The Art of Prescribing: Pharmacological Management of Psychosis in Alzheimer's Disease
Posted on: Thursday, 24 April 2008, 06:00 CDT
By Antai-Otong, Deborah
QUESTION. There is growing concern about the use of second- generation or atypical antipsychotic medications in the management of psychosis in patients with Alzheimer's disease (AD). As a practicing advanced practice psychiatric nurse in a local nursing home, this issue is a frequent clinical challenge. Please discuss the most recent clinical findings concerning the pharmacological management of psychosis in patients with AD, specifically the second- generation antipsychotic medications and the implications for prescribing psychiatric nurses. DEBORAH ANTAI-OTONG REPLIES. You are correct about the growing concerns involving the use of second- generation antipsychotic medication in patients with AD. In fact, although these agents are widely used to treat neuropsychiatrie disorders in older adults, many questions linger about the efficacy and safety, further complicating clinical decision-making. As our society ages, the number of individuals with psychosis increases. The rise in AD in the U.S. population makes this discussion especially timely and relevant to the safe and quality management of psychosis in persons with AD.
Off-label use of second-generation antipsychotic (SGA) medications is extensively used to treat psychosis in individuals with dementia, despite the lack of approval by the U.S. Food and Drug Administration (U.S. FDA). Psychosis occurs in as much as 80% of patients with Alzheimer's disease (AD) at some time during the course of their illness (Jeste & Finkel, 2000; Lyketsos et al., 2002). Typical symptoms of psychosis include hallucinations, delusions, aggression, and agitation. Psychosis produces considerable distress in patients and stress and depression in caregivers, an increased probability for hospitalization, and the likelihood of nursing home placement (Kales, Chen, Blow, Welsh, & Mellow, 2005; Wancata, Windhaber, Krautgartner, & Alexandrowicz, 2003). Treating dementia-related psychosis is perplexing because of the risk of movement disorders, anticholinergic side effects, and death associated with typical or firstgeneration antipsychotic agents, and cardiovascular, metabolic disturbances, and death associated with SGAs in older adults (Wang et al, 2005).
In 2005, the FDA issued a "black box" warning on a higher mortality rate in older patients with dementiarelated psychosis and behavioral disturbances treated with SGAs. This warning was based on 15 out of 17 placebo-controlled clinical trials with quetiapine, olanzapine, aripiprazole, or risperidone in older clients with dementia-related neuropsychiatrie symptoms, which revealed a 1.7- fold greater mortality. Deaths from these data were primarily cardiac or infection related (U.S. FDA, 2005).
Based on these data, psychiatric nurses must carefully review the basis of their decisions to prescribe these medications in older adults. Major challenges for prescribing these agents include determining the risk-benefit ratio and recognizing age-related physiological changes along with the impact of polypharmacy and coexisting medical conditions that complicate pharmacological therapy in older adults. Together, these factors increase the risk of adverse drug effects and associated medical, quality, and safety consequences (Pirmohamed et al., 2004).
There are inconsistent data concerning the efficacy of SGAs used in the treatment of dementia-related psychosis, agitation, and aggression. Several randomized, placebo-controlled, double-blind trials using SGAs in older adults residing in nursing homes implicate their efficacy in the management of psychosis, agitation, and aggression associated with AD (Brodaty etal., 2005; De Deyn et al., 2005).
De Deyn et al. (2005), in a pooled analysis of three randomized, placebo-controlled, double-blind trials in which placebo and risperidone were used (average dose of 1 mg), concluded that SGAs are effective and safe in the treatment of dementia-related psychosis, agitation, and aggression. They also found that risperidone had a favorable side-effect profile concerning extrapyramidal side effects and sedation, and it was not associated with orthostasis or increased risk of falls in older adults.
Daniel (2000) also recommended a starting dose of risperidone 0.25 to 0.5 mg/day and gradually titrating the dose to a maximum of 2-3 mg/day. Most researchers suggest a maximum dose of 1 mg/day, but the dose must be governed by individual response, clinical outcome, tolerability, and co-occurring psychiatric and medical conditions.
In comparison, results from another randomized, double-blind, placebo-controlled trial (n = 93) involving the use of quetiapine and rivastigmine to manage agitation and cognitive decline in AD demonstrated a poor response or lack of efficacy (Ballard et al., 2005). Moreover, they concluded that when compared to placebo, quetiapine was associated with marked cognitive decline. Quetiapine is also associated with somnolence, dizziness, and risk of QT interval prolongation (Yeung, Tariot, Schneider, Saltzman, & Rak, 2000). Findings from a recent larger study (n = 333) involving the use of quetiapine (200 mg/day) in the management of dementia- related agitation confirmed these earlier results (Zhong, Tariot, Mintzer, Minkwitz, & Devine, 2007).
