The Use of Risperidone in Behavioral and Psychological Symptoms of Dementia: A Review of Pharmacology, Clinical Evidence, Regulatory Approvals, and Off-Label Use.
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SUBMITTER: Yunusa I
PROVIDER: S-EPMC7256877 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
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The Use of Risperidone in Behavioral and Psychological Symptoms of Dementia: A Review of Pharmacology, Clinical Evidence, Regulatory Approvals, and Off-Label Use.
Yunusa Ismaeel I El Helou Marie Line ML
Frontiers in pharmacology 20200520
Dementia represents a global health challenge due to the increase in elderly population worldwide. In addition to memory loss, dementia often results in severe behavioral and psychological changes where pharmacological treatments might be considered in addition to nonpharmacological strategies for optimal symptomatic control. Risperidone, the second oldest atypical antipsychotic, has been widely used off-label to treat behavioral and psychological symptoms of dementia (BPSD), including agitation ...[more]
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Project description:The risk/benefit ratio of pharmacotherapy for behavioral symptoms of dementia is questionable: second-generation antipsychotics are poorly tolerated, and the efficacy of alternative treatments, for example, selective serotonin-reuptake inhibitors (SSRIs), is uncertain. Biomarkers of treatment response may improve this risk/benefit ratio. The length polymorphism of the serotonin transporter promoter gene (5-HTTLPR/SLC6A4) may moderate tolerability of SSRIs and expression of behavioral symptoms in dementia. We assessed the effect of 5-HTTLPR on tolerability and efficacy of citalopram and risperidone in a 12-week randomized controlled trial, which included nondepressed patients with dementia hospitalized for behavioral or psychotic symptoms. Genotypes including the A/G polymorphism of the L allele (rs25531) were determined in 92 of 103 participants. We used pattern-mixture models to account for dropout. Low-expression alleles (S and Lg) predicted greater early and overall side effects of citalopram and early treatment discontinuation. These results remained unchanged after excluding African-American participants and in covariate analyses. Unexpectedly, low-expression alleles seemed to predict greater early side effects of risperidone (but not early discontinuation) and poorer early response of psychosis symptoms to risperidone. In conclusion, 5-HTTLPR may be a useful biomarker of SSRI intolerance in dementia. Our findings of intolerance of a second-generation antipsychotics and persistence of psychosis in patients with low-expression alleles needs to be replicated.
| S-EPMC2887732 | biostudies-literature
Project description:Background: Identifying the characteristics of behavioral and psychological symptoms of dementia (BPSD) associated with different dementia types may be a promising strategy to effectively deal with BPSD. We aimed to synthesize the prevalence rates of BPSD characteristics in community-dwelling dementia patients. Methods: We searched Medline, EMBASE, and PsycARTICLES databases for original clinical studies published until December 2020 that enrolled at least 300 community-dwelling dementia patients. The methodological qualities of prevalence studies were assessed using the Joanna Briggs Institute's critical appraisal checklist. Results: Thirty studies were included. The prevalence of the BPSD characteristic ranged from 4 (elation and mania) to 32% (apathy) in the pooled samples. The prevalence of delusions, anxiety, apathy, irritability, elation and mania, and aberrant motor behavior in Alzheimer's disease patients was 1.72-2.88 times greater than that in vascular dementia (VD) patients, while the prevalence of disinhibition in VD patients was 1.38 times greater. The prevalence of anxiety, irritability, and agitation and aggression, delusion, hallucinations, apathy, disinhibition, and aberrant motor behavior tended to increase as the severity of dementia increased, while that of depression, eating disorder, sleep disorders, and elation and mania tended to stable. In community-dwelling patients with dementia, the pooled prevalence of apathy, depression, anxiety, irritability, agitation and aggression, sleep disorders, and eating disorder was higher than 20%, while that of disinhibition and elation and mania was lower than 10%. Conclusion: Overall, the pooled prevalence of apathy, depression, anxiety, irritability, agitation and aggression, sleep disorders, and eating disorder was generally high in patients with dementia. Also, the prevalence of some BPSD characteristics differed according to the type and the severity of dementia. The methodological quality of the included studies is not the best, and high heterogeneity may affect the certainty of the findings. However, the results of this review can deepen our understanding of the prevalence of BPSD. Systematic Review Registration: https://osf.io/dmj7k, identifier: 10.17605/OSF.IO/DMJ7K.
