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1
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Cohen-Mansfield J, Golander H. Responses and Interventions to Delusions Experienced by Community-Dwelling Older Persons With Dementia. J Geriatr Psychiatry Neurol 2022; 35:627-635. [PMID: 34510943 PMCID: PMC9210107 DOI: 10.1177/08919887211042937] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
We examined how family caregivers react, and what interventions they use in response to delusions exhibited by relatives with dementia in a community setting. Structured interviews were conducted with 68 family caregivers whose relatives were described as experiencing delusions based on the BEHAVE-AD or the NPI. Quantitatively, we cross-tabulated the type of response to delusion by the type of person providing the response and by the type of delusion manifested. Qualitatively, we analyzed open-ended responses to understand the types of caregivers' responses to delusions, the contextual circumstances, and the impact of the responses. Caregiver responses to delusions included "Explaining that the delusion was wrong" (34% of responses), "Trying to calm down" (27%), "Agreeing with the delusion" (13%), "Distracting" (12%), and "Ignoring" (10%). Responses including "Anger, yelling or scolding," were rare. The vast majority of reactions were by family caregivers of the persons with dementia. The relative frequency of the type of reaction tended to be consistent across delusion types. The qualitative analyses added some categories of reactions, but mostly highlighted issues to be considered when examining responses and their efficacy, including the use of multiple responses, and the manner and mood in which responses are conveyed. To cope with delusions, family caregivers develop intuitive intervention techniques. Understanding those interventions and reactions by caregivers and their relative efficacy can inform guidance programs for family caregivers. Improved support for family caregivers has the potential to positively influence the behavior of caregivers and older adults with dementia and improve their respective quality of life.
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Affiliation(s)
- Jiska Cohen-Mansfield
- Department of Health Promotion, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel,Minerva Center for the Interdisciplinary Study of End of Life, Tel Aviv University, Tel Aviv, Israel,The Herczeg Institute on Aging, Tel Aviv University, Tel Aviv, Israel,Jiska Cohen-Mansfield, Tel-Aviv University, P.O.B. 39040, Ramat Aviv, Tel Aviv, 6139001, Israel.
| | - Hava Golander
- Minerva Center for the Interdisciplinary Study of End of Life, Tel Aviv University, Tel Aviv, Israel,The Herczeg Institute on Aging, Tel Aviv University, Tel Aviv, Israel,Department of Nursing, The Stanley Seyer School of Health Professions, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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2
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Malekizadeh Y, Williams G, Kelson M, Whitfield D, Mill J, Collier DA, Ballard C, Jeffries AR, Creese B. Whole transcriptome in silico screening implicates cardiovascular and infectious disease in the mechanism of action underlying atypical antipsychotic side effects. ALZHEIMER'S & DEMENTIA (NEW YORK, N. Y.) 2020; 6:e12078. [PMID: 32864416 PMCID: PMC7443741 DOI: 10.1002/trc2.12078] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 07/09/2020] [Accepted: 07/28/2020] [Indexed: 01/05/2023]
Abstract
BACKGROUND Stroke/thromboembolic events, infections, and death are all significantly increased by antipsychotics in dementia but little is known about why they can be harmful. Using a novel application of a drug repurposing paradigm, we aimed to identify potential mechanisms underlying adverse events. METHODS Whole transcriptome signatures were generated for SH-SY5Y cells treated with amisulpride, risperidone, and volinanserin using RNA sequencing. Bioinformatic analysis was performed that scored the association between antipsychotic signatures and expression data from 415,252 samples in the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) repository. RESULTS Atherosclerosis, venous thromboembolism, and influenza NCBI GEO-derived samples scored positively against antipsychotic signatures. Pathways enriched in antipsychotic signatures were linked to the cardiovascular and immune systems (eg, brain derived neurotrophic factor [BDNF], platelet derived growth factor receptor [PDGFR]-beta, tumor necrosis factor [TNF], transforming growth factor [TGF]-beta, selenoamino acid metabolism, and influenza infection). CONCLUSIONS These findings for the first time mechanistically link antipsychotics to specific cardiovascular and infectious diseases which are known side effects of their use in dementia, providing new information to explain related adverse events.
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Affiliation(s)
- Yasaman Malekizadeh
- College of Medicine and HealthUniversity of Exeter Medical SchoolUniversity of ExeterExeterUK
| | - Gareth Williams
- College of Engineering Mathematics and Physical SciencesUniversity of ExeterExeterUK
| | - Mark Kelson
- Wolfson Centre for Age‐Related DiseaseInstitute of Psychiatry, Psychology and NeuroscienceKing's College LondonLondonUK
| | - David Whitfield
- College of Medicine and HealthUniversity of Exeter Medical SchoolUniversity of ExeterExeterUK
| | - Jonathan Mill
- College of Medicine and HealthUniversity of Exeter Medical SchoolUniversity of ExeterExeterUK
| | | | - Clive Ballard
- College of Medicine and HealthUniversity of Exeter Medical SchoolUniversity of ExeterExeterUK
| | - Aaron R. Jeffries
- College of Medicine and HealthUniversity of Exeter Medical SchoolUniversity of ExeterExeterUK
| | - Byron Creese
- College of Medicine and HealthUniversity of Exeter Medical SchoolUniversity of ExeterExeterUK
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3
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BozkurtZincir S, Ozdilek BF, Zincir S. Association of quetiapine with ischemic brain stem stroke: a case report and discussion. Ther Adv Psychopharmacol 2015; 5:246-9. [PMID: 26301082 PMCID: PMC4535042 DOI: 10.1177/2045125315583819] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Affiliation(s)
- Selma BozkurtZincir
- Associate Professor of Psychiatry, Erenkoy Training and Research Hospital for Psychiatric and Neurological Diseases, Istanbul, Turkey
| | - Betul F Ozdilek
- Associate Professor of Neurology, Erenkoy Training and Research Hospital for Psychiatric and Neurological Diseases, Istanbul, Turkey
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Trifiró G, Sultana J, Spina E. Are the safety profiles of antipsychotic drugs used in dementia the same? An updated review of observational studies. Drug Saf 2015; 37:501-20. [PMID: 24859163 DOI: 10.1007/s40264-014-0170-y] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
With an increase in the global prevalence of dementia, there is also an increase in behavioural and psychological symptoms of dementia (BPSD) for which antipsychotic drugs are often used. Despite several safety warnings on antipsychotic use in dementia, there is little evidence to support the efficacy of antipsychotics in individual BPSD symptoms or to evaluate the drug safety profile by individual antipsychotic drug. There is emerging but scarce evidence that suggests an inter-drug variability between antipsychotic safety outcomes in BPSD. The objective of this review was to examine the existing literature on antipsychotic drug use in dementia patients; in particular to see whether inter-drug differences regarding antipsychotic safety were reported. A literature search was conducted for observational studies published in the English language from 2004 to 2014 that reported the risk of all-cause mortality, cerebrovascular events, pneumonia and other outcomes such as hip/femur fracture, deep vein thrombosis (DVT) and hyperglycaemia. Six of 16 mortality studies (38%), 7 of 28 stroke studies (25%), 1 of 6 pneumonia (17%) studies and 2 of 6 fracture studies (33%) investigated inter-drug safety outcomes in elderly patients/dementia patients, while to our knowledge, there are no studies investigating the inter-drug variation of deep-vein thrombosis and hyperglycaemia risk. The results of the observational studies provide mixed results on the safety of antipsychotics in BPSD but it is clear that there are differences between the safety profiles of antipsychotic drugs. Robust evidence of such inter-drug variability could significantly improve patient safety as antipsychotics become more targeted to clinical risk factors.
