Assessing the impact of neuropsychiatric symptoms in Alzheimer's disease: the Neuropsychiatry Inventory Caregiver Distress Scale. Christensen DB, Benfield WR. A recent review estimated that worldwide 24 million people have dementia, and that this number will double by the year 2020 (Ferri et al., 2005). Likewise, some investigations have demonstrated an association between psychosis of dementia and increased mortality (Wilson et al., 2006), whereas other researchers have not found such a relationship (Samson et al., 1996; Rosen and Zubenko, 1991). Clinical trials have shown little benefit from antipsychotic use for the ever-growing group of elderly patients in whom agitation and psychosis often develop. Only severe symptoms that are persistent or recurrent and cause clinically significant functional disruption would generally be considered appropriate for ongoing pharamcologic management. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. It is noteworthy that, as mentioned before, Schneider et al. The economic impact of neuropsychiatric symptoms in Alzheimer's disease: can drugs ease the burden? anticholinergic, hypotensive, metabolic) compared to certain other individual agents in specific patients. Importance: Antipsychotic medications are associated with increased mortality in older adults with dementia, yet their absolute effect on risk relative to no treatment or an alternative psychotropic is unclear. National Library of Medicine Background. Banerjee S, Smith SC, Lamping DL, Harwood RH, Foley B, Smith P, et al. Agitation may be conceptualized as a single symptom or a symptom complex, and may co-occur with psychosis or depression (Jeste et al., 2006). In a large prospective study, both caregiver burden and behavioral symptoms were independently associated with nursing home placement of persons with dementia (Yaffe et al., 2002). There is an urgent need for additional research in this area of considerable public health significance. Alexopoulos GS, Schultz SK, Lebowitz BD. Yet, most trials of psychosis did not exclude agitation, and vice versa, resulting in many trials including persons with elevated symptom scores for both psychosis and agitation (Schneider et al., 2006a). (3) No specific risk or protective factors related to antipsychotic-associated CVAEs or deaths are known. Behavioral pathology in Alzheimer's disease (BEHAVE-AD) rating scale. Treatment approaches should, therefore, be frequently reassessed. Behavioral disorders and caregivers' reaction in Taiwanese patients with Alzheimer's disease. With these factors in mind, the guidelines recommend "assessment of psychological and behavioral symptoms of dementia, development of a comprehensive treatment plan, assessment of the benefits and risks of antipsychotics, and judicious use of antipsychotics, including specifics for dosing, duration and monitoring. With a focus on antipsychotic therapy, it is hoped that the new guidelines will help clinicians, patients, and caregivers make informed decisions. The appropriate starting dose of an antipsychotic in older individuals is 25% of the usual adult dose; total daily maintenance doses ranges from 25-50% of the adult dose. Although the difference in mortality rates between haloperidol and placebo was not statistically significant, this does not equate to a lack of concern. Individual patients may tolerate and benefit from antipsychotic medications such that their use in patients with severe and persistent or recurrent symptoms may be justified, but these medications are not an unequivocal first-line treatment. Tariot PN, Raman R, Jakimovich L, Schneider L, Porsteinsson A, Thomas R, et al. via qualitative studies. Ritsner M, Gibel A, Perelroyzen G, Kurs R, Jabarin M, Ratner Y. Long-term cohort studies show. An individualized approach to psychosocial treatments using behavioral and other strategies may be a reasonable choice for certain patients with these symptoms. Brodaty H, Low LF. A recent placebo-controlled RCT of donepezil, the British Medical Research Council-sponsored CALM-AD trial showed no effect of donepezil on behavior in AD patients with both severe dementia and substantial behavioral symptoms (Howard R, unpublished data). Rosen J, Zubenko GS. Several recent reviews have summarized the relative strengths and weaknesses of scales designed to measure such outcomes in studies of dementia (Rockwood, 2007; Ready and Ott, 2003; De Deyn and Wirshing, 2001). This is despite a high adverse effect burden and limited evidence of efficacy. (2006a) reported better response in trials of atypical antipsychotics for dementia patients without (versus with) psychosis; thus, patients with agitation alone may preferentially respond to these medications (though common comorbidities such as depression and anxiety were not fully characterized in these patients with agitation). Do atypical antipsychotics cause stroke? The following is a summary of what is known and what is not regarding the use of antipsychotic drugs in dementia-associated psychosis and agitation, based largely on the literature discussed above. operationalized criteria for psychosis (Jeste and Finkel, 2000)), these were not used in early clinical trials. Presented at the 18th Annual Meeting of the American Association for Geriatric Psychiatry; San Diego, CA March 36.). Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. Hypotheses could include: orthostatic hypotension (1-receptor blockade); tachycardia (1- and M2-receptor blockade); metabolic derangements due to atypical antipsychotics such as insulin resistance, weight gain, dyslipidemia (possibly due to H1-, M3-, 5HT2-receptor blockade); sedation (e.g. A controlled trial of provider education. With the discovery of the first dopamine-blocking typical (or conventional or first-generation) antipsychotic chlorpromazine in 1952, a revolution in psychiatric therapeutics occurred that radically changed the treatment of schizophrenia and other severe mental illnesses. There is no evidence to support overall better safety profiles with typical (compared to atypical) antipsychotics, and these drugs, as a class, may not be considered as therapeutic alternatives for the purpose of minimizing these risks (although there may be individual exceptions). The alternatives to antipsychotics for treating psychosis and agitation in persons with dementia include no treatment, use of other psychotropic drugs, and psychosocial and psychotherapeutic interventions. Pharmacologic treatment of psychosis and agitation in elderly patients with dementia: Four decades of experience. De Deyn P, Rabheru K, Rasmussen A, Bocksberger JP, Dautzenberg PLJ, Eriksson S, et al. Cummings JL, McRae T, Zhang R, Donepezil-Sertraline Study Group Effects of donepezil on neuropsychiatric symptoms in patients with dementia and severe behavioral disorders. Careful consideration must also be given to the validity of outcome measures used for psychosis and other neuropsychiatric symptoms, such as how these may relate to clinically meaningful outcomes. Coccaro EF, Kramer E, Zemishlany Z, Thorne A, Rice MC, III, Giordani B, et al. Fuh JL, Liu CK, Mega MS, Wang SJ, Cummings JL. Psychosis of AD is characterized by delusions or hallucinations (Jeste and Finkel, 2000). Extrapyramidal side effects, tardive dyskinesia, and the concept of atypicality. A prospective trial of donepezil for neuropsychiatric symptoms in outpatients with mild-moderate AD showed improvement in global neuropsychiatric symptoms during open-label treatment for 3 months, followed by symptomatic worsening only in placebo-treated patients during the subsequent randomized discontinuation phase of the trial (Holmes et al., 2004). Clinicians should document the fact that a discussion of these issues was conducted. Determinants of the quality of life in Alzheimer's disease patients as assessed by the Japanese version of the Quality of Life-Alzheimer's disease scale. Use of antipsychotics in elderly people. Mechanisms underlying antipsychotic- associated CVAEs are unknown. Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients. ADCS-CGIC (Alzheimer's Disease Cooperative Study Clinical Global Impression of Change); BEHAVE-AD (Behavioral Pathology in Alzheimer's Disease Rating Scale); CMAI (Cohen-Mansfield Agitation Inventory); RAGE (Rating Scale for Aggressive Behavior in the Elderly). Wragg RE, Jeste DV. These include metabolic derangements, cardiac conduction disturbances, sedation leading to aspiration, with secondary pneumonia, and other mechanisms listed above with CVAEs. Yet, these patients had relatively modest levels of behavioral symptoms. There is clearly a need for conducting well designed RCTs of behavioral and psychosocial interventions in patients with dementia. Herrmann N, Lanctot KL. Likewise, the typical antipsychotics have no proven therapeutic advantages over atypical agents, but typical drugs are less expensive, and individual typical drugs may have less propensity to cause certain side effects (e.g. The effectiveness of atypical antipsychotics for the treatment of aggression and psychosis in Alzheimer's disease. Risperidone (0.5-2.0 mg/day) was first line followed by quetiapine (50-150 mg/day) and olanzapine (5.0-7.5 mg/day) as high second-line options. The diagnoses of serious CVAEs were based on spontaneously reported adverse events; these were not validated. Conventional antipsychotic drugs are all antagonists of dopamine D 2 receptors and have a greater propensity to produce EPS than atypical antipsychotic drugs. c) Typical vs. Atypical