Australasian Psychiatry

Managing severe aggression in frontotemporal dementia Alice Powell, Patrick Flynn, Sally Rischbieth and Duncan McKellar Australas Psychiatry 2014 22: 86 originally published online 31 October 2013 DOI: 10.1177/1039856213510576 The online version of this article can be found at:

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APY22110.1177/1039856213510576Australasian PsychiatryPowell et al.


Case report

Managing severe aggression in frontotemporal dementia

Australasian Psychiatry 2014, Vol 22(1) 86­–89 © The Royal Australian and New Zealand College of Psychiatrists 2013 Reprints and permissions: DOI: 10.1177/1039856213510576

Alice Powell  Psychiatry RMO, Older Persons Mental Health Services, Northern Adelaide Local Health Network, Adelaide, SA, Australia

Patrick Flynn  Senior Psychiatrist, Older Persons Mental Health Services, Northern Adelaide Local Health Network, Adelaide, SA, Australia

Sally Rischbieth  Senior Psychiatrist, Older Persons Mental Health Services, Northern Adelaide Local Health Network, Adelaide, SA, Australia

Duncan McKellar  Senior Psychiatry Registrar, Older Persons Mental Health Services, Northern Adelaide Local Health Network, Adelaide, SA, Australia

Abstract Objective: The aim of this paper is to present a case and discussion illustrating the limitations in the evidence base to guide practice in relationship to managing severe aggression in people with dementia. It also calls attention to the association between haloperidol use and increased mortality in dementia. Method: Case report and review of the literature. Results: A 60-year-old man with rapidly progressive frontotemporal dementia complicated by severe aggression was managed in specialised psychogeriatric services and high-dose haloperidol was used. This treatment decision was made following literature review, consultation with experts and a detailed risk–benefit analysis. Unfortunately, his physical condition deteriorated swiftly and he died soon after. Conclusions: Haloperidol is associated with increased mortality in patients with dementia. This case exposes the difficulties in managing severe aggression in dementia, with few safe and effective treatment options and a lack of consensus guidance in the area of very severe aggression in dementia. Keywords:  frontotemporal dementia, aggression, haloperidol, extra-pyramidal side effects (EPSE), behavioural and psychological symptoms of dementia (BPSD)


ggression is a common behavioural symptom of dementia. Current guidelines advocate undertaking a comprehensive assessment of such patients and the usage of non-pharmacological therapies before trialling low-dose pharmacotherapies including antipsychotic agents. Nevertheless, there is limited guidance regarding the management of severe aggression in dementia. There is also substantial evidence of significant adverse effects associated with the use of antipsychotic agents in dementia. Consequently, clinicians must consider the risks and benefits of medication in individual patients and may need to make difficult treatment decisions. We discuss the complex management and the use of high-dose haloperidol for severe aggression in a man with early onset frontotemporal dementia (FTD). The rapidly progressive nature of this patient’s dementia in conjunction with side effects of his medical treatment resulted in swift physical deterioration and death.

Case report Mr AB was a 60-year-old man with a history of rapidly progressive FTD complicated by extreme aggression. He had been the perpetrator of domestic violence several years prior to diagnosis and he was estranged from his family. There was a history of depression with previous high-lethality suicide attempts. He also had a history of ischaemic heart disease, type 2 diabetes, obstructive sleep apnoea and a bronchial adenoma. Mr AB initially presented at the age of 59 with seizures, cognitive decline and behavioural change progressing over a period of 4 months. He had suspected Hashimoto’s Correspondence: Dr Alice Powell, Older Persons Mental Health Services, Northern Adelaide Local Health Network, 200 Fosters Road, Adelaide, SA 5086, Australia. Email: [email protected]

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Powell et al.