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Affiliation(s)
- Gianluca Trifiró
- Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Messina, Policlinco Universitario, Via Consolare Valeria, 98125, Messina, Italy,
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5
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Yap KZ, Chan SY. Role of antipsychotics for treating behavioral and psychological symptoms of dementia. World J Pharmacol 2014; 3:174-185. [DOI: 10.5497/wjp.v3.i4.174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2014] [Revised: 10/02/2014] [Accepted: 10/27/2014] [Indexed: 02/06/2023] Open
Abstract
Over the past three decades, concerns about the high prevalence of antipsychotic use in the nursing homes (NHs) for the management of behavioral and psychological symptoms of dementia continue to be emphasized and intervened by many. However, despite the numerous side effects and the recent blackbox warning by the United States Food and Drug Administration about the increased risks for stroke and sudden death associated with the use of antipsychotics in dementia, the prevalence of antipsychotic use in NHs remains high. While the use of antipsychotics appeared to have modest efficacy in reducing symptoms of aggression and psychosis in dementia, there is insufficient evidence to routinely recommend the use of alternative psychopharmacological treatments for these symptoms. Hence, clinicians have to balance the safety warnings against the need to treat these symptoms in order to prevent harm to the resident that may result from his/her dangerous behaviors. Although the use of antipsychotics may be warranted in some cases, organizational, resource and training support should be provided to encourage and equip NH staff to participate in interventions so as to minimize inappropriate use of these medicines in NHs. This review will discuss the place in therapy, the trend and appropriateness of antipsychotic use in NHs, as well as the effectiveness of current and future strategies for reducing antipsychotic use in the NHs.
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Abstract
AbstractWith advancements in medical science over past decades, our aging population has increased substantially. Census studies in 2001 showed that 429,100 of the population of the Republic of Ireland were aged 65yrs and older, making up 11.2% of the overall population. While the overall population of the Republic is expected to remain stable over the next ten years, the demographic projections for the elderly population is for significant growth: numbers of over 65yrs are expected to increase by nearly 108,000 people between 1996 - 2011, comprising over 14.1% of the overall population. In particular, our communities will contain a much higher proportion of octogenarians and nonagenarians: at present 21% of our over 65's are 80 yrs or older; by 2011, it is projected that this number will increase to 25%. In tandem, the prevalence of dementia will increase.In 2000, it was estimated that 31,000 people suffered with dementia in the Republic of Ireland, and this figure is expected to increase by 5000 cases per year between 2001-2011. The ultimate outcome of this demographic shift, will be higher demands on medical services for older people, especially geriatric medicine and old age psychiatry. This paper will focus on two particular aspects of management which will increasingly impact on the work of old age psychiatrists – medicolegal issues and management issues in dementia.
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Shin JY, Choi NK, Jung SY, Lee J, Kwon JS, Park BJ. Risk of ischemic stroke with the use of risperidone, quetiapine and olanzapine in elderly patients: a population-based, case-crossover study. J Psychopharmacol 2013; 27:638-44. [PMID: 23535349 DOI: 10.1177/0269881113482530] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
We conducted a case-crossover study to evaluate the comparative risk of ischemic stroke associated with the use of risperidone, quetiapine and olanzapine in geriatric patients using the Korean Health Insurance Review and Assessment Service database. Cases included elderly patients >64 years old who had experienced their first ischemic stroke (International Classification of Disease, Tenth Revision (ICD-10), I63) hospitalization from July 2005 to June 2006 and who had been without prior cerebrovascular diseases (ICD-10, I60-I69), or transient ischemic attack (ICD-10, G45). Exposures to risperidone, quetiapine and olanzapine were assessed during the 30 days prior to the stroke episode. We set two control periods with lengths which were the same as the hazard periods. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were estimated by conditional logistic regression. A total of 1601 cases of ischemic stroke with a mean age of 75.6 (±6.7) years were identified, among which 933 (58.3%) were female. An increased risk of ischemic stroke was associated with the use of risperidone (aOR=3.5, 95% CI 3.3-4.6) and quetiapine (aOR=2.7, 95% CI 2.0-3.6) during the 30 days prior to stroke: however, no significant risk was observed with olanzapine (aOR=1.2, 95% CI 0.7-2.0). The increased stroke risk in demented patients, assessed within 30 days after exposure, was also observed with olanzapine. However, the sample of olanzapine users was small and underpowered.
