Prazosin for the Treatment of Behavioral Symptoms in Patients With Alzheimer Disease With Agitation and Aggression

VA Northwest Network Mental Illness Research, Education, and Clinical Center (MIRECC), Seattle, WA 98115, USA.
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry (Impact Factor: 4.24). 10/2009; 17(9):744-51. DOI: 10.1097/JGP.0b013e3181ab8c61
Source: PubMed


Agitation/aggression in Alzheimer disease (AD) is a major cause of patient distress, caregiver burden, and institutionalization. Enhanced behavioral responsiveness to central nervous system norepinephrine (NE) release may contribute to the pathophysiology of agitation/aggression in AD. Prazosin, a nonsedating generic medication used for hypertension and benign prostatic hypertrophy, antagonizes NE effects at brain postsynaptic alpha-1 adrenoreceptors. This pilot study examined the efficacy and tolerability of prazosin for behavioral symptoms in patients with agitation/aggression in AD.
Double-blind, placebo controlled, parallel group study.
A university AD center and a nursing home in Seattle, WA.
Twenty-two nursing home and community-dwelling participants with agitation/aggression and probable or possible AD (mean age: 80.6 +/- 11.2).
Randomization to placebo (N = 11) or prazosin (N = 11). Medication was initiated at 1 mg/day and increased up to 6 mg/day using a flexible dosing algorithm.
The Brief Psychiatric Rating Scale (BPRS) and Neuropsychiatric Inventory (NPI) at Weeks 1, 2, 4, 6, and 8. The Clinical Global Impression of Change (CGIC) at Week 8.
Participants taking prazosin (mean dose: 5.7 +/- 0.9 mg/day) had greater improvements than those taking placebo (mean dose: 5.6 +/- 1.2 mg/day) on the NPI (mean change: -19 +/- 21 versus -2 +/- 15, chi = 6.32, df = 1, p = 0.012) and BPRS (mean change: -9 +/- 9 versus -3 +/- 5, chi = 4.42, df = 1, p = 0.036) based on linear mixed effects models and the CGIC (mean: 2.6 +/- 1.0 versus 4.5 +/- 1.6, z = 2.57, p = 0.011 [Mann-Whitney test]). Adverse effects and blood pressure changes were similar between prazosin and placebo groups.
Prazosin was well tolerated and improved behavioral symptoms in patients with agitation/aggression in AD.

