Antipsychotic Use In Dementia Research Articles

Healthcare professionals' experiences with the use of antipsychotics in dementia

BackgroundAntipsychotics are commonly administered to nursing home residents with dementia, despite the associated risk of severe adverse events. ObjectiveThis study aimed to explore healthcare professionals' experiences in caring for nursing home residents with dementia, with a focus on rationales behind the use of antipsychotics. MethodTwelve semi-structured interviews with healthcare professionals' from Danish nursing homes were conducted and analyzed using the method Systematic Text Condensation. ResultsNonpharmacological interventions were reported as the primary approach to care and the first-choice treatment for behavioral and psychological symptoms of dementia (BPSD). Use of antipsychotics was considered to serve as a last resort, reserved for residents with severe symptoms. However, most informants preferred a more limited use. The study identified four main barriers to reduce the use of antipsychotics: “Scarcity of resources”, “Perceiving antipsychotic use to provide relieve”, “Reluctance towards deprescribing” and “Limited access to medical counseling”, and three potential enablers: “Updating knowledge and nonpharmacological competencies”, “Management support and clear procedures” and “Regularity in interdisciplinary collaboration”. ConclusionThe treatment and care were reported as primarily following guidelines in BPSD. Several barriers were perceived to challenge the healthcare professionals' preference of limited use of antipsychotics. To further reduce the use, this study highlights the importance of understanding the adverse effects caused by limited resources, enhancing employee knowledge and competencies and ensuring regular interprofessional collaboration for assessing and reassessing the need to use antipsychotics.

Rethinking antipsychotic use in dementia: a literature review on efficacy, safety, and alternatives

Background an objectives. Dementia and its associated behavioral and psychological symptoms (BPSD) significantly impact patients’ quality of life, healthcare systems, and caregivers. Current treatments often include antipsychotic medications; however, their efficacy and safety profiles require careful evaluation. This review aimed to examine the use of antipsychotics in dementia, focusing on their role, efficacy, adverse effects, and clinical monitoring guidelines. Materials and methods. We conducted a thorough literature review in PubMed and Medline databases, using search terms like “dementia”, “BPSD”, “antipsychotics”, “adverse effects”, and “clinical guidelines”. Our analysis encompassed a range of research studies, including meta-analyses, randomized controlled trials, observational studies, and clinical practice guidelines. Results. While antipsychotics can be effective in managing severe BPSD symptoms like agitation and psychosis, their use carries an increased risk of mortality, stroke, and other adverse effects. Therefore, strict adherence to clinical guidelines and close monitoring are crucial to minimize these risks. Importantly, non-pharmacological interventions should always be the first-line treatment for BPSD whenever possible. Conclusions. Antipsychotics may be necessary for severe BPSD when nonpharmacological approaches are insufficient. Clinicians must carefully weigh the potential benefits against significant risks, utilizing the lowest effective doses, strict monitoring protocols, and considering alternative pharmacological options when possible. Unveiling safer and more specific BPSD treatments is a critical area for continued research.

Impact of the COVID-19 pandemic on antipsychotic prescribing in individuals with autism, dementia, learning disability, serious mental illness or living in a care home: a federated analysis of 59 million patients’ primary care records in situ using OpenSAFELY

BackgroundThe COVID-19 pandemic affected how care was delivered to vulnerable patients, such as those with dementia or learning disability.ObjectiveTo explore whether this affected antipsychotic prescribing in at-risk populations.MethodsWith the approval...

Implications of Adverse Outcomes Associated with Antipsychotics in Older Patients with Dementia: A 2011-2022 Update.

Neuropsychiatric symptoms affect most patients with dementia over the course of the disease. They include a wide variety of symptoms from apathy and depression to psychosis, irritability, impulsivity and agitation. These symptoms are associated with significant distress to the patient and caregivers, as well as more rapid progression of dementia, institutionalisation and higher mortality. The first-line management of the neuropsychiatric symptoms of dementia should be non-pharmacological. If medications are required, antipsychotics are commonly chosen. Second-generation antipsychotics such as risperidone, olanzapine, quetiapine and aripiprazole are prescribed more often than first-generation antipsychotics, such as haloperidol. The aim of this review is to provide an update on findings on adverse outcomes and clinical implications of antipsychotic use in dementia. These medications may increase mortality and can be associated with adverse events including pneumonia, cerebrovascular events, parkinsonian symptoms or higher rates of venous thromboembolism. Risks related to antipsychotic use in dementia are moderated by a number of modifiable and non-modifiable factors such as co-prescribing of other medications, medical and psychiatric co-morbidities, and demographics such as age and sex, making individualised treatment decisions challenging. Antipsychotics have further been associated with an increased risk of reliance on long-term care and institutionalisation, and they might not be cost-effective for healthcare systems. Many of these risks can potentially be mitigated by close physical health monitoring of antipsychotic treatment, as well as early withdrawal of pharmacotherapy when clinically possible.

