- Email: [email protected]
Efficacy and Safety of ECT for Behavioral and Psychological Symptoms of Dementia (BPSD): A Retrospective Chart Review
ARTICLE IN PRESS Am J of Geriatric Psychiatry &&:&& (2019) &&−&&
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.ajgponline.org
Regular Research Article
Efficacy and Safety of ECT for Behavioral and Psychological Symptoms of Dementia (BPSD): A Retrospective Chart Review Adriana P. Hermida, M.D., Yi-lang Tang, M.D., Ph.D., Oliver Glass, M.D., A. Umair Janjua, M.D., William M. McDonald, M.D. ARTICLE INFO
ABSTRACT
Article history: Received August, 14 2019 Revised September, 21 2019 Accepted September, 23 2019
Objective: Much of the functional disturbance in patients with dementia reflects the presence of noncognitive behavioral and psychological symptoms of dementia (BPSD). Agitation is among the most distressing symptoms for patients, clinicians, and caregivers. Currently no pharmacotherapy has clearly been shown to be of value for this condition. This study used a chart review method to examine the safety and efficacy of electroconvulsive therapy (ECT) for patients with dementia receiving ECT for agitation. Methods: A retrospective chart review was conducted of patients with dementia presenting with symptoms of aggression or agitation and who received ECT treatments. Aggression and agitation were measured by pre- and post-ECT Pittsburg Agitation Scale (PAS) scores. Detailed history of the use of psychotropic medications as well as other clinically relevant variables was analyzed. Findings: Sixty elderly patients (45 women and 15 men, 75% female, mean age 77.5 § 8.0 years) were included in the analysis. Most patients were treatment resistant to multiple psychotropic medications prior to ECT (mean number 6.1§1.5). The baseline PAS total was 9.3 § 3.7 and it decreased significantly after three (2.5§2.8) and six (1.5§2.3) ECT treatments. No significant ECTrelated medical complications were observed except transient confusion. A decrease in the number of psychotropics prescribed along with an increase in the GAF score was observed after the ECT treatment course. Conclusion: ECT was safe in this sample of patients who had co-morbid medical conditions. ECT was associated with the following observations: 1) a reduction in agitation; 2) a reduction in psychotropic polypharmacy; and 3) an improvement in global functioning level. Further research evaluating the effects of ECT in the setting of dementia is warranted. (Am J Geriatr Psychiatry 2019; &&:&&−&&)
Key Words: ECT electroconvulsive therapy dementia BPSD agitation Alzheimer’s disease
From the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA. Send correspondence and reprint requests to Adriana P. Hermida, M.D., Division of Geriatric Psychiatry, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 12 Executive Park Drive NE, Atlanta, GA 30329. e-mail: [email protected] © 2019 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jagp.2019.09.008
Am J Geriatr Psychiatry &&:&&, && 2019
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ARTICLE IN PRESS Efficacy and Safety of ECT for Behavioral and Psychological Symptoms of Dementia
INTRODUCTION
B
ehavioral and psychological symptoms of dementia (BPSD), which include agitation, aggression, anxiety, and psychosis, are a common consequence of dementia.1 Reports show that BPSD is nearly universal in patients with dementia, where it is correlated with the advanced stage of the illness.2−4 Agitation is among the most distressing symptom of dementia, which not only affects patients but also clinicians and caregivers. BPSD is of clinical significance as it is often strongly associated with functional impairment. Therefore, in addition to treating the cognitive impairments, targeting BPSD should be considered a priority by mental health providers.5 Nonpharmacological interventions should be first line when treating BPSD6 although many barriers exist in clinical settings to implement such interventions.7 Pharmacological interventions are often required, yet there are no medications approved by US Food and Drug Administration (FDA) for BPSD due to modest efficacy and tolerability concerns. Further, polypharmacy becomes more common with increasing severity of clinical symptoms. Commonly used medications that are prescribed off-label for BPSD include antipsychotics, antidepressants, mood stabilizers, and cholinesterase inhibitors. Though commonly used, antipsychotics are only modestly effective and are associated with significant side effects, including a FDA boxed warning for increased mortality.8,9 Providers who decide to prescribe antipsychotic medications should evaluate each case thoroughly and carefully, weighing the risk of side effects, and black box warning10 Although antidepressants may have a better risk to benefit ratio, sufficiently powered trials evaluating their safety and efficacy in dementia are still lacking but continue to be an area of research.11 The evidence regarding mood stabilizers is mixed, where only carbamazepine has been reported to be effective in a few studies and a metaanalysis.12 The use of mood stabilizers is limited in the clinical setting due to often lengthy side effect profiles, drug-drug interactions, and the need for therapeutic drug monitoring. Cumbo et al. (2014)13 reported that for patients with mild to moderate dementia, memantine, and rivastigmine may be effective in the improvement of BPSD, without major side effects, but the findings need to be replicated in larger samples. A randomized clinical trial by
2
