Electroconvulsive therapy for treating patients with agitation and related behavioral disorders due to dementia: a systematic review

Stella, Florindo; Radanovic, Márcia; Gallucci-Neto, José; Forlenza, Orestes Vicente

doi:10.1590/1980-5764-DN-2023-0007

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Dementia & Neuropsychologia

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Original Article • Dement. neuropsychol. 17 • 2023 • https://doi.org/10.1590/1980-5764-DN-2023-0007 copy

Electroconvulsive therapy for treating patients with agitation and related behavioral disorders due to dementia: a systematic review

Eletroconvulsoterapia no tratamento de pacientes com agitação e outros distúrbios de comportamento devido à demência: uma revisão sistemática

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Behavioral disturbances are clinically relevant in patients with dementia, and pharmacological regimens to mitigate these symptoms have provided limited results. Proven to be effective in several psychiatric conditions, electroconvulsive therapy is a potentially beneficial strategy for treating severe agitation due to dementia.

Objective:

This review aimed to examine the publications on the efficacy, safety and tolerability of electroconvulsive therapy in treating patients with agitation due to dementia.

Methods:

We performed a systematic analysis on the electroconvulsive therapy to treat patients with dementia and coexisting severe agitation. Articles were classified according to the level of evidence based on methodological design. Patients received an acute course of electroconvulsive therapy, often followed by maintenance intervention.

Results:

We selected 19 studies (156 patients; 64.1% women; 51–98 years old), which met the inclusion criteria: one case-control study by chart analysis (level of evidence 2); one open-label study (level of evidence 3); three historical/retrospective chart analyses (level of evidence 4); and 14 case series/reports (level of evidence 5). No randomized, sham-controlled clinical trials (level of evidence 1) were identified, which represents the main methodological weakness. Some patients had postictal delirium, cardiovascular decompensation and cognitive changes, lasting for a short time.

Conclusions:

Overall, patients achieved significant improvement in agitation. However, the main finding of the present review was the absence of methodological design based on randomized and sham-controlled clinical trials. Despite methodological limitations and side effects requiring attention, electroconvulsive therapy was considered a safe and effective treatment of patients with severe agitation and related behavioral disorders due to dementia.

Keywords:
Aggression; Dementia; Electroconvulsive Therapy; Behavioral and Psychological Symptoms of Dementia