In‐silico high throughput whole transcriptome screening implicates cardiovascular disease and the immune system in the mechanism of action underlying adverse effects of atypical antipsychotics

AbstractBackgroundRisks of stroke/thromboembolic events, infections and death are all significantly increased by antipsychotics in people with dementia but specific mechanisms are unclear. In a novel application of a drug repurposing paradigm, we aimed to identify candidate underlying mechanisms in‐silico by leveraging publicly available transcriptomic data.MethodsWhole transcriptome signatures were first generated for three antipsychotics (amisulpride, risperidone and volinanserin) using RNA‐sequencing in SHSY‐5Y cell lines. These compounds were chosen to represent a range of mechanisms of action relevant to clinically used compounds and novel compounds in development. An unbiased high throughput screen generated correlations between each compound and a public repository of over 100,000 human disease samples. From a long list of statistically significant hits, correlations between each antipsychotic and conditions/diseases related to known side effects of antipsychotic use in dementia were identified and gene set enrichment analysis performed.ResultsStatistically significant associations were found between antipsychotic transcriptional signatures and atherosclerosis (amisulpride p=0.002; risperidone p=6.98x10‐6; volinanserin p=5.5x10‐8), venous thromboembolism (risperidone p=8.13x10‐7; volinanserin p=0.002) and influenza (amisulpride p=0.002). Pathways enriched in antipsychotic signatures were linked to the cardiovascular system, the immune system and inflammation (including brain derived neurotrophic factor, platelet derived growth factor receptor beta, tumor necrosis factor alpha signalling).ConclusionUsing a novel, high throughput approach, these findings implicate cardiovascular disease and the immune system in the mechanisms of action of atypical antipsychotics, providing a list of priority candidate mechanisms of harm relevant to dementia research. This approach could have implications for drug safety screening of psychotropic drugs in dementia.

Antipsychotic use in dementia: The relationship between neuropsychiatric symptom profiles and adverse outcomes

AbstractBackgroundAntipsychotic treatments are associated with safety concerns in people with dementia. The authors aimed to investigate whether risk of adverse outcomes related to antipsychotic prescribing differed according to major neuropsychiatric syndromes – specifically psychosis, agitation, or a combination – in order to inform a precision medicine approach to management of key neuropsychiatric symptoms.MethodA cohort of 10,106 patients with a diagnosis of dementia was assembled from a large dementia care database in southeast London. Neuropsychiatric symptoms closest to the time of first dementia diagnosis were determined according to Health of the Nation Outcome Scales (HoNOS) mental and behavioural problem scores and the sample was divided into four groups: ‘agitated psychosis’, ‘agitation, but no psychosis’, ‘psychosis, but no agitation’, and ‘neither psychosis nor agitation’. Antipsychotic prescription in a six‐months window around first dementia diagnosis was ascertained as exposure variable through natural language processing from free text. Cox regression models were used to analyse associations of antipsychotic prescription with all‐cause and stroke‐specific mortality, emergency hospitalisation and hospitalised stroke adjusting for sixteen potential confounders including demographics, cognition, functioning, as well as physical and mental health.ResultOnly in the group ‘psychosis, but no agitation’ (n=579), 30% of whom were prescribed an antipsychotic, a significant antipsychotic‐associated increased risk of hospitalised stroke was present after adjustment (adjusted hazard ratio (HR) 2.16; 95% confidence interval (CI) 1.09‐4.25). An increased antipsychotic‐related all‐cause (adjusted HR 1.14; 95% CI 1.04‐1.24) and stroke‐specific mortality risk (adjusted HR 1.28; 95% CI 1.01‐1.63) was detected in the whole sample, but was no interaction between the strata and antipsychotic‐related mortality.ConclusionThe adverse effects of antipsychotics in dementia are complex. Stroke risk may be highest when used in patients presenting with psychosis without agitation, indicating the need for novel interventions for this group.

