- Email: [email protected]
Optimizing Care for Older Adults With Dementia-Associated Psychosis
Optimizing Care for Older Adults With Dementia-Associated Psychosis Cynthia L. Blevins, DNP, FNP-BC ABSTRACT
Dementia continues to escalate as the aging population increases, and there are no medications available to reverse this disease. Dementia-associated psychosis/behavioral disturbances can be attributed to frontal lobe, vascular, Alzheimer, Parkinson, and Lewy body dementia, but patients must be assessed for other etiologies. Care for these patients can be challenging. Some studies find certain medications to be effective, but they are not without risk. Medications can lead to falls and even demonstrate paradoxical effects, causing significant distress in patients as well as their families. Nonpharmacologic interventions may prove helpful and should be used first if possible. Keywords: Alzheimer, antipsychotics, dementia, dementia-associated psychosis, frontal lobe dementia, Lewy body dementia, Parkinson dementia, potentially inappropriate medications, vascular dementia Ó 2018 Elsevier Inc. All rights reserved.
S
arah, a 78-year-old retired schoolteacher with vascular dementia, was newly admitted to a local skilled nursing facility memory support unit. Upon admission, her medications consisted of 24 medications associated with hypertension, diabetes, heart disease, and dementia. Over time, her dementia worsened, and despite stable blood pressures and blood sugars, she showed the following signs of psychosis: constant agitation, confusion, and combative behaviors. Despite increases in antipsychotic medications and dementia medications, she unfortunately progressed and ultimately died of a fat embolus sustained after falling and fracturing her hip. Although the family was glad their loved one was no longer suffering, they stated that “this was difficult to observe, for our Mother would never have wanted to behave this way.” A review of the literature was subsequently conducted to determine additional interventions available for those caring with patients with dementia-related psychosis.
PREVALENCE OF DEMENTIA-ASSOCIATED PSYCHOSIS
Dementia is prevalent in 40% of the world’s population, with predictions for an even higher percentage by 2022.1 Subtypes include Alzheimer dementia, 178
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which is the most common, vascular dementia, Lewy body dementia, frontal lobe dementia, and Parkinson dementia.2 Dementia typically presents with cognitive decline and short-term memory loss. Unfortunately, cognitive impairment labeled as dementia can arise from many medications, such as antipsychotics, benzodiazepines, selective serotonin reuptake inhibitors, and anticonvulsants,3 leading to a misdiagnosis and inappropriate care. One study found that 24% of patients given a diagnosis of dementia who exhibited psychosis were found to not have dementia.4 Dementia symptoms can also be present in patients with thyroid disease, normal pressure hydrocephalus, brain tumors, subdural hematomas, and other etiologies.2 Dementia-associated psychosis can often occur at later stages of dementia, but this can vary.2 Psychotic behaviors include delusions, hallucinations, aggression, paranoia, and depression. One study showed a 40% prevalence of psychotic behaviors in Alzheimer patients, the most common type of dementia.5 This group demonstrated significantly more agitation than patients with mild cognitive impairment,5 reinforcing that psychosis is more prevalent as the disease progresses. Among patients Volume 14, Issue 3, March 2018
with Parkinson disease, 50% have psychosis.6 Frontotemporal dementia has consistently resulted in psychosis7 because this part of the brain affects the filter of patient’s thoughts and speech. Lewy body dementia and vascular dementia can also exacerbate into psychosis as the disease progresses.2 RISKS ASSOCIATED WITH PSYCHOSIS IN DEMENTIA PATIENTS
Agitation, aggressive, and combative behaviors associated with psychosis can create a domino effect within a memory support unit, contributing to a tense atmosphere for other patients. Patients with less severe conditions may become fearful that they too “may act that way some day.” Dementia-associated psychosis can be variable throughout the day, so patients can feel trapped in a dementia unit during fleeting moments of clarity. Those with dementia and psychosis have a higher rate of depression than dementia patients without psychosis,5 so it is not surprising that quality of life screening test scores were lower in patients with dementia and neuropsychiatric symptoms.8 Dementia-associated psychosis impairs judgment, which can lead to falls and associated injuries. When psychosis is present, it is challenging to meet the nutritional needs of patients, making them more prone to wounds and weight loss. When patients lose weight, a reduction in both diabetic and hypertension medications may be needed. Person-centered care can be difficult if patients are unable to express advanced directive wishes or share preferences regarding lifestyle choices or activities. Caregivers have a low to moderate agreement with patient choices for end-of-life care according to 1 study, reinforcing the need for early discussion of end-oflife choices before dementia ensues.9 CAREFUL DIAGNOSIS OF PSYCHOSIS ETIOLOGY IS ESSENTIAL
Psychosis is multifactorial and may be present in patients without dementia who have delirium, pain, uncontrolled diabetes or hypertension, neurologic impairment, or side effects from medications.10 A study examined case notes of 660 patients with psychotic behaviors and found that health care providers missed www.npjournal.org
various associated diagnoses, leading to the unnecessary use of antipsychotic medication. Sixty-eight percent of the sample had delirium, 27% had pain, 93% had depression or anxiety, and 71% had just started new medications before psychotic behaviors.11 According to 1 systematic review,11 poor control of pain can alter cognitive function and lead to psychosis behaviors. Inversely, patients with an actual diagnosis of dementia may not be able to verbalize that they have pain, so a careful assessment is necessary.12 A retrospective analysis with a large sample showed that the use of bladder antimuscarinics has been associated with cognitive decline.13 Anticholinergics should be avoided whenever possible in older patients with psychosis.2 There are conflicting reports about an association between urinary tract infections and psychosis, and, unfortunately, many older adults with colonized bacteria in their urine are actually treated unnecessarily for this presumed condition.14 PHARMACOLOGIC INTERVENTIONS FOR PSYCHOSIS IN DEMENTIA PATIENTS Benefits of Medications