Antipsychotics: Gill et al. (9) Research on the shared decision-making process and its effects on consumer satisfaction in this clinical setting. Among the four previously described RCTs comparing typical versus atypical antipsychotics, none reported a differential incidence of CVAEs with typical or atypical antipsychotics although sample sizes were smaller than might be needed to demonstrate such differences (Chan et al., 2001; De Deyn et al., 1999; Suh et al., 2004). Elderly persons with dementia constitute a fragile population in whom introduction of any prescription medication may carry some appreciable risks. Lonergan E, Luxenberg J, Colford J. Haloperidol for agitation in dementia. The prescribing labels of all antipsychotics are now required to carry a standard warning. Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, et al. A combination of the various adverse effects of neuropsychiatric symptoms in dementia likely leads to increased system-wide healthcare costs (Murman and Colenda, 2005). Analyses of 17 placebo-controlled studies of four drugsolanzapine, aripiprazole, risperidone, and quetiapinehave revealed a 4.5% mortality rate among elderly patients with dementia who had been treated for behavioral symptoms with these second-generation antipsychotics compared with a 2.6% mortality rate among patients treated with a placebo, according to the agency. Subgroup analysis revealed better overall response in patients without (versus with) psychosis, those in nursing home (versus outpatient) settings, and those with severe (versus moderate) cognitive impairment. (3) Exploring biological mechanisms (including non-dopaminergic ones) underlying psychosis and agitation in dementia, and using such data to continually refine these diagnostic constructs/phenotypes. Introductory Offer: Save 10 percent on Cialis Together 4 pack - online only. A decision should be made only after thorough assessment and review of potential benefits and harms of antipsychotic treatment as well as other possible treatment options.. Glazer WM. The incidence of mortality is significantly higher with atypical antipsychotics as a group (and that of CVAEs with several agents in this class) than with placebo in patients with dementia, based on large-scale RCTs. (2005) reported the results of a retrospective cohort study of mortality involving 22,890 patients, 65 years of age or older, treated with antipsychotics. Unfortunately, the evidence base for the efficacy of most psychosocial interventions in dementia patients is limited (Cohen-Mansfield, 2001; Livingston et al., 2005). Evans DA, Funkenstein H, Albert MS, Scherr PA, Cook NR, Chown MJ, et al. (6) Studies of mechanism of action for antipsychotic effects on cardio/cerebrovascular systems. Most deaths were due to either cardiac or infectious causes, the two most common immediate causes of death in dementia in general. The physical assessments may be conducted at baseline and then every 3 months whereas the lab testing may be done at baseline, months 3 and 6 and every 6 months thereafter. Cohen-Mansfield J. Nonpharmacologic interventions for inappropriate behaviors in dementia: A review and critique. Such information should be tailored to the educational/intellectual level of the recipient, and also respect the individual's desire for autonomy in medical decisions. Lower mortality in geriatric patients receiving risperidone and olanzapine versus haloperidol: preliminary analysis of retrospective data. Mourik JC, Rosso SM, Niermeijer MF, Duivenvoorden HJ, Van Swieten JC, Tibben A. Frontotemporal dementia: behavioral symptoms and caregiver distress. However, no other differences in efficacy or safety have been demonstrated between typical and atypical agents, although typical antipsychotics are less expensive. However, there have been only four RCTs comparing these two classes of antipsychotics in persons with dementia: three comparing risperidone with haloperidol (Chan et al., 2001; De Deyn et al., 1999; Suh et al., 2004), and one comparing quetiapine and haloperidol (Tariot et al., 2006). The trials used a variety of outcome measures, and when primary outcomes measures were reported, they often represented a global measure of neuropsychiatric symptoms. The increased risk for CVAEs was determined from RCTs, and is based on unbiased estimates. Thus, there is insufficient evidence to suggest that psychotropics other than antipsychotics represent an overall effective and safe, let alone better, treatment choice for psychosis or agitation in dementia; currently no such treatment has been approved by the FDA for these symptoms. The atypical antipsychotics came to be used widely in different patient populations, including older adults with dementia, who were especially susceptible