Full-text preview

Available from:
  • Source
    • "Among the remaining molecules, Prazosin was a non-sedating generic medication used for hypertension and benign prostatic hypertrophy. It antagonizes NE effects at brain postsynaptic alpha-1 adreno receptors and new study said the prazosin improved patients' behavioural symptoms such as agitation/aggression in AD [47]. Fulvestrant was an interesting drug, known to block estrogen receptors [48]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Animal models are indispensable tools in studying the cause of human diseases and searching for the treatments. The scientific value of an animal model depends on the accurate mimicry of human diseases. The primary goal of the current study was to develop a cross-species method by using the animal models' expression data to evaluate the similarity to human diseases' and assess drug molecules' efficiency in drug research. Therefore, we hoped to reveal that it is feasible and useful to compare gene expression profiles across species in the studies of pathology, toxicology, drug repositioning, and drug action mechanism. Results We developed a cross-species analysis method to analyze animal models' similarity to human diseases and effectiveness in drug research by utilizing the existing animal gene expression data in the public database, and mined some meaningful information to help drug research, such as potential drug candidates, possible drug repositioning, side effects and analysis in pharmacology. New animal models could be evaluated by our method before they are used in drug discovery. We applied the method to several cases of known animal model expression profiles and obtained some useful information to help drug research. We found that trichostatin A and some other HDACs could have very similar response across cell lines and species at gene expression level. Mouse hypoxia model could accurately mimic the human hypoxia, while mouse diabetes drug model might have some limitation. The transgenic mouse of Alzheimer was a useful model and we deeply analyzed the biological mechanisms of some drugs in this case. In addition, all the cases could provide some ideas for drug discovery and drug repositioning. Conclusions We developed a new cross-species gene expression module comparison method to use animal models' expression data to analyse the effectiveness of animal models in drug research. Moreover, through data integration, our method could be applied for drug research, such as potential drug candidates, possible drug repositioning, side effects and information about pharmacology.
    Full-text · Article · Dec 2012 · BMC Systems Biology
  • Source
    • "The median trial duration was 56 days (range = 1–90 days). A variety of outcome measures were reported in studies including composite measures of NPS (Barnes et al., 1982; Cantillon et al., 1996; Tariot et al., 1998; 2001; 2005; 2006; De Deyn et al., 1999; 2004; Katz et al., 1999; Street et al., 2000; Porsteinsson et al., 2001; Fontaine et al., 2003; Peskind et al., 2005; Gehrman et al., 2009; Sommer et al., 2009; Wang et al., 2009), agitation (Gaber et al., 2001; Ballard et al., 2005; Verhey et al., 2006; Holmes et al., 2007; Zhong et al., 2007; Rappaport et al., 2009,), aggression (Kyomen et al., 1999; Brodaty et al., 2003; Hall et al., 2005; Huertas et al., 2007), or psychosis (Mintzer et al., 2006; 2007; Streim et al., 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Medications are frequently prescribed for neuropsychiatric symptoms (NPS) associated with dementia, although information on the efficacy and safety of medications for NPS specifically in long-term care (LTC) settings is limited. The objective of this study was to provide a current review of the efficacy and safety of pharmacological treatments for NPS in LTC. Methods: We searched MEDLINE, EMBASE, PsychINFO, and the Cochrane Library for randomized controlled trials comparing medications with either placebo or other interventions in LTC. Study quality was described using the Cochrane collaboration risk of bias tool. The efficacy of medications was evaluated using NPS symptom rating scales. Safety was evaluated through rates of trial withdrawals, trial withdrawals due to adverse events, and mortality. Results: A total of 29 studies met inclusion criteria. The most common medications evaluated in studies were atypical antipsychotics (N = 15), typical antipsychotics (N = 7), anticonvulsants (N = 4), and cholinesterase inhibitors (N = 3). Statistically significant improvements in NPS were noted in some studies evaluating risperidone, olanzapine, and single studies of aripiprazole, carbamazepine, estrogen, cyproterone, propranolol, and prazosin. Study quality was difficult to rate in many cases due to incomplete reporting of details. Some studies reported higher rates of trial withdrawals, adverse events, and mortality associated with medications. Conclusions: We conclude that there is limited evidence to support the use of some atypical antipsychotics and other medications for NPS in LTC populations. However, the generally modest efficacy and risks of adverse events highlight the need for the development of safe and effective pharmacological and non-pharmacological interventions for this population.
    Full-text · Article · Oct 2012 · International Psychogeriatrics
  • Source
    • ", which is also com - monly observed in AD . The aggressive behavior in AD has been correlated with an increase in a 1 - AR binding sites in the cortex and hippocampus of patients with AD ( Szot et al . , 2006 , 2007 ; Sharp et al . , 2007 ) . The a 1 - AR antagonist , prazosin , is demonstrating success in treating the aggressive behavior in AD ( Wang et al . , 2009 ) , suggesting that the loss of LC noradrenergic neurons in AD does result in altered noradrenergic function associ - ated with a behavioral consequence ."
    [Show abstract] [Hide abstract]
    ABSTRACT: The neurodegenerative disorders Alzheimer's disease (AD) and Parkinson's disease (PD) share in common the neuropathologic loss of locus coeruleus (LC) noradrenergic neurons. In addition, these two neurodegenerative disorders share two symptoms that define these disorders: cognitive impairment and depression. The hippocampus is a region that is known to play a role in cognition and depression, and the hippocampus receives sole noradrenergic innervation from LC neurons. However, it is unclear how the loss of LC noradrenergic neurons contributes to these common symptoms in these two disorders. Epilepsy is not considered a neurodegenerative disorder, but the hippocampus is severely affected in temporal lobe epilepsy. Of interest, cognitive impairment and depression are also common comorbid disorders in temporal lobe epilepsy. This article describes common symptoms among these three neurologic disorders and a possible role of the noradrenergic nervous system.
    Full-text · Article · Jun 2012 · Epilepsia
Show more