Cholinesterase inhibitors may slow the progression of dementia but are not associated with the prevention of psychosis.15 In 1 study, 14 mg/d galantamine showed reduced agitation and was better tolerated than other medications in this class.16 Pimavanserin was approved by the Food and Drug Administration for Parkinson diseaseeassociated psychosis.17 A study of 181 patients receiving 34 mg pimavanserin daily showed a significant reduction in psychosis. However, this medication is currently considered off-label for use in patients with psychosis who do not have Parkinson disease. A randomized double-blind trial of risperidone (dosing not specified) versus placebo use in patients with dementia psychosis found that risperidone had a favorable risk versus benefit ratio.18 This study did state that this medication should only be used in cases with prominent psychotic and behavioral symptoms associated with distress, functional impairment, or danger to the patient. A retrospective study of 179 patients with dementia and behavioral disturbance showed buspirone to be effective in reducing agitation/ aggressive behaviors in 68.6% of the sample.19 The Journal for Nurse Practitioners - JNP
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Risks of Medications
A systematic review of articles about the safety and tolerability of psychotropic medications found that many times providers who prescribe these medications base this more on experience than science, and there are typically mixed results.20 Atypical antipsychotics such as aripiprazole, risperidone, quetiapine, and olanzapine are associated with an increased risk of acute myocardial infarction, and risperidone or olanzapine use increase the risk of hip fractures.21 A large study of patients with Alzheimer dementia treated with antipsychotic medications showed increased death rates from cancer, heart disease, infection, and intentional self-harm.22 The use of antipsychotic medications in patients with Parkinson disease increased physical morbidity in this group.23 Other guidelines, including the Beers criteria and STOPFrail, refer to antipsychotic medications as potentially inappropriate for older adults.24,25 Olanzapine, quetiapine, and risperidone have demonstrated variable efficacy in regard to psychosis management.26 Antipsychotics can increase QT prolongation, which can lead to falls and even a life-threatening arrhythmia.27 Underlying pain can exacerbate psychosis, but, unfortunately, pain medications such as opioids can increase the risk of falls.24 Benzodiazepines and antipsychotic medications, especially in higher doses, are also associated with falls.28,29 Antidepressants, antiepileptics, antipsychotics, benzodiazepine, and opioid receptor agonists are medications that are considered in the category of central nervous system burden. The use of more than 3 single doses of antipsychotic medications within 24 hours has been associated with falls.30 Medications prescribed to slow dementia progression may have a higher risk versus benefit because they are not always effective and can also increase fall risks.31 Citalopram reduced agitation in Alzheimer dementia patients but increased cognitive decline in 1 study.32 Because of the incidence of potential QT prolongation, another study found that citalopram should only be used in those with early-onset dementia.33 Genetic testing should be considered to determine the most effective medication to treat patients for psychosis.34 This testing is covered by Medicare and can be confusing 180
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to interpret but can indicate which medications are best metabolized by the individual patient. In some cases, the patient may require a lower or higher dose of specific medications because of their metabolic pathways. The benefit of this testing is that there is less experimentation with which medication is most effective, and it may reduce adverse drug reactions.35 Evaluation of Medication
As with treatment of any type of psychosis behavior, secondary causes must be eliminated first, and, unless there are adverse effects, adequate time should be given to evaluate the effectiveness of the medication. Medications should be administered first with the lowest possible dose, tapered upward slowly, and evaluated carefully. After starting citalopram with patients with Alzheimer dementia, they should be monitored for at least 9 weeks to determine effectiveness.36 Pimavanserin should be monitored for at least 6 weeks, not only for efficacy but also for side effects such as a prolonged QT interval or paradoxical effects when used for Parkinson diseaseeassociated psychosis.16 Should concerns be present, antipsychotics should not be stopped suddenly or hallucinations may occur.37 Prescribers should consider using the lowest doses possible and avoiding the use of multiple antipsychotics.22 EVIDENCE-BASED NONPHARMACOLOGIC TREATMENT FOR PSYCHOSIS IN DEMENTIA PATIENTS
Multiple geriatric and dementia organizations as well as research studies endorse nonpharmacologic treatments for patients who exhibit psychosis symptoms. It is recommended that these interventions be used as first-line treatment before any medications are implemented unless a patient exhibits potential harm to themselves or others.2 In 1 study of dementia patients with neuropsychiatric conditions, 41.9% of 123 patients with dementia and psychotic behaviors were given medication without any attempts to use nonpharmacologic interventions.36 The American Geriatrics Society recommends that comorbid conditions, such as hypertension and diabetes, are treated with the promotion of exercise, a balanced diet, and stress reduction.2 These interventions are clinically supported in the research Volume 14, Issue 3, March 2018