Cummings et al. (2015)14 evaluated the effects of dextromethorphan-quinidine on 194 patients with probable Alzheimer disease. The results of the study showed that this novel treatment modality was efficacious for agitation and was generally well tolerated. ECT has been used worldwide for severe and treatment-resistant psychiatric disorders in elderly patients. Research studies have shown that ECT is the most effective and rapid treatment available for elderly patients with depression, bipolar disorder, and psychosis.15 The efficacy of ECT in late life major depressive disorder with or without psychotic features has been well-documented.16,17 In addition, it has also been shown to be effective in treating acute mania,18 including mania in patients with dementia,19 and psychotic disorders.20,21 Increasing evidence shows that ECT is relatively safe when used among the elderly even though they may be more vulnerable to cognitive side effects and may present with more medical comorbidities.22−24 The use of ECT for agitation and aggression in patients with dementia started in the early 1990s.25 In the past two decades, growing interest in the use of ECT in patients with dementia has led to several key reports and case series about its role in the management of agitation in elderly dementia patients.26−32 Common target symptoms described in the studies include yelling, screaming, and aggression. A chart review (N = 16) by Ujkaj et al. (2012)33 utilized the Pittsburgh Agitation Scale (PAS) as the primary measure. The authors reported a significant reduction in the total PAS scores from baseline after ECT (from 11.0 § 5.0 to 3.9 § 4.3). Most of the ECT treatments were bilateral, with an average of nine sessions. Per the data provided Ujkaj et al., only one patient did not show improvement. Acharya et al. (2014),34 conducted a prospective study which included 23 patients from two psychiatric hospitals in Massachusetts and Michigan. All of the patients were diagnosed with dementia and were referred for ECT to treat agitation and/or aggression. The authors found a significant decrease from baseline to discharge on the Cohen Mansfield Agitation Inventory CMAI-SF (F(4,8) = 13.3; p = 0.006) and Neuropsychiatric Inventory NPI-NH (F(4,31) = 14.6; p < 0.001). The authors reported that ECT is generally well tolerated in patients with BPSD, with only five patients discontinuing ECT. In the Acharya study (2014), ECT was
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ARTICLE IN PRESS Hermida et al. discontinued for two participants because of poor treatment response. One participant died the day before he was to be discharged to a nursing home with palliative care. The authors reported that the patient’s death, which occurred approximately 1 month after his final ECT session, was related to end-stage dementia and was unrelated to ECT. ECT was discontinued for two participants because of delirium that was thought to be secondary, in part, to treatment with diphenhydramine and a urinary tract infection, respectively. Emory University’s ECT center, located at Emory University’s Wesley Woods Geriatric Hospital (WWGH), treats patients with various psychiatric diagnoses, including patients with dementia who exhibit moderate to severe behavioral and psychological disturbances. Patients often come from another psychiatric facility or a nursing home setting. This manuscript reports efficacy and safety data from a retrospective case series of individuals receiving ECT to treat agitation in dementia (Fig. 1).
METHODS Clinical Setting Sixty patients were identified with agitation in the setting of dementia who received ECT at Emory University’s Wesley Woods Geriatric Hospital (WWGH) between January 1, 2012 and February 28, 2014. A retrospective chart review was conducted of those patients. Agitation was measured by pre- and postECT Pittsburg Agitation Scale (PAS) scores. A detailed history of the use of psychotropic medications as well as other clinically relevant variables were analyzed. Sample The log book at the Wesley Woods ECT Center was used to screen potential patients. All diagnoses were made by board-certified geriatric psychiatrists. All cases included in the final analysis have been reviewed for eligibility and which was agreed on by at least two
FIGURE 1. Changes from baseline in number of psychotropic medications and PAS scores.
Changes in the number of psychotropic medications, PAS total score, and subscores at baseline and after ECT treatment in dementia with agitation.
Am J Geriatr Psychiatry &&:&&, && 2019
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ARTICLE IN PRESS Efficacy and Safety of ECT for Behavioral and Psychological Symptoms of Dementia authors. Author APH, a board-certified geriatric psychiatrist reviewed all the included cases. Sixty patients were selected based the following criteria: 1) on admission, the primary psychiatric diagnosis included dementia (any type); 2) the presenting symptoms on admission included behavioral disturbance or agitation associated with dementia; 3) availability of PAS scores (4 were missing the PAS score but met the first two criteria, and were therefore included). Assessments (1) PAS: PAS has been widely used in geriatric psychiatric wards or nursing homes and it is based on direct observations of the patients. It assesses four general behavioral groups: Aberrant vocalization, motor agitation, aggressiveness, and resisting care. The PAS was performed by nurses as a part of clinical assessment. (2) The Global Assessment of Functioning (GAF): GAF is a numeric scale (0 through 100) used to rate subjectively the social, occupational, and psychological functioning of adults. (3) Psychiatric consult notes, discharge summary, and progress notes: These notes usually included current medications and co-morbid medical diagnoses, which were included in the analysis. ECT Procedures All patients were treated with a MECTA spectrum 5000 ECT machine. The anesthetic agent was methohexital at 0.75−1 mg per kg. The muscle relaxant was succinylcholine at a dose of 0.75−1.5 mg per kg. The seizure threshold was determined at the first treatment using a titration method with an algorithm of stimulations. All the subjects received right unilateral (RUL) lead placement with ultrabrief (UB) pulse width (0.37 msec). The Emory protocol was followed, which recommends treating at 6 times initial seizure threshold (IST), with an increase to 8 X IST if no response after the fifth or sixth treatment and 10 X IST if there is no response thereafter with 10 X IST being the maximal dose increment. Patients who were treated with bilateral lead placement were provided with brief pulse width treatments at 1.5 X IST. All patients were continued on their psychotropic medications, but an attempt was made to reduce benzodiazepines to the minimal tolerated dose. Patients
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who remained on a benzodiazepine were provided flumazenil prior to treatment. In addition, lithium, and other anticonvulsants were held the night before ECT treatment to ensure adequate seizures. Statistical Analysis Statistical Package for the Social Sciences, version 22.0 (Windows) was used in all analyses. All data was retrieved and entered in a SPSS file. Analysis of Variance for repeated measures was used to analyze the PAS total and subscale scores, GAF, and number of psychotropic trials, pre- and post-ECT.
