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You are prohibited from making this PDF publicly available. isIt illegal to post this copyrighted PDF on any website. J ClinPsychiatry 82:4,July/August 2021 For [email protected]. reprints orpermissions, contact ♦ © Copyright 2021Physicians Postgraduate Press, Inc. To https://doi.org/10.4088/JCP.AD19038AH5C share: Psychiatry. treatmentevidence-based for dementia-related psychosis. JClin cite: To 2021;82(4):AD19038AH5C J ClinPsychiatry page.appears onthenext personal financialrelationships. Faculty financialdisclosure any staffreported CMEInstitute relevant the member of Data Committee Safety andMonitoring for Janssen.No Independent the and Sunovion; andhasbeenamemberof Alkermes, boards for Otsuka, advisory the been amemberof Chief, hasreceived research fundingfrom has JayMac andSage; identified. thepastyear, In P. Marlene Freeman, MD, Editor in hasresolvedCME Institute any ofinterest conflicts that were andany commercialor theirspouse/partner interest. The relevant personalfinancial relationships between themselves were askedtoactivity complete astatement regarding all this All individualsinapositionto influence thecontent of Financial Disclosure material was2023. May 2021. this The latest review of eligible 1Credit for™ through Category AMAPRA August 31, was publishedinJune2021andis This educational activity Release, Expiration, andReview Dates continuing medicaleducation for physicians. for Continuing Education Medical to provide Inc., isaccredited by theAccreditation Council The ofPhysicians CMEInstitute Postgraduate Press, This in thePosttest, andcomplete theEvaluation. To questions obtaincredit, answer correctly read the thearticle, needs withdesired results. areActivities plannedusingaprocess that linksidentified throughout eachvolume.topics of onavariety CME articles ofprovidingwith thepurpose readers of withacurriculum educational needsofCMEparticipants, the assessment of are for selected creditArticles designation basedonan CME Background Accreditation Statement youAfter shouldbeableto: studyingthisarticle, CME Objective Neuroscience at King’s College London. NHS Foundation ofPsychiatry, andInstitute Psychology & Biomedical Research Centre London at South andMaudsley Aarsland, MD, PhD,National for Institute HealthResearch andHealth,UK. of Medicine member wasThe Dag faculty MRCPsych,MMedSci, MD,University ofExeter College The teleconference was chaired by Clive Ballard, MBChB, educational grant from ACADIA Pharmaceuticals Inc. of Physicians Postgraduate Press, by an Inc.,andwas supported prepared andindependently developed by theCMEInstitute which was heldinMay andJune2020. was This report “Dementia-Related Psychosis: Recognition and Treatment,” teleconferencethe series presentsPsychiatry thehighlights of • patients withdementia Provide therapies to managepsychosis in evidence-based A c Ballard C, Aarsland D. Aarsland Ballard C, through burden caregiver Relieving ademic 2021;82(4):AD19038AH5C H Academic Highlights Academic ighligts section ofTheClinical Journal section A 20%. dementiavascular (VaD) with aprevalence of about depression. dementia, such as psychosis, aggression, agitation, and behavioralexperience and psychological symptoms of cognitive decline, 90%of patients with dementia experiences oftenexperiences feature people or animals. patients complex experiencing hallucinations daily. The dementia. for about 60%–70%of dementia cases, of dementia is Alzheimer’s (AD),accounting disease feature of DLB (18%). Recurrent hallucinations visual are acore moreoccurred frequently (36%)than hallucinations inaboutoccurred 40%of patients with AD;delusions burden. institutionalization, cognitive decline, and caregiver includes delusions and hallucinations, contributes to and frontotemporal dementia (FTD). (DLB), Parkinson bodies (PD) dementia,Lewy disease and DagAarsland, MD, PhD Clive Ballard, MBChB, MMedSci, MRCPsych, MD, Related Psychosis Treatment for Dementia- Through Evidence-Based Relieving Caregiver Burden factors that contribute to DRP indiscussions with the (Figure 1). delusions and hallucinations inpeople with dementia in some individuals. may increase over infrequency and time persistent be people living with DRP and care their partners. addresswill practices for best improving outcomes for symptoms, and 14(17%)were severely distressed. patients (45%)were distressed mildly by psychotic their daily and between frequency weekly. Thirty-seven most patients psychotic experienced symptoms at a patients with dementia and at least 1psychotic symptom, PSYCHOSIS OVERVIEW OF DEMENTIA-RELATED According to Dr Aarsland, clinicians must probe A complex interplay of factors can contribute to Dr Aarsland stated that delusions and hallucinations A review In Academic this Highlights, Drs Ballard and Aarsland © 2021Copyright Physicians Postgraduate Press, Inc. 2 living with dementia. n estimated 50million people worldwide are Other types of types dementia Other include dementia with 5 8 13–16 Simple hallucinations are rare, with most 4 6 Dementia-related psychosis (DRP), which of 55studies showed that psychosis 7 and are acommon characteristic of PD 10,11 According to astudy 1 The most common type 3 Along with 1 followed by 8,9 12 of 83 12