literature to be effective in most cases, but some studies refute the efficacy of such interventions. For example, a randomized controlled trial showed that a high-intensity functional exercise program reduced agitation and improved balance,37 yet another study demonstrated that regular long-term exercise intervention did not help Alzheimer dementia patients with the reduction of neuropsychiatric symptoms.38 Tai chi was shown to enhance cognitive function in older adults, especially among those with early-stage dementia.39 A systematic review showed that although electroconvulsive therapy may be an option, there is the need for more clinical trials.40 Song writing was found to be helpful in another case study.41 Reminiscence group therapy has proven to be effective in providing pleasant memories for patients with dementia who can recall things in the past, improves cognitive ability, and reduces depression according to a meta-analysis.42 This therapy involves discussing pleasant memories such as “my first car” or “my favorite trip.” Although there is no documented research that it prevents the progression of psychosis symptoms, it certainly bears further investigation. It may very well assist this population to hold on to good memories and be less agitated. What brings joy to one patient may certainly seem meaningless to another, reinforcing the need for individualized approaches, which can be quite challenging given staffing issues in most skilled nursing facilities. It is not unusual for a lack of understanding of what each patient truly is like underneath their façade of dementia or psychosis behaviors. A volunteer program can be very helpful for patients and benefit the volunteer as well. This may facilitate the fostering of a consistent relationship for the patient. Training nursing home staff about how to interpret behavioral and psychological symptoms of dementia reduced the use of antipsychotics in 1 skilled care facility.43 It also stands to reason that having a degree of consistency among caregivers, which is challenging for any skilled care facility, can help reduce the incidence of additional issues such as delirium, which would further exacerbate agitated behaviors. Individuals with dementia who attend specialized day care centers showed a higher quality of life, which is also promising.44 www.npjournal.org
IMPLICATIONS FOR FURTHER RESEARCH
More research must be done to further identify best practices for individualized care for those with dementia-associated psychosis. Although there is compelling evidence regarding the risks and benefits of current medications used for dementia psychosis, it is clear that establishing a firm diagnosis and associated etiologies for behaviors must be done first. Nonpharmacologic interventions should be tried with a patient-centered focus. Ongoing investigation regarding ways to provide the best care possible for patients with dementia-associated psychosis needs to continue. If pharmacologic intervention is used, it must be introduced slowly with an upward taper as needed and very close monitoring. Sadly, a review of the literature did not demonstrate consistent efficacy for dementia psychosis medication treatment. Consulting with those who specialize in the management of behavioral and psychological conditions is always wise, especially once all known options have not been effective. Perhaps the most compelling issue at this time is that providers need to submit data for publication if they find interventions that help this population so that all may benefit. As we continue to provide care for those with dementiaassociated psychosis, continued study must take place so that we can provide the best quality of life possible for those with this condition. References 1. Jacqmin-Gadda H, Alperovitch A, Joly P, et al. 20-year prevalence projections for dementia and impact of preventive policy about risk factors. Eur J Epidemiol. 2013;28(6):493-502. https://doi.org/10.1007/s10654-013-9818-7. 2. Reuben DB, Herr KA, Pacala JT, et al. Geriatrics at Your Fingertips: 2016. 18th ed. New York, NY: The American Geriatrics Society; 2016. 3. Aspinall SL, Zhao X, Semla TP, et al. Epidemiology of drug-disease interactions in older veteran nursing home residents. J Am Geriatr Soc. 2015;63:77-84. https://doi.org/10.1111/jgs.13197. 4. Fischer C, Qian W, Schweizer T, et al. Determining the impact of psychosis on rates of false-positive and false-negative diagnosis in Alzheimer’s disease. Alzheimers Dement (N Y). 2017;3:385-392. https://doi.org/10.1016/j.trci.2017/ .06.001. 5. Van der Mussele S, Marien P, Engelborgs S, et al. Psychosis associated behavioral and psychological signs and symptoms in mild cognitive impairment and Alzheimer’s dementia. Aging Ment Health. September 2015;19(9):818-828. https://doi.org/10.1080/13607863.2014.967170. 6. Ravina B, Marder K, Fernandez H, et al. Diagnostic criteria for psychosis in Parkinson’s disease report of an NINDS, NIMH work group. Mov Disord. 2014;29:1615-1622. 7. Schinagawa S, Nakajima S, Plitman E, et al. Psychosis in frontotemporal dementia. J Alzheimers Dis. 2014;42:485-499. https://doi.org/10.3233/JAD-140312. 8. Mjorud M, Kirkebold M, Rosvik J, Selaek G, Engedal K. Variables associated to quality of life among nursing home patients with dementia. Aging Ment Health. 2014;18(8):1013-1021. https://doi.org/10.1080/13607863.2014.903468. 9. Harrison Dening K, King M, Jones L, Vickerstaff V, Sampson EL. Advance care planning in dementia: do family carers know the treatment preferences of people with early dementia? PLoS One. 2016;11(7):e0159056. https://doi.org/ 10.1371/journal.pone.0159056. PMID: 27410259.
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10. Habiger T, Flo W, Achterberg W, Husebo B. The interactive relationship between pain, psychosis, and agitation in people with dementia: results from a cluster-randomised clinical trial. Behav Neurol. 2016;7036415:1-8. https:// doi.org/10.1155/2016/7036415. 11. O’Shea E, Timmons S, Kennelly S, deSiun A, Gallagher P, O’Neill D. Symptom assessment for a palliative care approach in people with dementia admitted to acute hospitals: results from a national audit. J Geriatr Psychiatry Neurol. 2015;28(4):255-259. https://doi.org/10.1177/0891988715588835. 12. Flo E, Gulla C, Husebo B. Effective pain management in patients with dementia: benefits beyond pain? Drugs Aging. 2014;31:863-871. https://doi.org/10.1007/ s40266-014-0222-0. 13. Moga D, Abner E, Wu Q, Jicha G. Bladder antimuscarinics and cognitive decline in elderly patients. Alzheimers Dement (N Y). 2017;3:139-148. https://doi.org/10.1016/j.trci.2017.01.003. 14. Hartley S, Valley S, Kuhn L, et al. Overtreatment of asymptomatic bacteriuria: Identifying targets for improvement. Infect Control Hosp Epidemiol. 2015;36(4):470-473. 15. Tampi R, Tampi D, Balachandran S. Antipsychotics, antidepressants, anticonvulsants, melatonin, and benzodiazepines for behavioral and psychological symptoms of dementia: a systematic review of meta-analysis. Curr Treat Options Psychiatry. 2017;4:55-79. https://doi.org/10.1007/s40501 -017-0104-2. 