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Affiliation(s)
- Ju-Young Shin
- Office of Drug Utilization Review, Korea Institute of Drug Safety and Risk Management, Seoul, Republic of Korea
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8
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Liu ME, Tsai SJ, Chang WC, Hsu CH, Lu T, Hung KS, Chiu WT, Chang WP. Population-based 5-year follow-up study in Taiwan of dementia and risk of stroke. PLoS One 2013; 8:e61771. [PMID: 23626726 PMCID: PMC3634021 DOI: 10.1371/journal.pone.0061771] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2012] [Accepted: 03/13/2013] [Indexed: 11/23/2022] Open
Abstract
Background This study estimates the risk of stroke within 5 years of newly diagnosed dementia among elderly persons aged 65 and above. We examined the relationship between antipsychotic usage and development of stroke in patients with dementia. Methods We conducted a nationwide 5-year population-based study using data retrieved from the Longitudinal Health Insurance Database 2005 (LHID2005) in Taiwan. The study cohort comprised 2243 patients with dementia aged ≥65 years who had at least one inpatient service claim or at least 2 ambulatory care claims, whereas the comparison cohort consisted of 6714 randomly selected subjects (3 for every dementia patient) and were matched with the study group according to sex, age, and index year. We further classified dementia patients into 2 groups based on their history of antipsychotic usage. A total of 1450 patients were classified into the antipsychotic usage group and the remaining 793 patients were classified into the non-antipsychotic usage group. Cox proportional-hazards regressions were performed to compute the 5-year stroke-free survival rates after adjusting for potentially confounding factors. Results The dementia patients have a 2-fold greater risk of developing stroke within 5 years of diagnosis compared to non-dementia age- and sex-matched subjects, after adjusting for other risk factors (95% confidence interval (CI) = 2.58–3.08; P<.001). Antipsychotic usage among patients with dementia increases risk of stroke 1.17-fold compared to patients without antipsychotic treatment (95% CI = 1.01–1.40; P<.05). Conclusions Dementia may be an independent risk factor for stroke, and the use of antipsychotics may further increase the risk of stroke in dementia patients.
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Affiliation(s)
- Mu-En Liu
- Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Shih-Jen Tsai
- Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Wei-Chiao Chang
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Chun-Hung Hsu
- Department of Healthcare Management, Yuanpei University, Hsinchu, Taiwan
| | - Ti Lu
- Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Kuo-Sheng Hung
- Department of Neurosurgery Center of Excellence for Clinical Trial and Research, Taipei Medical University- Wan Fang Medical Center, Taipei, Taiwan
| | - Wen-Ta Chiu
- Graduate Institute of Injury Prevention and Control, Taipei Medical University, Taipei, Taiwan
| | - Wei-Pin Chang
- Department of Healthcare Management, Yuanpei University, Hsinchu, Taiwan
- * E-mail:
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9
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Song SW, Sun Y, Su BL, Liu C, Yang C, Godfraind T, Su DF. Risperidone enhances the vulnerability to stroke in hypertensive rats. CNS Neurosci Ther 2013; 18:343-9. [PMID: 22486847 DOI: 10.1111/j.1755-5949.2012.00302.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Stroke is the second most common cause of death and a major cause of disability worldwide. Risperidone is an atypical antipsychotic drug that may increase the risk of stroke. The present work examined whether risperidone enhances the vulnerability to stroke in hypertensive rats and the potential mechanisms underlying such action. METHODS Experiment 1: Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHRs) and stroke-prone SHRs (SHR-SPs) were treated with risperidone (0.8 and 2.4 mg/kg/d) or vehicle for 30 consecutive days. Tissue damage in response to middle cerebral artery occlusion (MCAO) was measured microscopically. The activity of superoxide dismutase, glutathione peroxidase, the levels of malondialdehyde were also determined. Experiment 2: Survival data were recorded in SHR-SPs that received daily risperidone perpetually. Experiment 3: Effect of risperidone on interleukin-6 and tumor necrosis factor-α was examined in quiescent or LPS-activated cortical microglias from WKY rats. Experiment 4: Potential damage of risperidone exposure to neurons was examined in primary neuronal culture obtained from WKY rats, SHRs, and SHR-SPs. RESULTS Risperidone increased infarct areas upon MCAO in SHR-SPs and SHRs, but not in WKY rats. Survival time in SHR-SPs was shortened by risperidone. Apoptosis was augmented by risperidone through enhanced Bax. Risperidone also increased endothelial injury. CONCLUSIONS Risperidone enhances the vulnerability to stroke in hypertensive rats through increasing neuronal apoptosis and endothelial injury.
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Affiliation(s)
- Shu-Wei Song
- Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, China
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Chatterjee S, Chen H, Johnson ML, Aparasu RR. Comparative Risk of Cerebrovascular Adverse Events in Community-Dwelling Older Adults using Risperidone, Olanzapine and Quetiapine. Drugs Aging 2012; 29:807-17. [DOI: 10.1007/s40266-012-0013-4] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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Kochhann R, Borba E, Cerveira MO, Onyszko D, de Jesus A, Forster L, Franciscatto L, Godinho C, Camozzato AL, Chaves MLF. Neuropsychiatric symptoms as the main determinant of caregiver burden in Alzheimer's disease. Dement Neuropsychol 2011; 5:203-208. [PMID: 29213745 PMCID: PMC5619480 DOI: 10.1590/s1980-57642011dn05030008] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2022] Open
Abstract
Caregiver burden is common in Alzheimer’s disease (AD), decreasing the quality of
life among caregivers and patients. Projections of aging and aging-related
diseases such as AD in developing countries justify additional data about this
issue because people living in these countries have shown similarly high levels
of caregiver strain as in the developed world.