1 Academic Highlights 2 For [email protected]. reprints orpermissions, contact ♦ It isIt illegal to post this copyrighted PDF on any website. tasks, patient’sthe ability to perform cognitive and functional reaction. understand and acknowledge patient’s the emotional impressions are not real; it is more to helpful to try to convinceor try that them thoughts these or sensory helpful for clinicians or carers to argue with patients on DrAarsland’s it experience, clinical is usually not that might initiate or maintain behaviors. the Based therewhether are factors before or after occurrence the apparentwhether delusions and true might be infact patients and carers, it is important to always explore both patient (ifpossible) and care the partner. When to talking person” for police the or evencall help. housethe should who not there, be may after “the run hallucinations,experiencing such aperson in as seeing adding to carer distress, DrAarsland explained, patients CAREGIVERS PSYCHOSIS ON PATIENTS AND IMPACT OF DEMENTIA-RELATED publisher orthecommercial supporter. CMEprovider and the theopinionsof not necessarily reflect anddo faculty the The opinionsexpressed herein are thoseof of interest. balance by theChairandapeerreviewer whoiswithoutconflict was evaluated foractivity accuracy, useofevidence, andfair submitted content was validated by staff, CMEInstitute andthe theplanningsessions. during CME objective(s) The faculty’s presentation anddiscussed thetopic(s)evidence-based and member(s)agreedThe faculty to provide a balanced and Review Process Heptares, Cura. andMentis asapaidconsultant forand hasserved Lundbeck, Eisai, from AstraZeneca, Biogen,andGEHealth Lundbeck, Novartis, AarslandhasreceivedDr and/orhonoraria research support boards for Acadia, Roche, AARP, Synexus, andNovo Nordisk. speakers/advisory the and Novo Nordisk;andisamemberof Nordisk; hasreceived grant/research from Synexus support Acadia, Roche, Lundbeck, Exevia, AARP, Synexus, andNovo BallardDr isaconsultant for andhasreceived honoraria from Financial Disclosure the ACCME. 1Credit™ from Category AMA PRA organizations accredited by for for certified educational activities ofparticipation certificates Academythe American ofPhysician Assistants (AAPA) accept Note: The NursesCredentialing American Center (ANCC) and the activity. in participation their credit commensurate withtheextentof 1Credit™. Physicians Category 1 AMAPRA shouldclaimonlythe fordesignates amaximumof CMEactivity thisjournal-based The ofPhysicians CMEInstitute Postgraduate Press, Inc., Credit Designation