16. Freund-Levi Y, Bloniecki V, Auestad B, et al. Galantamine versus risperidone for agitation in people with dementia: a randomized twelve-week, single-center study. Dement Geriatr Cogn Disord. 2014;38(3-4):234-244. https://doi.org/10 .1159/000462204. 17. Hawkins T, Berman B. Pimavanserin. A novel therapeutic option for Parkinson disease psychosis. Neurol Clin Pract. 2017;1:157-162. 18. Tan L, Tan L, Wang HF, et al. Efficacy and safety of atypical antipsychotic drug treatment for dementia: a systematic review and meta-analysis. Alzheimers Res Ther. 2015;7(1):1-13. https://doi.org/10.1186/s13195-015-0102-9. 19. Santa Cruz MR, Hidalgo PC, Lee MS, et al. Buspirone for the treatment of dementia with behavioral disturbance. Int Psychogeriatr. 2017;5:859-862. https://doi.org/10.1017/S1041610216002441. 20. Forlenza O, Loureiro J, Pais M, Stella F. Recent advances in the management of neuropsychiatric symptoms in dementia. Curr Opin Psychiatry. 2017;30:151-158. https://doi.org/10.1097/YCO.0000000000000309. 21. Farlow MR, Shamliyan TA. Benefits and harms of atypical antipsychotics for agitation in adults with dementia. European Neuropsychopharmacol. 2017;27:217-231. https://doi.org/10.1016/jeuroneuro.2017.01.002. 22. Nielsen RE, Lolk A, Rodrigo-Domingo M, Valentin JB, Anderson K. Antipsychotic treatment effects on cardiovascular, cancer, infection and intentional self-harm as cause of death in patients with Alzheimer’s dementia. Eur Psychiatry. 2016;42:14-23. https://doi.org/10.1016/j.eurpsy.2016.11.013. 23. Weintraub D, Chiang C, Kim HM, et al. Antipsychotic use and physical morbidity in Parkinson disease. Am J Geriatr Psychiatry. 2017;25:697-705. https://doi.org/10.1016./j.jagp.2017.01.076. 24. Lavan A, Gallagher P, Parsons C, O’Mahony D. STOPPFrail (Screening Tool of Older Persons Prescriptions in Frail adults with limited life expectancy): consensus validation. Age Ageing. 2017;46(4):600-607. 25. American Geriatrics Society. American Geriatrics Society updated Beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63(11):2227-2246. https://doi.org/10.1111/jgs.13702. 26. Nowrangi MA, Lyketsos CG, Rosenberg PB. Principles and management of neuropsychiatric symptoms in Alzheimer’s dementia. Alzheimers Res Ther. 2015;7:12. https://doi.org/10.1186/s13195-015-0096-3. 27. Wu CS, Tsai YT, Tsai HJ. Antipsychotic drugs and cardiovascular safety: current studies of prolonged QT interval and risk. J Am Heart Assoc. 2015;23(4):62-72. https://doi.org/10.1161/JAHA.114.001568. 28. Bozat-Emre S, Doupe M, Kozyrskyj AL, Grymonpre R, Mahmud SM. Atypical antipsychotic drug use and falls among nursing home patients in Winnipeg, Canada. Int J Geriatr Psychiatry. 2015;30(8):842-850. https://doi.org/10.1002/ gps.4223. 29. Echt MA, Samelson EJ, Hannan MT, Dufour AB, Berry SD. Psychotropic drug initiation or increased dosage and the acute risk of falls: a prospective cohort study of nursing home residents. BMC Geriatr. 2013;13(19):1-8. https://doi.org/ 10.1186/1471-2318-13-19.
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30. Hanlon J, Zhao X, Thorpe C, et al. Central nervous system (CNS) medication burden and serious falls in older nursing home residents. J Am Geriatr Soc. 2017;65(6):1183-1189. 31. Epstein NU, Guo R, Farlow MR, Singh JP, Fisher M. Medication for Alzheimer’s disease and associated fall hazard: a retrospective cohort study from the Alzheimer’s disease neuroimaging initiative. Drugs Aging. 2014;31(2):125-129. https://doi.org/10.1007/s40266-013-0143-3. 32. Lyketsos CG, Pollock BG, Schneider L, Porsteinsson AP. Citalopram for agitation in AD: pharmacokinetic studies, subgroup analyses, and effect on other neuropsychiatric symptoms. AAGP Annual Meeting, Session 412. Am J Geriatr Psychiatry. 2016;24(suppl 1):3. https://doi.org/10.1002/gps.4223. 33. Schneider L, Frangakis C, Lyketsos C, et al. Heterogeneity of treatment response to Citalopram for patients with Alzheimer’s disease with aggression or agitation: the CitAD Randomised Clinical Trial. Am J Psychiatry. 2016;173(5):465-472. https://doi.org/10.1176/appi.ajp.2015.150648. 34. Santini S, Panza F, Lozupone M, Bellomo A, Seripa D. Genetics of tailored medicine: focus on CNS drugs. Microchem J. 2018;136:164-169. https://doi.org/ 10.1016/j.microc.2017.02.018. 35. Weintraub D, Drye L, Posteinson A, et al. Time to response to citalopram treatment for agitation in Alzheimer disease. Am J Geriatr Psychiatry. 2015;23(11):1127-1133. https://doi.org/10.1016/j.jagp.2015.05.006. 36. Patel A, Lee S, Andrews H, et al. Prediction of relapse after discontinuation of antipsychotic treatment in Alzheimer’s disease: the role of hallucinations. Am J Psychiatry. 2017;174(4):362-369. 37. Telenius EW, Engedal K, Bergnald A. Long-term effects of a 12 weeks highintensity functional exercise program on physical function and mental health in nursing home patients with dementia: a single blinded randomized controlled trial. BMC Geriatr. 2015;15:158. https://doi.org/10.1186/s12877-015-0151-8. 38. Ohman H, Savikko N, Strandberg T, et al. Research paper: effects of frequent and long term exercise on neuropsychiatric symptoms in patients with Alzheimer’s disease-secondary analyses of a randomized, controlled trial (FINALEX). Eur Geriatr Med. 2017;8:153-157. https://doi.org/10.1016/jurger.2017.01.004. 39. Wayne P, Walsh J, Yeh G, et al. Effect of tai chi on cognitive performance in older adults: systematic review and meta-analysis. J Am Geriatr Soc. 2014;62(1):25-39. 40. Glass O, Forester B, Hermida A. Electroconvulsive therapy (ECT) for treating agitation in dementia (major neurocognitive disorder)-a promising option. Int Psychogeriatr. 2017;29(5):717-726. https://doi.org/10.1017/S1041610216002258. 41. Ahessy B. Research article: song writing with clients who have dementia: a case study. Arts Psychother. 2017;55:23-31. https://doi.org/10.1016/j.aip.2017.03.002. 42. Huang HC, Chen TJ, Chen PY, et al. Reminiscence therapy improves cognitive functions, and reduces depressive symptoms in elderly people with dementia: a meta-analysis of randomized controlled trials. J Am Med Dir Assoc. 2015;16(12):1087-1094. https://doi.org/10.1016/j.jamda.2015.07.010. 43. Tija J, Hunnicutt J, Herndon L, Blanks C, Lapane K, Wehry S. Association of a communication training program with use of antipsychotics in nursing homes. JAMA Intern Med. 2017;177(6):846-853. https://doi.org/10.1001/ jamainternmed.2017.0746. 44. Rokstad AM, Engedal K, Kirkevold O, Benth J, Barca M, Selbaek G. The association between attending specialized day care centers and the quality of life of people with dementia. Int Psychogeriatr. 2017;29(4):627-636. https:// doi.org/10.1017/S1041610216002015.