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Affiliation(s)
- Renata Kochhann
- Dementia Clinic, Neurology Service, Hospital de Clínicas de Porto Alegre, Porto Alegre RS, Brazil.,Medical Sciences Post-Graduation Course, UFRGS School of Medicine, Porto Alegre RS, Brazil
| | - Ericksen Borba
- Dementia Clinic, Neurology Service, Hospital de Clínicas de Porto Alegre, Porto Alegre RS, Brazil.,Medical Sciences Post-Graduation Course, UFRGS School of Medicine, Porto Alegre RS, Brazil
| | - Maria Otília Cerveira
- Dementia Clinic, Neurology Service, Hospital de Clínicas de Porto Alegre, Porto Alegre RS, Brazil
| | - Diego Onyszko
- Dementia Clinic, Neurology Service, Hospital de Clínicas de Porto Alegre, Porto Alegre RS, Brazil
| | - Alyne de Jesus
- Dementia Clinic, Neurology Service, Hospital de Clínicas de Porto Alegre, Porto Alegre RS, Brazil
| | - Letícia Forster
- Dementia Clinic, Neurology Service, Hospital de Clínicas de Porto Alegre, Porto Alegre RS, Brazil
| | - Luisa Franciscatto
- Dementia Clinic, Neurology Service, Hospital de Clínicas de Porto Alegre, Porto Alegre RS, Brazil
| | - Cláudia Godinho
- Dementia Clinic, Neurology Service, Hospital de Clínicas de Porto Alegre, Porto Alegre RS, Brazil.,Medical Sciences Post-Graduation Course, UFRGS School of Medicine, Porto Alegre RS, Brazil
| | - Ana Luiza Camozzato
- Dementia Clinic, Neurology Service, Hospital de Clínicas de Porto Alegre, Porto Alegre RS, Brazil.,Medical Sciences Post-Graduation Course, UFRGS School of Medicine, Porto Alegre RS, Brazil.,Internal Medicine Department and Health Sciences Post-Graduation Course, UFCSPA School of Medicine, Porto Alegre RS, Brazil
| | - Márcia Lorena F Chaves
- Dementia Clinic, Neurology Service, Hospital de Clínicas de Porto Alegre, Porto Alegre RS, Brazil.,Medical Sciences Post-Graduation Course, UFRGS School of Medicine, Porto Alegre RS, Brazil.,Internal Medicine Department, UFRGS School of Medicine, Porto Alegre RS, Brazil
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Mittal V, Kurup L, Williamson D, Muralee S, Tampi RR. Risk of cerebrovascular adverse events and death in elderly patients with dementia when treated with antipsychotic medications: a literature review of evidence. Am J Alzheimers Dis Other Demen 2011; 26:10-28. [PMID: 21282274 PMCID: PMC10845396 DOI: 10.1177/1533317510390351] [Citation(s) in RCA: 99] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Behavioral and Psychological Symptoms of Dementia (BPSD) are increasingly recognized as a major risk factor for caregiver burden, institutionalization, greater impairment in activities of daily living (ADLs), more rapid cognitive decline, and a poorer quality of life. BPSD contribute significantly to the direct and indirect costs of caring for patients with dementia even after adjusting for the severity of cognitive impairment and other co-morbidities. Research on these symptoms has indicated a complex interplay between the biological, psychological and social factors involved in the disease process. Although some psychotropic medications have shown modest efficacy in the treatment of these behaviors, their use has generated controversy due to increasing recognition of the side effects of these medications especially the antipsychotic medications. In this review, we examine the risk of cerebrovascular adverse events (CVAEs) and death with antipsychotic medications when used to treat elderly patients with dementia.
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Chan MC, Chong CSY, Wu AYK, Wong KC, Dunn ELW, Tang OWN, Chan WF. Antipsychotics and risk of cerebrovascular events in treatment of behavioural and psychological symptoms of dementia in Hong Kong: a hospital-based, retrospective, cohort study. Int J Geriatr Psychiatry 2010; 25:362-70. [PMID: 19650162 DOI: 10.1002/gps.2347] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVE The purpose of this study was to investigate the risk of cerebrovascular adverse events (CVAEs) in patients with behavioural and psychological symptoms of dementia (BPSD) treated with typical or atypical antipsychotics in Hong Kong METHOD This was a retrospective cohort study. Patients aged 65 or above, diagnosed with Alzheimer's disease, vascular or mixed dementia, and first attended the psychiatric service of our unit between 1st January 2000 to 30th June 2007 were studied. The patients were divided into three groups according to their antipsychotic usage. They were compared on sociodemographic and clinical characteristics. The risk of CVAEs was studied by means of Cox regression analysis. RESULTS The studied cohort consisted of 1089 patients. The antipsychotic non-user, typical and atypical users groups consisted of 363, 654 and 72 patients, respectively. Incidence rate of CVAE for the three groups were 44.6/1000, 32.7/1000 and 49.6/1000 person years, respectively. The risk of developing CVAEs did not differ in typical or atypical antipsychotic user groups compared with non-user group. The adjusted hazard ratio of typical and atypical antipsychotic user groups were 0.964 (95% CI = 0.584-1.591) and 1.036 (95% CI = 0.350-3.066), respectively. Subgroup analyses of individual antipsychotic did not show a significant increase in risk of CVAEs. CONCLUSION This study showed that there was no statistical difference in risk of cerebrovascular events in treatment of BPSD with typical and atypical antipsychotics compared with non-user group. Nonetheless, given the side effects of antipsychotics, prescription of antipsychotics should be reserved for severe and distressing symptoms with careful consideration.
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Affiliation(s)
- Man-chak Chan
- Department of Psychiatry, Pamela Youde Nethersole Eastern Hospital, Hong Kong.