Characteristics of the 19 selected studies
Authors	Sample (n), age (years), gender		Dementia and staging	ECT therapeutic scheme	Symptoms assessment	Outcome/efficacy	Safety and tolerability	Cognition
Case-control study by chart analysis – level of evidence 2
	Zhang et al.¹⁹19 Zhang QE, Sha S, Ungvari GS, Chiu HFK, Ng CH, He HB, et al, Demographic and clinical profile of patients with dementia receiving electroconvulsive therapy: a case-control study. J ECT. 2016;32(3):183-6. https://doi.org/10.1097/YCT.0000000000000314 https://doi.org/10.1097/YCT.000000000000...	ECT: n=23 (age: 60y and older; M: 30.4%); Comparison group n=71 (age: 60y and older; M: 31%)	Mild to severe dementia (AD, VD, mixed/AD+VD, other types) with agitation, aggression and suicide risk	Bitemporal; mean sessions: 6.1 (±3.0); seizures greater than 25 seconds; pulse width: 0.25 and 1.0 ms	CGI	91.3% fully or partially responded to ECT behavioral disorders and risk of suicide	47.8% experienced mild-moderate transient headache, myalgia, nausea, dyspnea, hypertension; no postictal confusion reported	Transient memory impairment; no persistent memory changes
Open-label and naturalistic study – level of evidence 3
	Acharya et al.²⁰20 Acharya D, Harper DG, Achtyes ED, Seiner SJ, Mahdasian JA, Nykamp LJ, et al. Safety and utility of acute electroconvulsive therapy for agitation and aggression in dementia. Int J Geriatr Psychiatry. 2015;30(3):265-73. https://doi.org/10.1002/gps.4137 https://doi.org/10.1002/gps.4137...	n=23 age: 73.8 y F: 14 M: 9	Moderate to severe AD, VD, mixed/AD+VD, FTD, unspecified dementia	Right unilateral (n=17), bilateral (n=4) transitioned to bitemporal (n=2) due to no response; 12 sessions; seizures duration not mentioned; pulse width: 0.5–1.0 ms	CMAI-short form, NPI, CSDD, CGI	Significant improvement in behavioral dyscontrol and agitation; no changes in mood and psychosis domains of the NPI	Well tolerated by most participants; 3 patients presented delirium; 1 patient developed atrial fibrillation; 1 patient presented visual hallucinations	From before to after ECT, the MMSE increased by approximately 2 points on average
Retrospective and systematic analysis of chart review of case series – level of evidence 4)
	Sutor and Rasmussen²¹21 Sutor B, Rasmussen KG. Electroconvulsive therapy for agitation in Alzheimer disease: a case series. J ECT. 2008;24(3):239-41. https://doi.org/10.1097/YCT.0b013e3181587416 https://doi.org/10.1097/YCT.0b013e318158...	n=11 Age: 81.4y (59-98y) F: 10 M: 1	Severe AD with psychosis, physical and verbal aggression; 8 patients had history of primary psychiatric disorders (depression, generalized anxiety, BP)	Bitemporal (n=8), bifrontal (n=1), right unilateral (n=2); 4–8 sessions, duration of seizures unspecified dementia	Objective behavior assessment not reported	Improvement for 9 patients; no benefits in 2 patients	Most patients tolerated the ECT well; one patient developed atrial fibrillation	Decreased cognition in 2 patients, no information for the other 9 patients
	Ujkaj et al.²²22 Ujkaj M, Davidoff DA, Seiner SJ, Ellison JM, Harper DG, Forester BP. Safety and efficacy of electroconvulsive therapy for the treatment of agitation and aggression in patients with dementia. Am J Geriatr Psychiatry. 2012;20(1):61-72. https://doi.org/10.1097/JGP.0b013e3182051bbc https://doi.org/10.1097/JGP.0b013e318205...	n=16 age: 66.6y F: 15 M: 1 (retrospective systematic chart review)	Mild to severe AD (n=8); FTD (n=3), VD (n=2); unspecified dementia (n=3) with aggression and agitation	9 sessions (from 2 to 15); bilateral (n=12), right unilateral (n=4), transitioned to bilateral when insufficient response (n=4); 9 patients received ETC maintenance; seizure duration not reported.	PAS, CGI	Significant improvement in aberrant vocalizations, motor agitation, aggressiveness, and care resistance	In general, well tolerated; 10 patients developed postictal transient confusion.	Cognition not reported after ECT course
