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A high percentage of patients who receive electroconvulsive therapy (ECT) have late-life depression (1). Among US community hospital inpatients diagnosed with recurrent major depression, persons aged 65 years or older were 7 times more likely to receive ECT than were persons aged 18 to 34 years (2). Several factors contribute to the higher rate of ECT use in elderly depression patients. Compared with younger patients, older patients are more sensitive to the adverse effects of psychotropic medications and, therefore, may be less able to tolerate a therapeutic trial of antidepressant medication (3). Further, the elderly are more likely to have comorbid medical or neurological conditions that may complicate the use of antidepressant medication or compromise response to pharmacologic treatment (3). The elderly are also more vulnerable than are younger persons to the physical and functional complications of severe depression, such as dehydration, malnutrition, and the effects of sustained inactivity. As a result, they are more likely to be referred for ECT, which may result in more rapid clinical improvement than that achieved with pharmacotherapy (4,5). Finally, psychotic and melancholic features of major depression are more prevalent in later life (6). These features predict response to ECT (7,8). Indeed, many psychiatrists consider ECT to be the treatment of choice for psychotic depression (9). This article reviews the use of ECT in older depression patients. It focuses on recent research findings pertaining to efficacy, tolerability, and safety and also addresses the issue of post-ECT relapse of depression. Efficacy of ECT in the ElderlySeveral studies have found a positive association between advancing age and response to ECT (10–12). O’Connor and others (11) reported the results of a study of 253 patients aged 18 to 85 years who had major depression and were treated with bitemporal ECT administered at a stimulus intensity 1.5 times the patient’s seizure threshold. Among patients who completed the course of ECT, the rate of remission was 90% for those aged 65 years or older, compared with 90% for those aged 46 to 64 years and 70% for those aged 18 to 45 years. Tew and others reported rates of response among 241 patients with unipolar major depression who completed at least 5 treatments of unilateral or bilateral ECT administered at a stimulus intensity 2.5 times seizure threshold (12). Patients aged under 60 years experienced a significantly lower rate of response than did patients aged 60 to 74 years (54% vs 73%, respectively), while patients aged 75 years or over had an intermediate rate of response (67%). In both these studies, the average number of ECT treatments did not differ as a function of age. Younger patients in the Tew and others study had a lengthier depressive episode and were more likely to have pharmacotherapy-resistant depression before starting ECT—2 factors associated with diminished response to ECT. Further, older patients were significantly more likely to have melancholic features, which, as previously noted, are a positive predictor of response to ECT. These clinical differences may well have contributed to the higher response rate in older patients. This is despite the fact that older age was associated with a higher burden of physical illness and greater cognitive impairment at baseline. O’Connor and others found that the higher rate of response among patients aged over 45 years was partly attributable to the greater prevalence of psychotic depression in later life (11). Thus, the superior response to ECT among older patients may not be due to aging per se but to clinical factors that differentiate them from younger patients. Optimizing ECT EfficacyElectrode PositionWith respect to the goal of maximizing efficacy, yet minimizing cognitive side effects, controversy continues about the use of unilateral vs bilateral electrode position. Right unilateral (RUL) ECT is thought to cause less cognitive impairment than bitemporal ECT, but bitemporal ECT is viewed by some as being more effective than unilateral ECT (13). Central to this controversy is the relation between electrode position and electrical dose relative to a patient’s seizure threshold (seizure threshold is the minimum electrical intensity required to induce an adequate generalized grand mal seizure). Based on the results of randomized controlled trials (RCTs) comparing real ECT with sham ECT (that is, the repeated administration of anesthesia alone), it is well established that a generalized tonic-clonic seizure is necessary for ECT to exert its antidepressant effect (1). However, several studies have demonstrated that, while eliciting a generalized seizure is sufficient for the efficacy of bilateral ECT, this is not the case for RUL treatment (14–17). In