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14
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Morley JE. Citation Indexing and JAMDA. J Am Med Dir Assoc 2009. [DOI: 10.1016/j.jamda.2009.06.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Lövheim H, Karlsson S, Gustafson Y. The use of central nervous system drugs and analgesics among very old people with and without dementia. Pharmacoepidemiol Drug Saf 2008; 17:912-8. [DOI: 10.1002/pds.1600] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
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Passmore MJ, Gardner DM, Polak Y, Rabheru K. Alternatives to atypical antipsychotics for the management of dementia-related agitation. Drugs Aging 2008; 25:381-98. [PMID: 18447403 DOI: 10.2165/00002512-200825050-00003] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Numerous recent studies have challenged the widely held belief that atypical antipsychotics are safe and effective options for the treatment of behavioural problems such as agitation in patients with dementia. Accordingly, there is a need to reconsider the place of atypical antipsychotics in the treatment of patients with dementia. The present article is intended to assist clinicians with the assessment and pharmacological management of agitation in patients with dementia. We review the risk-benefit evidence for the use of atypical antipsychotics in patients with dementia-related agitation (DRA). Emerging evidence indicates that, for patients with dementia, the risks associated with atypical antipsychotics may outweigh the benefits except for patients with severe agitation who require short-term chemical restraint. We then discuss the importance of a careful assessment to rule out potentially reversible factors contributing to DRA. Finally, we summarize the evidence supporting the use of medications other than antipsychotics to treat DRA. There is wide variability in the levels of evidence supporting the use of non-antipsychotic medication for the treatment of DRA. The best evidence currently exists for cholinesterase inhibitors and serotonin-specific reuptake inhibitor antidepressants. Emerging reports suggest that numerous other medications, for example, antiepileptics, lithium, anxiolytics, analgesics, beta-adrenoceptor antagonists, cannabinoid receptor agonists and hormonal agents, may prove to be viable alternatives to antipsychotics for the treatment of severe DRA and more research is urgently needed to help assess the effectiveness of these agents. A comprehensive biopsychosocial assessment and treatment plan is likely the most effective way to manage DRA.
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Affiliation(s)
- Michael J Passmore
- Department of Psychiatry, Division of Geriatric Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.
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Abuhamdah S, Chazot PL. Lemon Balm and Lavender herbal essential oils: Old and new ways to treat emotional disorders? ACTA ACUST UNITED AC 2008. [DOI: 10.1016/j.cacc.2008.05.005] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
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Sacchetti E, Trifirò G, Caputi A, Turrina C, Spina E, Cricelli C, Brignoli O, Sessa E, Mazzaglia G. Risk of stroke with typical and atypical anti-psychotics: a retrospective cohort study including unexposed subjects. J Psychopharmacol 2008; 22:39-46. [PMID: 18187531 DOI: 10.1177/0269881107080792] [Citation(s) in RCA: 78] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
The purpose of the study was to investigate the risk of stroke with typical and atypical anti-psychotics in elderly subjects, weighting for a number of known risk factors, including dementia. Data were retrospectively drawn from the primary care setting from the Health Search Database, which stores information on about 1.5% of the total Italian population served by general practitioners. All elderly patients (65+ years) prescribed an anti-psychotic in monotherapy from January 2000 to June 2003 were selected for the study. A cohort of patients not exposed to anti-psychotics was taken from the same database. Subjects who had previously had a stroke were excluded. The main outcome measure was the incidence of first-ever stroke during exposure to an anti-psychotic.The sample included non-users (69,939), users of atypicals (599), butyrophenones (749), phenotiazines (907) and substituted benzamides (1,968). The crude incidence of stroke in subjects not exposed to anti-psychotics was 12.0/1000 person-years. Risk was significantly higher for those on butyrophenones (47.1/1000), phenotiazines (72.7/1000) and in the atypical anti-psychotic group (47.4/1000). Substituted benzamides had an almost significant higher risk (25.0/1000). Cox regression modelling, weighting for demographic and clinical variables with non-users as the reference group, showed that the risk for stroke was 5.79 times for phenotiazines, 3.55 times for butyrophenones, and 2.46 times for atypicals. Clinicians should be cautious in prescribing phenotiazines and butyrophenones in elderly patients, since the risk for stroke would seem comparable or even greater than with atypicals.
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Affiliation(s)
- Emilio Sacchetti
- University Psychiatric Unit, Brescia University School of Medicine and Department of Mental Health, Brescia Spedali Civili, Italy.
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Antoine V, Souid M, Bodenan L. La population âgée hémodialysée : évaluer et prendre en charge le risque de déclin cognitif. Nephrol Ther 2007; 3:11-26. [PMID: 17383587 DOI: 10.1016/j.nephro.2006.11.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2005] [Revised: 04/14/2006] [Accepted: 11/14/2006] [Indexed: 12/25/2022]
Abstract
Epidemiological data suggest a large prevalence of cognitive impairment in elderly patients on haemodialysis. They are frequently exposed to pathologies that affect the brain, and hold a plurality of risk factors for neurodegenerative and vascular dementia. Cognitive dysfunctions, because of their medical and socio-economical consequences, may led to discuss the indication for haemodialysis and its profit for the elderly patient. These facts highlight the advantage of a regular assessment of cognitive functions in this population. They also suggest the need in the future of a multidisciplinary intervention for these patients, for a better evaluation of interventions aimed on primary and secondary prevention of cognitive decline in the elderly group.
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Affiliation(s)
- Valéry Antoine
- Consultation de la mémoire, unité mobile de gériatrie, hôpital de Poissy, CHI de Poissy-Saint-Germain-en-Laye, Les Maisonnées, Poissy, France.