RESULTS Basic Data of the Patients Sixty patients (45 women and 15 men, mean age = 77.5 § 8.0 years) were included in the analysis. With respect to the dementia subtype classification, 28 were labeled as unspecified, 22 as Alzheimer’s type, 2 as vascular, 2 as frontotemporal dementia, and 6 as mixed. The average number of medical comorbidities was 6.0 § 2.2. Most did not respond to multiple psychotropic medications (mean number = 6.0 § 1.6) prior to the ECT referral. Table 1 shows all clinical variables, including demographics and diagnoses. Changes in PAS and GAF At discharge, all of the patients’ PAS scores decreased significantly from baseline. The baseline PAS total was 9.3§3.7 and it decreased significantly after three (2.5§2.8, p <0.001) and six (1.5§2.3, p <0.0001) ECT treatments. PAS scores in two patients (both female) increased after 3 treatments (one was 7 at baseline increased to 11, another increased from 3 to 7); however these two patients also improved after the acute course was completed. On average, the change of PAS total from baseline was 7.8 § 3.7 (median = 8). The percentage of reduction on PAS was 88.5%. Only two cases were readmitted and one received another acute course of ECT treatment within 1 year after discharge, though rehospitalization at other facilities cannot be ruled out.
Am J Geriatr Psychiatry &&:&&, && 2019
ARTICLE IN PRESS Hermida et al. TABLE 1. Basic data of Patients with Dementia Receiving ECT for Agitation Characteristics
N = 60
Sex, women, n Age (years) Race/Ethnicity EA/AA/other (N) GAF on admission Length of stay (days) Pre-ECT length of stay Total number of ECT Living situation ALF/NH/family (N) Number of medical comorbidities Diagnosis of hypertension (N) Diagnosis of CAD (N) History of heart failure (yes/total) Diagnosis of stroke (yes/total)
45 77.5 § 7.9 50/9/1 20.8 § 4.8 26.7 § 10.4 7.1 § 4.1 9.6 § 9.7 21/19/20 6.0 § 2.2 42/54 13/54 3/54 5/54
Note: AA: African-American; ALF: assisted living facility; CAD: cardiovascular disease; EA: European-American; GAF: Global assessment of functioning; NH: nursing homes. (Number in table is mean § S.D. unless labeled otherwise).
patients were provided with orally dissolving olanzapine 5 mg thirty minutes prior to the subsequent ECT session, which prevented the recurrence of PIA.35 Other than PIA, no other major ECT-related medical complications were observed. One patient developed transient delirium described in the medical chart. No objective measure was utilized. One patient’s medical condition worsened (hypotension, tachycardia, and possible pneumonia) after the second ECT treatment (8 days after psychiatric admission). She had to be transferred to the medical ER and later to the medical floor for further treatment. She was discharged directly from the medical floor without returning to the psychiatric inpatient unit.
DISCUSSION Change in the GAF: GAF score also increased significantly after ECT treatment, from 20.8 § 4.9 to 34.5 § 4.4 (p <0.0001). Changes in Other Variables The number of psychotropic medications at baseline was 6.0 § 1.6 and it was not uncommon that a patient had been on one or two antipsychotic medications, plus one antidepressant, a mood stabilizer and one benzodiazepine. At discharge, the number of psychotropic medications was 4.9 § 1.6 (p <0.001). Clinical Variables of ECT Treatments Patients received UB-RUL or brief bifrontal ECT and the number of treatments ranged from 2 to 10 (median = 6). All but three patients were started with UB-RUL treatment. Eight patients were switched to bifrontal placement due to poor response to suprathreshold ultrabrief right unilateral. Most patients were discharged after 4−6 treatments as inpatients. Seven patients (2 men and 5 women) received more than 12 treatments (maintenance therapy). All maintenance treatments were performed after discharge. No further data regarding the maintenance treatments is available. Safety and Complications Six patients developed postictal agitation (PIA) and mild confusion after their first treatment. These Am J Geriatr Psychiatry &&:&&, && 2019
Based on our review of literature, our retrospective chart review is the largest sample of dementia patients receiving ECT for agitation. We found that ECT was safe in our sample of patients who had multiple medical conditions, and it appeared to be very effective in reducing agitation and decreasing the number of psychotropic agents prescribed. The global functioning level also significantly improved after ECT treatment. For most patients, significant improvement was observed after three treatments and the median number of treatments was 6. Our analysis suggests that, ECT may be a safe and effective treatment option for patients with dementia who have refractory BPSD. Our findings are consistent with previous reports, particularly the one by Ujkai et al. (2012).33 One difference is the overall length of stay in Ujkai’s report was significantly longer (59.7 § 39.7 days) than the one in our sample (25.2 § 10.3 days). Similarly, the number of pre-ECT days in their study (23 § 15.7 days) was also significantly longer than in our report (7.3 § 4.4 days). This was primarily because some of our patients were transferred from another facility and they had been worked up and prepared for ECT. Decreasing the days of hospitalization is crucial for this population as longer hospital stays often worsen disabilities in the older population and contribute to medical complications. In contrast to the reports by Ujikai et al. (2012)33 and Acharya et al. (2014),34 most patients in our study received the ultra-brief pulse (UBP) unilateral ECT, an