Delusions and hallucinations may directly impact

17 which can which contribute to carer distress. 18,19 Further Scale (NPI-D). Scale and Neuropsychiatric the Inventory Caregiver Distress connection care the between and partner patient. the symptoms adversely can also impact emotional the hallucinations threatening. to be of insight appears consider they to whether affect patient that psychotic symptoms are not persistent inevery distress. with caregivers may own helptheir to relieve some of patients. DrBallard said that discussing perspective this that 40%of delusions didnot cause discomfort to the describe symptomsdescribe according to presentations. their if providers avoid terms such as psychotic schizophrenia. Individuals may more be comfortable understanding of psychosis patients and caregivers. DrBallard noted that lay the options. possible for people to knowledgeably treatment discuss risks of medications to treat used DRP. Then, it is insight), potential the course of DRP, and potential the DRP on well-being, level their of distress (and patients’ with patientsto talk and caregivers about impact the of but may also cause lack of for sleep carers. in patients, are which challenging for carers to address, to increased agitation and reduced daytime functioning associated with psychotic symptoms may not only lead stressful forbe carer. the For instance, disturbances sleep troublesome affective and behavioral symptoms that can might not dramatic, be are they often accompanied by Burden Interview, impactthe of DRP on care including partners, Zarit the negative impact on carers, help care cope partners with DRP. emotion-based and problem-focused interventions necessarily cause distress to patients. it’s my health.” affecting succeed isbecause ofCOVID. I’m inaconstant state ofpanicand to seehertoa lawyer doanewwill. The onlyreason theydidn’t everything. Ieven foundoutthat [ascammer] triedgettingin scammers thatare stillinregular contact withher. Shetells them is. Shealsowants to knowhow much there is. Shehasfinancial her money. Sheisalways hermoneyandwhere about it asking barely understandswhatthatisandthinksIjustgoshoppingwith for losingherindependence. I’m herpower ofattorney andshe bitteryears towards ago .Sheisvery mesince sheblamesme motherwas“My diagnosedwithvascular dementiaalmost2 Here, arelative herongoingstress: describes Another point that may help care is partners Terminology is important discussing when DRP with Dr Ballard explained that he has found it important Additionally, although some psychotic symptoms Dr Aarsland to recommended measure scales several Although psychotic symptoms can have an immense Family Perspectives © 2021Copyright Physicians Postgraduate Press, Inc. 32–34 ; they can last; they for less than 3months. 25 Cognitive-behavioral therapy 23 the Relatives’ the Stress (RSS), Scale 22 J ClinPsychiatry 82:4,July/August 2021 28,29 is usually associated with the symptoms the donot 30 One study 12 Patients’ degree and instead 20 Psychotic 31 26,27 found 35 or or 26 24 may may 21

You are prohibited from making this PDF publicly available. You are prohibited from making this PDF publicly available. Administration (FDA) requires a“black box” warning in patients with dementia, risk of mortality, other known harms, and limited efficacy on atypical antipsychotic labels indicating an increased similar warnings. for agitation or psychosis inindividuals with dementia, people with DLB, a pharmacologic treatment alternative for psychosis in (APA) practice guideline Guidance onAtypical Antipsychotics inDRP with other dementias. psychosis inpatients with dementia, may play alimited role short-term inthe management of J ClinPsychiatry 82:4,July/August 2021 For [email protected]. reprints orpermissions, contact ♦ others indanger. not causing aggressive behavior that puts patient the and probably ifsymptoms not necessary are not severe and are BasedonCerejeira etal, 2 against balanced be risk of the significant harms (Figure EVIDENCE-BASED TREATMENT It isIt illegal to post this copyrighted PDF on any website. Figure 1. Factors Contributing to Psychotic Symptoms inPatients With Dementia 41,42 According to American the Psychiatric Association Dr Ballard explained that pharmacologic treatment is ). 38 DrBallard noted that US Food and the Drug imbic structures Frontostriatal circuits Prefrontal cortex Social Environmental, factors Psychosocial 36–38 44 45 Cholinesterase inhibitors may provide but are benefits less clear inpeople 13 ElHajetal, Although atypical antipsychotics Drugs 46 4 on of use the antipsychotics and European agencies have brain changes Structural 14 Cohen-Mansfield etal, 39,40 any has benefit to Pain Hallucinatins elusins and 15 and Targum. Genes 43