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20
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Beier MT. Treatment Strategies for the Behavioral Symptoms of Alzheimer's Disease: Focus on Early Pharmacologic Intervention. Pharmacotherapy 2007; 27:399-411. [PMID: 17316151 DOI: 10.1592/phco.27.3.399] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
The impact of behavioral symptoms associated with Alzheimer's disease is substantial. These symptoms contribute to diminished quality of life for patients and caregivers and increase the cost of care in nursing homes. Early recognition of behavioral symptoms and appropriate treatment are important for successful management. Nonpharmacologic strategies remain the cornerstone of the management of Alzheimer's disease-related behavioral symptoms. However, nonpharmacologic strategies may not be effective for problem behaviors, and pharmacologic intervention may be necessary. Relevant articles were identified through various MEDLINE searches with no date restrictions, with an emphasis on recent studies that used cholinesterase inhibitors and memantine. Additional reports of interest were identified from the reference lists of these articles. To facilitate cross-study analyses in the review of cholinesterase inhibitors and memantine, the database search was limited to randomized, placebo-controlled trials that used the Neuropsychiatric Inventory to assess behavioral symptoms of Alzheimer's disease. Overall, evidence from trials of cholinesterase inhibitors and memantine suggests that when these agents are optimized for the various stages of Alzheimer's disease, they can also prevent the emergence of neuropsychiatric symptoms. Although results from the literature are not uniformly positive, cholinesterase inhibitors have been shown to produce significant improvements in behavioral symptoms in patients with both mild- to-moderate and moderate-to-severe Alzheimer's disease. Evidence also indicates that memantine might be of benefit as an adjunct to long-term cholinesterase inhibitor treatment in patients with moderate-to-severe Alzheimer's disease and that memantine monotherapy may have some beneficial effects on behavior in patients with mild-to-moderate disease. Of importance, although no direct comparisons have been performed, these agents seem to have an improved safety and tolerability profile compared with the frequently used antipsychotic drugs. When nonpharmacologic strategies are deemed insufficient to ease problem behaviors in patients with Alzheimer's disease, treatment with cholinesterase inhibitors, alone or in combination with memantine as appropriate for the stage of disease, may be considered as a first-line option in the early pharmacologic management of Alzheimer's disease-related behavioral symptoms.
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Affiliation(s)
- Manju T Beier
- College of Pharmacy, University of Michigan, and Geriatric Consultant Resources LLC, Ann Arbor, Michigan 48105, USA.
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Abstract
Antipsychotic drugs are the primary treatment for symptoms of delirium, but their side effects can be problematic. Treatment of delirium with aripiprazole has yet to be evaluated. The authors report on 14 patients with delirium treated with aripiprazole. Twelve patients had a >or=50% reduction in Delirium Rating Scale, Revised-98 scores, and 13 showed improvement on Clinical Global Impression scale scores. There was a low rate of adverse side effects. Aripiprazole may be an appropriate first-line agent for the treatment of delirium because of its minimal effect on QTc interval, weight, lipids, and glucose levels. Controlled comparison studies should be performed to confirm this impression.
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Affiliation(s)
- David A Straker
- Department of Consultation-Liasion Psychiatry at New York Presbyterian Hospital, New York, USA.
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Yulug B, Yildiz A, Güzel O, Kilic E, Schäbitz WR, Kilic E. Risperidone attenuates brain damage after focal cerebral ischemia in vivo. Brain Res Bull 2006; 69:656-9. [PMID: 16716834 DOI: 10.1016/j.brainresbull.2006.03.017] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2005] [Revised: 03/11/2006] [Accepted: 03/20/2006] [Indexed: 11/24/2022]
Abstract
Since their introduction, atypical neuroleptic agents have been discovered to have some beneficial effects beyond their effectiveness as neuroleptic drugs. Among these initially unexpected effects are their potential effects as mood stabilizers in bipolar disorder and their efficacy in improving long-term outcome in schizophrenia. These effects recently raised the question whether these drugs may also have some neuroprotective effect in the brain. To examine this matter, in this study we evaluated the neuroprotective effect of risperidone after permanent focal cerebral ischemia. Anaesthetized male C57BL/6j mice were submitted to permanent thread occlusion of the middle cerebral artery (MCA). Risperidone (0.1, 1 or 10 mg/kg) or vehicle was applied intraperitoneally just after permanent ischemia. Twenty-four hours after permanent ischemia, brain injury was evaluated by triphenyltetrazolium chloride staining (TTC). Risperidone (0.1, 1 and 10 mg/kg) showed significant neuroprotection after permanent focal cerebral ischemia.
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Affiliation(s)
- Burak Yulug
- Department of Neurology, University of Uludag, Bursa, Turkey.
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Shah A. Can risperidone and olanzapine in elderly patients with dementia and other mental disorders be discontinued? Int J Geriatr Psychiatry 2006; 21:140-6. [PMID: 16416461 DOI: 10.1002/gps.1438] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND In March 2004, the UK Committee of Safety of Medicines (CSM) informed clinicians that risperidone and olanzapine should not be used to treat behavioural and psychological symptoms of dementia (BPSD) because of increased risk of strokes with both drugs and increased risk of mortality with olanzapine. An audit to examine the implications of the implementation of the CSM guidance was undertaken. METHODS All patients receiving these two drugs, in one psychogeriatric service, at the time of CSM guidance were identified and reviewed. Data on clinical and demographic features, patient and carer involvement in the review and clinical outcome of the efficacy of the overall treatment package at 6 month follow-up was ascertained from the case-notes. RESULTS The main findings were: (i) all patients receiving risperidone or olanzapine were identified and reviewed at a median interval of 8 days after the CSM guidance; (ii) most patients and carers were involved in the initial review; (iii) risperidone and olanzapine were discontinued in 22 and 12 of the patients respectively, and in 19 of these patients another neuroleptic was substituted; (iv) there was no relationship between discontinuation of these two drugs and presence of cerebrovascular and cardiovascular risk factors; and, (v) there was no relationship between the clinical outcome of efficacy at six months and discontinuation of these two drugs. CONCLUSIONS This study illustrates that it is possible to identify, review and follow-up patients on these two drugs and involve the patient and carer in the review, and clinical outcome of efficacy of the overall treatment package is not adversely affected by continuation or discontinuation of these two drugs.
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Affiliation(s)
- Ajit Shah
- West London Mental Health NHS Trust, London and Imperial College School of Medicine, London, UK.
