration of pre-ECT medications was followed by its steady statistically non-significant increase during the first 20 sec after seizure cessation. Thereafter, a steady larger and statistically significant decrease of QTc emerged during the ensuing 21-50 sec interval. Finally, this decrease was gradually reversed within the following 2 min approximately with return of QTc interval to stable baseline levels.

Overall, QTc interval changes remained within normal limits (fixed at 470 msec in women), without the occurrence of any cardiac adverse events, especially severe arrhythmias such as torsades-de-pointes. Our findings suggest that the co-administration of these treatments might be safe, at least with respect to QTc interval changes.