Differential heart rate response to magnetic seizure therapy (MST) relative to electroconvulsive therapy: a nonhuman primate model

Abstract

Electroconvulsive therapy (ECT) is an effective treatment for severe depression; however, the induced therapeutic seizure acts on the autonomic nervous system and results in significant cardiac effects. This is an important consideration particularly in the elderly. Magnetic seizure therapy (MST) is in development as a less invasive alternative, but its effects on cardiac function have not been studied. We sought to model those effects in nonhuman primates to inform the development of safer neurostimulation interventions. Twenty four rhesus monkeys were randomly assigned to receive 6 weeks of daily treatment with electroconvulsive stimulation (ECS), magnetic seizure therapy (MST) or anesthesia-alone sham. Digitally acquired ECG and an automated R-wave and inter-R interval (IRI) sampling were used to measure intervention effects on heart rate (HR). Significant differences between experimental conditions were found in the HR as evidenced by changes in the immediate post-stimulus, ictal and postictal epochs. Immediate post-stimulus bradycardia was seen with ECS but not with MST. ECS induced significantly more tachycardia than MST or sham in both the ictal and postictal periods. MST resulted in a small, but statistically significant increase in HR during the postictal period relative to baseline. HR was found to increase by 25% and 8% in the ECS and MST conditions, respectively. MST resulted in significantly less marked sympathetic and parasympathetic response than did ECS. This differential physiological response is consistent with MST having a more superficial cortical site of action with less impact on deeper brain structures implicated in cardiac control relative to ECT. The clinical relevance of the topographical seizure spread of MST and its associated effects on the autonomic nervous system remain to be determined in human clinical trials.

Figures

Fig. 1

Average heart rate (beats/min) for each of the 4 recording epochs (baseline, ictal, postictal-1, and postictal-2) and for each of the 3 groups (ECS, MST, and sham). Points indicate mean heart rate within each recording epoch. Bars indicate standard error of the mean.

Fig. 2

Change in heart rate (beats/min), from baseline to the ictal and combined postictal epochs, for ECS, MST and sham based.

Fig. 3

Percent change in heart rate from baseline to immediate post-stimulation period monkey for ECS and MST groups. Stimulations that led to seizure are designated “convulsive”, while those that did not lead to seizure are designated “subconvulsive.”