16 (NPI) Dr Ballard recommended Neuropsychiatric the Inventory Response with should aquantitative assessed be measure. haloperidol should absence inthe of not used delirium.) be as tolerated. low and dose titrated up to minimum the dose effective an antipsychotic, treatment the should initiated be at a maker. assessment risk-benefit favorsthe If of use the (if feasible), family, and/or surrogate the decision byassessed clinician the with patient the and discussed is initiated, potential the risks and must benefits be that, before nonemergency treatment with an antipsychotic significant distress to patient. the The APA recommends symptoms are severe, are dangerous, and/or cause antipsychotic medication only should used when be antipsychotic agent should not used. be recurrence of symptoms. Along-acting injectable previous attempts at tapering were associated with medicationthe should made within 16 weeks be unless respond adequately, an attempt to taper and withdraw should tapered be and withdrawn. disease Physical If no response is evident after 4weeks, medication the 47–49 © 2021Copyright Physicians Postgraduate Press, Inc. changes Neurochemical for assessment and monitoring. 41,46 (The first-generation antipsychotic deficits Sensory deficits Cognitive needs Unmet 46 Acetylcholine Serotonin oradrenaline Dopamine Among who those Academic Highlights

3 Academic Highlights Zhang etal pimavanserin, 5-HT aselective symptoms among nursing home residents with severe psychotic with AD, PD dementia, VaD, DLB, and FTD(including may hallucinations decrease and delusions inpatients receptors. antagonism of dopaminergic, muscarinic, or histaminergic antipsychotics, pimavanserin has no clinically significant treatmentin the of PD psychosis. Unlike other atypical widespread, long-term treatment solution. short-term treatment. Atypical antipsychotics are not a with severe symptoms, risks may the worthwhile be with context of many potential harms; however, for patients antipsychotic for DRP may have marginal inthe benefits indication. 4 For [email protected]. reprints orpermissions, contact ♦ APAthe guidelines, and delusions associated with PD. is FDA-approved for treatmenthallucinations the of It isIt illegal to post this copyrighted PDF on any website. hallucinations and getsaggressive down.” whenthesun goes phases. He’s generally happy, thenhasafewdaysofconstant antipsychotic] madehimhallucinate more. through .He goes medications. father-in-law sensitive"My to isvery certain [One a patient withPD-related psychosis: Here, thestruggleto afamilymemberdescribes findtherapy for Dr Ballard summarized that apatient treated with an Dr Ballard explained that since 2016publication the of

Family Perspectives Basedon Tampi etal Figure 2. Potential Adverse Serious Effects With Atypical Antipsychotics inPatients With Dementia 52 54 51 Evidence ), but it is not FDA-approved for this concluded that pimavanserin is effective edema urinary tract infection, Urinary incontinence, 46 53 evidence has become evidence available on Pneumonia indicates that pimavanserin 41 Death and Yunusa etal. 2A inverse agonist, which 50 Ameta-analysis by 42 55 56 Trials at 30mg/d the dose. however, adverse may effects limit its application practical interventions, BPSD recommend first-line of use non-pharmacologic beneficial treatmentbeneficial for BPSD inpatients with AD. Alternatives to Antipsychotics the treatmentthe of agitation than psychosis. that, although practice guidelines psychotic symptoms, hallucinations, visual particularly with LBD have inreducing shown significant efficacy reduced with citalopram compared with placebo Association, which of the following statementsthe isaccurate? Association, which of According to guidelinesprovided by Psychiatric theAmerican She hasbecome increasingly suspiciousover thelast5days. moderate severity. Annette lives at homewithherhusband. Annette, aged85years, hasParkinson diseasedementia of activity. the response best can foundattheendof be the of Discussion d. c. b. a. Medications. Nonpharmacologic interventions. Case Practice Question A nonpharmacologic isthetop intervention priority. delirium. The firststep shouldbeinvestigation ofpossiblecauses assoonpossible.antipsychotic shouldbe started Given ofAnnette’s theseverity symptoms, anatypical This isaclearpresentation ofdementia-related psychosis. 45,62,63 © 2021Copyright Physicians Postgraduate Press, Inc. assessing cholinesterase inhibitors inpeople 38,57,58 Both delusions Both and hallucinations were effects/parkinsonism extrapyramidal cognitive decline, Sedation, stroke, these strategies these are more for effective 60 Masupirdine is apotentially J ClinPsychiatry 82:4,July/August 2021 effects Cardiovascular gait Abnormal 38 for treatment the of DrBallard stated 59 ; 61