Antipsychotic use in dementia: the relationship between neuropsychiatric symptom profiles and adverse outcomes

Antipsychotic treatments are associated with safety concerns in people with dementia. The authors aimed to investigate whether risk of adverse outcomes related to antipsychotic prescribing differed according to major neuropsychiatric syndromes—specifically psychosis, agitation, or a combination. A cohort of 10,106 patients with a diagnosis of dementia was assembled from a large dementia care database in South East London. Neuropsychiatric symptoms closest to first dementia diagnosis were determined according to the Health of the Nation Outcome Scales’ mental and behavioural problem scores and the sample was divided into four groups: ‘agitation and psychosis’, ‘agitation, but no psychosis’, ‘psychosis, but no agitation’, and ‘neither psychosis nor agitation’. Antipsychotic prescription in a one-year window around first dementia diagnosis was ascertained as exposure variable through natural language processing from free text. Cox regression models were used to analyse associations of antipsychotic prescription with all-cause and stroke-specific mortality, emergency hospitalisation and hospitalised stroke adjusting for sixteen potential confounders including demographics, cognition, functioning, as well as physical and mental health. Only in the group ‘psychosis, but no agitation’ (n = 579), 30% of whom were prescribed an antipsychotic, a significant antipsychotic-associated increased risk of hospitalised stroke was present after adjustment (adjusted hazard ratio (HR) 2.16; 95% confidence interval (CI) 1.09–4.25). An increased antipsychotic-related all-cause (adjusted HR 1.14; 95% CI 1.04–1.24) and stroke-specific mortality risk (adjusted HR 1.28; 95% CI 1.01–1.63) was detected in the whole sample, but no interaction between the strata and antipsychotic-related mortality. In conclusion, the adverse effects of antipsychotics in dementia are complex. Stroke risk may be highest when used in patients presenting with psychosis without agitation, indicating the need for novel interventions for this group.

When and How to Treat Agitation in Alzheimer's Disease Dementia With Citalopram and Escitalopram

Agitation is a common neuropsychiatric symptom (NPS) in the early and middle stages of Alzheimer's disease (AD) dementia, which is difficult to treat and causes much distress. The U.S. Food and Drug Administration (U.S. FDA) issued black box warnings against the use of antipsychotics in dementia in 2005 and 2008 due to the increased risk of morbidity and mortality, resulting in the reduction in antipsychotic use for treating dementia-related NPS and spurring the quest for safer and more effective pharmacological options. The data favoring the use of citalopram for treating agitation in AD dementia is particularly compelling, and this may be a class effect for all selective serotonin reuptake inhibitors. However, concerns about the cardiac side-effects of citalopram have limited its widespread use for this indication. In this article, available efficacy and safety data for the use of citalopram and escitalopram in treating agitation in AD dementia is reviewed, using a composite case to illustrate key points. Practical recommendations are made to facilitate the use of these medications in routine clinical practice, risk mitigation strategies are discussed and salient issues for future clinical research are emphasized.

A Needs Assessment of Family Physicians to Inform Development of Educational Resources on Antipsychotic Use in Dementia.

Objectives: Objectives of this study were to (1) assess the needs and preferred resources of Iowa physicians to inform the development of educational resources for best practice dementia care and (2) compare the responses of nursing home medical directors with nonmedical directors. Methods: Of 498 physicians, 101 (20%) completed and returned the survey. Family physicians were obtained from a list of family physicians from the Iowa Board of Medical Examiners. Respondent answers were summarized and presented as total numbers and percentages in tables. Significant differences between medical directors and nonmedical directors were evaluated using chi-square tests, Fisher exact tests, and Wilcoxon rank-sum tests. Results: Medical directors and nonmedical directors had similar preferences for resources used and information needs. Online resources, pocket guides, a handbook, consulting pharmacists, and facility in-services were the most commonly preferred sources of new information. Medical directors were significantly more aware of the Food and Drug Administration warning on antipsychotic use in dementia and treated more nursing home patients. No differences were observed between groups related to confidence in and use of nondrug strategies instead of antipsychotics to manage behavioral symptoms of dementia. Conclusion: The results of this survey illustrate physician preferences for information and resources on the management of behavioral and psychological symptoms in dementia. Information was used to inform the development of resources to aid physicians and other health care providers in making decisions about managing these symptoms.

