The efficacy of electroconvulsive therapy in major depression is established, but the importance of the electrical dosage and electrode placement in relation to efficacy and side effects is uncertain.
In a double-blind study, we randomly assigned 96 depressed patients to receive right unilateral or bilateral electroconvulsive therapy at either a low electrical dose (just above the seizure threshold) or a high dose (2.5 times the threshold). Symptoms of depression and cognitive functioning were assessed before, during, immediately after, and two months after therapy. Patients who responded to treatment were followed for one year to assess the rate of relapse.
The response rate for low-dose unilateral electroconvulsive therapy was 17 percent, as compared with 43 percent for high-dose unilateral therapy (P = 0.054), 65 percent for low-dose bilateral therapy (P = 0.001), and 63 percent for high-dose bilateral therapy (P = 0.001). Regardless of electrode placement, high dosage resulted in more rapid improvement (P < 0.05). Compared with the low-dose unilateral group, the high-dose unilateral group took 83 percent longer (P < 0.001) to recover orientation after seizure induction, whereas the combined bilateral groups took 252 percent longer (P < 0.001). During the week after treatment, there was three times more retrograde amnesia about personal information with bilateral therapy (P < 0.001). There were no differences between treatment groups in cognitive effects two months after treatment. Forty-one of the 70 patients who responded to therapy (59 percent) relapsed, and there were no differences between treatment groups.
Increasing the electrical dosage increases the efficacy of right unilateral electroconvulsive therapy, although not to the level of bilateral therapy. High electrical dosage is associated with a more rapid response, and unilateral treatment is associated with less severe cognitive side effects after treatment.
"Although alternative therapies have been developed during recent years, such as vagus nerve stimulation, repetitive transcranial magnetic stimulation, and deep brain stimulation, the use of ECT has not yet been superseded.3 Encouragingly, more and more methods have been explored to alleviate ECT-induced memory deficits and to improve the final cognitive outcomes of psychiatric patients after ECT, including ECT parameter setting, electrode placement, and drug assistance.4,5 Anesthesia is required for modern ECT (modified ECT [MECT]) to enhance its safety by preventing its complications, such as fracture, asphyxia, and cardiovascular instability.6 "
[Show abstract][Hide abstract] ABSTRACT: Background
Although a rapid and efficient psychiatric treatment, electroconvulsive therapy (ECT) induces memory impairment. Modified ECT requires anesthesia for safety purposes. Although traditionally found to exert amnesic effects in general anesthesia, which is an inherent part of modified ECT, some anesthetics have been found to protect against ECT-induced cognitive impairment. However, the mechanisms remain unclear. We investigated the effects of propofol (2,6-diisopropylphenol) on memory in depressed rats undergoing electroconvulsive shock (ECS), the analog of ECT in animals, under anesthesia as well as its mechanisms.
Chronic unpredictable mild stresses were adopted to reproduce depression in a rodent model. Rats underwent ECS (or sham ECS) with anesthesia with propofol or normal saline. Behavior was assessed in sucrose preference, open field and Morris water maze tests. Hippocampal long-term potentiation (LTP) was measured using electrophysiological techniques. PSD-95, CREB, and p-CREB protein expression was assayed with Western blotting.
Depression induced memory damage, and downregulated LTP, PSD-95, CREB, and p-CREB; these effects were exacerbated in depressed rats by ECS; propofol did not reverse the depression-induced changes, but when administered in modified ECS, propofol improved memory and reversed the downregulation of LTP and the proteins.
These findings suggest that propofol prevents ECS-induced memory impairment, and modified ECS under anesthesia with propofol improves memory in depressed rats, possibly by reversing the excessive changes in hippocampal synaptic plasticity. These observations provide a novel insight into potential targets for optimizing the clinical use of ECT for psychiatric disorders.