Cynthia L. Blevins , DNP, is an Adult and Family nurse practitioner at Penn State Health General Internal Medicine of Lancaster, PA. She is available at [email protected]. In compliance with national ethical guidelines, the author reports no relationship with business or industry that would pose a conflict of interest. 1555-4155/18/$ see front matter © 2018 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.nurpra.2017.11.027
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Dementia continues to escalate as the aging population increases, and there are no medications available to reverse this disease. Dementia-associated psychosis/behavioral disturbances can be attributed to frontal lobe, vascular, Alzheimer, Parkinson, and Lewy body dementia, but patients must be assessed for other etiologies. Care for these patients can be challenging. Some studies find certain medications to be effective, but they are not without risk. Medications can lead to falls and even demonstrate paradoxical effects, causing significant distress in patients as well as their families. Nonpharmacologic interventions may prove helpful and should be used first if possible. Keywords: Alzheimer, antipsychotics, dementia, dementia-associated psychosis, frontal lobe dementia, Lewy body dementia, Parkinson dementia, potentially inappropriate medications, vascular dementia Ó 2018 Elsevier Inc. All rights reserved.
S
arah, a 78-year-old retired schoolteacher with vascular dementia, was newly admitted to a local skilled nursing facility memory support unit. Upon admission, her medications consisted of 24 medications associated with hypertension, diabetes, heart disease, and dementia. Over time, her dementia worsened, and despite stable blood pressures and blood sugars, she showed the following signs of psychosis: constant agitation, confusion, and combative behaviors. Despite increases in antipsychotic medications and dementia medications, she unfortunately progressed and ultimately died of a fat embolus sustained after falling and fracturing her hip. Although the family was glad their loved one was no longer suffering, they stated that “this was difficult to observe, for our Mother would never have wanted to behave this way.” A review of the literature was subsequently conducted to determine additional interventions available for those caring with patients with dementia-related psychosis.
PREVALENCE OF DEMENTIA-ASSOCIATED PSYCHOSIS
Dementia is prevalent in 40% of the world’s population, with predictions for an even higher percentage by 2022.1 Subtypes include Alzheimer dementia, 178
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which is the most common, vascular dementia, Lewy body dementia, frontal lobe dementia, and Parkinson dementia.2 Dementia typically presents with cognitive decline and short-term memory loss. Unfortunately, cognitive impairment labeled as dementia can arise from many medications, such as antipsychotics, benzodiazepines, selective serotonin reuptake inhibitors, and anticonvulsants,3 leading to a misdiagnosis and inappropriate care. One study found that 24% of patients given a diagnosis of dementia who exhibited psychosis were found to not have dementia.4 Dementia symptoms can also be present in patients with thyroid disease, normal pressure hydrocephalus, brain tumors, subdural hematomas, and other etiologies.2 Dementia-associated psychosis can often occur at later stages of dementia, but this can vary.2 Psychotic behaviors include delusions, hallucinations, aggression, paranoia, and depression. One study showed a 40% prevalence of psychotic behaviors in Alzheimer patients, the most common type of dementia.5 This group demonstrated significantly more agitation than patients with mild cognitive impairment,5 reinforcing that psychosis is more prevalent as the disease progresses. Among patients Volume 14, Issue 3, March 2018
with Parkinson disease, 50% have psychosis.6 Frontotemporal dementia has consistently resulted in psychosis7 because this part of the brain affects the filter of patient’s thoughts and speech. Lewy body dementia and vascular dementia can also exacerbate into psychosis as the disease progresses.2 RISKS ASSOCIATED WITH PSYCHOSIS IN DEMENTIA PATIENTS
Agitation, aggressive, and combative behaviors associated with psychosis can create a domino effect within a memory support unit, contributing to a tense atmosphere for other patients. Patients with less severe conditions may become fearful that they too “may act that way some day.” Dementia-associated psychosis can be variable throughout the day, so patients can feel trapped in a dementia unit during fleeting moments of clarity. Those with dementia and psychosis have a higher rate of depression than dementia patients without psychosis,5 so it is not surprising that quality of life screening test scores were lower in patients with dementia and neuropsychiatric symptoms.8 Dementia-associated psychosis impairs judgment, which can lead to falls and associated injuries. When psychosis is present, it is challenging to meet the nutritional needs of patients, making them more prone to wounds and weight loss. When patients lose weight, a reduction in both diabetic and hypertension medications may be needed. Person-centered care can be difficult if patients are unable to express advanced directive wishes or share preferences regarding lifestyle choices or activities. Caregivers have a low to moderate agreement with patient choices for end-of-life care according to 1 study, reinforcing the need for early discussion of end-oflife choices before dementia ensues.9 CAREFUL DIAGNOSIS OF PSYCHOSIS ETIOLOGY IS ESSENTIAL
Psychosis is multifactorial and may be present in patients without dementia who have delirium, pain, uncontrolled diabetes or hypertension, neurologic impairment, or side effects from medications.10 A study examined case notes of 660 patients with psychotic behaviors and found that health care providers missed www.npjournal.org
various associated diagnoses, leading to the unnecessary use of antipsychotic medication. Sixty-eight percent of the sample had delirium, 27% had pain, 93% had depression or anxiety, and 71% had just started new medications before psychotic behaviors.11 According to 1 systematic review,11 poor control of pain can alter cognitive function and lead to psychosis behaviors. Inversely, patients with an actual diagnosis of dementia may not be able to verbalize that they have pain, so a careful assessment is necessary.12 A retrospective analysis with a large sample showed that the use of bladder antimuscarinics has been associated with cognitive decline.13 Anticholinergics should be avoided whenever possible in older patients with psychosis.2 There are conflicting reports about an association between urinary tract infections and psychosis, and, unfortunately, many older adults with colonized bacteria in their urine are actually treated unnecessarily for this presumed condition.14 PHARMACOLOGIC INTERVENTIONS FOR PSYCHOSIS IN DEMENTIA PATIENTS Benefits of Medications
