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The Use of Opioids and Antipsychotics in Elderly with Dementia - Have Opioids Replaced Antipsychotics in Treating Behavioral Symptoms in Dementia?

ABSTRACT: BACKGROUND:Opioids are used with increasing frequency. Elderly with dementia are prescribed opioids more frequent than elderly without. One possible explanation is that opioids may be used not only to treat pain but also behavioral symptoms. OBJECTIVE:To test the hypothesis that strong opioid use, especially transdermal formulations, had increased, especially in elderly with dementia, in parallel with a decrease in antipsychotic use. METHODS:Population-based cross-sectional study conducted using nationwide Danish registers with data on Denmark's entire elderly population age ?65 (2000: n?=?802,106; 2015: n?=?1,056,476). The registers were used to identify elderly with and without dementia and filled prescriptions for opioids and antipsychotics. Annual prevalence of opioid and antipsychotic use from 2000-2015 was calculated. RESULTS:Prevalence of opioid use increased by 35% (24.2 to 32.5%) among elderly with dementia and by 13% among elderly without (14.9 to 16.8%) from 2000-2015. The disproportionate increase in opioid use among elderly with dementia was mainly driven by an increase in strong opioids (dementia: 11.7 to 23.1%; without dementia: 5.9 to 7.4%). Use of antipsychotics decreased during the same period (dementia: 31.3 to 19.3%; no dementia: 4.5 to 2.7%). CONCLUSION:From 2000-2015, use of opioids among the elderly increased with a disproportionately higher increase among elderly with dementia. The parallel decrease in the use of antipsychotics may suggest that opioids to some extent have replaced antipsychotics in managing behavioral symptoms, despite safety concerns and lack of evidence for effect of opioids. Future research should focus on potential risks associated with increased opioid use.

SUBMITTER: Jensen-Dahm C

PROVIDER: S-EPMC7029326 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The Use of Opioids and Antipsychotics in Elderly with Dementia - Have Opioids Replaced Antipsychotics in Treating Behavioral Symptoms in Dementia?

Jensen-Dahm Christina C Christensen Ane Nørgaard AN Gasse Christiane C Waldemar Gunhild G

Journal of Alzheimer's disease : JAD 20200101 1

<h4>Background</h4>Opioids are used with increasing frequency. Elderly with dementia are prescribed opioids more frequent than elderly without. One possible explanation is that opioids may be used not only to treat pain but also behavioral symptoms.<h4>Objective</h4>To test the hypothesis that strong opioid use, especially transdermal formulations, had increased, especially in elderly with dementia, in parallel with a decrease in antipsychotic use.<h4>Methods</h4>Population-based cross-sectional ...[more]

PMID: 31771062

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Project description:Background:A typical antipsychotics for neuropsychiatric symptoms in dementia have been tested in much larger trials than the older conventional drugs. The advantage of larger sample sizes is that negative findings become less likely and the effect estimates more precise. However, as sample sizes increase, the trials also get more expensive and time consuming while exposing more patients to drugs with unknown safety profiles. Moreover, a large sample size might yield a statistically significant effect that is not necessarily clinically relevant. Objective:To assess (1) the variation in sample size and sample size calculations of antipsychotic trials in dementia, (2) the size of reported treatment effects and related statistical significance, and (3) general study characteristics that might be related to sample size. Study Design and Setting:We performed a meta-epidemiological study of randomized trials that tested antipsychotics for neuropsychiatric symptoms in dementia. The trials compared conventional or atypical antipsychotics with placebo or another antipsychotic. Two reviewers independently extracted sample size, sample size calculations, reported treatment effects with p-values, and general study characteristics (drug type, trial duration, type of funding). We calculated a reference sample size of 83 and 433 per study group for the placebo-controlled and head-to-head trials respectively. Results:We identified 33 placebo-controlled trials, and 18 head-to-head trials. Only 14 (42%) and 2 (11%), respectively, reported a sample size calculation. The average sample size per arm was 34 (range 6-179) in placebo-controlled trials testing conventional drugs, 107 (8-237) in such trials testing atypical drugs, and 104 (95-115) in such trials testing both drug types; it was 31 (10-88) in head-to-head trials. Thirteen out of 18 trials with sample sizes larger than required (72%) reported a statistically significant treatment effect, of which two (15%) were clinically relevant. None of the head-to-head trials reported a statistically significant treatment effect, even though some suggested non-inferiority. In placebo-controlled trials of atypical drugs, longer trial duration (>6 weeks) and commercial funding were associated with higher sample size. Conclusion:Sample size calculations were poorly reported in antipsychotic trials for dementia. Placebo-controlled trials of atypical antipsychotics showed large sample size fallacy while head-to-head trials were massively underpowered.