Time for Australia to revisit antipsychotic use in dementia in residential aged care

Time for Australia to revisit antipsychotic use in dementia in residential aged care

Choosing wisely? Quantifying the extent of three low value psychotropic prescribing practices in Australia

BackgroundThe global Choosing Wisely campaign has identified the following psychotropic prescribing as low-value (harmful or wasteful): (1) benzodiazepine use in the elderly, (2) antipsychotic use in dementia and (3) prescribing two or more antipsychotics concurrently. We aimed to quantify the extent of these prescribing practices in the Australian population.MethodsWe applied indicators to dispensing claims of a 10% random sample of Australian Pharmaceutical Benefits Scheme beneficiaries to quantify annual rates of each low-value practice from 2013 to 2016. We also assessed patient factors and direct medicine costs (extrapolated to the entire Australian population) associated with each practice in 2016.ResultsWe observed little change in the rates of the three practices between 2013 and 2016. In 2016, 15.3% of people aged ≥65 years were prescribed a benzodiazepine, 0.5% were prescribed antipsychotics in the context of dementia and 0.2% of people aged ≥18 years received two or more antipsychotics concurrently. The likelihood of elderly people receiving benzodiazepines or antipsychotics in the context of dementia increased with age and the likelihood of receiving all three practices increased with comorbidity burden. In 2016, direct medicine costs to the government of all three practices combined, extrapolated to national figures, were > $21 million AUD.ConclusionsOur indicators suggest that the frequency of these three practices has not changed appreciably in recent years and that they incur significant costs. Worryingly, people with the greatest risk of harm from these prescribing practices are often the most likely to receive them.

CORRECTIONS.

EDITORIALS Hallucinations Predict Relapse After Discontinuation of Risperidone in Patients With Alzheimer’s Disease and Psychosis or Agitation Helen Lavretsky, M.D., M.S. An article in this issue by Patel and colleagues (1) provides new evidence of the predictors of relapse after discontinuing anti- psychotic medications in older adults with Alzheimer’s disease and psychosis or agitation. This is a post hoc analysis following the initial publication of the multicenter Antipsychotic Dis- continuation in Alzheimer’s Disease trial results, which indi- cated that patients who responded to risperidone over 16 weeks of open-label treatment showed a twofold to fourfold higher risk of relapse 16–32 weeks after discontinuation of risperidone compared with continuation on risperidone (2). In the present study, the researchers examined the associa- tions between neuropsychiatric symptoms, both at study base- line and immediately after open risperidone treatment, and the likelihood of relapse after subsequent randomization to con- tinued risperidone treatment or discontinuation to placebo. Of 180 patients with Alzheimer’s disease and symptoms of agita- tion or psychosis who received treatment with risperidone for 16 weeks, 110 responded and were randomly assigned to 1) continue risperidone for 32 weeks, 2) continue risperidone for 16 weeks followed by a switch to placebo for 16 weeks, or 3) switch to placebo for 32 weeks. Compared with patients who had mild hallucinations or no hallucinations at baseline, patients with severe hallucinations showed a higher likelihood of relapse (hazard ratio52.96, 95% CI51.52, 5.76; p50.001). This effect was present for the subsample of patients with auditory hallucina- tions but not those with visual hallucinations. Among patients with baseline hallucinations, 13 of 17 (76.5%) who discontinued risperidone relapsed, compared with 10 of 26 (38.5%) who continued risperidone (p,0.02). This group difference remained for severe (77.8%) compared with mild (36%) hallucinations (p50.02). Neuropsychiatric Inventory domain scores after the initial open-treatment phase prior to randomization were not as- sociated with relapse. The authors conclude with a caution that physicians must be mindful of the potential for relapse in patients with Alzheimer’s disease who present with severe hallucinations at baseline, particularly auditory hallucinations. The study results provide important information that could contribute to guidelines for discontinuation of antipsychotics in patients with Alzheimer’s disease and related dementing illnesses (3). With the global aging trend, our society is deal- ing with rising rates of Alzheimer’s disease and other forms of dementia that currently afflict an estimated 5.4 million Am J Psychiatry 174:4, April 2017 individuals in the United States, 96% of whom are over 65 years of age (Alzheimer’s Facts and Figures, 2016; http://m.alz.org/ facts-and-figures.asp). As of 2016, the aggregated cost of care for all individuals with Alzheimer’s disease and other dementias is estimated at $236 billion, with 68% of the cost covered by Medicare and Medicaid (Alzheimer’s Facts and Figures, 2016). Besides cognitive decline, noncognitive behavioral symptoms or neuropsychiatric symptoms (4) accompany dementia in 80%290% of patients and are associated with excess morbidity and mortality as well as more suffering on the part of both patients and caregivers (5, 6). Nonetheless, compared with in- vestments made to develop pharmacotherapy for cognitive symptoms, systematic efforts to improve the use of medications to treat noncognitive behavioral symptoms have been modest. While numerous stud- ies have provided vari- The study results provide ous degrees of efficacy for important information noncognitive behavioral that could contribute symptoms for a wide va- to guidelines for riety of medications, in- discontinuation of cluding antipsychotics, there is still limited evi- antipsychotics in patients dence to provide guid- with Alzheimer’s disease and ance on their continuous related dementing illnesses. use (7, 8). For individuals who have a good response to antipsychotics, withdrawal from them has been associated with significant relapse (2). At the same time, the efficacy of antipsychotics has been called into question by reports suggesting that the existing evidence is based on trials of short duration that use small samples and varying assessment instruments and often show a high placebo response (9). The use of antipsychotics in dementia is com- plicated by a variety of concerning side effects, including ex- trapyramidal symptoms (particularly tardive dyskinesia [10]), hyperglycemia, diabetes mellitus, weight gain, increases in serum lipid levels, and cardiovascular effects (11, 12). A review of the literature found a 1.3- to 2-fold increased risk of cere- brovascular accidents in case-control studies of elderly pa- tients on antipsychotics, which was highest in the first weeks of treatment and among those who had certain risk factors, such as higher age, cognitive impairment, and vascular disease (11). A review of 17 studies on antipsychotics in individuals with ajp.psychiatryonline.org

