Journal of ECT:
Is Electroconvulsive Therapy (ECT) Effective and Safe for Treatment of Depression in Dementia?: A Short Review
Oudman, Erik Msc
From the Rijnmond Care Group, Location Nursing Home Slingedael, Centre for Korsakoff and Psychogeriatry, Rotterdam, The Netherlands.
Received for publication December 12, 2010; accepted July 19, 2011.
Reprints: Erik Oudman, Msc, Rijnmond Care Group, Location Nursing Home Slingedael, Centre for Korsakoff and Psychogeriatry, Krabbendijkestraat 495, 3084 LP Rotterdam, The Netherlands (e-mail: email@example.com).
The author declares that no conflict of interest exists. The author also declares no existence of financial interests that might have an impact on the views expressed in the article.
Abstract: Depression is one of the most frequently diagnosed psychiatric disorders in patients with dementia with a prevalence of up to 50%. The detrimental effects of depression in dementia include disability in daily living, worse quality of life, and faster cognitive decline. Although electroconvulsive therapy (ECT) is a well-established and effective treatment for depression in the elderly, it is currently an overlooked treatment option in the elderly with dementia and depression. The aim of this review was to provide a critical analysis of the efficacy and safety of ECT in depression superimposed on dementia by reviewing the current literature on this topic. Current evidence suggests that ECT is an effective treatment for depression in dementia, although the relatively small number of controlled studies hampers the comparison of effectiveness between healthy nongeriatric patients and those with dementia. Moreover, the systematic reports on cognitive side effects are very limited in number and currently only apply to moderately mild or mild dementia of nonvascular origin. Some studies do suggest that cognitive side effects are likely in later stages of dementia and in patients with vascular dementia. It is therefore of crucial relevance to prospectively study effects of ECT in different types and phases of dementia in controlled trials. From a clinical perspective, it is essential to inform and educate patients and family about the possible risks and benefits of ECT treatment for depression in dementia.
Depression is one of the most frequently diagnosed psychiatric disorders of Alzheimer disease and other types of dementia.1 The prevalence of major and minor depression has been estimated to range between 30% and 50%; however, many cases are undiagnosed because symptoms of depression overlap dementia,2 and dementia patients themselves underestimate depressive symptoms.3,4 The implications of depression in dementia are detrimental: Depression in dementia has been associated with greater disability of daily living, a worse quality of life, a faster cognitive decline, higher rates of nursing home placements, and relatively higher mortality rates compared to nondepressed individuals with dementia.5,6 In treatment, most often, selective serotonergic reuptake inhibitors are described because of their known significant efficacy over placebo.7 However, selective serotonergic reuptake inhibitors sometimes have adverse effects such as agitation, anxiety, and sleep problems; and the depression is frequently refractory.8 Although electroconvulsive therapy (ECT) has been speculated as a possible treatment of depression in dementia, it is often an overlooked treatment option.9 This is strange because ECT is a well-established, highly effective treatment option for depression in the elderly,10 with a higher immediate efficacy than antidepressant medication.11 However, the hesitation to perform ECT on patients with dementia could possibly relate to cognitive side effects of ECT treatment in patients with dementia.12 In healthy nongeriatric patients, ECT sometimes results in transient cognitive side effects, such as reduced concentration, sustained disorientation, and retrograde memory loss.13,14 However, the effects in dementia possibly vary. As a result, there is currently a reluctance of treating elderly depressed patients with pre-existing dementia.15 The aim of the present review was therefore to provide a critical analysis of the efficacy and safety of ECT in depression superimposed on dementia by reviewing the current literature on this topic.
MATERIALS AND METHODS
Clinical trials describing the use of ECT in the treatment of depression in dementia were identified in MEDLINE and Scopus. A search was performed up to April 15, 2011, and used the following terms: “ECT,” “electroconvulsive therapy,” in combination with “depression,” “dementia,” and “depression and dementia.” Only references with abstracts and original articles were considered. There was no search for unpublished works.
