Medical management of behavioural and psychological symptoms of dementia

Contributed by:vLesley Charles, MBChB, FCFP(COE – View bio

Case

Mr. Evans is 86 and presenting with a four-month history of escalating agitation in the evening despite non-pharmacological measures utilizing music therapy and a robotic pet. His past medical history includes moderate-severe mixed dementia, hypertension, dyslipidemia, STEMI, LBBB and benign prostatic hyperplasia. His current medications include: Reminyl ER 16 mg daily, ramipril 5 mg daily, atorvastatin 40 mg daily, ECASA 81 mg daily and tamsulosin 0.4 mg daily.

Issue

Behavioural and psychological symptoms of dementia (BPSD) can adversely affect quality of life and function. It can pose a problem both in the community and in long-term care necessitating a higher level of care.

Background

Dementia is common and affects 50 million worldwide.¹ 90% of patients with dementia experience BPSD symptoms at some point.² BPSD can be classified into five domains: cognitive/perceptual (delusions, hallucinations), motor (e.g., pacing, wandering, repetitive movements, physical aggression), verbal (e.g., yelling, calling out, repetitive speech, verbal aggression), emotional (e.g., euphoria, depression, apathy, anxiety, irritability), and vegetative (disturbances in sleep and appetite).³ The most common BPSD symptoms are depression or apathy, although delusions, particularly paranoia, agitation and aberrant motor behaviour (e.g., fidgeting, repetitive behaviours, wandering) occur in about a third of patients.³  Hallucinations are not as prevalent as delusions with estimates as low as 7% at baseline.⁴ Behavioural disturbances can occur in the evening, which is known as 'sundowning.' Some studies suggest that this phenomenon affects up to two-thirds of patients with dementia.⁵

Evidence

Initial management should include history collecting of which symptoms are present and their frequency and severity. It should look at onset (i.e., acute, sub-acute or chronic/progressive), timing and timeline of the disturbances, and any relationship to environmental changes, medication changes or other antecedents.³ History should also identify potentially reversible exacerbating factors, including environmental factors, medications, discomfort, substance use and pre-morbid psychiatric disorders. The physical exam should concentrate on any evidence of delirium and causes including pain, constipation and urinary retention. Look for any painful conditions like neuropathy, osteoarthritis and peripheral vascular disease. Caregivers should be asked about both the patient’s self-report about pain and nonverbal signs of pain, because patients with dementia may demonstrate nonverbal signs of pain even though they do not report it.⁶ Unless there is evidence from the history or physical exam to suggest something more acute, evaluation with laboratory or imaging is not necessary for patients with dementia who present with gradually worsening BPSD.

Next, establish any safety issues to the patient like refusal of basic care or others such as aggressive behaviours that would necessitate hospitalization. Review medications as patients with dementia are especially susceptible to CNS effects of medications including less suspected ones like antibiotics, digoxin, levetiracetam and the more common anticholinergics, antihistamines, antidepressants, benzodiazepines and muscle relaxants. Standardized instrument such as the Neuropsychiatric Inventory (NPI) or the Behavioural Pathology in Alzheimer’s Disease rating scale (BEHAVE-AD) can be used but are time consuming. Clinicians may prefer to document the nature of symptoms, frequency and severity so can monitor for response to any treatment.

Patients with delirium or safety issues should be hospitalized. Treat any pain, and if pain is suspected try regular Tylenol as first line. Generally, try non-pharmacologic measures first. Music therapy has evidence for success in BPSD as well as massage in treating depression.⁷ Caregivers should be trained to understand behavioural disturbances as responses to discomfort, unmet needs or attempts to communicate. Responding to these with de-escalating techniques can reduce BPSD.⁸

Lastly, consider pharmacologic treatment. In a Cochrane review of antidepressants for agitation and psychosis in dementia, Selective serotonin reuptake inhibitors (SSRIs) and trazodone were tolerated well compared with placebo, typical and atypical antipsychotics.⁹ Citalopram was shown to be effective for agitation in Alzheimer’s but cognition declined and QTC was prolonged.¹⁰ A very small, open label study showed potential benefit with mirtazapine for agitation in patients with Alzheimer’s.¹¹ Acetyl cholinesterase inhibitors have also been shown to improve behaviour in Alzheimer’s.¹² Memantine has shown similar benefit on behaviour and mood.¹³ Gabapentin and pregabalin have also shown some benefit except for those with Dementia of Lewy Body.¹⁴

In summary, try non-pharmacologic first. Treat any pain. Unless contraindicated, any patient with BPSD should be started on an acetyl cholinesterase inhibitor. If the patient is non-responsive and has severe mood and agitation symptoms, try an SSRI, trazodone or Mirtazapine. If the patient is experiencing severe agitation, aggression or psychosis, cautiously try antipsychotic. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death and stroke. In Canada, only risperidone has been approved for use in dementia, but the other antipsychotics can be used “off label.” When starting an antipsychotic, document discussion with family of pros and cons. Remember to always reassess response to any medication and taper off if it is not working.