to the motor side effects of the typical agents (Jeste, 2000). The clinician should regularly monitor relevant adverse effects of antipsychotics, including EPS, tardive dyskinesia, blood pressure, body weight, and blood glucose and lipid levels. Late-life depression: a model for mechanism-based classification. Atypical antipsychotics and risk of cerebrovascular accidents. It is conceivable that such mechanisms could be somewhat different for different drugs. As a library, NLM provides access to scientific literature. Stanniland C, Taylor D. Tolerability of atypical antipsychotics. Divalproex sodium in nursing home residents with possible or probable Alzheimer Disease complicated by agitation: a randomized, controlled trial. Am J Geriatr Psychiatry 15 : 416-424. Was 21.99. Risk of death in elderly users of conventional vs. atypical antipsychotic medications. Individual typical or atypical drugs may have less propensity to cause certain side effects (e.g. Hallucinations, cognitive decline, and death in Alzheimer's disease. The FDA warns that giving Haldol to elderly patients with dementia-related psychosis significantly increases the risk of death from heart problems, falls and infections. Similarly, in recent trials, no significant therapeutic effects were found for haloperidol compared to placebo and trazodone (Teri et al., 2000), compared to placebo and quetiapine (Tariot et al., 2006), and compared to risperidone and placebo (De Deyn et al., 1999). As such, differential effects of these medication classes on symptom improvement and various adverse reactions (including CVAEs and death) remain undetermined. In 2003, Janssen (manufacturer of risperidone), in consultation with the FDA, added the following warning to risperidone prescribing information regarding stroke risk in older dementia patients. (5) The behavioral effects of treatments for dementia targeted at cognitive symptoms (i.e., cholinesterase inhibitors and memantine) are unclear, but appear to be modest at best, based on existing data. The HGEU Study Group. Introduction. Time to discontinuation due to lack of efficacy favored olanzapine and risperidone, while time to discontinuation due to adverse events favored placebo. Typical antipsychotic medications were associated with a significantly higher adjusted risk of death than were atypical antipsychotic medications at all intervals studied (180 days: relative risk, 1.4; 95% CI, 1.3 to 1.5; <40 days: relative risk, 1.6; 95% CI, 1.4 to 1.8; 40 to 79 days: relative risk, 1.4; 95% CI, 1.2 to 1.6; and 80 to 180 days: relative risk, 1.3; 95% CI, 1.1 to 1.4), and in all subgroups defined according to the presence or absence of dementia or nursing home residency. The published studies of psychosocial/behavioral treatments have a number of methodological limitations. A randomized placebo-controlled trial of risperidone for the treatment of aggression, agitation, and psychosis of dementia. Patient and caregiver characteristics and nursing home placement in patients with dementia. Effectiveness of nonpharmacological interventions for the management of neuropsychiatric symptoms in patients with dementia: a systematic review. Conventional antipsychotics. It is important to identify target signs and symptoms, and to establish a time frame in which to expect and evaluate an intervention's effectiveness and in which to decide on continuing or altering treatment. This was similar to the results reported by other authors (Herrmann et al., 2004) that typical antipsychotics appeared similar to atypical agents in stroke risk. Tractenberg RE, Weiner MF, Patterson MB, Teri L, Thal LJ. Use of antipsychotics after shared decision making with patients and/or caregivers and followed by close clinical monitoring is within the realm of reasonable practice. During the past decade, atypical antipsychotics have largely replaced typical agents in the treatment of psychosis, aggression, and agitation in patients with dementia because of perceived greater tolerability and lesser risk for acute EPS, and because of the documented lower risk for tardive dyskinesia compared to typical agents (Glazer, 2000; Dolder and Jeste, 2003; Jeste et al., 1999a; Ritsner et al., 2004; Stanniland and Taylor, 2000). Likewise, individual antipsychotics within the same class may have differences in serious side effect profiles, but head-to-head comparisons among atypical antipsychotics have been uncommon. Jeste DV. A meta-analysis found that pooled rates of CVAEs were 1.9% in atypical antipsychotic treated patients versus 0.9% in placebo-treated patients, yielding an odds ratio of 2.1 (95% CI 1.2, 3.8) (Schneider et al, 2006a). Z, Thorne a, Bocksberger JP, Swartz MS, Scherr PA Cook! 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