Antipsychotic use in dementia: a systematic review of benefits and risks from meta-analyses.

The purpose of this review is to evaluate the data on the use of antipsychotics in individuals with dementia from meta-analyses. We performed a literature search of PubMed, MEDLINE, EMBASE, PsycINFO and Cochrane collaboration databases through 30 November, 2015 using the following keywords: 'antipsychotics', 'dementia' and 'meta-analysis'. The search was not restricted by the age of the patients or the language of the study. However, in the final analysis we only included studies involving patients that were published in English language journals or had official English translations. In addition, we reviewed the bibliographic databases of published articles for additional studies. This systematic review of the literature identified a total of 16 meta-analyses that evaluated the use of antipsychotics in individuals with dementia. Overall, 12 meta-analyses evaluated the efficacy of antipsychotics among individuals with dementia. Of these, eight also assessed adverse effects. A further two studies evaluated the adverse effects of antipsychotics (i.e. death). A total of two meta-analyses evaluated the discontinuation of antipsychotics in individuals with dementia. Overall, three meta-analyses were conducted in individuals with Alzheimer's disease (AD) whereas one focused on individuals with Lewy Body Dementia (LBD). The rest of the 12 meta-analyses included individuals with dementia. Antipsychotics have demonstrated modest efficacy in treating psychosis, aggression and agitation in individuals with dementia. Their use in individuals with dementia is often limited by their adverse effect profile. The use of antipsychotics should be reserved for severe symptoms that have failed to respond adequately to nonpharmacological management strategies.

The Effect of Safety Warnings on Antipsychotic Drug Prescribing in Elderly Persons with Dementia in the United Kingdom and Italy: A Population-Based Study