Cholinesterase inhibitors may slow the progression of dementia but are not associated with the prevention of psychosis.15 In 1 study, 14 mg/d galantamine showed reduced agitation and was better tolerated than other medications in this class.16 Pimavanserin was approved by the Food and Drug Administration for Parkinson diseaseeassociated psychosis.17 A study of 181 patients receiving 34 mg pimavanserin daily showed a significant reduction in psychosis. However, this medication is currently considered off-label for use in patients with psychosis who do not have Parkinson disease. A randomized double-blind trial of risperidone (dosing not specified) versus placebo use in patients with dementia psychosis found that risperidone had a favorable risk versus benefit ratio.18 This study did state that this medication should only be used in cases with prominent psychotic and behavioral symptoms associated with distress, functional impairment, or danger to the patient. A retrospective study of 179 patients with dementia and behavioral disturbance showed buspirone to be effective in reducing agitation/ aggressive behaviors in 68.6% of the sample.19 The Journal for Nurse Practitioners - JNP
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Risks of Medications
A systematic review of articles about the safety and tolerability of psychotropic medications found that many times providers who prescribe these medications base this more on experience than science, and there are typically mixed results.20 Atypical antipsychotics such as aripiprazole, risperidone, quetiapine, and olanzapine are associated with an increased risk of acute myocardial infarction, and risperidone or olanzapine use increase the risk of hip fractures.21 A large study of patients with Alzheimer dementia treated with antipsychotic medications showed increased death rates from cancer, heart disease, infection, and intentional self-harm.22 The use of antipsychotic medications in patients with Parkinson disease increased physical morbidity in this group.23 Other guidelines, including the Beers criteria and STOPFrail, refer to antipsychotic medications as potentially inappropriate for older adults.24,25 Olanzapine, quetiapine, and risperidone have demonstrated variable efficacy in regard to psychosis management.26 Antipsychotics can increase QT prolongation, which can lead to falls and even a life-threatening arrhythmia.27 Underlying pain can exacerbate psychosis, but, unfortunately, pain medications such as opioids can increase the risk of falls.24 Benzodiazepines and antipsychotic medications, especially in higher doses, are also associated with falls.28,29 Antidepressants, antiepileptics, antipsychotics, benzodiazepine, and opioid receptor agonists are medications that are considered in the category of central nervous system burden. The use of more than 3 single doses of antipsychotic medications within 24 hours has been associated with falls.30 Medications prescribed to slow dementia progression may have a higher risk versus benefit because they are not always effective and can also increase fall risks.31 Citalopram reduced agitation in Alzheimer dementia patients but increased cognitive decline in 1 study.32 Because of the incidence of potential QT prolongation, another study found that citalopram should only be used in those with early-onset dementia.33 Genetic testing should be considered to determine the most effective medication to treat patients for psychosis.34 This testing is covered by Medicare and can be confusing 180
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to interpret but can indicate which medications are best metabolized by the individual patient. In some cases, the patient may require a lower or higher dose of specific medications because of their metabolic pathways. The benefit of this testing is that there is less experimentation with which medication is most effective, and it may reduce adverse drug reactions.35 Evaluation of Medication
As with treatment of any type of psychosis behavior, secondary causes must be eliminated first, and, unless there are adverse effects, adequate time should be given to evaluate the effectiveness of the medication. Medications should be administered first with the lowest possible dose, tapered upward slowly, and evaluated carefully. After starting citalopram with patients with Alzheimer dementia, they should be monitored for at least 9 weeks to determine effectiveness.36 Pimavanserin should be monitored for at least 6 weeks, not only for efficacy but also for side effects such as a prolonged QT interval or paradoxical effects when used for Parkinson diseaseeassociated psychosis.16 Should concerns be present, antipsychotics should not be stopped suddenly or hallucinations may occur.37 Prescribers should consider using the lowest doses possible and avoiding the use of multiple antipsychotics.22 EVIDENCE-BASED NONPHARMACOLOGIC TREATMENT FOR PSYCHOSIS IN DEMENTIA PATIENTS
Multiple geriatric and dementia organizations as well as research studies endorse nonpharmacologic treatments for patients who exhibit psychosis symptoms. It is recommended that these interventions be used as first-line treatment before any medications are implemented unless a patient exhibits potential harm to themselves or others.2 In 1 study of dementia patients with neuropsychiatric conditions, 41.9% of 123 patients with dementia and psychotic behaviors were given medication without any attempts to use nonpharmacologic interventions.36 The American Geriatrics Society recommends that comorbid conditions, such as hypertension and diabetes, are treated with the promotion of exercise, a balanced diet, and stress reduction.2 These interventions are clinically supported in the research Volume 14, Issue 3, March 2018
literature to be effective in most cases, but some studies refute the efficacy of such interventions. For example, a randomized controlled trial showed that a high-intensity functional exercise program reduced agitation and improved balance,37 yet another study demonstrated that regular long-term exercise intervention did not help Alzheimer dementia patients with the reduction of neuropsychiatric symptoms.38 Tai chi was shown to enhance cognitive function in older adults, especially among those with early-stage dementia.39 A systematic review showed that although electroconvulsive therapy may be an option, there is the need for more clinical trials.40 Song writing was found to be helpful in another case study.41 Reminiscence group therapy has proven to be effective in providing pleasant memories for patients with dementia who can recall things in the past, improves cognitive ability, and reduces depression according to a meta-analysis.42 This therapy involves discussing pleasant memories such as “my first car” or “my favorite trip.” Although there is no documented research that it prevents the progression of psychosis symptoms, it certainly bears further investigation. It may very well assist this population to hold on to good memories and be less agitated. What brings joy to one patient may certainly seem meaningless to another, reinforcing the need for individualized approaches, which can be quite challenging given staffing issues in most skilled nursing facilities. It is not unusual for a lack of understanding of what each patient truly is like underneath their façade of dementia or psychosis behaviors. A volunteer program can be very helpful for patients and benefit the volunteer as well. This may facilitate the fostering of a consistent relationship for the patient. Training nursing home staff about how to interpret behavioral and psychological symptoms of dementia reduced the use of antipsychotics in 1 skilled care facility.43 It also stands to reason that having a degree of consistency among caregivers, which is challenging for any skilled care facility, can help reduce the incidence of additional issues such as delirium, which would further exacerbate agitated behaviors. Individuals with dementia who attend specialized day care centers showed a higher quality of life, which is also promising.44 www.npjournal.org
IMPLICATIONS FOR FURTHER RESEARCH