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ARTICLE IN PRESS Efficacy and Safety of ECT for Behavioral and Psychological Symptoms of Dementia approach that has been found to be associated with comparable efficacy and less cognitive impairment when compared with brief-pulse RUL ECT. However most of the data available come from studies of patients with major depression.36 The prolonging remission in the depressed elderly (PRIDE) study demonstrated safety and efficacy of UB RUL in the geriatric population.37 As argued in a recent review article,7 ECT shows promise “as an emerging treatment strategy for neuropsychiatric symptoms in dementia.” However, most clinicians are hesitant to use ECT in patients with dementia, largely due to limited evidence supporting its efficacy and safety. Most published studies examining ECT in patients with dementia and agitation or other behavioral problems19,27,28,30 were either case reports or retrospective chart reviews. Another concern is that ECT might worsen the already impaired cognitive function of patients. This concern has not been supported in well-controlled studies. Some studies have shown that ECT is a safe and efficacious treatment in patients with dementia who have comorbid depression,24,38,39 but this evidence does not address the concern about the risk for cognitive worsening. A few limitations need to be acknowledged. First, this is a retrospective chart review based on a relatively small clinical sample, which comes with inherent methodological limitations such as information that is unrecoverable or unrecorded, problematic verification of information and variance in the quality of information recorded by medical professionals, lack of randomization and limitations on outcome measures. Second, some important data were not available, such as the measurements on cognitive function before and after ECT treatment. Future studies would benefit from objective measures including the Confusion Assessment Method and Severity Battery Inventory (SIB), a test to evaluate cognition where the mini-mental status examination (MMSE) is not a feasible tool due to the baseline severity of cognitive impairment. We were limited on this data considering our retrospective approach. Finally, due to the nature of the study,
the role of other factors could also have contributed to the improvement in agitation, such as medication changes, environmental modifications, and behavioral interventions. Despite these limitations, this study, along with previous reports, supports the use of ECT treatment for agitation and aggression in patients with dementia, especially for cases that failed to respond to multiple psychiatric medications. In clinical practice, ECT for agitation in the setting of dementia is not a first line treatment and there are no FDA approved medication options. Prior to ECT, treatment approaches include ruling out medical causes, implementing environmental modifications and behavioral interventions, and also attempt to treat BPSD with psychotropics. A reasonable approach would be to attempt less invasive treatment options first but to consider ECT when other options have been exhausted. As patients with dementia may lack capacity to consent to treatment, it is essential to have discussions with family and/or legally authorized representative to thoroughly address the potential risks and benefits of this modality of treatment. Standardized assessments of cognitive function, behavioral symptoms of dementia, and measures of quality of life including the Severity Impairment Battery, Cohen-Mansfield Agitation Inventory, Confusion Assessment method (CAM), and the Neuropsychiatry Inventory are warranted in future studies. Including a control group, ideally in a randomized fashion, would contribute to the field to better understand the value of ECT in the management of agitation in dementia. Furthermore, studies on continuation and maintenance ECT could also provide evidence beyond short-term efficacy and safety. Conflicts of interest: The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. Other disclosures have been submitted by the authors in the disclosure form.
References 1. Cerejeira J, Lagarto L, Mukaetova-Ladinska EB: Behavioral and psychological symptoms of dementia. Front Neurol 2012; 3:73 2. Steinberg M, Shao H, Zandi P, et al: Point and 5-year period prevalence of neuropsychiatric symptoms in dementia: the Cache County Study. Int J Geriatr Psychiatry 2008; 23:170–177
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3. Bartels SJ, Horn SD, Smout RJ, et al: Agitation and depression in frail nursing home elderly patients with dementia: treatment characteristics and service use. Am J Geriatr Psychiatry 2003; 11:231–238
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ARTICLE IN PRESS Hermida et al. 4. Lyketsos CG, Lopez O, Jones B, et al: Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study. JAMA 2002; 288:1475–1483 5. Katona C, Livingston G, Cooper C, et al: International Psychogeriatric Association consensus statement on defining and measuring treatment benefits in dementia. Int Psychogeriatr 2007; 19:345–354 6. Gauthier S, Cummings J, Ballard C, et al: Management of behavioral problems in Alzheimer’s disease. Int Psychogeriatr 2010; 22:346–372 7. McClam TD, Marano CM, Rosenberg PB, et al: Interventions for neuropsychiatric symptoms in neurocognitive impairment due to Alzheimer’s disease: a review of the literature. Harv Rev Psychiatry 2015; 23:377–393 8. Sink KM, Holden KF, Yaffe K: Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence. JAMA 2005; 293:596–608 9. Schneider LS, Dagerman KS, Insel P: Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA 2005; 294:1934–1943 10. Gareri P, De Fazio P, Manfredi VG, et al: Use and safety of antipsychotics in behavioral disorders in elderly people with dementia. J Clin Psychopharm 2014; 34:109–123 11. Drye LT, Ismail Z, Porsteinsson AP, et al: Citalopram for agitation in Alzheimer’s disease: design and methods. Alzheimers Dement 2012; 8:121–130 12. Yeh YC, Ouyang WC: Mood stabilizers for the treatment of behavioral and psychological symptoms of dementia: an update review. Kaohsiung J Med Sci 2012; 28:185–193 13. Cumbo E, Ligori LD: Differential effects of current specific treatments on behavioral and psychological symptoms in patients with Alzheimer’s disease: a 12-month, randomized, open-label trial. J Alzheimers Dis 2014; 39:477–485 14. Cummings JL, Lyketsos CG, Peskind ER, et al: Effect of dextromethorphan-quinidine on agitation in patients with Alzheimer disease dementia: a randomized clinical trial. JAMA 2015; 314:1242–1254 15. Kerner N, Prudic J: Current electroconvulsive therapy practice and research in the geriatric population. Neuropsychiatry 2014; 4:33–54 16. Kellner CH, Greenberg RM, Murrough JW, et al: ECT in treatment-resistant depression. Am J Psychiatry 2012; 169:1238–1244 17. Greenberg RM, Kellner CH: Electroconvulsive therapy: a selected review. Am J Geriatr Psychiatry 2005; 13:268–281 18. Mukherjee S, Sackeim HA, Schnur DB: Electroconvulsive therapy of acute manic episodes: a review of 50 years’ experience. Am J Psychiatry 1994; 151:169–176 19. McDonald WM, Thompson TR: Treatment of mania in dementia with electroconvulsive therapy. Psychopharmacol Bull 2001; 35:72–82 20. Kramer BA: ECT in elderly patients with schizophrenia. Am J Geriatr Psychiatry 1999; 7:171–174 21. Suzuki K, Awata S, Matsuoka H: One-year outcome after response to ECT in middle-aged and elderly patients with