a landmark study, Sackeim and others (14) found that RUL ECT administered at either low-dose (that is, just above the determined seizure threshold) or moderate-dose (that is, 2.5 times seizure threshold) was significantly less effective than either of these doses of bitemporal ECT. Response rates for low-dose and moderate-dose RUL ECT were 17% and 43%, respectively, compared with 65% and 63% for low-dose and moderate-dose bilateral treatment. These findings prompted Sackeim and his colleagues to undertake another RCT comparing moderate-dose bitemporal treatment with 3 doses of RUL treatment as follows: 1.5, 2.5, and 6 times seizure threshold (15). Consistent with their previous study, the lower doses of RUL ECT were considerably less effective than bilateral treatment. Conversely, the high-dose RUL treatment had efficacy comparable with moderate-dose bilateral treatment, with response rates of 65% in each group. The moderate-dose bilateral and high-dose RUL groups were also equivalent in number of treatments required for response. Patients treated with moderate-dose bilateral ECT, however, had greater memory impairment at 1 week and 2 months after finishing ECT. These results led the authors to conclude that "right unilateral ECT at high dose is as efficacious as a robust form of bilateral ECT but produces less severe and persistent cognitive effects" (15). There are, however, several caveats to Sackeim and others’ findings (15). Even though all patients had major depression, they were well enough to complete a battery of neuropsychological tests before starting ECT. Many elderly patients undergoing ECT have illness too severe for such testing, and thus it is unclear whether these results generalize to the most severely ill patients. Second, bilateral ECT was administered at a stimulus intensity 2.5 times seizure threshold. Prior research demonstrated that the antidepressant effect of bitemporal ECT is not sensitive to the dose of energy above seizure threshold, but cognitive side effects are (14). Thus, it is possible that a lower dose of bitemporal ECT (that is, 1.5 times seizure threshold) would have resulted in less severe and persistent cognitive impairment. Third, most patients who did not respond to a minimum 8 to 10 treatments of high-dose unilateral ECT eventually responded to bitemporal ECT. This raises the possibility that some patients preferentially respond to bitemporal ECT, regardless of the dose of unilateral treatment. Finally, Sackeim and others’ study (15) used a customized ECT device that could deliver an electrical dose well above the maximum of standard ECT devices (federal regulations limit the maximum output of ECT devices sold in North America to 576 millicoulombs). Of the 20 patients in the high-dose RUL group, 14 were initially treated at the maximum energy deliverable by a standard ECT device, and 2 patients required higher-than-conventional energy levels during the course of ECT. The mean age of patients in the high-dose RUL group was 54 years (SD 17). It has been consistently demonstrated that seizure threshold increases with advancing age, with some studies showing a greater increase in elderly men than in elderly women (for a review of studies see Boylan and others [18]). Further, seizure threshold may be higher in older patients with dementia (19). Sackeim and colleagues’ findings therefore raise the possibility that, in North America, it may not be possible to treat a substantial minority of elderly patients with RUL ECT at a stimulus intensity 6 times seizure threshold. To date, debate concerning the use of unilateral vs bilateral ECT has focused on the use of bitemporal electrode placement. Bifrontal ECT, wherein electrodes are placed 5 cm above the outer angle of the orbit on a line parallel to the sagittal plane, has been investigated as an alternative to bitemporal ECT in 2 double-blind RCTs (16,21). In a study that used threshold-level (that is, low-dose) electrical stimulus to compare bifrontal, bitemporal, and RUL electrode placement, both bilateral positions had superior efficacy to unilateral treatment (16); however, there was no significant difference between the bilateral placements in cognitive side effects 7 days or 3 months after ECT (20). Bailine and others compared bifrontal ECT with bitemporal ECT given at an electrical dose 1.5 times seizure threshold (21). Both electrode positions had similar efficacy in terms of the proportion of patients responding and the number of treatments required to attain response. After the last treatment, however, bifrontal ECT was associated with slightly less cognitive impairment than was bitemporal ECT. Further investigation of bifrontal ECT is required to determine how its efficacy and cognitive side effects compare with high-dose RUL treatment.
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