encephalopathy supported by elevated anti-thyroid peroxidise antibody, mildly deranged thyroid function tests and elevated cerebrospinal fluid protein levels. However, he did not respond to high-dose prednisolone, unlike the majority of patients with Hashimoto’s encephalopathy. There was supporting evidence from a SPECT scan for a diagnosis of FTD, and other organic causes for dementia, including Creutzfeldt-Jakob disease, were excluded. Aggression was prominent during his initial admission to a neurology unit and he was commenced on risperidone, clonazepam and venlafaxine on the advice of the liaison psychiatry team. Following his transfer to a specialised acute inpatient psychogeriatric unit, Mr AB required physical and chemical restraint on several occasions to ensure his safety and that of other patients. His medications were changed to sodium valproate, quetiapine and oxazepam. His aggression diminished but he continued to make threatening remarks and he expressed suicidal ideation. He was then transferred to a specialised psychogeriatric nursing home but his behaviour became increasingly aggressive and unpredictable, resulting in substantial property damage to the facility and a significantly increased risk of harm to himself and others. On one occasion, when he was stopped from pushing a chair-bound resident, he started attempting to punch staff. He did not respond to reassurance or redirection outside. He had to be physically restrained by three male nurses and given intramuscular (IM) haloperidol. In the process of this restraint, he seriously injured one staff member who was forced to take 2 weeks off work to recover. He did not respond to the IM injection. He began taking picture frames off the walls before throwing these at staff members and at the ground. He also began using pieces of the broken frames and glass as weapons. He was taken to one end of the ward away from the other residents but managed to kick his way through a locked door and back into the ward. During these episodes, he made statements such as ‘I’m going to flatten you’ and ‘I will kill you’. He was placed in seclusion at the psychogeriatric nursing home but he took the headboard off his bed and used this to break back into the ward. At this point, a decision was made to transfer him back to an acute psychiatric inpatient unit where difficulties with his ongoing management continued. He caused damage to the ward environment and injured staff members, necessitating prolonged periods of seclusion and a one-to-one nurse special. Some examples of his violent behaviours include throwing furniture, an attempt to strangle staff, and kicking, hitting, headbutting and spitting at staff while they were attending to his personal care. It was almost impossible to get close enough to Mr AB to perform an assessment of his vital signs or take blood for testing. He frequently made verbal threats such as ‘I will cut your throat and kill you’. He required a general anaesthetic in order to perform a CT brain scan, which was unremarkable.

It is important to note that staff in both the psychogeriatric nursing home and the acute psychiatric inpatient unit had extensive experience with behavioural management strategies in patients with dementia, but Mr AB’s extreme level of aggression rendered these strategies ineffective. Numerous medications were trialled in an attempt to reduce agitation and moderate his behaviour. Quetiapine, olanzapine, risperidone, oxazepam, clonazepam, sodium valproate and zuclopenthixol acetate produced limited benefit. It is significant that much of this pharmacological management was instituted outside of current evidence-based guidelines. Concern was raised over hypotensive episodes with quetiapine and worsening confusion with olanzapine. Electroconvulsive therapy was also considered. Finally, haloperidol was introduced and its dose was steadily increased to 60 mg daily in divided doses. A further dose of up to 20 mg daily of haloperidol was sometimes needed due to severe agitation. When he developed extra-pyramidal side effects (EPSE) including tremor, rigidity, shuffling gait and bradykinesia, benztropine was commenced. These treatment decisions were made after extensive collaboration with psychiatrists, a psychopharmacist, other medical specialists and senior nursing staff. There was also input from the state Chief Psychiatrist, hospital CEO and Director of Nursing. The risks and benefits of using haloperidol at these doses were explored and it was thought that there was no better alternative to treat Mr AB’s severe and ongoing aggression. On discharge back to the psychogeriatric nursing home, Mr AB had marked EPSE and mild dysphagia. He was still making attempts to assault staff but had become increasingly sedated following discharge from the acute unit. Haloperidol was decreased to 40 mg daily and regular benztropine was added. Mr AB subsequently became more sedated with decreased food and fluid intake. He was no longer able to ambulate and marked muscle rigidity was noted. He quickly developed pressure injuries on his sacrum and heel. Haloperidol was further decreased to 30 mg daily and his benztropine dose was increased. Mr AB continued to make threatening gestures towards staff. He became increasingly drowsy, pyrexia developed and he was transferred to hospital. He was found to be septic, probably due to infected pressure injuries. Neuroleptic malignant syndrome was excluded and a further CT brain scan was unremarkable. He underwent surgical debridement of his pressure injuries and he was commenced on intravenous antibiotics. His haloperidol was withheld and there was a liaison psychiatry review. He became transiently more alert before again deteriorating. Palliative care was instituted in discussion with his guardian and he died shortly afterwards. This case illustrates the significant issues that may arise in treating extreme aggression associated with dementia. The situation is further complicated by incomplete guidelines on the topic.