You are prohibited from making this PDF publicly available. You are prohibited from making this PDF publicly available. 2. directed therapies apotential could be treatment for DRP. J ClinPsychiatry 82:4,July/August 2021 For [email protected]. reprints orpermissions, contact ♦ 8. 7. 6. 5. 3. 1. Disclosure of off-labelusage: Published online: be needed. danger to patients or others, short-term medication may care on Depending partners. levels the of distress and support to relieve burden the of DRP on patients and their must prepared be to offer strategies and educational environmental, and psychological social, factors. Clinicians but quetiapine 4. Administration psychosis. for the treatment of dementia-related Drug and USFood the by approved are therapies no knowledge, his of REFERENCES CONCLUSION It isIt illegal to post this copyrighted PDF on any website. significant distress to thepatient. only whensymptoms are severe, are dangerous, and/orcause recommend that antipsychotic medication shouldbeused Guidelines provided by Psychiatric theAmerican Association confusion, investigation shouldbethefirststep. ofdelirium Given theacute presentation associated withincreased Preferred response isc. ■ ■ ■ ■ ■

■ ■ ■ considerable. is marginal, adverse ofserious andtherisk effects is treatmentrole asshort-term for DRP; long-term efficacy that antipsychoticsExplain to care have partners alimited to feel lessdistressed themselves. are causingdistress to patients; ifnot, caregivers may beable Talk withcaregivers aboutwhetherthepsychotic symptoms usingappropriatecare rating partners scales. Assess thedistress andburden ofDRPinbothpatients and behind DRP. Consider environmental, social, andpsychological factors Mechanisms DRP behind include neurobiological, Accessed July 14, July 2020. Accessed 19, 2019. September Published Organization. Health World Dementia. symptoms-dementia-related-psychosis/ neurologyreviews.com/newsletter/prevalence-neuropsychiatric- Int Res BioMed Alzheimer’s and vascular types. dementia: of epidemiology Global M. Roriz-Cruz I, Rosset L, Rizzi detail/dementia Mosimann UP, Rowan EN, Partington CE, et al. Characteristics of visual visual of Characteristics al. et CE, UP, Partington EN, Mosimann Rowan JPsychiatry Am 1990 2003. to from published 55 of studies areview disease: Alzheimer’s of psychosis for factors risk and of DV. Epidemiology Jeste SA, Ropacki Cognition. Than More Psychosis. Dementia-Related in Symptoms Neuropsychiatric of Prevalence The DP,Devanand GT, Grossberg Z, Khachaturian et al. Cognition: Than More Consortium. Neurology DLB the of report consensus fourth bodies: Lewy with dementia of management and Diagnosis DW, al. BF, et Boeve Dickson IG, McKeith dementia. Am J Psychiatry Geriatr in psychosis of epidemiology The al. et JCS, Breitner A, Voulgari I, Leroi Drugs of potential CNS drug candidates. and clinical effects pharmacology the of areview aggression: and agitation psychosis, dementia-related of Management al. et N, Fajkis J, Śniecikowska M, Marcinkowska Discussion ofCaseDiscussion Practice Question PointsClinical . 2020;34(3):243–268. July 6, 2021. 6, July 65 . 2005;162(11):2022–2030. has not demonstrated Finally, benefit. tau- . 2017;89(1):88–100. https://www.who.int/news-room/fact-sheets/ Dr Ballard PubMed