Currently, most of what is known on ECT as a treatment option for depression in dementia is the result of case studies. An early review on case studies was published by Price and McAllister.12 This study accumulated and summarizes findings of 50 case reports on the treatment of ECT during depression in all different types of dementia. The authors suggest that ECT is a rather successful way of treating depression during Alzheimer disease and vascular dementia, with minor evidence of risk on transient cognitive side effects. On Alzheimer, 11 case studies, most of them published in the 1980s, were incorporated. The total group analyzed for this review consisted of 19 patients who received a mean of 8.3 ECT sessions to treat depression in dementia with various electrode placements.10,16–25
Thirteen of the 19 patients exhibited improvements in depressive symptoms after ECT. Nine of them experienced either significant or full remission. In 6 cases, there was worsening of cognition in general, orientation, or memory after ECT.10,16,21,25 The changes abated over 10 to 65 days in 5 of the 6 patients and persisted in one patient who died after 3 months. In their report on vascular dementia, the authors describe 5 case studies in prior literature reported on patients with multi-infarct dementia receiving ECT.12,16,26,27 The case studies were published in the course of 1948–1988 and represented 6 patients with probable or definite multi-infarct dementia. The patients received a mean of 7.6 ECTs, and all improved significantly with ECT. However, 3 of the 6 patients experienced significant cognitive or memory improvement as a result of treatment with ECT.16,27 One had cognitive side effects, which were transient and cleared completely after ECT. In this review, specifically the early studies describe cognitive problems as the result of ECT during dementia of vascular origin. Moreover, also the studies in which bilateral ECT was applied resulted in more cognitive side effects.
However, not only early studies suggest a relative increased risk for development of additional cognitive problems after ECT in patients with dementia of vascular origin. Blackburn and Decalmer28 describe the case of a 70-year-old patient who had multiple strokes who was given ECT after an unsuccessful treatment with antidepressants. He developed an acute episode of delirium after bilateral ECT, but recovered fully from delirium and experienced amelioration for his depressive symptoms. Four years later, the patient relapsed and received additional ECT. Shortly after, he developed a multi-infarct brain with widespread atherosclerosis. The authors suggest that ECT might cause permanent impairment of cognitive functioning through ischemia of an already compromised cerebral circulation.
Although the resulting multi-infarct brain is possibly caused by underlying progressive illness, the suggestion of Blackburn and Decalmer28 has been partially supported by a case study by Currier et al,29 which prospectively studied the effects of ECT on poststroke depression. In their sample of 20 stroke patients, 3 patients experienced post-ECT transient development of amnesia. However, all 3 cases already developed milder forms of amnesia as the result of the strokes, suggesting that ECT can possibly relate to worsening of memory in case of reduced memory functioning after cerebrovascular accidents.
Årsland and Odberg30 describe the case of a 67-year-old woman who showed gradual decline, possibly caused by Alzheimer disease, in cognitive functioning over a course of 6 years. Although she was prescribed a daily dose of 20 mg of paroxetine and 2 mg of haloperidol, her depression increased rapidly. She was rated with the Cornell Scale for Depression in Dementia with a score of 22 out of 38 points, which represents a severe depression. A course of 4 unilateral ECT sessions was administered. After this, she recovered from her depression and scored 6 of the 38 points on the Cornell scale. Her appetite improved, she slept better, and enjoyed contact with the staff and family. Although cognition or cognitive improvements were not of primary interest for this study, the case study suggests that ECT is a feasible and safe treatment option.
Moreover, Bright-Long and Fink31 report on amelioration of cognition after treating depression in dementia. The authors report on the rip Van Winkle syndrome/pseudodementia, which appears as a classical Alzheimer dementia but is treatable with ECT. In their case report, the authors describe a 58-year-old woman whose condition had been diagnosed as Alzheimer for 9 years before antidepressants and unilateral ECT (various placements) completely resolved the cognitive symptoms. These authors suggest that ECT and antidepressant medication regimes should be started as long as the etiology of the dementia is not certain to rule out possible cases of treatable pseudodementia.
Weintraub and Lippmann32 describe 2 case reports of patients with moderate to severe dementia with bipolar mania and depression. Both patients were successfully treated without any cognitive side effects. Also, McDonald and Thompson33 explain the effects of ECT during mania in dementia. All 3 case reports experienced significant improvement in signs of mania. However, both Weintraub and Lippmann32 and McDonald and Thompson33 were not primarily interested in cognitive functioning.
Kung and O’Connor34 portray the case of a 60-year-old woman with Lewy Body dementia who experienced depressive and neuropsychiatric symptoms and was treated with sertraline and citalopram without significant improvement. She received a course of 7 unilateral ECT sessions with an episode of autonomic instability after her first ECT session but tolerated the remaining ECT sessions without incident. Her mood and neuropsychiatric symptoms improved for 2 weeks after ECT, but the benefits were not sustained.