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intractable catatonic schizophrenia. J ECT 2004; 20:99– 106 Kamat SM, Lefevre PJ, Grossberg GT: Electroconvulsive therapy in the elderly. Clin Geriatr Med 2003; 19:825–839 van Schaik AM, Comijs HC, Sonnenberg CM, et al: Efficacy and safety of continuation and maintenance electroconvulsive therapy in depressed elderly patients: a systematic review. Am J Geriatr Psychiatry 2012; 20:5–17 van der Wurff FB, Stek ML, Hoogendijk WJ, et al: The efficacy and safety of ECT in depressed older adults: a literature review. Int J Geriatr Psychiatry 2003; 18:894–904 Carlyle W, Killick L, Ancill R: ECT: an effective treatment in the screaming demented patient. J Am Geriatr Soc 1991; 39:637 Price TR, McAllister TW: Safety and efficacy of ECT in depressed patients with dementia: a review of clinical experience. Convuls Ther 1989; 5:61–74 Roccaforte WH, Wengel SP, Burke WJ: ECT for screaming in dementia. Am J Geriatr Psychiatry 2000; 8:177 Grant JE, Mohan SN: Treatment of agitation and aggression in four demented patients using ECT. J ECT 2001; 17:205–209 Bang J, Price D, Prentice G, et al: ECT treatment for two cases of dementia-related pathological yelling. J Neuropsychiatry Clin Neurosci 2008; 20:379–380 Sutor B, Rasmussen KG: Electroconvulsive therapy for agitation in Alzheimer disease: a case series. J ECT 2008; 24:239–241 Katagai H, Yasui-Furukori N, Kikuchi A, et al: Effective electroconvulsive therapy in a 92-year-old dementia patient with psychotic feature. Psychiatry Clin Neurosci 2007; 61:568–570 Aksay SS, Hausner L, Frolich L, et al: Severe agitation in severe early-onset Alzheimer’s disease resolves with ECT. Neuropsychiatr Dis Treat 2014; 10:2147–2151 Ujkaj M, Davidoff DA, Seiner SJ, et al: Safety and efficacy of electroconvulsive therapy for the treatment of agitation and aggression in patients with dementia. Am J Geriatr Psychiatry 2012; 20:61–72 Acharya D, Harper DG, Achtyes ED, et al: Safety and utility of acute electroconvulsive therapy for agitation and aggression in dementia. Int J Geriatr Psychiatry 2014; 30:265–273 Hermida AP, Janjua U, Tang YL, et al: Use of orally disintegrating olanzapine during electroconvulsive therapy for prevention of postictal agitation. J Pyschiatry Pract 2016; 22:459–462 Loo CK, Katalinic N, Smith DJ, et al: A randomized controlled trial of brief and ultrabrief pulse right unilateral electroconvulsive therapy. Int J Neuropsychopharmacol 2015; 18(1) Kellner CH, Husain MM, Knapp RG, et al: Right unilateral ultrabrief pulse ECT in geriatric depression: phase 1 of the PRIDE study. Am J Psychiatry 2016; 173:1101–1109 Roa V, Lyketsos CG: The benefits and risks of ECT for patients with primary dementia who also suffer from depression. Int J Geriatr Psychiatry 2000; 15:729–735 Glass OM, Forester B, Hermida AP: Electroconvulsive therapy (ECT) for treating agitation in dementia (major neurocognitive disorder)—a promising option. Int Psychogeriatr 2017; 29:717– 726
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Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.ajgponline.org
Regular Research Article
Efficacy and Safety of ECT for Behavioral and Psychological Symptoms of Dementia (BPSD): A Retrospective Chart Review Adriana P. Hermida, M.D., Yi-lang Tang, M.D., Ph.D., Oliver Glass, M.D., A. Umair Janjua, M.D., William M. McDonald, M.D. ARTICLE INFO
ABSTRACT
Article history: Received August, 14 2019 Revised September, 21 2019 Accepted September, 23 2019
Objective: Much of the functional disturbance in patients with dementia reflects the presence of noncognitive behavioral and psychological symptoms of dementia (BPSD). Agitation is among the most distressing symptoms for patients, clinicians, and caregivers. Currently no pharmacotherapy has clearly been shown to be of value for this condition. This study used a chart review method to examine the safety and efficacy of electroconvulsive therapy (ECT) for patients with dementia receiving ECT for agitation. Methods: A retrospective chart review was conducted of patients with dementia presenting with symptoms of aggression or agitation and who received ECT treatments. Aggression and agitation were measured by pre- and post-ECT Pittsburg Agitation Scale (PAS) scores. Detailed history of the use of psychotropic medications as well as other clinically relevant variables was analyzed. Findings: Sixty elderly patients (45 women and 15 men, 75% female, mean age 77.5 § 8.0 years) were included in the analysis. Most patients were treatment resistant to multiple psychotropic medications prior to ECT (mean number 6.1§1.5). The baseline PAS total was 9.3 § 3.7 and it decreased significantly after three (2.5§2.8) and six (1.5§2.3) ECT treatments. No significant ECTrelated medical complications were observed except transient confusion. A decrease in the number of psychotropics prescribed along with an increase in the GAF score was observed after the ECT treatment course. Conclusion: ECT was safe in this sample of patients who had co-morbid medical conditions. ECT was associated with the following observations: 1) a reduction in agitation; 2) a reduction in psychotropic polypharmacy; and 3) an improvement in global functioning level. Further research evaluating the effects of ECT in the setting of dementia is warranted. (Am J Geriatr Psychiatry 2019; &&:&&−&&)
Key Words: ECT electroconvulsive therapy dementia BPSD agitation Alzheimer’s disease
From the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA. Send correspondence and reprint requests to Adriana P. Hermida, M.D., Division of Geriatric Psychiatry, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 12 Executive Park Drive NE, Atlanta, GA 30329. e-mail: [email protected] © 2019 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jagp.2019.09.008