	Hermida et al.¹⁴14 Hermida AP, Tang YL, Glass O, Janjua AU, McDonald WM. Efficacy and safety of ECT for symptoms of dementia (BPSD): a retrospective chart review. Am J Geriatr Psychiatry. 2020;28(2):157-63. https://doi.org/10.1016/j.jagp.2019.09.008 https://doi.org/10.1016/j.jagp.2019.09.0...	n=60 age: 77.5y F: 45 M: 15 (case series from a chart review)	Moderate to severe AD n=28), VD (n=2), FTD (n=2), mixed (n=6), unspecified dementia (n=22) with aggression and agitation.	Right unilateral; 8 patients transitioned to bifrontal due to poor response; 4−12 sessions (average: 9.6); seizure duration not mentioned; width pulse: 0.37 ms	PAS, GAF, psychiatric consult notes	Improvement in global functioning with decrease of psychotropic polypharmacy	Postictal agitationand mild postictal confusion in 6 patients; delirium in 1 patient	Cognition not reported after ECT course
Case reports – level of evidence 5
	Carlyle et al.¹⁵15 Carlyle W, Killick L, Angill R. ECT: an effective treatment in the screaming demented patient. J Am Geritr Society. 1991;39(6):637. https://doi.org/10.1111/j.1532-5415.1991.tb03610.x https://doi.org/10.1111/j.1532-5415.1991...	n=3 Age and gender not reported	Unspecified dementia characterized by substantial cognitive decline and agitation	Bilateral; number of sessions and seizure duration not mentioned	Objective behavior assessment not reported	Rapid resolution of screaming	Tolerability or side effects not reported	Cognition not reported after ECT course
	Holmberg et al.¹⁶16 Holmberg SK, Tariot PN, Challapalli R. Efficacy of ECT for agitation in dementia: a case report. Am J Geriatr Psychiatry. 1996;4(4):330-4. https://doi.org/10.1097/00019442-199622440-00007 https://doi.org/10.1097/00019442-1996224...	n=1 age: 78y, F	Severe VD	Bilateral; seizure duration from 45 to 60 seconds; 54 sessions; maintenance for 2 years; brief-pulse width	Behavioral rating scale	Dramatic improvement in agitation and aggression at the beginning of treatment; maintenance of ECT for 2 years with response oscillation	Well tolerated	Cognition not reported after ECT course
	Roccaforte et al.³²32 Roccaforte WH, Wengel SP, Burke WJ. ECT for screaming in dementia. Am J Geriatr Psychiatry. 2000;8(2):177. PMID: 10804080	n=1 age: 77y, F	Language advanced dementia; disruptive vocalizations, verbal aggression, warbling, loudly, obscenely	6 sessions; lead placement not reported; seizure duration not reported	Objective behavior assessment not reported	Substantial improvement	Tolerability or side effects not reported	Before ECT the MMSE was 0, but not assessed after the procedure course
	Grant et al.²³23 Grant JE, Mohan SN. Treatment of agitation and aggression in four demented patients using ECT. J ECT. 2001;17(3):205-9. https://doi.org/10.1097/00124509-200109000-00012 https://doi.org/10.1097/00124509-2001090...	n=4 Case 1: age: 56y, F	Severe pre-senile AD with agitation and suspected visual hallucinations	Bilateral, 4 sessions; seizures lasting 37–43 seconds; brief-pulse width	Objective behavior assessment not reported	Improvement in agitation and aggression	Postictal confusion lasting several hours after treatment	In the 4 cases, since dementia was severe, the risk of cognitive worsening was considered moot
		Case 2: age: 78y, M	Severe AD with agitation and aggression	Bilateral; 7 sessions; seizures lasting 26–39 seconds; brief-pulse width	Objective behavior assessment not reported	Dramatically reduction of agitation and aggression	Tolerability or side effects not reported
		Case 3: age: 77y, F	Severe AD with agitation, sleep disorder	Bilateral; 2 sessions; seizures with 46 seconds and 52 seconds; brief-pulse width	Objective behavior assessment not reported	Improvement in agitation, verbal aggression, and sleeping	Tolerability or side effects not reported
		Case 4: age: 78y, F	Severe AD with agitation and verbal aggression	Bilateral; 4 sessions in the first period and 4 additional sessions after three months (8 sessions); seizures lasting 30–54 seconds; brief-pulse width	Objective behavior assessment not reported	Improvement in verbal aggression and repetitive speaking after first course; no additional information	Tolerability or side effects not reported
