Atypical Antipsychotics for the Treatment of Delirious Elders

Department of Psychiatry and Behavioral Sciences, Mental Health Hospital Center, University of Miami Miller School of Medicine, Miami, FL 33136 USA.
Journal of the American Medical Directors Association (Impact Factor: 4.94). 02/2008; 9(1):18-28. DOI: 10.1016/j.jamda.2007.08.007
Source: PubMed


Delirium occurs frequently in hospitalized patients and is reported to occur at a rate of 10% to 40% in hospitalized elderly patients. The gold standard of treatment is to treat the underlying cause of delirium and use high-potency antipsychotics such as haloperidol to target the behavioral disturbances. Since the development of atypical antipsychotics, many psychiatric conditions that were previously only treatable using high-potency antipsychotics may now be managed with the atypical agents. This review will examine the current literature on atypical antipsychotics and summarize the results from published trials in order to evaluate the efficacy and potential benefits of atypical antipsychotics for the treatment of delirium in the elderly population.
A search of the published literature was conducted using MEDLINE and PubMed. The PubMed search was limited to articles that were (1) written in the English language, (2) focused on human subjects above age 65, and (3) were in the format of review articles, randomized controlled trials (RCTs), clinical trials, or meta-analyses. The initial PubMed search was conducted in March 2006 with follow-up investigations in April 2006 and July 2007.
Risperidone, the most thoroughly studied atypical antipsychotic, was found to be approximately 80% to 85% effective in treating the behavioral disturbances of delirium at a dosage of 0.5 to 4 mg daily. Studies of olanzapine indicated that it was approximately 70% to 76% effective in treating delirium at doses of 2.5 to 11.6 mg daily. Very few studies have been conducted using quetiapine; it also appears to be a safe and effective alternative to high-potency antipsychotics. In comparison to haloperidol, the frequency of adverse reactions and side effects was found to be much lower with the use of atypical antipsychotic medications. In the limited number of trials comparing atypical antipsychotics to haloperidol, haloperidol consistently produced a higher rate (an additional 10% to 13%) of extrapyramidal side effects.
A review of current literature supports the conclusion that atypical antipsychotic medications demonstrate similar rates of efficacy as haloperidol for the treatment of delirium in the elderly patient, with a lower rate of extrapyramidal side effects. There is limited evidence of true efficacy, since no double-blind placebo trials exist.

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    • "In order to overcome this limitation, we used a linear mixed model, in which all available data can be included and missing data can be appropriately addressed [54,55]. By using the average area under each subject’s rating scale trajectory, we could compare treatment groups across whole study period; ⓙ The safety analysis was focused only on extrapyramidal side effects and could not evaluate other potential adverse events, such as QTc prolongation or arrhythmia associated with use of antipsychotic drugs [19,21-23]. Overall, six patients were transferred to the intensive care unit due to aggravation of an underlying medical or postsurgical condition during the study. "
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    ABSTRACT: Most previous studies on the efficacy of antipsychotic medication for the treatment of delirium have reported that there is no significant difference between typical and atypical antipsychotic medications. It is known, however, that older age might be a predictor of poor response to antipsychotics in the treatment of delirium. The objective of this study was to compare the efficacy and safety of haloperidol versus three atypical antipsychotic medications (risperidone, olanzapine, and quetiapine) for the treatment of delirium with consideration of patient age. This study was a 6-day, prospective, comparative clinical observational study of haloperidol versus atypical antipsychotic medications (risperidone, olanzapine, and quetiapine) in patients with delirium at a tertiary level hospital. The subjects were referred to the consultation-liaison psychiatric service for management of delirium and were screened before enrollment in this study. A total of 80 subjects were assigned to receive either haloperidol (N = 23), risperidone (N = 21), olanzapine (N = 18), or quetiapine (N = 18). The efficacy was evaluated using the Korean version of the Delirium Rating Scale-Revised-98 (DRS-K) and the Korean version of the Mini Mental Status Examination (K-MMSE). The safety was evaluated by the Udvalg Kliniske Undersogelser side effect rating scale. There were no significant differences in mean DRS-K severity or K-MMSE scores among the four groups at baseline. In all groups, the DRS-K severity score decreased and the K-MMSE score increased significantly over the study period. However, there were no significant differences in the improvement of DRS-K or K-MMSE scores among the four groups. Similarly, cognitive and non-cognitive subscale DRS-K scores decreased regardless of the treatment group. The treatment response rate was lower in patients over 75 years old than in patients under 75 years old. Particularly, the response rate to olanzapine was poorer in the older age group. Fifteen subjects experienced a few adverse events, but there were no significant differences in adverse event profiles among the four groups. Haloperidol, risperidone, olanzapine, and quetiapine were equally efficacious and safe in the treatment of delirium. However, age is a factor that needs to be considered when making a choice of antipsychotic medication for the treatment of delirium.Trial registration: Clinical Research Information Service, Republic of Korea, (, Registered Trial No. KCT0000632).
    Full-text · Article · Sep 2013 · BMC Psychiatry
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    • "Second-generation antipsychotics, commonly known as atypical antipsychotics, include risperidone (Risperdal), olanzapine (Zyprexa), and quetiapine (Seroquel). They are equally effective in treating delirium and have fewer side effects than haloperidol [89,90]. Atypical antipsychotics may reduce the duration of delirium in the ICU according to the 2013 SCCM PAD guidelines [30]. "
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    ABSTRACT: Delirium is a serious complication that commonly occurs in critically ill patients in the intensive care unit (ICU). Delirium is frequently unrecognized or missed despite its high incidence and prevalence, and leads to poor clinical outcomes and an increased cost by increasing morbidity, mortality, and hospital and ICU length of stay. Although its pathophysiology is poorly understood, numerous risk factors for delirium have been suggested. To improve clinical outcomes, it is crucial to perform preventive measures against delirium, to detect delirium early using valid and reliable screening tools, and to treat the underlying causes or hazard symptoms of delirium in a timely manner.
    Full-text · Article · Sep 2013 · Korean journal of anesthesiology
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    • "In some distressed patients with hyperactive symptoms, such as agitation or hallucinations, haloperidol or olanzapine can be used cautiously (lowest effective dose for less than 1 week) [25]. Risperidone (0.5–1 mg) and quetiapine (25–50 mg) are reasonable alternatives [95]. Benzodiazepines are the mainstay pharmacological treatment for delirium associated with alcohol withdrawal (delirium tremens) but not for other causes. "
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    ABSTRACT: Delirium is a neuropsychiatric syndrome characterized by altered consciousness and attention with cognitive, emotional and behavioural symptoms. It is particularly frequent in elderly people with medical or surgical conditions and is associated with adverse outcomes. Predisposing factors render the subject more vulnerable to a congregation of precipitating factors which potentially affect brain function and induce an imbalance in all the major neurotransmitter systems. Early diagnosis of delirium is crucial to improve the prognosis of patients requiring the identification of subtle and fluctuating signs. Increased awareness of clinical staff, particularly nurses, and routine screening of cognitive function with standardized instruments, can be decisive to increase detection rates of delirium. General measures to prevent delirium include the implementation of protocols to systematically identify and minimize all risk factors present in a particular clinical setting. As soon as delirium is recognized, prompt removal of precipitating factors is warranted together with environmental changes and early mobilization of patients. Low doses of haloperidol or olanzapine can be used for brief periods, for the behavioural control of delirium. All of these measures are a part of the multicomponent strategy for prevention and treatment of delirium, in which the nursing care plays a vital role.
    Full-text · Article · Jun 2011
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