| S-EPMC8566725 | biostudies-literature
Project description:BackgroundBehavioral and psychological symptoms of dementia (BPSD) are present in a majority of patients with dementia contributing to increased morbidity, health care costs, and caregiver burden. While there are no United States Food and Drug Administration (FDA)-approved medications for these symptoms, off-label use of medications such as antipsychotics have been shown to have significant adverse effects including increased mortality. The goal of this review is to examine the efficacy and safety of anticonvulsants in the treatment of BPSD.MethodsWe will systematically search for randomized trials of anticonvulsants compared to placebo or other treatments such as antidepressants and antipsychotics from the following sources: The Cochrane Library, MEDLINE (OVID SP) in Process and Other Non-Indexed Citations (latest version), EMBASE, clinicalTrials.gov , and the WHO Clinical Trials Registry. The studies will be limited to those published in English but the study location can be worldwide. We will include studies pertaining to individuals with dementia and symptoms of BPSD. The primary outcomes will be behavioral change as measured by validated scales and secondary outcomes will include caregiver burden, quality of life, placement in long term care facility, serious adverse effects, and treatment discontinuation due to adverse effects. Two sets of reviewers will independently screen select and extract data. We will narratively describe the major findings and conclusions from individual studies. Patients who are prescribed antiepileptic drugs (AEDs) for other indications, including seizures, will be excluded. Outcomes of interest will include a change in a validated scale that measures BPSD, serious adverse events, and caregiver quality of life outcomes. If the data are found to be appropriate for a meta-analysis, we will use a random effects model to compute summary estimates of treatment effects.DiscussionThis is a protocol for a systematic review addressing the anticonvulsant group of medications as a whole, and as such, our results will inform current clinical practice in the use of anticonvulsants for BPSD. It will also help clinicians and policy makers compare the efficacy of anticonvulsants compared to antidepressants and antipsychotics as well as identify areas which will need further study.Systematic review registrationPROSPERO CRD42017079826.
| S-EPMC6525967 | biostudies-literature
Project description:BackgroundDementia is a major mental health problem worldwide, and an optimal anti-dementia drug that could modify its core symptoms has not been developed yet. Behavioral and psychological symptoms of dementia (BPSD), an important clinical manifestation of dementia, is closely related to disease burden, caregiver burden, and consequent social burden. In general, many experts and international guidelines prefer non-pharmacological interventions, including psychosocial intervention, and complementary and integrative medicine in the management of BPSD. However, in clinical settings, psychotropic drugs are frequently used; therefore, the need to establish and actively use effective non-pharmacological interventions is emphasized. Therefore, in this systematic review, we will evaluate the effectiveness and safety of acupuncture, a promising non-pharmacological complementary and integrative medicine, for BPSD.Methods and analysisA comprehensive search will be conducted in 13 electronic medical databases. Regardless of its design, original clinical studies, such as randomized controlled clinical trials, nonrandomized controlled clinical trials, and before-after studies, will be included to assess the beneficial effects and safety of acupuncture on BPSD. The severity of BPSD symptoms assessed by the validated tool will be considered as a primary outcome. The secondary outcome included the total effective rate, daily living activities and quality of life of patients, burden and quality of life of caregiver, placement in a long-term care facility from home, and safety data. The study selection, data extraction, and quality assessment process were performed by 2 independent researchers. The methodological quality of the included studies will be assessed using validated tools according to its design, such as the Cochrane Collaboration's risk of bias tool. RevMan version 5.3 will be used to perform the meta-analysis, with mean differences for continuous outcomes and risk ratio for binary outcomes, and 95% confidence intervals. A fixed- or random-effects model will be used according to the heterogeneity and number of included studies.Ethics and disseminationAs this protocol is for a systematic review, ethical approval is not required. The results of the systematic review will be disseminated by the publication of a manuscript in a peer-reviewed journal or presentation at a relevant conference.Registration numberOSF (URL: https://osf.io/hu5ac), PROSPERO (CRD42020211005) (URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020211005).
