Cognitive effects of atypical antipsychotics in patients with Alzheimer's disease and comorbid psychiatric or behavioral problems: a retrospective study.

College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA.
Clinical Therapeutics (Impact Factor: 2.59). 10/2006; 28(10):1695-700. DOI: 10.1016/j.clinthera.2006.10.008
Source: PubMed

ABSTRACT In addition to cognitive decline, 30% to 40% of patients with Alzheimer's disease (AD) experience concomitant psychiatric and behavioral complications, such as hallucinations, delusions, and aggression. Atypical antipsychotics (AAs) are used to treat psychosis and aggressive behaviors in these patients; however, data regarding their early effects on cognition are conflicting. Based on a literature search, the cognitive effects of long-term treatment with AAs in outpatients with AD have not been studied.
The aim of this study was to describe and compare the rate of cognitive decline with longterm AA use in adult patients with AD receiving concomitant treatment with cholinesterase inhibitors.
This study was conducted at the Department of Neurology, The Ohio State University, Columbus, Ohio. Data were collected from the charts of adult outpatients who (1) received care at Memory Disorders Clinic, Columbus, Ohio, between April 2003 and June 2005; (2) were aged > or =55 years with a diagnosis of mild to severe definite or probable AD; (3) received an AA for > or =6 months or did not receive any AA; and (4) received a cholinesterase inhibitor during the entire evaluation period. Cognitive function, as measured using the Mini-Mental State Examination (MMSE), was compared between those who received AA treatment and those who did not. The end point was the rate of decline in cognitive function, defined as annualized change in mean MMSE score from baseline to the end of follow-up.
Ninety-two outpatients were included in the final analysis (67 women, 25 men; mean age, 72.4 years). Thirty-four patients received treatment with an AA for 6 > or =months (mean duration of treatment, 421 days) and 58 did not receive any AA treatment. Quetiapine (mean dose, 67 mg/d) was prescribed to 28 (82 %) of the patients receiving an AA. The AAs were prescribed for psychosis (15 [44%] patients), psychosis/agitation (11 [32%]), and agitation/aggression (8 [24%]). The baseline mean MMSE scores in patients receiving and not receiving an AA were 14.65 and 17.88, respectively (P = 0.021), with mean (SD) annual rates of cognitive decline of 3.03 (1.84) and 2.24 (1.27), respectively (P = NS).
The results from this retrospective study of data from a small, selected group of outpatients with AD did not find a significant difference in the rate of cognitive decline between those who received an AA for > or =6 months and those who did not.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Quetiapine, an atypical antipsychotic drug, is effective in treating the behavioral and psychological symptoms in Alzheimer's disease (AD). However, it is presently unclear whether quetiapine has beneficial effects on memory and whether the effects of quetiapine on psychological symptoms are associated with its effect on memory in AD. The present study was designed to examine the effect of chronic administration of quetiapine on the conditioned (generalized) anxiety that is related to learning experience of open arm exposure in the elevated T-maze (ETM) test in an amyloid precursor protein (APP)/presenilin 1 (PS1) double transgenic mouse model of AD. In a 2nd experiment, the effect of quetiapine on memory per se was investigated in a Y-maze test in AD mice. Non-transgenic and transgenic mice were treated with quetiapine in drinking water from the age of 2 months. After continuous treatment with quetiapine (5 mg/kg/day) for 10 months, mice were tested for conditioned anxiety on the ETM task. After ETM testing, the expression of brain-derived neurotrophic factor (BDNF), a neuroprotective protein, was examined by immunohistochemistry in the basolateral amygdala (BLA) and hippocampus. In the 2nd experiment, the effect of quetiapine (2.5 or 5 mg/kg/day) on the short-term memory in AD mice was tested in a Y-maze test. After 10 months of administration, quetiapine prevented the decrease of conditioned anxiety and cerebral BDNF in AD mice. In addition, quetiapine also prevented memory impairment in the Y-maze test in AD mice. These findings suggest that the therapeutic mechanism of quetiapine on anxiety in AD may be associated with its beneficial effect on memory and its neuroprotective effect on cerebral BDNF expression.
    Current Alzheimer research 08/2012; DOI:10.2174/1567205011310020010 · 3.80 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Growing evidence shows a high correlation between extensive use of central nervous system-acting drugs (CNSADs) in elderly patients and adverse drug reactions (ADRs) such as falls, fractures, and mortality. Are results of cognitive testing with the Mini Mental Status Examination (MMSE) influenced by use of CNSADs? Geriatric inpatient service for acute, subacute, and rehabilitation care. Secondary combined analysis of two prospective, single-center study cohorts (PROPSYC, 2011 and AGE OUT, 2012) with identical procedure for the MMSE at a tertiary hospital. Overall, 395 patients were included, 144 male (M) and 251 female (F). Mean age was 80.0 +/- 8.4 years (M 76.7 +/- 9.1, F 81.9 +/- 7.3, p = 0.0000). Mean MMSE points were 22.9 +/- 4.8 (M 23.2 +/- 4.6, F 22.6 +/- 5.0, p = 0.211). In total, 258 patients (65.3 %) used drugs with potential adverse cognitive properties. Analgesics with central activity were given to 117 of 395 patients (29.6 %). Low-potency opioids (tramadol hydrochloride, tilidine) were identified in 60 patients and high-potency opioids in 57 patients. Antidepressants were used in 66 patients, benzodiazepines in 26, and hypnotics in 11, while 38 patients received other CNSADs. We only found significant correlations with the results of cognitive testing for sedatives (diazepam and oxazepam, Pearson's r -aEuro parts per thousand 0.79, p = 0.05), but not for lorazepam. Our analysis shows an influence of sedatives (diazepam and oxazepam, but not lorazepam) on cognitive testing with the MMSE in users of CNSADs.
    Zeitschrift für Gerontologie + Geriatrie 06/2014; 47(4):279-284. DOI:10.1007/s00391-014-0654-5 · 1.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Neuropsychiatric symptoms such as agitation and delusions occur commonly in elderly patients with dementia and often cause significant distress. Data on treatment efficacy are strongest for atypical antipsychotics, but these agents must be used with great caution. Adverse effects in patients with dementia include an increased risk of mortality and cerebrovascular events, as well as metabolic effects, extrapyramidal symptoms, falls, cognitive worsening, cardiac arrhythmia, and pneumonia. Conventional antipsychotics may pose an even greater safety risk. No clear efficacy evidence exists to support the use of alternative psychotropic classes (e.g., antidepressants, anticonvulsants), although they may be safer options. An antipsychotic trial is warranted when nonpharmacological intervention is unsuccessful and neuropsychiatric symptoms or associated behaviors cause severe distress or pose a significant safety risk. Before an atypical antipsychotic is started, a comprehensive assessment should be performed to rule out medical causes of the neuropsychiatric symptoms and to ascertain whether any contributing environmental or caregiver factors are present. Risks, benefits, and alternatives should be discussed with the patient and surrogate decision maker, with an opportunity given to ask questions. Dosages should be the lowest necessary, and metabolic parameters should be regularly monitored. Face-to-face visits are important to monitor response, tolerance, and the need for continued treatment. For patients in whom neuropsychiatric symptoms have been much improved or have been in remission for 3-6 months, a discontinuation trial should be considered. Through careful selection of appropriate patients for treatment, education of patients and caregivers, and close monitoring, safety risks can be minimized.
    American Journal of Psychiatry 09/2012; 169(9):900-6. DOI:10.1176/appi.ajp.2012.12030342 · 13.56 Impact Factor