A more recent prospective case study of 7 cases by Rasmussen et al35 describes how 7 patients with Lewy Body dementia received ECT treatment. All 7 cases experienced improvement in depression, and 2 of them had a successful decline in hallucinations. In this study, cognitive status did not adversely affect beyond the acute ECT period, but this topic was not the main focus of the article either. Various electrode placements were used: right unilateral, bitemporal, and bifrontal. A recent case report on a 69-year-old patient with frontotemporal degeneration with Cotard delusions describes how bilateral electroconvulsive therapy was beneficial for his mood, cognition, and anxiety symptoms. Depression eventually remitted in this case example.36
Currently, only 5 studies have prospectively studied the effects of ECT treatment on depression in dementia. The first preliminary prospective study was conducted by Nelson and Rosenberg.37 This study enrolled 21 not-further-specified patients with dementia with depression and a control group of 84 patients without dementia with depression during a course of 4 years. The mean number of ECT sessions was 9.1 for the group of patients with dementia and 8.9 for the group without dementia. Electrode placement was nondominant unilateral. If clinical progress was not evident, bilateral electrode placements were used after 5 to 7 treatments (unclear in which instances). Both groups had an average improvement on depressive symptoms and had a comparable amount of cardiac side effects. Confusion was assessed with a simple standardized scale consisting of 4 categories: no confusion, mild confusion (<24 hours), moderate confusion (1–2 days), and marked confusion (>2 days). Post-ECT confusion scores correlated with the degree of dementia (ρ = 0.53, P < 0.01), and women experienced more confusion than men. A relative weakness of this original study was the measurement of depression and confusion, which was not prospectively studied from the start of the admission but graded after ECT according to a self-developed rating scale.
In 1991, Mulsant et al38 performed a study to investigate the cognitive effects of ECT on 40 participants with late-life depression. Nineteen participants experienced cognitive impairments (most of the cases with dementia) on admission. In total, confusion was noted during 13 courses (31%) and persisted in 4 (10%) at discharge. Both unilateral and bilateral treatments were performed. The mean number of ECT sessions was 8.3 treatments. However, from the original data, it is unclear whether the patients with dementia were more vulnerable for confusion than those without dementia. For the group total, a nonsignificant increase in Mini-Mental State Examination (MMSE) scores of 1.1 was found.
An influential prospective report by Rao and Lyketsos39 adapted standardized measures of depression and confusion. In their study, a patient group of 31 patients with a discharge diagnosis of “dementia with depression” were treated with ECT. Admission and discharge ratings were made on the MMSE and the Montgomery-Åsberg Depression Rating Scale as a part of clinical routine. Fifty-five percent of this group had vascular dementia, 13% had Alzheimer disease, and 32% had uncertain or mixed etiology. Both unipolar and bipolar depressed patients were included in the sample. During admission, the mean MMSE score was 18.8 (range, 3–28). All patients received between 1 and 23 ECTs, with a mean of 9 ECTs. Twenty-two patients received unilateral ECT and 9 patients received bilateral ECT. At discharge, there was a statistically significant mean decline on the Montgomery-Åsberg Depression Rating Scale of 12.28 points. Moreover, there was a significant increase in MMSE of 1.62 points. Importantly, 15 of the 31 patients developed delirium at some time during the course of ECT. In all, the duration of the delirium was short (1–3 days). One patient developed atrial fibrillation 2 days after stopping ECT; another patient developed an episode of ventricular tachycardia. A third patient had prolonged seizures of 2.5 minutes, and a fourth patient had a transient ischemic attack after ECT treatment. It is unclear whether patients were more vulnerable to develop adverse effects after bilateral ECT.
Stoudemire et al40 sought to ascertain the affective and cognitive outcome after tricyclic and electroconvulsive treatment of elderly medical-psychiatric patients meeting diagnostic criteria for major depression, some of whom had normal cognitive functioning and some of whom were cognitively impaired before treatment. Thirty participants received ECT, of which 19 had impaired cognitive functioning on admission measured with the Mattis Dementia Rating Scale (MDRS). Subjects with cerebrovascular changes such as stroke or multi-infarct dementia were excluded from the study. Electroconvulsive therapy was given 3 times a week, with unilateral electrode placements over the nondominant hemisphere. The mean number of treatments per patient was 9.6. The mean length of stay was 26 days. Post-ECT MDRS scores were significantly improved for the group with impaired cognitive functioning (on average, 14.8%). However, the authors argue that 4 of the patients in the ECT group were observed to have a complete reversal of pretreatment cognitive dysfunction, with a return to normal levels, indicating that their initial cognitive dysfunction was most likely related to the presence of major depression. Furthermore, the authors argue that in retrospect, this subgroup represented patients who have traditionally been referred to as having the “pseudodementia” syndrome. The other 15 patients did not experience improvements or deterioration in dementia after ECT.