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Abstract
In many countries, prescribing guidelines recommend the use of atypical or second-generation antipsychotics (SGAs) in the first-line treatment of individuals with newly diagnosed schizophrenia. This recommendation has increased the utilisation of these agents and, consequently, produced a progressive increase in the proportion of total direct costs in schizophrenia accounted for by drug therapy. In this still-evolving context of care, it becomes relevant to critically investigate the literature base on the relative cost effectiveness of each SGA in comparison with the others, the purpose being to ascertain whether the data reveal any one agent to be truly more cost effective than the others.A systematic search of economic evaluations comparing two or more SGAs yielded 19 studies meeting the inclusion criteria. Of these, 11 were retrospective database or chart review analyses, six were observational prospective or mirror-image studies, and two were randomised clinical trials. Olanzapine and risperidone were compared in 16 studies, two studies compared clozapine, olanzapine and risperidone, and one compared clozapine and risperidone. While experimental studies indicated an absence of differences among the SGAs in terms of total expenditure, database analyses found contrasting evidence. These latter studies, although susceptible to bias and confounding, should theoretically provide an added dimension, in that they are based on observations from 'real world' practice. However, there were too many potential threats to the validity of these analyses to draw a firm conclusion that any one agent is truly more cost effective than the others. In this uncertain situation, clinicians and policy makers should be aware that indirect evidence from independent randomised controlled trials comparing individual SGAs with haloperidol suggested similar cost effectiveness. As healthcare providers in different settings are ultimately the ones who pay for new innovations, it seems appropriate that they commission research into the cost effectiveness of SGAs.
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Affiliation(s)
- Corrado Barbui
- Department of Medicine and Public Health, Section of Psychiatry and Clinical Psychology, University of Verona, Verona, Italy
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Burn D, Emre M, McKeith I, De Deyn PP, Aarsland D, Hsu C, Lane R. Effects of rivastigmine in patients with and without visual hallucinations in dementia associated with Parkinson's disease. Mov Disord 2006; 21:1899-907. [PMID: 16960863 DOI: 10.1002/mds.21077] [Citation(s) in RCA: 166] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Abstract
We aimed to determine prospectively whether rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase, provided benefits in patients with and without visual hallucinations in a population with dementia associated with Parkinson's disease (PDD). This was a 24-week double-blind placebo-controlled study. Primary efficacy measures were the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) and Alzheimer's Disease Cooperative Study-Clinician's Global Impression of Change (ADCS-CGIC). Secondary efficacy measures included activities of daily living, behavioral symptoms, and executive and attentional functions. Patients were stratified according to the presence of visual hallucinations at baseline. The study included 188 visual hallucinators (118 on rivastigmine, 70 on placebo) and 348 nonvisual hallucinators (239 on rivastigmine, 109 on placebo). Rivastigmine provided benefits in both visual hallucinators and nonvisual hallucinators. Absolute responses to rivastigmine on the ADAS-cog were comparable over 6 months, although rivastigmine-placebo differences tended to be larger in visual hallucinators (4.27; P = 0.002) than in nonhallucinators (2.09; P = 0.015). On the ADCS-CGIC, differences between rivastigmine and placebo were 0.5 in visual hallucinators (P = 0.030) and 0.3 in nonhallucinators (P = 0.111). Rivastigmine provided benefits on all secondary efficacy measures, and placebo declines and treatment differences were more marked in visual hallucinators. Adverse events were reported more frequently by rivastigmine-treated patients, although this difference was less marked in visual hallucinators. Visual hallucinations appear to predict more rapid decline and possibly greater therapeutic benefit from rivastigmine treatment in PDD.
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Affiliation(s)
- David Burn
- Regional Neuroscience Center, Newcastle General Hospital, Newcastle-upon-Tyne, United Kingdom.
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Lanari A, Amenta F, Silvestrelli G, Tomassoni D, Parnetti L. Neurotransmitter deficits in behavioural and psychological symptoms of Alzheimer's disease. Mech Ageing Dev 2005; 127:158-65. [PMID: 16297434 DOI: 10.1016/j.mad.2005.09.016] [Citation(s) in RCA: 129] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2005] [Revised: 05/17/2005] [Accepted: 09/15/2005] [Indexed: 11/28/2022]
Abstract
Behavioural and psychological symptoms of dementia (BPSD) occur in 50-90% of Alzheimer's disease (AD) patients. Imbalance of different neurotransmitters (acetylcholine, dopamine, noradrenaline and serotonin), involvement of specific brain regions responsible for emotional activities (parahippocampal gyrus, dorsal raphe and locus coeruleus) and cortical hypometabolism have been proposed as neurobiological substrate of BPSD. Compared to with respect to the neurochemical component, the cholinergic dysfunction seems to play a major role in contributing to BPSD occurrence. This view is also supported by the findings of recent trials with cholinesterase inhibitors, showing that these drugs are effective in controlling and/or improving BPSD, independent on effects on cognitive dysfunction. On the site of psychotropic drugs, atypical or novel antipsychotics represent the reference drugs for treating BPSD, whereas classic antipsychotic drugs for their profile and the potential side effects should be avoided.
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Affiliation(s)
- Alessia Lanari
- Dipartimento di Neuroscienze, Università di Perugia, Perugia, Italy
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Percudani M, Barbui C, Fortino I, Tansella M, Petrovich L. Second-generation antipsychotics and risk of cerebrovascular accidents in the elderly. J Clin Psychopharmacol 2005; 25:468-70. [PMID: 16160623 DOI: 10.1097/01.jcp.0000178414.14685.c4] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Concern has been recently raised for risperidone and olanzapine, possibly associated with cerebrovascular events in placebo-controlled trials conducted in elderly subjects with dementia. We investigated the relationship between exposure to second-generation antipsychotics (SGAs) and occurrence of cerebrovascular accidents in the elderly. From the regional database of hospital admissions of Lombardy, Italy, we extracted all patients aged 65 or older with cerebrovascular-related outcomes for the year 2002. From the regional database of prescriptions reimbursed by the National Health Service, we extracted all patients aged 65 or older who received antipsychotic prescriptions during 2001. The 2 databases were linked anonymously using the individual patient code. The proportions of cerebrovascular accidents were 3.31% (95% confidence interval, 2.95-3.69) in elderly subjects exclusively exposed to SGAs and 2.37% (95% confidence interval, 2.19-2.57) in elderly subjects exclusively exposed to first-generation antipsychotics. After background group differences were controlled for, exposure to SGAs significantly increased the risk of accidents. The analysis of cerebrovascular events in elderly subjects exposed to each individual SGA, in comparison with exposure to haloperidol, showed a significantly increased risk for risperidone only (adjusted odds ratio, 1.43; 95% confidence interval, 1.12-1.93). These data provide preliminary epidemiological evidence that exposure to SGAs, in comparison with exposure to first-generation antipsychotics, significantly increased the risk of cerebrovascular accidents in the elderly.