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Australasian Psychiatry 22(1)

Discussion Behavioural and psychological symptoms of dementia (BPSD) are almost ubiquitous in dementia,1 with prevalence increasing with disease severity.2 Some studies suggest an association between premorbid personality and BPSD.3 Prevalence statistics for aggressive behaviour vary. A study of female primary caregivers found that 58% reported being victims of physical aggression.4 Aggression is associated with FTD, greater dementia severity, cognitive decline and other behavioural and psychological disturbances.5 Associated negative outcomes include nursing home placement,1,2,5–7 the use of antipsychotic medications, physical restraints and increased healthcare costs.6 While significant risk is associated with the use of antipsychotic medication in the elderly, it is frequently prescribed for aggression in patients with dementia. Most clinical guidelines advocate a comprehensive assessment of the potential underlying causes of aggression in dementia patients including the consideration of delirium, agitated depression, undetected pain or other physical symptoms.1,7–9 Non-pharmacological therapies are usually recommended as first-line interventions.2,6,8–9 Low dose, slow titration and short-term use is advised when utilising antipsychotic agents.2,6,9 The control of BPSD becomes a priority if violence, aggression and extreme agitation threaten the safety of the person with dementia or others.9 A recent Cochrane Review found that haloperidol was useful in decreasing aggression in dementia but should not be used routinely.10 Considering the significant adverse effects of antipsychotic medications in patients with dementia, these conservative directives are prudent. Age-related pharmacokinetic changes can result in higher and/or more variable drug concentrations.11 EPSE such as Parkinsonism are twice as likely to occur in the elderly,12 and risk is also increased with the use of high-potency agents such as haloperidol.12,13 Exposure to antipsychotic medication for 60 or more days dramatically increases risk of EPSE.12 There are also specific concerns regarding increased mortality, specifically cerebrovascular adverse events (CAEs). CAEs were initially reported with second-generation antipsychotic medications, leading to the United States Food and Drug Administration in 2005 issuing a blackbox warning regarding their use in elderly patients with dementia.2,14 Subsequent research has shown that the risk of death with conventional antipsychotic medications is comparable with and possibly greater than that associated with atypical agents.15 A 2012 cohort study of elderly nursing home residents found that the risk of mortality with antipsychotics in this population was generally increased with higher doses, and was greatest for haloperidol and least for quetiapine.16 Both shortterm and long-term treatment with antipsychotics appears to be problematic.2 How antipsychotics increase mortality is unclear. Hypothetically, antipsychotic treatment may lead to

somnolence and decreased activity. This increases vulnerability to pneumonia and is associated with a greater use of diuretics, which combine to confer an increased mortality risk.17 In Mr AB’s case, it appears that his drowsiness and decreased mobility together with his decreased fluid and nutritional intake contributed to the development of pressure injuries and resultant sepsis. It is uncertain whether Mr AB would have physically deteriorated so rapidly if the haloperidol had been reduced earlier. A Cochrane Review published in 2013 has concluded that elderly patients with dementia can be withdrawn from long-term antipsychotics without detrimental effects on their behaviour. However, the review advised caution in patients with more severe BPSD as their symptoms may worsen if antipsychotic medication is ceased.18 In addition, there was no evidence that the risk of harmful adverse events was reduced by drug withdrawal.18 Clinicians not only have imperfect tools to deal with severe BPSD, but are left to make ethically difficult clinical decisions that may ultimately lead to unintended incapacitation or premature death of their patients. While the severity of symptoms displayed by the patient in this case is unusual, it serves to illustrate the difficulties in managing aggression in dementia. It also highlights the paucity of research and incompleteness of consensus guidelines on the topic. Careful risk–benefit analysis was undertaken before using high-dose haloperidol for the patient in this case. The outcome is indicative of the clinical challenges associated with managing what can be such a complex and tragic illness. Acknowledgements We would like to thank Professor Robert Goldney for his assistance in the preparation of this manuscript.