Am J Geriatr Psychiatry &&:&&, && 2019
1
ARTICLE IN PRESS Efficacy and Safety of ECT for Behavioral and Psychological Symptoms of Dementia
INTRODUCTION
B
ehavioral and psychological symptoms of dementia (BPSD), which include agitation, aggression, anxiety, and psychosis, are a common consequence of dementia.1 Reports show that BPSD is nearly universal in patients with dementia, where it is correlated with the advanced stage of the illness.2−4 Agitation is among the most distressing symptom of dementia, which not only affects patients but also clinicians and caregivers. BPSD is of clinical significance as it is often strongly associated with functional impairment. Therefore, in addition to treating the cognitive impairments, targeting BPSD should be considered a priority by mental health providers.5 Nonpharmacological interventions should be first line when treating BPSD6 although many barriers exist in clinical settings to implement such interventions.7 Pharmacological interventions are often required, yet there are no medications approved by US Food and Drug Administration (FDA) for BPSD due to modest efficacy and tolerability concerns. Further, polypharmacy becomes more common with increasing severity of clinical symptoms. Commonly used medications that are prescribed off-label for BPSD include antipsychotics, antidepressants, mood stabilizers, and cholinesterase inhibitors. Though commonly used, antipsychotics are only modestly effective and are associated with significant side effects, including a FDA boxed warning for increased mortality.8,9 Providers who decide to prescribe antipsychotic medications should evaluate each case thoroughly and carefully, weighing the risk of side effects, and black box warning10 Although antidepressants may have a better risk to benefit ratio, sufficiently powered trials evaluating their safety and efficacy in dementia are still lacking but continue to be an area of research.11 The evidence regarding mood stabilizers is mixed, where only carbamazepine has been reported to be effective in a few studies and a metaanalysis.12 The use of mood stabilizers is limited in the clinical setting due to often lengthy side effect profiles, drug-drug interactions, and the need for therapeutic drug monitoring. Cumbo et al. (2014)13 reported that for patients with mild to moderate dementia, memantine, and rivastigmine may be effective in the improvement of BPSD, without major side effects, but the findings need to be replicated in larger samples. A randomized clinical trial by
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Cummings et al. (2015)14 evaluated the effects of dextromethorphan-quinidine on 194 patients with probable Alzheimer disease. The results of the study showed that this novel treatment modality was efficacious for agitation and was generally well tolerated. ECT has been used worldwide for severe and treatment-resistant psychiatric disorders in elderly patients. Research studies have shown that ECT is the most effective and rapid treatment available for elderly patients with depression, bipolar disorder, and psychosis.15 The efficacy of ECT in late life major depressive disorder with or without psychotic features has been well-documented.16,17 In addition, it has also been shown to be effective in treating acute mania,18 including mania in patients with dementia,19 and psychotic disorders.20,21 Increasing evidence shows that ECT is relatively safe when used among the elderly even though they may be more vulnerable to cognitive side effects and may present with more medical comorbidities.22−24 The use of ECT for agitation and aggression in patients with dementia started in the early 1990s.25 In the past two decades, growing interest in the use of ECT in patients with dementia has led to several key reports and case series about its role in the management of agitation in elderly dementia patients.26−32 Common target symptoms described in the studies include yelling, screaming, and aggression. A chart review (N = 16) by Ujkaj et al. (2012)33 utilized the Pittsburgh Agitation Scale (PAS) as the primary measure. The authors reported a significant reduction in the total PAS scores from baseline after ECT (from 11.0 § 5.0 to 3.9 § 4.3). Most of the ECT treatments were bilateral, with an average of nine sessions. Per the data provided Ujkaj et al., only one patient did not show improvement. Acharya et al. (2014),34 conducted a prospective study which included 23 patients from two psychiatric hospitals in Massachusetts and Michigan. All of the patients were diagnosed with dementia and were referred for ECT to treat agitation and/or aggression. The authors found a significant decrease from baseline to discharge on the Cohen Mansfield Agitation Inventory CMAI-SF (F(4,8) = 13.3; p = 0.006) and Neuropsychiatric Inventory NPI-NH (F(4,31) = 14.6; p < 0.001). The authors reported that ECT is generally well tolerated in patients with BPSD, with only five patients discontinuing ECT. In the Acharya study (2014), ECT was
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ARTICLE IN PRESS Hermida et al. discontinued for two participants because of poor treatment response. One participant died the day before he was to be discharged to a nursing home with palliative care. The authors reported that the patient’s death, which occurred approximately 1 month after his final ECT session, was related to end-stage dementia and was unrelated to ECT. ECT was discontinued for two participants because of delirium that was thought to be secondary, in part, to treatment with diphenhydramine and a urinary tract infection, respectively. Emory University’s ECT center, located at Emory University’s Wesley Woods Geriatric Hospital (WWGH), treats patients with various psychiatric diagnoses, including patients with dementia who exhibit moderate to severe behavioral and psychological disturbances. Patients often come from another psychiatric facility or a nursing home setting. This manuscript reports efficacy and safety data from a retrospective case series of individuals receiving ECT to treat agitation in dementia (Fig. 1).