More research must be done to further identify best practices for individualized care for those with dementia-associated psychosis. Although there is compelling evidence regarding the risks and benefits of current medications used for dementia psychosis, it is clear that establishing a firm diagnosis and associated etiologies for behaviors must be done first. Nonpharmacologic interventions should be tried with a patient-centered focus. Ongoing investigation regarding ways to provide the best care possible for patients with dementia-associated psychosis needs to continue. If pharmacologic intervention is used, it must be introduced slowly with an upward taper as needed and very close monitoring. Sadly, a review of the literature did not demonstrate consistent efficacy for dementia psychosis medication treatment. Consulting with those who specialize in the management of behavioral and psychological conditions is always wise, especially once all known options have not been effective. Perhaps the most compelling issue at this time is that providers need to submit data for publication if they find interventions that help this population so that all may benefit. As we continue to provide care for those with dementiaassociated psychosis, continued study must take place so that we can provide the best quality of life possible for those with this condition. References 1. Jacqmin-Gadda H, Alperovitch A, Joly P, et al. 20-year prevalence projections for dementia and impact of preventive policy about risk factors. Eur J Epidemiol. 2013;28(6):493-502. https://doi.org/10.1007/s10654-013-9818-7. 2. Reuben DB, Herr KA, Pacala JT, et al. Geriatrics at Your Fingertips: 2016. 18th ed. New York, NY: The American Geriatrics Society; 2016. 3. Aspinall SL, Zhao X, Semla TP, et al. Epidemiology of drug-disease interactions in older veteran nursing home residents. J Am Geriatr Soc. 2015;63:77-84. https://doi.org/10.1111/jgs.13197. 4. Fischer C, Qian W, Schweizer T, et al. Determining the impact of psychosis on rates of false-positive and false-negative diagnosis in Alzheimer’s disease. Alzheimers Dement (N Y). 2017;3:385-392. https://doi.org/10.1016/j.trci.2017/ .06.001. 5. Van der Mussele S, Marien P, Engelborgs S, et al. Psychosis associated behavioral and psychological signs and symptoms in mild cognitive impairment and Alzheimer’s dementia. Aging Ment Health. September 2015;19(9):818-828. https://doi.org/10.1080/13607863.2014.967170. 6. Ravina B, Marder K, Fernandez H, et al. Diagnostic criteria for psychosis in Parkinson’s disease report of an NINDS, NIMH work group. Mov Disord. 2014;29:1615-1622. 7. Schinagawa S, Nakajima S, Plitman E, et al. Psychosis in frontotemporal dementia. J Alzheimers Dis. 2014;42:485-499. https://doi.org/10.3233/JAD-140312. 8. Mjorud M, Kirkebold M, Rosvik J, Selaek G, Engedal K. Variables associated to quality of life among nursing home patients with dementia. Aging Ment Health. 2014;18(8):1013-1021. https://doi.org/10.1080/13607863.2014.903468. 9. Harrison Dening K, King M, Jones L, Vickerstaff V, Sampson EL. Advance care planning in dementia: do family carers know the treatment preferences of people with early dementia? PLoS One. 2016;11(7):e0159056. https://doi.org/ 10.1371/journal.pone.0159056. PMID: 27410259.
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10. Habiger T, Flo W, Achterberg W, Husebo B. The interactive relationship between pain, psychosis, and agitation in people with dementia: results from a cluster-randomised clinical trial. Behav Neurol. 2016;7036415:1-8. https:// doi.org/10.1155/2016/7036415. 11. O’Shea E, Timmons S, Kennelly S, deSiun A, Gallagher P, O’Neill D. Symptom assessment for a palliative care approach in people with dementia admitted to acute hospitals: results from a national audit. J Geriatr Psychiatry Neurol. 2015;28(4):255-259. https://doi.org/10.1177/0891988715588835. 12. Flo E, Gulla C, Husebo B. Effective pain management in patients with dementia: benefits beyond pain? Drugs Aging. 2014;31:863-871. https://doi.org/10.1007/ s40266-014-0222-0. 13. Moga D, Abner E, Wu Q, Jicha G. Bladder antimuscarinics and cognitive decline in elderly patients. Alzheimers Dement (N Y). 2017;3:139-148. https://doi.org/10.1016/j.trci.2017.01.003. 14. Hartley S, Valley S, Kuhn L, et al. Overtreatment of asymptomatic bacteriuria: Identifying targets for improvement. Infect Control Hosp Epidemiol. 2015;36(4):470-473. 15. Tampi R, Tampi D, Balachandran S. Antipsychotics, antidepressants, anticonvulsants, melatonin, and benzodiazepines for behavioral and psychological symptoms of dementia: a systematic review of meta-analysis. Curr Treat Options Psychiatry. 2017;4:55-79. https://doi.org/10.1007/s40501 -017-0104-2. 16. Freund-Levi Y, Bloniecki V, Auestad B, et al. Galantamine versus risperidone for agitation in people with dementia: a randomized twelve-week, single-center study. Dement Geriatr Cogn Disord. 2014;38(3-4):234-244. https://doi.org/10 .1159/000462204. 17. Hawkins T, Berman B. Pimavanserin. A novel therapeutic option for Parkinson disease psychosis. Neurol Clin Pract. 2017;1:157-162. 18. Tan L, Tan L, Wang HF, et al. Efficacy and safety of atypical antipsychotic drug treatment for dementia: a systematic review and meta-analysis. Alzheimers Res Ther. 2015;7(1):1-13. https://doi.org/10.1186/s13195-015-0102-9. 19. Santa Cruz MR, Hidalgo PC, Lee MS, et al. Buspirone for the treatment of dementia with behavioral disturbance. Int Psychogeriatr. 2017;5:859-862. https://doi.org/10.1017/S1041610216002441. 20. Forlenza O, Loureiro J, Pais M, Stella F. Recent advances in the management of neuropsychiatric symptoms in dementia. Curr Opin Psychiatry. 2017;30:151-158. https://doi.org/10.1097/YCO.0000000000000309. 21. Farlow MR, Shamliyan TA. Benefits and harms of atypical antipsychotics for agitation in adults with dementia. European Neuropsychopharmacol. 2017;27:217-231. https://doi.org/10.1016/jeuroneuro.2017.01.002. 22. Nielsen RE, Lolk A, Rodrigo-Domingo M, Valentin JB, Anderson K. Antipsychotic treatment effects on cardiovascular, cancer, infection and intentional self-harm as cause of death in patients with Alzheimer’s dementia. Eur Psychiatry. 2016;42:14-23. https://doi.org/10.1016/j.eurpsy.2016.11.013. 23. Weintraub D, Chiang C, Kim HM, et al. Antipsychotic use and physical morbidity in Parkinson disease. Am J Geriatr Psychiatry. 2017;25:697-705. https://doi.org/10.1016./j.jagp.2017.01.076. 24. Lavan A, Gallagher P, Parsons C, O’Mahony D. STOPPFrail (Screening Tool of Older Persons Prescriptions in Frail adults with limited life expectancy): consensus validation. Age Ageing. 2017;46(4):600-607. 25. American Geriatrics Society. American Geriatrics Society updated Beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63(11):2227-2246. https://doi.org/10.1111/jgs.13702. 26. Nowrangi MA, Lyketsos CG, Rosenberg PB. Principles and management of neuropsychiatric symptoms in Alzheimer’s dementia. Alzheimers Res Ther. 2015;7:12. https://doi.org/10.1186/s13195-015-0096-3. 27. Wu CS, Tsai YT, Tsai HJ. Antipsychotic drugs and cardiovascular safety: current studies of prolonged QT interval and risk. J Am Heart Assoc. 2015;23(4):62-72. https://doi.org/10.1161/JAHA.114.001568. 28. Bozat-Emre S, Doupe M, Kozyrskyj AL, Grymonpre R, Mahmud SM. Atypical antipsychotic drug use and falls among nursing home patients in Winnipeg, Canada. Int J Geriatr Psychiatry. 2015;30(8):842-850. https://doi.org/10.1002/ gps.4223. 29. Echt MA, Samelson EJ, Hannan MT, Dufour AB, Berry SD. Psychotropic drug initiation or increased dosage and the acute risk of falls: a prospective cohort study of nursing home residents. BMC Geriatr. 2013;13(19):1-8. https://doi.org/ 10.1186/1471-2318-13-19.