One of the most notable studies involving SGAs used in the treatment of AD-related psychosis was the National Institute of Mental Health-funded Clinical Antipsychotic Trials of Intervention EffectivenessAlzheimer's Disease (CATIE-AD). The CATIE-AD study, involving older adults with AD (n = 421; mean age 78 years) who presented with psychosis and agitation, found that SGAs lack efficacy and even caused early discontinuation of use due to negative side-effects or death (Schneider, Tariot, et al., 2006).
The CATIE-AD study included a randomly selected group of patients who were prescribed SGAs, which included risperidone (average dose of 1 mg per day), olanzapine (average dose of 5.5 mg per day), quetiapine (average dose of 56.5 mg per day), and placebo for up to 36 weeks. Clinical outcomes from this study included discontinuation based on minimal improvement on the Clinical Global Impression of Change scale during weeks 8 to 12, and discontinuation due to poor response, adverse drug effects, or death. Average time of discontinuation was 8 weeks. Major side effects included sedation, weight gain, cognitive deficits, and increased prolactin levels. Marked prolactin levels were primarily associated with risperidone.
Overall, researchers concluded limited benefits for most of the subjects and that these agents are no more efficacious than placebo when factoring in adverse side effects (Schneider, Tariot, et al., 2006). In addition, these data also revealed a higher dropout rate in subjects taking SGAs, resulting in a modest number of patients who actually benefited from these agents (Schneider, Dagerman, & Insel, 2006). It is unclear if these data can be generalized to patients with dementia-related psychosis who reside in long-term care facilities because of significantly more severe cognitive decline and behavioral disturbances.
Overall, although antipsychotic medications have demonstrated efficacy in the treatment of psychosis, they are among the most extensively studied agents. Their limitations and potential adverse side effects must be recognized. Each SGA has discrete risks for side effects that include somnolence, gait disturbances, increased risk of falls, significant weight gain and subsequent metabolic disturbances, anticholinergic effects, and death (Lenzer, 2005; Schneider, Dagerman, & Insel, 2005). Postural orthostasis is very common when SGAs are prescribed in clients with coexisting cardiovascular disease. Risperidone has also been associated with cerebral vascular events when prescribed to older adults. The safety advantage of SGAs continues to be scrutinized because data from clinical trials demonstrate serious adverse effects, such as those previously discussed. As more clients present with dementia-related psychosis, psychiatric nurses must be prepared to make sound clinical decisions based on empirically based interventions.
Clinical Implications for Nursing Practice
Clinical implications for psychiatric nurses include the same as other pharmacological interventions used to treat neuropsychiatrie disorders in older adults. Age-related physiological changes must be considered along with a differential diagnosis of coexisting medical and psychiatric conditions, individual needs, and the emergent nature of psychosis and behavioral disturbances. The decision to prescribe these agents for dementia-related psychosis must be based on individual need, the drug's efficacy, co-occurring physical and psychiatric conditions, and the safety of viable treatment options. More importantly, SGAs should be used judiciously and based on empirically based interventions and guidelines.
Summary
Psychosis and behavioral disturbances affect a large percentage of patients with AD and other dementias. Although SGAs are extensively used to treat neuropsychiatrie disorders in older adults and they offer additional treatment options, their use has demonstrated equivocal efficacy in managing psychosis in older adults and reveals side effects that outweigh potential benefits. Given the risk of serious adverse side effects, including death, that are associated with SGAs, it is critical for psychiatric nurses to use these agents judiciously. Considerations to prescribe these agents must be based on the immediate needs of patients who present with overt and acute psychosis and potentially dangerous behavioral problems. Modest mitigation of dementia-related psychosis has been reported with risperidone and olanzapine; however, SGAs have not been approved by the FDA to treat AD-related psychosis. Despite inconsistent clinical findings involving the efficacy and adverse side effects of SGAs, psychiatric nurses may be called upon to make clinical decisions to manage dementia-related psychosis, aggression, and agitation. It is imperative to recognize that there are currently no specific guidelines to address the complexities of each patient, and sound clinical decision-making skills must be employed when prescribing these agents for AD-related psychosis. Moreover, whether it is prudent to prescribe SGAs to manage these symptoms must be determined by individual situations. This paper has provided salient issues confronting psychiatric nurses who treat psychosis and behavioral disturbances that are associated with AD.
References
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Deborah Antai-Otong, MS, APRN-BC, FAAN
Deborah Antai-Otong, MS, APRN-BC, FAAN, is
a Mental Health Provider at the Fort Worth Outpatient
Clinic, Department of Veterans Affairs in Fort Worth, TX.
Author contact: deborah.antai-otong@va.gov, with a copy to the Editor: mary@artwindows.com
Copyright Nursecom, Inc. Apr 2008
(c) 2008 Perspectives in Psychiatric Care. Provided by ProQuest Information and Learning. All rights Reserved.
Source: Perspectives in Psychiatric Care
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