A recent prospective study was conducted by Hausner et al.15 In the course of 4 years (April 2004 to April 2008), 44 elderly inpatients with major depressive disorder were included. Thirteen subjects were cognitively intact (MMSE, 27.6 ± 1.9), 12 subjects with dementia had pre-existing Alzheimer disease with or without vascular contribution (MMSE, 22.7 ± 4.4), and 19 subjects had mild cognitive impairment (MCI; MMSE, 23.6 ± 6.3). Subjects with major cerebrovascular changes or non-Alzheimer dementia were excluded from this study. The 3 groups did not differ in their initial depressive symptoms (HAM-D). After the sixth ECT session, subjects with dementia most frequently showed a decline in cognitive functioning (70%), whereas 66.7% of those with MCI and 46.2% of those without dementia showed a decline in cognitive functioning. Six months after the last ECT session, 33.3% of the subjects with dementia, 20.0% of those with MCI, and 12.5% of those without dementia showed a decline in cognitive functioning compared to baseline. Pre-ECT cognitive deficits were the best predictor of MMSE score decline from baseline at the follow-up time point 6 weeks after the last ECT treatment (P = 0.007). However, after 6 months, there was only a trend to statistical significance (P = 0.055). Moreover, the mean cognitive scores (MMSE) were 3.3 points higher (not significant) 6 months after the last ECT session than at admission.
Electroconvulsive therapy is an effective and safe treatment of depression, specifically for elderly patients.10 In healthy nongeriatric patients, ECT occasionally results in reversible cognitive side effects such as reduced concentration, sustained disorientation, and retrograde memory loss13,14; but the effects in dementia are currently greatly unknown.15 The aim of the present review was to provide a critical analysis of the efficacy and safety of ECT in depression superimposed on dementia by reviewing the current literature on this topic. Although literature is scarce on both the efficacy and cognitive safety of ECT treatment for depression in dementia, there is a general tendency to report positive effects of ECT on depressive symptoms in dementia. Because the number and extent of the studies included in this review is very limited, it is unclear if the effectiveness is comparable between patients with dementia and healthy nongeriatric elderly. Moreover, the reports on cognitive side effects are limited and show variable outcomes, either positive or negative. Factors contributing to this variability include the very low number of studies that ascertain this topic, the lack of discrimination between unilateral and bilateral ECT treatments, the relatively small sample sizes, the use of general tests for cognitive functioning (MMSE or MDRS) instead of specific neuropsychological tests and the lack of discrimination between types of dementia. On a group level, the prospective studies included in this review suggest no change up to small amelioration in general cognitive functioning after ECT in individuals with depression and dementia (Table 1). However, the results in all prospective studies so far have a lack of statistical power; these merely did not include patients with vascular dementia or stroke and investigated patients with moderately mild or mild dementia. Most of what has been prospectively studied and published on the performance of ECT in dementia applies to patients with either mild dementia (MMSE >21 points) or moderately mild dementia (MMSE, 15–20; Table 1). This is of great relevance to all published results because Nelson and Rosenberg37 concluded that post-ECT confusion scores correlated with the degree of dementia (ρ = 0.53, P < 0.01), and Hausner et al15 found that the extent of pre-ECT cognitive deficits was the best predictor of MMSE score decline from baseline to follow-up 6 weeks after the last ECT treatment (P = 0.007). This suggests that moderate to severe dementia might result in more adverse effects after ECT than in individuals without dementia. From a clinical perspective, cognitive testing and monitoring are recommended before, during, and after ECT in patients with dementia with depression. It is essential to inform both the family and the patients about possible risks and benefits of the treatment. From an experimental perspective, it is of primary interest to prospectively study the effects of ECT on cognition in depression superimposed on dementia in well-designed controlled trials both with homogenous groups of patients.
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Alzheimer disease; vascular dementia; dementia; depression; electroconvulsive therapy; ECT
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