Antipsychotic (AP) drugs are commonly used to manage the behavioural symptoms of dementia. Nevertheless, international (i.e. the European Medicines Agency in Europe) and national (i.e. the Medicines and Healthcare products Regulatory Agency in the UK and the Italian Drug Agency) regulatory agencies issued safety warnings against AP use in dementia in 2004 and 2009. The aim of this study is to investigate the short- and long-term impact of safety warnings on the use of APs in UK and Italian persons with dementia using two nationwide databases: The Health Improvement Network (THIN) from the UK and the Health Search Database-Cegedim-Strategic Data-Longitudinal Patient Database (HSD-CSD-LPD) from Italy. We calculated the overall quarterly prevalence of AP use by class and by individual drug in persons with dementia aged ≥65years and used generalized linear models to explore the effect of the safety warnings. We identified 58,497 and 10,857 individuals aged ≥65years with dementia from the THIN and HSD-CSD-LPD databases, respectively, over the period 2000-2012. After the 2004 warnings, the use of atypical APs decreased, whereas the use of conventional APs increased, in Italy and the UK until 2009. However, the trend for APs individually showed that the use of risperidone/olanzapine decreased, whereas the use of quetiapine increased in both countries. After the 2009 warnings (until 2012), the use of atypical and conventional APs decreased in the UK (from 11 to 9 and 5 to 3%, respectively), but such use increased in Italy (from 11 to 18 and 9 to 14%, respectively). The 2004 warnings led to a reduction in the use of olanzapine and risperidone and increased the use of quetiapine/conventional APs in both countries. From 2009, the use of APs decreased in persons with dementia in the UK but not in Italy. Possible reasons for the difference in AP use between the two countries include a more proactive approach towards reducing the use of APs in the UK than in Italy.

Session 303 - Managing Dementia Residents in Long-Term Care Using Telehealth

Abstract: A geriatric psychiatrist and gerontological nurse practitioner will present their personal experience using telehealth services to manage dementia, depression and other chronic mental illnesses in rural long-term care facilities. The session will discuss the logistics of being a clinical provider for services: scheduling, medical record review, interdisciplinary collaboration, billing, staff, family and resident acceptance. Benefits and challenges of offering remote dementia and geropsychiatric expertise will be reviewed. Case studies will be presented on common clinical presentations that the geriatric psychiatrist and gerontological nurse practitioner analyze in their facilities. An emphasis will be made on strategies to decrease antipsychotic use in dementia.

Are the safety profiles of antipsychotic drugs used in dementia the same? An updated review of observational studies.

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.

Second-generation antipsychotic drug use in hospital inpatients with dementia: the impact of a safety warning on rates of prescribing

Behavioural and psychological symptoms of dementia are distressing for patients and are frequently treated with second-generation antipsychotics. Concerns about the drugs' safety resulted in a Medicines and Healthcare Products Regulatory Agency (MHRA) warning against their use in March 2009. Second-generation antipsychotic drug use was determined amongst patients with dementia admitted to the University Hospitals Birmingham National Health Service Foundation Trust, between July 2005 and December 2011. An interrupted time series analysis was carried out to investigate changes in rates of prescribing following the safety warning. Risperidone was analysed separately, in accordance with its limited licence for use in older adults with dementia, granted in October 2008. Before the safety warning, second-generation antipsychotic use was increasing in patients with dementia. After the MHRA warning, their use fell by 1.9% per month compared with that before. Use of risperidone continued to rise over the same period, often against the terms of its licence. Drug safety warnings may influence prescribing practice, although continued use of antipsychotics in dementia could reflect a lack of alternative treatment options.

Challenges in Estimating Mortality Risk From Antipsychotics in People With Alzheimer’s Disease