Project description:ImportanceAtypical antipsychotics offer modest effectiveness compared with placebo but with serious safety risks, including a boxed warning for the risk of death in the treatment of behavioral and psychological symptoms of dementia (BPSD). Their comparative effectiveness and safety are not fully known.ObjectiveTo assess the relative benefits and safety of atypical antipsychotics in the treatment of BPSD shown in randomized clinical trials using network meta-analysis.Data sourcesPubMed/MEDLINE, Embase, PsychINFO, and Cochrane Library were searched from their inception until May 31, 2018. Key terms included dementia and atypical antipsychotics.Study selectionRandomized clinical trials comparing any atypical antipsychotic with another atypical antipsychotic or with placebo were included in the analysis.Data extraction and synthesisTwo independent reviewers used a standardized data extraction and quality assessment form. Random-effects network meta-analyses were performed. Effect sizes were reported as standardized mean differences (SMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes with 95% CIs. In addition to ORs, the surface under the cumulative ranking curve (SUCRA) was ascertained, which represents the percentage of the effectiveness or safety for each treatment compared with a hypothetical treatment that would be ranked first without uncertainty.Main outcomes and measuresThe primary effectiveness outcome assessed was the Neuropsychiatric Inventory (NPI); secondary effectiveness outcomes were the Brief Psychiatric Rating Scale (BPRS) and Cohen-Mansfield Agitation Inventory (CMAI). The primary safety outcomes were death and cerebrovascular adverse events (CVAEs). Secondary safety outcomes were extrapyramidal signs/symptoms; somnolence/sedation; falls, fracture, or injury; and urinary tract infection/incontinence.ResultsSeventeen studies (5373 patients) were included. The mean (SD) age of all participants was 80.8 (3.1) years, and most were women (3748 [69.8%]). Compared with placebo, aripiprazole was associated with improvement in outcomes on the NPI (SMD, -0.17; 95% CI, -0.31 to -0.02), BPRS (SMD, -0.20; 95% CI, -0.35 to -0.05), and CMAI (SMD, -0.30; 95% CI, -0.55 to -0.05); quetiapine was associated with improvement in outcomes on the BPRS (SMD, -0.24; 95% CI, -0.46 to -0.01), and risperidone was associated with improvement in outcomes on the CMAI (SMD, -0.26; 95% CI, -0.37 to -0.15). Differences between atypical antipsychotics were not significant for effectiveness, death, or CVAE. Compared with placebo, risperidone (OR, 3.85; 95% CI, 1.55-9.55) and olanzapine (OR, 4.28; 95% CI, 1.26-14.56) were associated with increased risk of CVAEs. The SUCRA estimated relative ranking of treatments suggested that aripiprazole might be the most effective and safe atypical antipsychotic and that olanzapine provides the least benefit overall; however, these results should be interpreted with caution where point estimates (OR and SMD) show that there is no statistically significant difference.Conclusions and relevanceThis network meta-analysis supports the existence of a trade-off between the effectiveness and safety of atypical antipsychotics in the treatment of BPSD and confirms that a single most effective and safe treatment option does not exist. Clinicians should individualize the assessment of safety risks against expected benefits when prescribing these medications to patients with dementia.

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.

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.

Dataset Information

The Use of Opioids and Antipsychotics in Elderly with Dementia - Have Opioids Replaced Antipsychotics in Treating Behavioral Symptoms in Dementia?

Publications

The Use of Opioids and Antipsychotics in Elderly with Dementia - Have Opioids Replaced Antipsychotics in Treating Behavioral Symptoms in Dementia?

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