Recommendation

Mr. Evans was advised to continue on his cholinesterase inhibitor. He was also recommended to continue his non-pharmacologic measures of music therapy and robotic pet that there is better evidence for. Mr. Evans and his wife were referred to the Alzheimer Society first link program for support. Mr. Evans was initiated on escitalopram 5 mg daily and showed response at follow up.

References

1. Alzheimer’s Disease International. World Alzheimer Report 2019: Attitudes to dementia. London: Alzheimer’s Disease International (2019). Available online at: https://www.alzint.org/u/WorldAlzheimerReport2019.pdf
2. Ballard C, Corbett A. Agitation and aggression in people with Alzheimer’s disease. Curr Opin Psychiatry. (2013) 26:252– 9. doi: 10.1097/YCO.0b013e32835f414b
3. Cloak N, Al Khalili Y. Behavioral And Psychological Symptoms In Dementia. 2022 Jul 21. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–. PMID: 31855379.
4. Mega MS, Cummings JL, Fiorello T, Gornbein J. The spectrum of behavioral changes in Alzheimer's disease. Neurology. 1996 Jan;46(1):130-5. 
5. Gallagher-Thompson D, Brooks JO, Bliwise D, Leader J, Yesavage JA. The relations among caregiver stress, "sundowning" symptoms, and cognitive decline in Alzheimer's disease. J Am Geriatr Soc. 1992 Aug;40(8):807-10.
6. Tan EC, Jokanovic N, Koponen MP, Thomas D, Hilmer SN, Bell JS. Prevalence of Analgesic Use and Pain in People with and without Dementia or Cognitive Impairment in Aged Care Facilities: A Systematic Review and Meta-Analysis. Curr Clin Pharmacol. 2015;10(3):194-203. 
7. Na R, Yang JH, Yeom Y, Kim YJ, Byun S, Kim K, Kim KW. A Systematic Review and Meta-Analysis of Nonpharmacological Interventions for Moderate to Severe Dementia. Psychiatry Investig. 2019 May;16(5):325-335. 
8. Gozalo P, Prakash S, Qato DM, Sloane PD, Mor V. Effect of the bathing without a battle training intervention on bathing-associated physical and verbal outcomes in nursing home residents with dementia: a randomized crossover diffusion study. J Am Geriatr Soc. 2014 May;62(5):797-804.
9. Seitz D P, Adunuri N, Gill SS, Gruneir A, Herrmann N, Rochon P. Antidepressants for agitation and psychosis in dementia. Cochrane Database Syst Rev. 2011 Feb 16;(2):CD008191. doi: 10.1002/14651858.CD008191.pub2. PMID: 21328305.
10. Porsteinsson AP, Drye LT, Pollock BG, Devanand DP, Frangakis C, Ismail Z, Marano C, Meinert CL, Mintzer JE, Munro CA, Pelton G, Rabins PV, Rosenberg PB, Schneider LS, Shade DM, Weintraub D, Yesavage J, Lyketsos CG; CitAD Research Group. Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial. JAMA. 2014 Feb 19;311(7):682-91. doi: 10.1001/jama.2014.93. PMID: 24549548; PMCID: PMC4086818.
11. Cakir S, Kulaksizoglu IB. The efficacy of mirtazapine in agitated patients with Alzheimer's disease: A 12-week open-label pilot study. Neuropsychiatr Dis Treat. 2008 Oct;4(5):963-6. doi: 10.2147/ndt.s3201. PMID: 19183787; PMCID: PMC2626919.
12. Rodda J, Morgan S, Walker Z. Are cholinesterase inhibitors effective in the management of the behavioral and psychological symptoms of dementia in Alzheimer's disease? A systematic review of randomized, placebo-controlled trials of donepezil, rivastigmine and galantamine. Int Psychogeriatr. 2009 Oct;21(5):813-24. doi: 10.1017/S1041610209990354. Epub 2009 Jun 19. PMID: 19538824.
13. McShane R, Westby MJ, Roberts E, Minakaran N, Schneider L, Farrimond LE, Maayan N, Ware J, Debarros J. Memantine for dementia. Cochrane Database Syst Rev. 2019 Mar 20;3(3):CD003154. doi: 10.1002/14651858.CD003154.pub6. PMID: 30891742; PMCID: PMC6425228.
14. Supasitthumrong T, Bolea-Alamanac BM, Asmer S, Woo VL, Abdool PS, Davies SJC. Gabapentin and pregabalin to treat aggressivity in dementia: a systematic review and illustrative case report. Br J Clin Pharmacol. 2019 Apr;85(4):690-703. doi: 10.1111/bcp.13844. Epub 2019 Feb 8. PMID: 30575088; PMCID: PMC6422659.