| S-EPMC7886446 | biostudies-literature
Project description:Background: Behavioral and psychological symptoms of dementia (BPSD, also known as neuropsychiatric symptoms (NPS), changed behaviors and responsive behaviors), occur in up to 90 percent of people living with dementia (PLWD). These symptoms and behaviors strongly correlate with functional and cognitive impairment and contribute to ~30% of overall dementia costs. As decisions regarding care and strategies for BPSD are generally based on professional frames of reference, this study investigates whether the perspectives of PLWD and families/care partner on BPSD terminology can inform a more nuanced conceptualization of BPSD. Methods: PLWD and families/care partners participated in one-on-one semi-structured interviews. A thematic iterative approach was used to code the data and identify common themes until theoretical saturation was reached. Themes were compared between groups. Data were analyzed deductively in relation to pre-existing terminology regarding BPSD, and inductively to discover new ideas on use of such terminology as perceived by PLWD and others. Results: Forty-one volunteers were interviewed: 21 PLWD, mean age 71 yrs, mean Mini-Mental State Examination score 25, and 20 family members/care partners. Three main themes emerged from the data: (1) descriptions of BPSD from people with lived experience compared to clinical terms, (2) viewpoints on interpreting causes, and (3) experiences of concurrent BPSD. The experiences described and terms used by PLWD and families/care partners differed from terms used in existing professional frameworks (e.g., "disinhibition" described as 'loss of filter') and there were differences between PLWD and family members' interpretations of BPSD causes. Discussion/Conclusion: Reports from PLWD and families/carers describing their experiences of BPSD suggest a reconceptualization of BPSD terminology is needed to understand and de-stigmatize these symptoms and behaviors. For example, the term "agitated/hard to handle" would benefit by clearer, contextualized description, such as "frustrated with cognitive decline, discriminatory behavior and inadequate support systems." In better understanding individual expressions of BPSD, families, professionals and societies will be able to respond in ways that are helpful for PLWD. An informed, integrated understanding of BPSD and improved terminology use will have the potential to improve the quality of care and support for PLWD.
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Project description:Dementia is an important health issue worldwide, and non-pharmacological strategies for the management of behavioral and psychological symptoms of dementia (BPSD) are considered to be important. This review analyzes the effectiveness and safety of acupuncture for BPSD. Thirteen electronic databases were comprehensively searched to find clinical studies using acupuncture on BPSD, published up to December 2020. Five randomized controlled clinical trials and two before-after studies, mainly on Alzheimer's disease (AD), were included. Meta-analysis suggested that the total effective rate based on BPSD symptoms in the acupuncture combined with psychotropic drugs group was significantly higher than that in the psychotropic drugs group (risk ratio, 1.27; 95% confidence interval, 1.11 to 1.45; I2 = 51%). In terms of other outcomes related to BPSD, acupuncture as an adjunctive therapy, but not as monotherapy, was associated with significant benefits in most included studies. However, the included studies did not have optimal methodological quality. Our review highlights the limited evidence proving the effectiveness and safety of acupuncture for BPSD in patients with AD. Although some clinical studies have reported the potential benefits of adjuvant acupuncture in managing BPSD, the evidence is not robust and is based on small studies. Therefore, high-quality research in this field is needed.
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Project description:BackgroundDementia is becoming a major public health problem worldwide with the aging of the world's population. Behavioral and psychological symptoms of dementia (BPSD), associated symptoms of dementia, not only predicts the poor prognosis of patients with dementia, but is also a major factor causing the care burden on caregivers, especially informal caregivers. For BPSD management, an alternative to existing psychotropic drugs is needed, given the benefit-harm ratio. Therefore, in this systematic review, we will evaluate the effectiveness and safety of herbal medicine for BPSD.Methods and analysisThirteen electronic databases will be comprehensively searched. Clinical studies reporting the efficacy (or effectiveness) and safety of herbal medicines in BSPD management published from their inception to December 2020 will be included. The primary outcome will be BPSD symptoms assessed by the validated tool. Moreover, total effective rate, daily living activities and quality of life of patients, burden and quality of life of caregiver, placement in a long-term care facility from home, and safety data will be regarded as the secondary outcome. Two independent researchers will perform the study selection, data extraction, and quality assessment process. To assess the methodological quality of the included studies, validated tools according to its design, such as the Cochrane Collaboration's risk of bias tool will be used. To perform meta-analysis, RevMan version 5.3 will be used, with mean differences for continuous outcomes and risk ratio for binary outcomes, and 95% confidence intervals. According to the heterogeneity and number of included studies, a fixed- or random-effects model will be used.Registration numberOSF (URL: https://osf.io/3u8ch), PROSPERO (CRD42020211000) (URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020211000).