	McDonald and Thompson¹¹11 McDonald WM, Thompson TR. Treatment of mania in dementia with electroconvulsive therapy. Psychopharmacol Bull. 2001;35(2):72-82. PMID: 12397888.	n=3 Case 1 Age: 73y M	Severe Lewy-body dementia and BP, with mania symptoms, agitation, and aggressiveness	Right-unilateral acute course; 8 sessions plus maintenance ECT every 2 weeks for the following 18 months; seizures duration not mentioned; 8 brief-pulse width	Objective behavior assessment not reported	Marked improvement in mood and behavior	No postictal confusion or worsening in dementia	Cognition improved – MMSE from unobtainable to 9 out of 30
		Case 2 Age: 85y F	Moderate dementia not otherwise specified with agitation and aggressiveness and mania symptoms; history of alcohol and benzodiazepines dependence	Right-unilateral ECT acute course; 6 sessions with maintenance course for 6 months; seizures duration not mentioned; 6 brief-pulse width	Objective behavior assessment not reported	Significant improvement in mood and behavior	No postictal confusion or worsening in dementia	Cognition remained stable; MMSE 15–16 out of 30
		Case 3 Age: 71y F	Mild-moderate dementia not otherwise specified and BP with mania symptoms and agitation	Right-unilateral ECT acute course; 7 sessions with maintenance course for the subsequent 18 months; seizures duration not mentioned; 7 brief-pulse width	Objective behavior assessment not reported	Complete resolution of mania and agitation	No postictal confusion or worsening in dementia	Cognition improved; MMSE from 24 to 28 out of 30. Later this patient was diagnosed with “pseudodementia”
	Bang et al.²⁴24 Bang J, Price D, Campbell J. ECT treatment for two cases of dementia-related pathological yelling. J Neuropsychiatry Clin Neurosci. 2008;20(3):379-80. https://doi.org/10.1176/jnp.2008.20.3.379 https://doi.org/10.1176/jnp.2008.20.3.37...	n=2 Case 1: age: 88y, F	Severe AD+PDD with verbal agitation, obscenities, hollering, palilalia, and screaming;	Bilateral; 11 sessions; seizures up to 84 seconds	Objective behavior assessment not reported	Marked improvement in verbal agitation	Well tolerated	The patient improved in verbal language and in nodding in response to questions
		Case 2: age 80y, F	Severe unspecified dementia, with agitation, screaming, spitting, striking	Bilateral; 5 sessions; seizures up to 56 seconds	Objective behavior assessment not reported	Improvement in verbal agitation and aggression	Well tolerated	Cognition not reported after ECT course
	Suzuki et al.²⁵25 Suzuki K, Awata S, Matsuoka H. One-year outcome after response to ECT in middle-aged and elderly patients with intractable catatonic schizophrenia. J ECT. 2004;20(2):99-106. https://doi.org/10.1097/00124509-200406000-00005 https://doi.org/10.1097/00124509-2004060...	n=1 age: 51y, M	FTD overlapping severe BP with angering, joking, followed by apathy or agitation	Bitemporal; 9 sessions; seizures lasting 39–70 seconds; brief-pulse width	Objective behavior assessment not reported	Improvement in behavioral disturbances	High fever, liver dysfunction and ECT interruption for 1 week, being resumed afterward	Improvement in attention and abstract thinking
	Wu et al.²⁶26 Wu Q, Prentice G, Campbell JJ. ECT treatment for two cases of dementia-related aggressive behavior. J Neuropsychiatry Clin Neurosci 2010;22(2):E10-11. https://doi.org/10.1176/jnp.2010.22.2.247.e10 https://doi.org/10.1176/jnp.2010.22.2.24...	n=2 Case 1: age: 78y, M	Severe AD with aggression	Bitemporal; 7 sessions, seizures lasted up to 65 seconds	Objective behavior assessment not reported	Marked improvement	Well tolerated	Cognition not reported after ECT course
		Case 2: age: 71y, M	Severe FTD with pushing, grabbing, choking	Bitemporal; 6 sessions, seizures lasted up to 58 seconds; maintenance for every 28 days	Objective behavior assessment not reported	Improvements in aggression	Well tolerated	Cognition not reported after ECT course