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Aarsland D, Sharp S, Ballard C. Psychiatric and behavioral symptoms in Alzheimer’s disease and other dementias: Etiology and management. Curr Neurol Neurosci Rep 2005; 5:345-54. [PMID: 16131417 DOI: 10.1007/s11910-005-0058-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Psychiatric and behavioral symptoms are common in all types of dementia and have important consequences for patients, caregivers, and society. This paper reviews recent studies of the etiology and management of these symptoms. Genetic and neurochemical studies indicate that cholinergic, serotonergic, and dopaminergic systems may influence the risk of psychiatric symptoms in patients with dementia. There is still no consensus regarding the management of such symptoms. Controlled studies of psychosocial interventions, usually performed in the nursing home setting, report encouraging results. Atypical antipsychotics may be effective in some cases but have a high risk of adverse events. There is emerging evidence that cholinesterase inhibitors may reduce and prevent such symptoms. More studies are needed to clarify the role of cholinergic and other psychotropic agents as well as nonpharmacologic interventions for psychiatric and behavioral symptoms in patients with dementia.
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Affiliation(s)
- Dag Aarsland
- Centre for Clinical Neuroscience Research, Stavanger University Hospital, PO Box 1163, 4095 Stavanger, Norway.
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Suh GH, Shah A. Effect of antipsychotics on mortality in elderly patients with dementia: a 1-year prospective study in a nursing home. Int Psychogeriatr 2005; 17:429-41. [PMID: 16252375 DOI: 10.1017/s1041610205002243] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND OBJECTIVES The use of risperidone or olanzapine to treat behavioral problems associated with dementia is no longer recommended in the U.K. because of the increased risk of cerebrovascular adverse effects (CVAEs) and/or mortality. To evaluate the risks and benefits of antipsychotics, we measured the rate of mortality in patients with dementia, Alzheimer's disease (AD) and vascular/mixed dementia and compared mortality rates between those who had received antipsychotics and those who had not received antipsychotics. METHODS A total of 273 subjects were assessed at baseline, 6 months and 12 months using a 1-year prospective follow-up design. Mortality rates between groups were compared using a Kaplan-Meier curve and log-rank statistics. Relative risks (RRs) were examined by the Cox proportional-hazards model. RESULTS The overall 1-year mortality rate in dementia was 23.8%. The mortality rate in those who had not received antipsychotics (26.8%) was higher than that in those who had received antipsychotics (20.6%). RR and 95% confidence interval (CI) of mortality, when we compared those who had not received antipsychotics with those who had received antipsychotics, was 1.277 (95% CI 1.134-1.437) after controlling for age, severity of dementia, medical comorbidities, cognitive impairment (measured by the Korean version of the Mini-mental State Examination (MMSE)) and behavioral and psychological symptoms of dementia (BPSD), measured by the Behavioral Pathology in Alzheimer's Disease Rating Scale, Korean version (BEHAVE-AD-K). When those who had not received antipsychotics were compared with those who had received both risperidone and haloperidol, RR (95% CI) was 1.225 (1.101-1.364). CONCLUSION This study does not support reports that antipsychotics increase mortality in dementia.
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Affiliation(s)
- Guk-Hee Suh
- Department of Psychiatry, Hallym University Medical Center, Hangang Sacred Heart Hospital, Seoul, Korea.
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Abstract
Psychotropic drug epidemiology is a discipline developed to study the use and the effects of drugs in large numbers of individuals. It describes how drugs are prescribed and utilized, investigates reasons underlying prescriptions, and monitors outcomes and variables which may affect these outcomes. In this article the main purposes, study designs and limitations of current pharmacoepidemiological approaches are reviewed with the aim of assessing whether this discipline can constitute a permanent link between the experimental world of clinical trials and the real world of everyday prescribing. We support the notion that evidence generated in clinical practice, by means of pharmacoepidemiological studies, should increasingly be used to develop and suggest innovative research hypotheses to be subsequently tested in pragmatic experimental studies.
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Affiliation(s)
- Corrado Barbui
- Department of Medicine and Public Health, Section of Psychiatry and Clinical Psychiatry, University of Verona, Policlinico GB Rossi, 37134 Verona, Italy.
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Abstract
Post hoc analyses of pooled results from 11 randomised controlled trials of risperidone and olanzapine in elderly dementia subjects revealed an increased incidence of cerebrovascular adverse events compared with placebo. Reanalysis of the risperidone trials suggests that some of the increased incidence may be accounted for by nonspecific events that were not strokes. Large observational administrative health database studies appear to confirm that risperidone and olanzapine are not associated with an increased risk of stroke in elderly patients compared with typical antipsychotics or untreated dementia patients. A larger number of subjects with vascular and mixed dementias were included in the risperidone studies compared with the olanzapine studies, which likely accounts for the increased incidence of cerebrovascular adverse events in the risperidone trials compared with the olanzapine studies. Potential mechanisms proposed to explain an association between atypical antipsychotics and cerebrovascular adverse events include thromboembolic effects, cardiovascular effects (e.g. orthostatic hypotension, arrhythmias), excessive sedation resulting in dehydration and haemoconcentration, and hyperprolactinaemia. However, there is little evidence to support these hypothesised mechanisms at present. The association between atypical antipsychotics and cerebrovascular adverse events requires further clarification. At the present time, this association is another factor that clinicians should consider when weighing the risks and benefits of treating behavioural and psychological disturbances in elderly dementia patients.
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Affiliation(s)
- Nathan Herrmann
- Division of Geriatric Psychiatry, University of Toronto, Toronto, Ontario, Canada.
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