"Electrode placement can also impact on the severity of the side-effects experienced following treatment. There is little difference between bitemporal and bifrontal electrode placement (Dunne and McLoughlin, 2012) while right unilateral electrode placement results in fewer cognitive side-effects but, unless higher stimulus doses are used, is not as effective as bitemporal ECT (Sackeim et al., 1993; Semkovska et al., 2011). Another mechanism to minimise the side-effects of ECT is to reduce the pulse width at which ECT is delivered from a brief pulse (BP) width of 0.5–1.5 ms to an ultrabrief pulse (UBP) width of 0.3 ms that is closer to the minimum pulse width required for neuronal depolarisation (0.1–0.2 ms) (Ranck, 1975). "
[Show abstract][Hide abstract] ABSTRACT: Brief pulse electroconvulsive therapy (BP ECT; pulse width 0.5-1.5 ms) is the most effective treatment available for severe depression. However, its use is associated with side-effects. The stimulus in ultrabrief pulse ECT (UBP ECT; pulse width 0.25-0.3 ms) is more physiological and has been reported to be associated with less cognitive side-effects, but its antidepressant effectiveness is not yet well established. Using electroconvulsive stimulation (ECS), the animal model of ECT, we previously reported UBP ECS to be significantly less effective than well-established BP ECS in eliciting behavioural, molecular and cellular antidepressant-related effects in naïve rats. We have now compared the effects of BP and UBP ECS in an animal model of depression related to exogenous supplementation with the stress-induced glucocorticoid hormone, corticosterone. Corticosterone administration resulted in an increase in immobility time in the forced swim test (FST) (p < 0.01) and decreases in the expression of brain-derived neurotrophic factor (BDNF) (p < 0.05) and glial fibrillary acidic protein (GFAP) (p < 0.001) in the hippocampus and frontal cortex. There was no significant difference in the duration or type of seizure induced by BP (0.5 ms) or UBP (0.3 ms) ECS. UBP ECS proved to be as effective as BP ECS at inducing a behavioural antidepressant response in the FST with a significant decrease (p < 0.001) in immobility seen following administration of ECS. Both forms of ECS also induced significant increases in BDNF protein (p < 0.01) expression in the hippocampus. BP ECS (p < 0.05) but not UBP ECS induced a significant increase in GFAP levels in the hippocampus and frontal cortex. Overall, UBP ECS effectively induced antidepressant-related behavioural and molecular responses in the corticosterone supplementation model, providing the first preclinical data on the potential role of this form of ECS to treat a depression phenotype related to elevated corticosterone.
The International Journal of Neuropsychopharmacology 03/2014; 17(09):1-10. DOI:10.1017/S1461145714000200 · 4.01 Impact Factor
"Almost all anesthetic agents have anticonvulsant properties because of their effects on the gamma-aminobutyric acid receptors and may, therefore, influence seizure variables and clinical outcome of ECT (Tan and Lee, 2009; Vaidya et al., 2012). Stimulation parameters, such as electrical dosage and electrode placement, are also known to affect response to ECT (Sackeim et al., 1993). Factors affecting the seizure threshold, such as age, sex, concomitant medication with anticonvulsive or proconvulsant properties and electrode placement, could affect both the quality and duration of seizures (Chung, 2002; Sackeim et al., 1991). "
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: To compare the effects of propofol and etomidate on the stimulus variables and efficacy of electroconvulsive therapy (ECT) in depressed inpatients. METHOD: This retrospective study included 54 inpatients (aged 18-75 years) who met the DSM-IV criteria for major depression and were treated with bilateral ECT. For the first part of the study, the primary outcome was the mean stimulus charge per ECT session. For the second part, the main outcome measure was the proportion of patients achieving full remission. RESULTS: Propofol-treated patients showed a higher mean stimulus charge (etomidate 227.58 ± 130.44, propofol 544.91 ± 237.56, p<0.001) despite the lack of a significant difference in starting threshold doses. The propofol group had a shorter mean electroencephalogram (etomidate 69.41 ± 22.50, propofol 42.95 ± 22.26, p<0.001) and motor (etomidate 46.11 ± 14.38, propofol 22.89 ± 7.13, p<0.001) seizure duration and a higher mean number of inadequate seizures (etomidate 0.12 ± 0.15, propofol 0.47 ± 0.26), p<0.001). No significant differences were found between the groups for the effects of the anesthetics on the efficacy of ECT. LIMITATIONS: Our study is limited by a retrospective design and the small number of patients treated with propofol restricted the sample size. CONCLUSIONS: Anesthesia with propofol has a significant reducing effect on seizure duration during the course of ECT which results in more inadequate seizures, despite the use of a higher mean stimulus charge. Regarding the possible effect of the anesthetics on ECT, randomized clinical trials with sufficient power to detect differences is warranted.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 06/2013; 45. DOI:10.1016/j.pnpbp.2013.06.003 · 3.69 Impact Factor
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