Disclosure The authors report no conflict of interest. The authors alone are responsible for the content and writing of this paper.

Patient confidentiality  All identifying information has been removed or altered. As the patient concerned is now deceased, written consent was obtained from the patient’s guardian for submission of this report. The patient’s guardian has also discussed the publication of this report with the patient’s family and they are supportive of this.

References 1. Australian Institute of Health and Welfare (AIHW) 2006. Dementia in Australia: National data analysis and development. AIHW cat. no. AGE 53. Canberra: AIHW. 2. Press D and Alexander M. Treatment of behavioural symptoms related to dementia [Online], (2013, accessed 17 March 2013). 3. Low LF, Brodaty H and Draper B. A study of premorbid personality and behavioural and psychological symptoms of dementia in nursing home residents. Int J Geriatr Psychiatry 2002; 17: 779–783. 4. Cahill S and Shapiro M. ‘I think he might have hit me once’: Aggression towards caregivers in dementia care. Aust J Ageing 1993; 12: 10–15. 5. Brodaty H and Low LF. Aggression in the elderly. J Clin Psychiatry 2003; 64(S4): 36-43.

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Powell et al. 6. Cipriani G, Vedovello M, Nuti A, et al. Aggressive behaviour in patients with dementia: Correlates and management. Geriatr Gerontol Int 2011; 11: 408–413.

13. Gardner DM, Baldessarini RJ and Waraich P. Modern antipsychotic drugs: A critical overview. CMAJ 2005; 172: 1703–1711.

7. Gauthier S, Cummings J, Ballard C, et al. Management of behavioural problems in Alzheimer’s disease. Int Geriatr 2010; 22: 346–372.

14. Newman WJ. Psychopharmacologic management of aggression. Psychiatr Clin North Am 2012; 35: 957–972.

8. Alexopoulos GS, Streim J, Carpenter D, et al. The Expert Consensus Guideline Series: Using antipsychotic agents in older patients. J Clin Psychiatry 2004; 65(S2): 5–99.

15. Schneeweiss S, Setoguchi S, Brookhart A, et al. Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients. CMAJ 2007; 176: 627–632.

9. National Institute for Health and Clinical Excellence. Dementia: Supporting people with dementia and their carers in health and social care. 2011. 42. London: National Institute for Health and Clinical Excellence. 10. Lonergan E, Luxenburg J, Colford JM, et  al. Haloperidol for agitation in dementia. Cochrane Database Syst Rev 2012; 5: CD002852. 11. Salzman C, Jeste D, Meyer RE, et al. Elderly patients with dementia-related symptoms of severe agitation and aggression: Consensus statement on treatment options, clinical trials methodology, and policy. J Clin Psychiatry 2008; 69: 889–898. 12. Blair DT. Risk management for extrapyramidal symptoms. QRB Qual Rev Bull 1990; 16: 116–124.

16. Huybrechts KF, Gerhard T, Crystal T, et al. Differential risk of death in older residents in nursing homes prescribed antipsychotic drugs: Population based cohort study. BMJ 2012; 344: e977. 17. Ballard C, Hanney ML, Theodoulou M, et  al.; DART-AD investigators. The dementia antipsychotic withdrawal trial (DART-AD): Long-term follow-up of a randomised placebo controlled trial. Lancet Neurol 2009; 8: 151–157. 18. Declercq T, Petrovic M, Azermai M, et  al. Withdrawal versus continuation of chronic antipsychotic drugs for behavioural and psychological symptoms in older people with dementia. Cochrane Database Syst Rev 2013; 3: CD007726.

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Managing severe aggression in frontotemporal dementia.

The aim of this paper is to present a case and discussion illustrating the limitations in the evidence base to guide practice in relationship to manag...
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