METHODS Clinical Setting Sixty patients were identified with agitation in the setting of dementia who received ECT at Emory University’s Wesley Woods Geriatric Hospital (WWGH) between January 1, 2012 and February 28, 2014. A retrospective chart review was conducted of those patients. Agitation was measured by pre- and postECT Pittsburg Agitation Scale (PAS) scores. A detailed history of the use of psychotropic medications as well as other clinically relevant variables were analyzed. Sample The log book at the Wesley Woods ECT Center was used to screen potential patients. All diagnoses were made by board-certified geriatric psychiatrists. All cases included in the final analysis have been reviewed for eligibility and which was agreed on by at least two
FIGURE 1. Changes from baseline in number of psychotropic medications and PAS scores.
Changes in the number of psychotropic medications, PAS total score, and subscores at baseline and after ECT treatment in dementia with agitation.
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ARTICLE IN PRESS Efficacy and Safety of ECT for Behavioral and Psychological Symptoms of Dementia authors. Author APH, a board-certified geriatric psychiatrist reviewed all the included cases. Sixty patients were selected based the following criteria: 1) on admission, the primary psychiatric diagnosis included dementia (any type); 2) the presenting symptoms on admission included behavioral disturbance or agitation associated with dementia; 3) availability of PAS scores (4 were missing the PAS score but met the first two criteria, and were therefore included). Assessments (1) PAS: PAS has been widely used in geriatric psychiatric wards or nursing homes and it is based on direct observations of the patients. It assesses four general behavioral groups: Aberrant vocalization, motor agitation, aggressiveness, and resisting care. The PAS was performed by nurses as a part of clinical assessment. (2) The Global Assessment of Functioning (GAF): GAF is a numeric scale (0 through 100) used to rate subjectively the social, occupational, and psychological functioning of adults. (3) Psychiatric consult notes, discharge summary, and progress notes: These notes usually included current medications and co-morbid medical diagnoses, which were included in the analysis. ECT Procedures All patients were treated with a MECTA spectrum 5000 ECT machine. The anesthetic agent was methohexital at 0.75−1 mg per kg. The muscle relaxant was succinylcholine at a dose of 0.75−1.5 mg per kg. The seizure threshold was determined at the first treatment using a titration method with an algorithm of stimulations. All the subjects received right unilateral (RUL) lead placement with ultrabrief (UB) pulse width (0.37 msec). The Emory protocol was followed, which recommends treating at 6 times initial seizure threshold (IST), with an increase to 8 X IST if no response after the fifth or sixth treatment and 10 X IST if there is no response thereafter with 10 X IST being the maximal dose increment. Patients who were treated with bilateral lead placement were provided with brief pulse width treatments at 1.5 X IST. All patients were continued on their psychotropic medications, but an attempt was made to reduce benzodiazepines to the minimal tolerated dose. Patients
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who remained on a benzodiazepine were provided flumazenil prior to treatment. In addition, lithium, and other anticonvulsants were held the night before ECT treatment to ensure adequate seizures. Statistical Analysis Statistical Package for the Social Sciences, version 22.0 (Windows) was used in all analyses. All data was retrieved and entered in a SPSS file. Analysis of Variance for repeated measures was used to analyze the PAS total and subscale scores, GAF, and number of psychotropic trials, pre- and post-ECT.
RESULTS Basic Data of the Patients Sixty patients (45 women and 15 men, mean age = 77.5 § 8.0 years) were included in the analysis. With respect to the dementia subtype classification, 28 were labeled as unspecified, 22 as Alzheimer’s type, 2 as vascular, 2 as frontotemporal dementia, and 6 as mixed. The average number of medical comorbidities was 6.0 § 2.2. Most did not respond to multiple psychotropic medications (mean number = 6.0 § 1.6) prior to the ECT referral. Table 1 shows all clinical variables, including demographics and diagnoses. Changes in PAS and GAF At discharge, all of the patients’ PAS scores decreased significantly from baseline. The baseline PAS total was 9.3§3.7 and it decreased significantly after three (2.5§2.8, p <0.001) and six (1.5§2.3, p <0.0001) ECT treatments. PAS scores in two patients (both female) increased after 3 treatments (one was 7 at baseline increased to 11, another increased from 3 to 7); however these two patients also improved after the acute course was completed. On average, the change of PAS total from baseline was 7.8 § 3.7 (median = 8). The percentage of reduction on PAS was 88.5%. Only two cases were readmitted and one received another acute course of ECT treatment within 1 year after discharge, though rehospitalization at other facilities cannot be ruled out.
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ARTICLE IN PRESS Hermida et al. TABLE 1. Basic data of Patients with Dementia Receiving ECT for Agitation Characteristics
N = 60
Sex, women, n Age (years) Race/Ethnicity EA/AA/other (N) GAF on admission Length of stay (days) Pre-ECT length of stay Total number of ECT Living situation ALF/NH/family (N) Number of medical comorbidities Diagnosis of hypertension (N) Diagnosis of CAD (N) History of heart failure (yes/total) Diagnosis of stroke (yes/total)
45 77.5 § 7.9 50/9/1 20.8 § 4.8 26.7 § 10.4 7.1 § 4.1 9.6 § 9.7 21/19/20 6.0 § 2.2 42/54 13/54 3/54 5/54
Note: AA: African-American; ALF: assisted living facility; CAD: cardiovascular disease; EA: European-American; GAF: Global assessment of functioning; NH: nursing homes. (Number in table is mean § S.D. unless labeled otherwise).
patients were provided with orally dissolving olanzapine 5 mg thirty minutes prior to the subsequent ECT session, which prevented the recurrence of PIA.35 Other than PIA, no other major ECT-related medical complications were observed. One patient developed transient delirium described in the medical chart. No objective measure was utilized. One patient’s medical condition worsened (hypotension, tachycardia, and possible pneumonia) after the second ECT treatment (8 days after psychiatric admission). She had to be transferred to the medical ER and later to the medical floor for further treatment. She was discharged directly from the medical floor without returning to the psychiatric inpatient unit.
