International Journal of Mental Health & PsychiatryISSN: 2471-4372

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Editorial, Int J Ment Health Psychiatry Vol: 1 Issue: 1

Using Anti psychotics in Older Individuals with Dementia: Balancing Efficacy with Adverse Effects

Rajesh R Tampi1* and Deena J Tampi2
1Department of Psychiatry, Metro Health, Cleveland, Ohio, USA
2Saint Francis Hospital and Medical Center, Hartford, Connecticut, USA
Corresponding author : Rajesh R Tampi
MD, MS, DFAPA, Vice Chairman for Education, Program Director, Psychiatry Residency, Department of Psychiatry, Metro Health 2500 Metro Health Drive, Cleveland, Ohio, 44109, USA
Tel: (203) 809 5223
E-mail: [email protected]com
Received: May 06, 2015 Accepted: May 08, 2015 Published: May 09, 2015
Citation: Tampi RR, Tampi DJ (2015) Using Antipsychotics in Older Individuals with Dementia: Balancing Efficacy with Adverse Effects. Int J Ment Health Psychiatry 1:1. doi:10.4172/2471-4372.1000e101

Abstract

A recent New York Times article highlighted the issue on the overuse of psychotropic medications in older adults with dementias who live in the United States. It was mentioned in this report that the US government had concerns regarding the inappropriate use of antipsychotic medications like aripiprazole, risperidone, olanzapine and clozapine in individuals with dementias who lived at home or at assisted living facilities and nursing homes. In view of this recent report, it is prudent to evaluate the evidence for the use of antipsychotic medications for treating behavioral symptoms of dementia.

Keywords: Dementia; Antipsychotics

Editorial
A recent New York Times article highlighted the issue on the overuse of psychotropic medications in older adults with dementias who live in the United States [1]. It was mentioned in this report that the US government had concerns regarding the inappropriate use of antipsychotic medications like aripiprazole, risperidone, olanzapine and clozapine in individuals with dementias who lived at home or at assisted living facilities and nursing homes. In view of this recent report, it is prudent to evaluate the evidence for the use of antipsychotic medications for treating behavioral symptoms of dementia.
Behavioral symptoms of dementia include a heterogeneous range of psychological reactions, psychiatric symptoms and behaviors that are unsafe and disruptive and impair the care of the individual in a given environment [2]. These symptoms are seen in about one third of community-dwelling individuals with dementia [3]. Their prevalence increases to approximately 80% in individuals with dementia who reside at skilled nursing facilities [4]. Evidence indicates that behavioral symptoms are associated with greater overall burden of care, increase the risk for institutionalization and inflate the cost of care for individuals with dementia [2,5-8].
Available evidence indicates that antipsychotic medications are commonly used to treat behavioral symptoms of dementia [9]. In a meta-analysis by Ballard et al., the investigators found that that there was significant improvement in aggression in individuals with dementia who were treated with risperidone and olanzapine when compared to placebo [10]. Additionally, individuals treated with risperidone also had significant improvements in psychosis when compared to placebo. A meta-analysis by Schneider et al found that there is evidence for the efficacy of aripiprazole and risperidone in the management of individuals with behavioral symptoms of dementia [11]. In the Clinical Antipsychotic Trials of Intervention Effectiveness - Alzheimer's Dementia (CATIE-AD) study, a randomized doubleblind, placebo-controlled trial of outpatients with Alzheimer's disease and psychosis, aggression or agitation, individuals were randomly assigned to receive olanzapine, quetiapine, risperidone or placebo [12]. The investigators found no significant difference among the active agents when compared to placebo for the time to the discontinuation of treatment for any reason but the median time to discontinuation of treatment due to a lack of efficacy favored olanzapine and risperidone when compared to quetiapine or placebo. They also found that the time to discontinuation of treatment due to adverse events or intolerability favored placebo when compared to the active agents.
The Canadian Health Regulatory Agency was the first to raise concerns regarding the association of cerebrovascular adverse events (CVAEs) with risperidone in clinical trials of older adults with dementia [13]. The FDA then published a warning and required changes in the prescribing information for risperidone. The European Agency for the Evaluation of Medicinal Products (EMEA) then issued a public advisory on the increased risk of CVAEs and mortality in older adults with dementia who were receiving risperidone. This was followed by the UK’s Committee on Safety of Medicines (CSM) who advised prescribers that risperidone and olanzapine should not be used to treat behavioral symptoms of dementia because of “clear evidence of an increased risk of strokes.”
In a meta-analysis, Herrmann and Lanctot evaluated data from eleven randomized controlled trials of risperidone and olanzapine in individuals with dementia [14]. They found an increased incidence of cerebrovascular adverse events (CVAEs) in the drug treated group when compared to the placebo group. An analysis of the risperidone trials found that some of the increased incidence could be accounted for by non-specific events that were not strokes. There were a greater number of individuals with vascular and mixed dementias in the risperidone trials when compared to the olanzapine trials. In contrast to this meta-analysis, two large observational database studies did not find an increased risk of stroke in older individuals treated with risperidone and olanzapine when compared to those individuals treated with typical antipsychotics or untreated individuals with dementia [15,16].
The Food and Drug Administration (FDA) data indicates that out of a total of seventeen placebo controlled trials of olanzapine, aripiprazole, risperidone orquetiapine in individuals with BPSD, fifteen trials showed numerical increases in mortality rates (1.6-1.7 fold) in the drug-treated group when compared to the placebo-treated groups [17]. Deaths were due to either heart related events (heart failure or sudden death) or infections (mainly pneumonia). The FDA then asked the manufacturers of these drugs and of typical antipsychotics to include a Boxed Warning in their labeling describing this risk and noting that these drugs are not approved for the treatment this indication [18].
Schneider et al. in their meta-analysis found that the risk of death was greater among individuals who were treated with atypical antipsychotics when compared to placebo [19]. The sensitivity analyses did not show any evidence for differential risks for individual drugs, severity of dementia, sample selection or the diagnosis. The retrospective cohort study by Wang et al found that typical antipsychotic medications were associated with higher adjusted risk of death when compared to atypical antipsychotic medications for all time-intervals studied (<40 days to ≥180 days) and for all subgroups based on the presence or absence of dementia or nursing home residence [13]. In the CATIE trial there were no CVAEs or deaths attributable to the prescription of antipsychotics [12]
In a review by Mittal et al., the investigators found that the risk of cerebrovascular adverse events (CVAEs) was higher in the drug treated groups when compared to placebo [13]. Similarly, the risk of death was also higher in the drug treated group compared to placebo. The data for both CVAEs and death indicates that the risk is similar for both typical and atypical antipsychotic agents. Risk factors for developing CVAEs include a higher than median doses of a drug, older age, a diagnosis of vascular dementia and comorbid atrial fibrillation. The risk for death includes older age, male gender, severe dementia and functional impairment. The time frame for elevated risk of CVAEs is approximately twenty months and for death is the first thirty days to two years.
In view of the adverse effects of antipsychotic medications in older adults with dementias, it is appropriate to be cautious when using these medications in high risk individuals; those who are ≥ 85 years in age, individuals with vascular or mixed dementias, individuals with active cerebrovascular or cardiovascular diseases and individuals who have significant impairments in activities of daily living [20]. However, if the behavioral symptoms of dementia are not sufficiently managed by other strategies, the use of antipsychotics may be justified. When using antipsychotic medications, it is prudent to use the minimum effective dose and for the shortest effective time period to manage the symptoms. Additionally, close monitoring of risk factors for adverse outcomes and their appropriate management will maximize efficacy and minimize serious adverse events.

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