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5 CrossRef . Academic Highlights 6 For [email protected]. reprints orpermissions, contact ♦ 52. 51. 50. 49. 48. 47. 46. 45. 44. 43. 42. 41. 40. 39. 38. It isIt illegal to post this copyrighted PDF on any website. Int Psychogeriatr Int consensus. Delphi international Yunusa I, El Helou ML, Alsahali S. Pimavanserin: a novel antipsychotic with with antipsychotic anovel Pimavanserin: S. Alsahali ML, Helou El I, Yunusa TreatDis Neuropsychiatr meta-analysis. and review a systematic psychosis: disease Parkinson’s for antipsychotics Fan Y, L, Wang Atypical H, al. et Zhang P&T Parkinson’s disease. with associated delusions and hallucinations for atreatment (Nuplazid): MP.Cruz Pimavanserin 2010;22(6):984–994. Psychogeriatr Int dementia. in symptoms neuropsychiatric of assessment arevised of validity and reliability (NPI-C): scale rating Clinician Inventory- Neuropsychiatric The al. P, et S, Robert Gauthier K, Medeiros de in dementia patients. Neurology psychopathology assessing Inventory: Neuropsychiatric The JL. Cummings 1994;44(12):2308–2314. comprehensive assessment of psychopathology in dementia. Neurology Inventory: Neuropsychiatric The al. et K, Gray M, Mega JL, Cummings 2016;173(5):543–546. JPsychiatry Am dementia. with patients in psychosis or agitation treat to antipsychotics of use the on guideline practice Association Psychiatric American The al. et AE, Eyler LJ, Fochtmann VI, Reus Ann Neurol trial. placebo-controlled arandomized, bodies: Lewy with dementia for Donepezil Investigators. Study Donepezil-DLB K; Kosaka M, Ikeda E, Mori Saf Drug practice. general UK in warnings: of study longitudinal nationalcontext guidance and drug safety the in psychosis of adiagnosis without dementia with diagnosed patients to prescribing Antipsychotic RT, al. Webb et E, Kontopantelis SJ, Stocks 2005;330(7497):922. BMJ dementia. for drugs antipsychotic using about FDA J. warns Lenzer Open Netw analysis. JAMA meta- anetwork dementia: of symptoms psychological and behavioral of treatment the in antipsychotics atypical of safety and effectiveness comparative reported of Assessment al. et AE, Garba A, Alsumali I, Yunusa Dis Chronic Adv Ther meta-analyses. from risks and benefits of review a systematic dementia: in use Antipsychotic al. et S, Tampi DJ,Tampi Balachandran RR, 2018;178(5):640–647. 2014. to Med 2009 Intern From JAMA States United the in Care Long-term in Psychotropics Other and Antipsychotics of Use the With Care Dementia Improve to Partnership National Services’ & Medicaid Medicare for Centers the of Association al. et C, Chiang DT, HM, Maust Kim Lancet study. Public Health cohort retrospective 2015: to 2005 from UK alongitudinal the in dementia with people for treatment and diagnosis Trends in al. et N, Black N, Fox K, Donegan Physician appropriate nondrug interventions and antipsychotic use. Fam Am dementia: in disorders Behavioral KE. DJ, Cocker Thiel TR, Reese

2. 1. . 2019;15:2137–2149. . . 2016;94(4):276–282. . 2012;72(1):41–52. . . 2016;7(5):229–245.. accurately treatment anevidence-based optionthat reflects you shouldadvisefor at Bonnie thistime? sleeping,delusions. care. alsohasdifficulty Bonnie andJuliaisexhausted by around-the-clock Which statement Several appointments later, Juliatells you that isnow Bonnie frequently experiencing hallucinations and psychosis (DRP), whichstatement would accurately explain thepotential causeofDRPto Julia? that seemscomforted by Bonnie the"dog," sosheignores it. As you relay information aboutdementia-related her to appointments, mentions that sometimeshermotherspeaksto adogthat Juliacannotsee. Juliasays loss, findsitdifficultto Bonnie communicate isolated. andis often Bonnie’s daughter Julia,whoaccompanies You have an85-year-old patient, Bonnie, whopresented care. withmilddementia ofhearing inprimary Because d. c. b. a. d. c. b. a. DRP dementias inpeople with all You that advise cholinesterase inhibitors provide treatment an evidence-based alternative to atypical antipsychotics for associated of with use the atypical antipsychotics in people like Bonnie You explain to Julia that increased mortality, stroke, and accelerated cognitive decline are well established adverse events as possible You tell Julia that ifher mother responds well to an atypical antipsychotic, treatment the should continued be for as long You prescription the advise of an atypical antipsychotic, is which approved for treatment the of DRP ofAll above the Bonnie’s environment social may contribute to risk of the DRP Neurochemical mechanisms are likely an to be important cause of DRP deficits, includingBonnie’sSensory hearing loss, may contributerisk the to of DRP PubMed

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