DISCUSSION Change in the GAF: GAF score also increased significantly after ECT treatment, from 20.8 § 4.9 to 34.5 § 4.4 (p <0.0001). Changes in Other Variables The number of psychotropic medications at baseline was 6.0 § 1.6 and it was not uncommon that a patient had been on one or two antipsychotic medications, plus one antidepressant, a mood stabilizer and one benzodiazepine. At discharge, the number of psychotropic medications was 4.9 § 1.6 (p <0.001). Clinical Variables of ECT Treatments Patients received UB-RUL or brief bifrontal ECT and the number of treatments ranged from 2 to 10 (median = 6). All but three patients were started with UB-RUL treatment. Eight patients were switched to bifrontal placement due to poor response to suprathreshold ultrabrief right unilateral. Most patients were discharged after 4−6 treatments as inpatients. Seven patients (2 men and 5 women) received more than 12 treatments (maintenance therapy). All maintenance treatments were performed after discharge. No further data regarding the maintenance treatments is available. Safety and Complications Six patients developed postictal agitation (PIA) and mild confusion after their first treatment. These Am J Geriatr Psychiatry &&:&&, && 2019
Based on our review of literature, our retrospective chart review is the largest sample of dementia patients receiving ECT for agitation. We found that ECT was safe in our sample of patients who had multiple medical conditions, and it appeared to be very effective in reducing agitation and decreasing the number of psychotropic agents prescribed. The global functioning level also significantly improved after ECT treatment. For most patients, significant improvement was observed after three treatments and the median number of treatments was 6. Our analysis suggests that, ECT may be a safe and effective treatment option for patients with dementia who have refractory BPSD. Our findings are consistent with previous reports, particularly the one by Ujkai et al. (2012).33 One difference is the overall length of stay in Ujkai’s report was significantly longer (59.7 § 39.7 days) than the one in our sample (25.2 § 10.3 days). Similarly, the number of pre-ECT days in their study (23 § 15.7 days) was also significantly longer than in our report (7.3 § 4.4 days). This was primarily because some of our patients were transferred from another facility and they had been worked up and prepared for ECT. Decreasing the days of hospitalization is crucial for this population as longer hospital stays often worsen disabilities in the older population and contribute to medical complications. In contrast to the reports by Ujikai et al. (2012)33 and Acharya et al. (2014),34 most patients in our study received the ultra-brief pulse (UBP) unilateral ECT, an
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ARTICLE IN PRESS Efficacy and Safety of ECT for Behavioral and Psychological Symptoms of Dementia approach that has been found to be associated with comparable efficacy and less cognitive impairment when compared with brief-pulse RUL ECT. However most of the data available come from studies of patients with major depression.36 The prolonging remission in the depressed elderly (PRIDE) study demonstrated safety and efficacy of UB RUL in the geriatric population.37 As argued in a recent review article,7 ECT shows promise “as an emerging treatment strategy for neuropsychiatric symptoms in dementia.” However, most clinicians are hesitant to use ECT in patients with dementia, largely due to limited evidence supporting its efficacy and safety. Most published studies examining ECT in patients with dementia and agitation or other behavioral problems19,27,28,30 were either case reports or retrospective chart reviews. Another concern is that ECT might worsen the already impaired cognitive function of patients. This concern has not been supported in well-controlled studies. Some studies have shown that ECT is a safe and efficacious treatment in patients with dementia who have comorbid depression,24,38,39 but this evidence does not address the concern about the risk for cognitive worsening. A few limitations need to be acknowledged. First, this is a retrospective chart review based on a relatively small clinical sample, which comes with inherent methodological limitations such as information that is unrecoverable or unrecorded, problematic verification of information and variance in the quality of information recorded by medical professionals, lack of randomization and limitations on outcome measures. Second, some important data were not available, such as the measurements on cognitive function before and after ECT treatment. Future studies would benefit from objective measures including the Confusion Assessment Method and Severity Battery Inventory (SIB), a test to evaluate cognition where the mini-mental status examination (MMSE) is not a feasible tool due to the baseline severity of cognitive impairment. We were limited on this data considering our retrospective approach. Finally, due to the nature of the study,
the role of other factors could also have contributed to the improvement in agitation, such as medication changes, environmental modifications, and behavioral interventions. Despite these limitations, this study, along with previous reports, supports the use of ECT treatment for agitation and aggression in patients with dementia, especially for cases that failed to respond to multiple psychiatric medications. In clinical practice, ECT for agitation in the setting of dementia is not a first line treatment and there are no FDA approved medication options. Prior to ECT, treatment approaches include ruling out medical causes, implementing environmental modifications and behavioral interventions, and also attempt to treat BPSD with psychotropics. A reasonable approach would be to attempt less invasive treatment options first but to consider ECT when other options have been exhausted. As patients with dementia may lack capacity to consent to treatment, it is essential to have discussions with family and/or legally authorized representative to thoroughly address the potential risks and benefits of this modality of treatment. Standardized assessments of cognitive function, behavioral symptoms of dementia, and measures of quality of life including the Severity Impairment Battery, Cohen-Mansfield Agitation Inventory, Confusion Assessment method (CAM), and the Neuropsychiatry Inventory are warranted in future studies. Including a control group, ideally in a randomized fashion, would contribute to the field to better understand the value of ECT in the management of agitation in dementia. Furthermore, studies on continuation and maintenance ECT could also provide evidence beyond short-term efficacy and safety. Conflicts of interest: The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. Other disclosures have been submitted by the authors in the disclosure form.
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