Effects of electrical stimulus composition on cardiac electrophysiology in a rodent model of electroconvulsive therapy.

BACKGROUND: No electroconvulsive therapy (ECT) study on humans or in animal models has so far examined whether differently composed electrical stimuli exert different cardiac electrophysiological effects at constant electrical dose. The subject is important because cardiac electrophysiological changes may provide indirect information about ECT seizure quality as modulated by stimulus composition. MATERIALS AND METHODS: Adult female Wistar rats (n = 20/group) received fixed, moderately suprathreshold (18 mC) electrical stimuli. This stimulus in each of eight groups was formed by varying pulse amplitude, pulse width, pulse frequency, and stimulus duration. The electrocardiogram was recorded, and time and frequency domain variables were examined in 30 s epochs in preictal (30 s before electroconvulsive shock [ECS]), early postictal (starting 15 s after stimulation), and late postictal (5 h after ECS) periods. Alpha for statistical significance was set at P < 0.01 to adjust for multiple hypothesis testing. RESULTS: Cardiac electrophysiological indices in the eight groups did not differ significantly at baseline. At both early and late postictal time points, almost no analysis yielded statistically significant differences between groups for four time domain variables, including heart rate and standard deviation of R-R intervals, and for six frequency domain variables, including low-frequency power, high-frequency power, and total power. CONCLUSIONS: Cardiac electrophysiological measures may not be helpful to identify differences in seizure quality that are driven by differences in the composition of electrical stimuli at constant, moderately suprathreshold electrical dose. The generalization of this conclusion to threshold electrical doses and to human contexts requires a study.

Early and late postictal cardiac electrophysiological changes associated with low, moderate, and high dose electroconvulsive shocks.

BACKGROUND: Studies have examined the effects of electroconvulsive therapy (ECT) on human cardiac electrophysiology. However, no study has so far examined whether these effects vary with the magnitude of the electrical dose used to elicit the seizure. Because the benefits and adverse effects of the ECT seizure are dose-dependent, we examined the effects of different electrical doses of electroconvulsive shocks (ECS) on cardiac electrophysiology in an animal model with a view to determine whether cardiac electrophysiology could be a useful proxy to evaluate the quality of the ECT seizure. METHODS: Adult female Wistar rats (n = 20/group) received sham, low dose (10 mC), moderate dose (18 mC), or high dose (25 mC) ECS. The electrocardiogram (ECG) was recorded and was analyzed for time and frequency domain variables in 30 s epochs in preictal (30 s before ECS), early postictal (starting 15 s after stimulation) and late postictal (5 h after ECS) periods. RESULTS: ECS was associated with substantial changes in most time and frequency domain measures during the early postictal period; a strong parasympathetic effect was observed. However, the effects of different ECS doses did not differ for any variable. All changes returned to levels that were similar to those of the sham controls in the late postictal period. CONCLUSIONS: The effect of ECS on time and frequency domain cardiac electrophysiological measures was not dose-dependent. This suggests that if higher electrical doses are associated with stronger central seizures, ECG-derived variables may not be useful proxies for the quality of the central seizure. The generalization of this conclusion from animal to clinical contexts requires study.

Impact of an educational module in antidepressant-naive patients prescribed antidepressants for depression: Pilot, proof-of-concept, randomized controlled trial.

BACKGROUND: Patients are educated about their illness and its treatment at the time of diagnosis. However, little is known about how much of this education is retained and how it influences knowledge about, attitudes toward, and experiences with medication in antidepressant-naive patients with depression. METHODS: Antidepressant-naive outpatients with International Classification of Diseases-10 dysthymia or mild to moderate depression, who were advised antidepressant monotherapy, were randomized to control (n = 22) or intervention (n = 17) groups. Control patients received treatment as usual, and intervention patients received, in addition, a face-to-face, individualized, 10-min education session about the nature of depression, antidepressant treatment, efficacy and adverse effects of the prescribed drug, and plan of management. Knowledge about the illness and its treatment were assessed at baseline (before the educational intervention) and 6 weeks later. At follow-up, experiences with treatment were also evaluated. The study was double-blind. RESULTS: At baseline, patients had poor knowledge about their illness and its treatment (most patients could not even name their diagnosis); however, few held unfavorable attitudes toward their prescribed medicines. At follow-up, there were modest improvements in both sets of outcomes. There were no differences between intervention and control groups in knowledge and attitude outcomes at baseline and end-point. Drug compliance did not differ between groups. However, importantly, intervention patients experienced a significantly larger number of adverse events than controls (mean, 3.5 vs. 1.7, respectively). CONCLUSIONS: For ethical reasons, patients need to be educated about their illness and its treatment. However, such education may be a two-edged sword, with an increased nocebo effect as the most salient consequence. Failure to identify benefits in our study may have been the result of a Type 2 error. This study provides a wealth of information on a large number of issues related to knowledge, attitudes, and experiences of depressed, mostly low-income outpatients in relation to education about depression and its treatment, and future research can build on the findings of this study. We also provide an extensive discussion on directions for further research.

Celecoxib as an in vivo probe of cyclooxygenase-2 mechanisms underlying retrograde amnesia in an animal model of ECT.

BACKGROUND: Cyclooxygenase-2 (COX-2) mechanisms are involved in glutamate-mediated learning and memory as well as in glutamatergic excitotoxicity. Electroconvulsive therapy (ECT)-induced amnesia may arise from glutamatergic excitotoxicity; if so, COX-2 inhibition may attenuate retrograde amnesia with ECT. METHODS: Wistar rats which received celecoxib (15 mg/kg per day) or vehicle for 18 days were trained for 3 days on a passive avoidance task. On each of the next 3 days, rats which showed perfect learning (n=51) received true or sham suprathreshold electroconvulsive shocks (ECS; 60 mC) in a factorial design; daily dosing with drug or vehicle was continued. One day after the last ECS, recall of pre-ECS learning was tested. RESULTS: ECS-treated rats showed impaired recall in the vehicle but not celecoxib group. Celecoxib significantly protected against ECS-induced retrograde amnesia; this benefit was independent of the drug-induced attenuation of ECS seizure duration. CONCLUSIONS: Celecoxib may protect against ECS-induced retrograde amnesia by attenuating ECS-induced, COX-2-mediated glutamatergic excitotoxicity.