Back to table of contents Previous article Next article Communications and UpdatesFull AccessChallenges in Estimating Mortality Risk From Antipsychotics in People With Alzheimer’s DiseaseRyan M. Carnahan, Pharm.D., M.S.Ryan M. CarnahanSearch for more papers by this author, Pharm.D., M.S.Published Online:1 Feb 2014https://doi.org/10.1176/appi.ajp.2013.13091231AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: I read with interest the article by Lopez et al. (1) in the September 2013 issue on the long-term effects of antipsychotics in people with Alzheimer’s disease, which suggested that after controlling for psychiatric symptoms, neither typical nor atypical antipsychotics were associated with time to death. I would like to expand on one of the limitations noted by the authors, as I believe it is critical to interpreting the results.Previous research suggests that the excess mortality associated with antipsychotics is greatest early in treatment, with the relative risk trending toward no mortality effect of drug as the duration of antipsychotic use increases (2). The Lopez et al. study assessed medications every 6 months, without tracking interim changes. Periodic assessments such as this create challenges when interpreting results that are related to adverse events for which the greatest excess risk occurs early in treatment. This is a particularly important issue in a dementia sample, where death is not a rare occurrence. That is, if someone both started an antipsychotic and died during the time between two assessments, there would be no record that the individual received an antipsychotic before they died, and only those who survived the early treatment period would be recorded as receiving an antipsychotic. Thus, data are lost from individuals who may be particularly vulnerable to the adverse event of interest, in this case death. This is termed “depletion of susceptibles” and may lead to bias in effect estimates, as those who survive treatment through an initial high-risk period are often less susceptible to an adverse effect. This is one reason that new-user designs are generally preferred in pharmacoepidemiology studies of adverse drug effects (3).Lopez et al. have presented a compelling case that psychotic symptoms are a prognostic marker for increased mortality in people with dementia and an influential unmeasured confounder in observational studies of antipsychotics and mortality. However, the design limitations make it difficult to fully discern the role of the psychiatric symptoms relative to that of antipsychotics that were received but not recorded. I admire the authors’ efforts to address this important question but do not place higher weight on these results than on those of randomized controlled trials that identify an increased risk of mortality associated with antipsychotic use in dementia. Randomized trials have their own limitations, such as highly selected samples, shorter follow-up, and small numbers of events in any given trial. Yet Schneider et al.’s meta-analysis of these trials (4) showing greater mortality with antipsychotics compared with placebo included more than 10 times as many antipsychotic users as were in the Lopez et al. study. I hope the null mortality result in this study is not interpreted as an indication that caution and restraint are not necessary when considering the use of antipsychotics in this vulnerable patient population.From The University of Iowa College of Public Health, Department of Epidemiology, Iowa City, Iowa.Dr. Carnahan reports no financial relationships with commercial interests. He has received funding for research and education related to antipsychotic use in dementia from the Agency for Healthcare Research and Quality, the Health Resources and Services Administration, and the Patient Centered Outcomes Research Institute.References1 Lopez OL, Becker JT, Chang YF, Sweet RA, Aizenstein H, Snitz B, Saxton J, McDade E, Kamboh MI, DeKosky ST, Reynolds CF, Klunk WE: The long-term effects of conventional and atypical antipsychotics in patients with probable Alzheimer’s disease. Am J Psychiatry 2013; 170:1051–1058Link, Google Scholar2 Wang PS, Schneeweiss S, Avorn J, Fischer MA, Mogun H, Solomon DH, Brookhart MA: Risk of death in elderly users of conventional vs atypical antipsychotic medications. N Engl J Med 2005; 353:2335–2341Crossref, Medline, Google Scholar3 Ray WA: Evaluating medication effects outside of clinical trials: new-user designs. Am J Epidemiol 2003; 158:915–920Crossref, Medline, Google Scholar4 Schneider LS, Dagerman KS, Insel P: Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA 2005; 294:1934–1943Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited byNone Volume 171Issue 2 February 2014Pages 227-227 Metrics PDF download History Accepted 1 December 2013 Published online 1 February 2014 Published in print 1 February 2014

Use and Safety of Antipsychotics in Behavioral Disorders in Elderly People With Dementia

In recent years, the use of antipsychotics has been widely debated for reasons concerning their safety in elderly patients affected with dementia. To update the use of antipsychotics in elderly demented people, a MEDLINE search was conducted using the following terms: elderly, conventional and atypical antipsychotics, adverse events, dementia, and behavioral and psychotic symptoms in dementia (BPSD). Owing to the large amounts of studies on antipsychotics, we mostly restricted the field of research to the last 10 years. Conventional antipsychotics have been widely used for BPSD; some studies showed they have an efficacy superior to placebo only at high doses, but they are associated with several and severe adverse effects. Atypical antipsychotics showed an efficacy superior to placebo in randomized studies in BPSD treatment, with a better tolerability profile versus conventional drugs. However, in 2002, trials with risperidone and olanzapine in elderly patients affected with dementia-related psychoses suggested the possible increase in cerebrovascular adverse events. Drug regulatory agencies issued specific recommendations for underlining that treatment of BPSD with atypical antipsychotics is "off-label." Conventional antipsychotics showed the same likelihood to increase the risk of death in the elderly as atypical agents, and they should not replace the atypical agents discontinued by Food and Drug Administration warnings. Before prescribing an antipsychotic drug, the following are factors to be seriously considered: the presence of cardiovascular diseases, QTc interval on electrocardiogram, electrolytic imbalances, familiar history for torsades des pointes, concomitant treatments, and use of drugs able to lengthen QTc. Use of antipsychotics in dementia needs a careful case-by-case assessment, together with the possible drug-drug, drug-disease, and drug-food interactions.

Role of antipsychotics for treating behavioral and psychological symptoms of dementia

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 rec ommend 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.