	Paul et al.³³33 Paul S, Goetz J, Bennett J, Korah T. Efficacy of electroconvulsive therapy for comorbid frontotemporal dementia with bipolar disorder. Case Rep Psychiatry. 2013;124719. https://doi.org/10.1155/2013/124719 https://doi.org/10.1155/2013/124719...	n=1 Age: 51y, M	FTD with history of bipolar disorder; unreported severity	9 sessions; localization not reported; seizures duration not reported	Objective behavior assessment not reported	Significant improvement in mood symptoms without benefits for erratic behavior and laughter	Tolerability or side effects not reported	The MMSE score went from 6/28 before ECT up to 20/28 after treatment (two items were excluded: the drawing and written portions of the exam)
	Aksay et al.³⁰30 Aksay SS, Hausner L, Frölich L, Sartorius A. Severe agitation in severe early-onset Alzheimer’s disease resolves with ECT. Neuropsychiatr Dis Treat. 2014;10:2147-51. https://doi.org/10.2147/NDT.S71008 https://doi.org/10.2147/NDT.S71008...	n=1 Age: 57y, F, right-handed	Severe pre-senile AD with agitation, aggressiveness, and repetitive outbursts	Right unilateral, 8 sessions; seizures duration not mentioned; pulse width: 0.25 ms	PAS	Significant improvement	Well tolerated despite headache; 3 spontaneous self-limiting generalized seizures.	ECT without any recognizable worsening of cognition
	Borisovskaya et al.³¹31 Borisovskaya A, Augsburger J, Pascualy M. Electroconvulsive therapy for frontotemporal dementia with comorbid major depressive disorder. J ECT. 2014;30(4):e45-6. https://doi.org/10.1097/YCT.0000000000000152 https://doi.org/10.1097/YCT.000000000000...	n=1 age: 70y, M	Moderate to severe FTD with perseverative behavior, psychosis, apathy, and depression	Right unilateral, 6 sessions; seizures average of 60 seconds; several months with maintenance treatment; ultrabrief pulse of 0.3 ms	FAB	Initial improvement and subsequent worsening	ST-segment depression at EKG.	No worsening in cognition
	Fazzari et al.²⁷27 Fazzari G, Marangoni C, Benzoni O. Maintenance ECT for the treatment and resolution of agitation in Alzheimer’s dementia. J Psychopathology. 2015;21:159-60.	n=1 age: 76y, F	Severe AD with agitation, insomnia, mood lability, weeping, anger, repetitive vocalization, and swearing	Bitemporal and bifrontal: 21 sessions including acute course and maintenance; seizure duration not mentioned.	Objective behavior assessment not reported	Resolution of confusional state, psychomotor agitation and behavioral disturbance	Tolerability or side effects not reported	Cognition not reported after ECT course
	Selvadurai et al.²⁸28 Selvadurai MI, Waxman R, Ghaffar O, Fischler I. Efficacy and safety of maintenance electroconvulsive for sustaining resolution of severe aggression in a major neurocognitive disorder. BMJ Case Rep. 2018;2018:bcr2017222100. https://doi.org/10.1136/bcr-2017-222100 https://doi.org/10.1136/bcr-2017-222100...	n=1 age: 64y, M	Severe unspecified dementia, with agitation and aggression	Bitemporal with 15 sessions for an acute course followed by a weekly and until every 5 weeks for maintenance was continued by a 17 month-period; seizure duration not reported	NPI-C	Substantial and sustained improvement of agitation and aggression	Discontinuation of the ECT acute phase due to pneumonia; later ECT was resumed	Prior ECT cognition assessment was not achievable due to aggressiveness; however, ECT was beneficial for cognition
	França et al.²⁹29 França GC, Barreto HCB, Paranhos T, Nunes JC, Oliveira-Souza R. Case report: catatonic stupor in behavioral variant frontotemporal dementia. Front Neurol. 2022;12:798264. https://doi.org/10.3389/fneur.2021.798264 https://doi.org/10.3389/fneur.2021.79826...	n=1 age: 95y, F	Severe late-onset FTD with sexual disinhibition, aggressiveness, agitation, bizarre social behavior, followed by catatonic stupor	Bitemporal; 6 sessions; seizures lasting 20–30 seconds; brief-pulse width	Bush-Francis Catatonia Rating Scale; Northoff Catatonia Scale	No benefits, and interruption of ECT course	Tolerability or side effects not reported	Cognition not reported after ECT course

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[1] Correspondence: Florindo Stella; Email: fstella.unesp@gmail.com.