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30. Hanlon J, Zhao X, Thorpe C, et al. Central nervous system (CNS) medication burden and serious falls in older nursing home residents. J Am Geriatr Soc. 2017;65(6):1183-1189. 31. Epstein NU, Guo R, Farlow MR, Singh JP, Fisher M. Medication for Alzheimer’s disease and associated fall hazard: a retrospective cohort study from the Alzheimer’s disease neuroimaging initiative. Drugs Aging. 2014;31(2):125-129. https://doi.org/10.1007/s40266-013-0143-3. 32. Lyketsos CG, Pollock BG, Schneider L, Porsteinsson AP. Citalopram for agitation in AD: pharmacokinetic studies, subgroup analyses, and effect on other neuropsychiatric symptoms. AAGP Annual Meeting, Session 412. Am J Geriatr Psychiatry. 2016;24(suppl 1):3. https://doi.org/10.1002/gps.4223. 33. Schneider L, Frangakis C, Lyketsos C, et al. Heterogeneity of treatment response to Citalopram for patients with Alzheimer’s disease with aggression or agitation: the CitAD Randomised Clinical Trial. Am J Psychiatry. 2016;173(5):465-472. https://doi.org/10.1176/appi.ajp.2015.150648. 34. Santini S, Panza F, Lozupone M, Bellomo A, Seripa D. Genetics of tailored medicine: focus on CNS drugs. Microchem J. 2018;136:164-169. https://doi.org/ 10.1016/j.microc.2017.02.018. 35. Weintraub D, Drye L, Posteinson A, et al. Time to response to citalopram treatment for agitation in Alzheimer disease. Am J Geriatr Psychiatry. 2015;23(11):1127-1133. https://doi.org/10.1016/j.jagp.2015.05.006. 36. Patel A, Lee S, Andrews H, et al. Prediction of relapse after discontinuation of antipsychotic treatment in Alzheimer’s disease: the role of hallucinations. Am J Psychiatry. 2017;174(4):362-369. 37. Telenius EW, Engedal K, Bergnald A. Long-term effects of a 12 weeks highintensity functional exercise program on physical function and mental health in nursing home patients with dementia: a single blinded randomized controlled trial. BMC Geriatr. 2015;15:158. https://doi.org/10.1186/s12877-015-0151-8. 38. Ohman H, Savikko N, Strandberg T, et al. Research paper: effects of frequent and long term exercise on neuropsychiatric symptoms in patients with Alzheimer’s disease-secondary analyses of a randomized, controlled trial (FINALEX). Eur Geriatr Med. 2017;8:153-157. https://doi.org/10.1016/jurger.2017.01.004. 39. Wayne P, Walsh J, Yeh G, et al. Effect of tai chi on cognitive performance in older adults: systematic review and meta-analysis. J Am Geriatr Soc. 2014;62(1):25-39. 40. Glass O, Forester B, Hermida A. Electroconvulsive therapy (ECT) for treating agitation in dementia (major neurocognitive disorder)-a promising option. Int Psychogeriatr. 2017;29(5):717-726. https://doi.org/10.1017/S1041610216002258. 41. Ahessy B. Research article: song writing with clients who have dementia: a case study. Arts Psychother. 2017;55:23-31. https://doi.org/10.1016/j.aip.2017.03.002. 42. Huang HC, Chen TJ, Chen PY, et al. Reminiscence therapy improves cognitive functions, and reduces depressive symptoms in elderly people with dementia: a meta-analysis of randomized controlled trials. J Am Med Dir Assoc. 2015;16(12):1087-1094. https://doi.org/10.1016/j.jamda.2015.07.010. 43. Tija J, Hunnicutt J, Herndon L, Blanks C, Lapane K, Wehry S. Association of a communication training program with use of antipsychotics in nursing homes. JAMA Intern Med. 2017;177(6):846-853. https://doi.org/10.1001/ jamainternmed.2017.0746. 44. Rokstad AM, Engedal K, Kirkevold O, Benth J, Barca M, Selbaek G. The association between attending specialized day care centers and the quality of life of people with dementia. Int Psychogeriatr. 2017;29(4):627-636. https:// doi.org/10.1017/S1041610216002015.
Cynthia L. Blevins , DNP, is an Adult and Family nurse practitioner at Penn State Health General Internal Medicine of Lancaster, PA. She is available at [email protected]. In compliance with national ethical guidelines, the author reports no relationship with business or industry that would pose a conflict of interest. 1555-4155/18/$ see front matter © 2018 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.nurpra.2017.11.027
Volume 14, Issue 3, March 2018