Use of antipsychotics in elderly patients with dementia: Do atypical and conventional agents have a similar safety profile?

Section of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Italy.
Pharmacological Research (Impact Factor: 4.41). 11/2008; 59(1):1-12. DOI: 10.1016/j.phrs.2008.09.017
Source: PubMed


Pharmacological treatment of dementia addresses two main clinical features of the disease: cognitive deterioration with predominantly memory loss and behavioural and psychological symptoms (BPSD). While cholinesterase inhibitors are recommended in an attempt to delay memory loss and disability, what should be considered the most appropriate pharmacological treatment for BPSD has remained questionable. Antipsychotic medications, conventional and atypical agents, have been increasingly utilized in clinical practice but only a small number of clinical studies have investigated their relative cost-benefit ratio. This review focuses on the safety of atypical and conventional antipsychotics when used in patients with BPSD. Overall, atypical and conventional antipsychotics are associated with a similarly increased risk for all-cause mortality and cerebrovascular events. Relative to atypical agents users, patients being treated with conventional antipsychotics have an increased incidence of cardiac arrhythmias and extrapyramidal symptoms. Conversely, users of atypical antipsychotics are exposed to an increased risk of venous thromboembolism and aspiration pneumonia. Also, metabolic effects (i.e. increased risk of diabetes, weight gain) have consistently been documented in clinical studies with atypical antipsychotics, although this effect tends to be attenuated with advancing age and in elderly patients with dementia. Antipsychotics, both conventional and atypical, should be used with caution only when nonpharmacologic approaches have failed to adequately control BPSD. More effective interventions are necessary to improve postmarket drug safety in vulnerable populations.

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    • "Atypical antipsychotics were found to be associated with the adverse side effects of weight gain, hyperlipidemia, and diabetes (Gianfrancesco et al., 2002; Koro et al., 2002: Lund et al., 2001). For elderly patients with dementia, who make up a large percentage of nursing home residents, the evidence of risks associated with taking antipsychotics is mounting (Crystal et al., 2009; Trufuro et al., 2009). Using a meta-analysis of randomized clinical trials, Schneider et al. (2005) found the absolute mortality risk for nursing home residents with dementia is about two percent higher for nursing home residents treated eight to twelve weeks with an antipsychotic compared to a placebo. "
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    • "Previous reviews of observational studies of antispychotics have focused on the clinical safety of conventional and atypical antipsychotics [10-13]. The aim of this review was to synthesise the current evidence from observational studies, regarding the serious adverse events of antipsychotics in elderly patients and to determine the impact of the observational study design utilised and the technique employed to control for confounding on study results. "
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    ABSTRACT: Antipsychotics are frequently and increasingly prescribed to treat the behavioural symptoms associated with dementia despite their modest efficacy. Evidence regarding the potential adverse events of antipsychotics is limited and little is known about the longer-term safety of these medicines in the elderly. The aim of this review was to determine the impact of the choice of observational study design and methods used to control for confounding on the measurement of antipsychotic risks in elderly patients. We searched PUBMED and the Cochrane controlled trials register for double-blind randomised controlled trials (RCTs), meta-analyses and published observational studies of antipsychotics. Forty four studies were identified for the endpoints; death, cerebrovascular events, hip fracture and pneumonia. RCTs found a 20% to 30% increased risk of death, or an absolute increase of 1extra death per 100 patients with atypical antipsychotics compared to non-use. Cohort and instrumental variable analyses estimated between 2 to 7 extra deaths per 100 patients with conventional compared to atypical antipsychotics. RCTs found a 2 to 3 times increased risk of all cerebrovascular events with atypical antipsychotics compared to placebo and no association with serious stroke that required hospitalisation. Observational studies using cohort and self-controlled case-series designs reported similar results; no association where the endpoint was stroke causing hospitalisation and a doubling of risk when minor stroke was included. No RCTs were available for the outcome of hip fracture or pneumonia. Observational studies reported a 20% to 40% increased risk of hip fracture with both antipsychotic classes compared to non-use. The risk of pneumonia was a 2 to 3 times greater with both classes compared to non-use while a self-controlled case-series study estimated a 60% increased risk. Conventional antipsychotics were associated with a 50% greater hip fracture risk than atypical antipsychotics, while the risk of pneumonia was similar between the classes. Choice of observational study design is critical in studying the adverse effects of antispychotics. Cohort and instrumental variable analyses gave more consistent results to clinical studies for mortality outcomes as have self-controlled case-series for the risk of cerebrovascular events and stroke. Observational evidence has highlighted the potential for antipsychotics to be associated with serious adverse events that were not reported in RCTs including hip fracture and pneumonia. Good quality observational studies are required, that employ appropriate study designs that are robust towards unmeasured confounding, to confirm the potential excess risk of hip fracture and pneumonia with antipsychotics.
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    • "The increasing use of atypical antipsychotics has resulted in a growing number of safety alerts that were launched in the past few years by international regulatory agencies, especially regarding off-label use of atypical antipsychotics in elderly persons with dementia and related disorders [5••]. In April 2005, a warning was issued by the Food and Drug Administration (FDA) to inform health professionals about the results of a pooled analysis of 17 randomized clinical trials reporting a 1.7 times increased risk of all-cause mortality associated with atypical antipsychotic use in elderly patients with dementia [6]. "
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    ABSTRACT: Antipsychotics are generally distinguished as atypical and typical agents, which are indicated in the treatment of acute and chronic psychoses and other psychiatric disorders. In April 2005, the US Food and Drug Administration issued a warning about the increased risk of all-cause mortality associated with atypical antipsychotic use in elderly patients with dementia. Pneumonia was one of the most frequently reported causes of death. The same warning was extended to typical antipsychotics in June 2008. In recent years, several observational studies have further explored the association between antipsychotic use, mainly in elderly patients, and the risk of fatal/nonfatal community-acquired pneumonia. The aim of this review is to revise and discuss the scientific evidence and biologic explanations for the association between atypical and typical antipsychotic use and pneumonia occurrence. Some general recommendations to clinicians are proposed to prevent the risk of pneumonia in patients requiring antipsychotic treatment.
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