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Project description:BackgroundAlthough disclosing the predictors of different behavioral and psychological symptoms of dementia (BPSD) is the first step in developing person-centered interventions, current understanding is limited, as it considers BPSD as a homogenous construct. This fails to account for their heterogeneity and hinders development of interventions that address the underlying causes of the target BPSD subsyndromes. Moreover, understanding the influence of proximal factors-circadian rhythm-related factors (ie, sleep and activity levels) and physical and psychosocial unmet needs states-on BPSD subsyndromes is limited, due to the challenges of obtaining objective and/or continuous time-varying measures.ObjectiveThe aim of this study was to explore factors associated with BPSD subsyndromes among community-dwelling older adults with dementia, considering sets of background and proximal factors (ie, actigraphy-measured sleep and physical activity levels and diary-based caregiver-perceived symptom triggers), guided by the need-driven dementia-compromised behavior model.MethodsA prospective observational study design was employed. Study participants included 145 older adults with dementia living at home. The mean age at baseline was 81.2 (SD 6.01) years and the sample consisted of 86 (59.3%) women. BPSD were measured with a BPSD diary kept by caregivers and were categorized into seven subsyndromes. Independent variables consisted of background characteristics and proximal factors (ie, sleep and physical activity levels measured using actigraphy and caregiver-reported contributing factors assessed using a BPSD diary). Generalized linear mixed models (GLMMs) were used to examine the factors that predicted the occurrence of BPSD subsyndromes. We compared the models based on the Akaike information criterion, the Bayesian information criterion, and likelihood ratio testing.ResultsCompared to the GLMMs with only background factors, the addition of actigraphy and diary-based data improved model fit for every BPSD subsyndrome. The number of hours of nighttime sleep was a predictor of the next day's sleep and nighttime behaviors (odds ratio [OR] 0.9, 95% CI 0.8-1.0; P=.005), and the amount of energy expenditure was a predictor for euphoria or elation (OR 0.02, 95% CI 0.0-0.5; P=.02). All subsyndromes, except for euphoria or elation, were significantly associated with hunger or thirst and urination or bowel movements, and all BPSD subsyndromes showed an association with environmental change. Age, marital status, premorbid personality, and taking sedatives were predictors of specific BPSD subsyndromes.ConclusionsBPSD are clinically heterogeneous, and their occurrence can be predicted by different contributing factors. Our results for various BPSD suggest a critical window for timely intervention and care planning. Findings from this study will help devise symptom-targeted and individualized interventions to prevent and manage BPSD and facilitate personalized dementia care.
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Project description:Alzheimer's Disease (AD) is a devastating neurodegenerative disorder currently affecting 45 million people worldwide, ranking as the 6th highest cause of death. Throughout the development and progression of AD, over 90% of patients display behavioral and psychological symptoms of dementia (BPSD), with some of these symptoms occurring before memory deficits and therefore serving as potential early predictors of AD-related cognitive decline. However, the biochemical links between AD and BPSD are not known. In this study, we explored the molecular interactions between AD and BPSD using protein-protein interaction (PPI) networks built from OMIM (Online Mendelian Inheritance in Man) genes that were related to AD and two distinct BPSD domains, the Affective Domain and the Hyperactivity, Impulsivity, Disinhibition, and Aggression (HIDA) Domain. Our results yielded 8 unique proteins for the Affective Domain (RHOA, GRB2, PIK3R1, HSPA4, HSP90AA1, GSK3beta, PRKCZ, and FYN), 5 unique proteins for the HIDA Domain (LRP1, EGFR, YWHAB, SUMO1, and EGR1), and 6 shared proteins between both BPSD domains (APP, UBC, ELAV1, YWHAZ, YWHAE, and SRC) and AD. These proteins might suggest specific targets and pathways that are involved in the pathogenesis of these BPSD domains in AD.
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Project description:Background/aimsBehavioral and psychological symptoms of dementia (BPSDs) negatively impact the prognosis of dementia patients and increase caregiver distress. The aims of this study were to clarify the differences of trajectories of 12 kinds of BPSDs by disease severity in four major dementias and to develop charts showing the frequency, severity, and associated caregiver distress (ACD) of BPSDs using the data of a Japan multicenter study (J-BIRD).MethodsWe gathered Neuropsychiatric Inventory (NPI) data of patients with Alzheimer's disease (AD; n = 1091), dementia with Lewy bodies (DLB; n = 249), vascular dementia (VaD; n = 156), and frontotemporal lobar degeneration (FTLD; n = 102) collected during a 5-year period up to July 31, 2013 in seven centers for dementia in Japan. The NPI composite scores (frequency × severity) of 12 kinds of items were analyzed using a principal component analysis (PCA) in each dementia. The factor scores of the PCA were compared in each dementia by disease severity, which was determined with Clinical Dementia Rating (CDR).ResultsSignificant increases with higher CDR scores were observed in 1) two of the three factor scores which were loaded for all items except euphoria in AD, 2) two of the four factor scores for apathy, aberrant motor behavior (AMB), sleep disturbances, agitation, irritability, disinhibition, and euphoria in DLB, and 3) one of the four factor scores for apathy, depression, anxiety, and sleep disturbances in VaD. However, no increases were observed in any of the five factor scores in FTLD.ConclusionsAs dementia progresses, several BPSDs become more severe, including 1) apathy and sleep disturbances in AD, DLB, and VaD, 2) all of the BPSDs except euphoria in AD, 3) AMB, agitation, irritability, disinhibition, and euphoria in DLB, and 4) depression and anxiety in VaD. Trajectories of BPSDs in FTLD were unclear.
| S-EPMC4990196 | biostudies-literature