Management of agitation and aggression associated with Alzheimer's disease: Controversies and possible solutions

Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
Current opinion in psychiatry (Impact Factor: 3.94). 09/2009; 22(6):532-40. DOI: 10.1097/YCO.0b013e32833111f9
Source: PubMed


Behavioral and psychological symptoms of dementia (BPSD) are frequent among people with Alzheimer's disease and other dementias, commonly confer risk to the person and others, and present a significant management challenge for clinicians. The purpose of this review is to describe the current state of knowledge regarding management of BPSD, with a particular focus on agitation.
There is increasing evidence to support the value of simple psychological interventions and staff-training programs as a first-line management strategy for agitation prior to pharmacotherapy. The most widely prescribed pharmacological treatments - atypical antipsychotics - have a modest but significant beneficial effect in the short-term treatment of aggression (over 6-12 weeks), but limited benefits in longer term therapy. In addition, there have been increasing concerns regarding the potential for serious adverse outcomes, including stroke and death. The potential pharmacological alternatives to atypical antipsychotics with the most encouraging preliminary evidence include memantine, carbamazepine and citalopram.
Large prospective, randomized, placebo-controlled trials are needed to establish the role of agents other than neuroleptics as clinical therapies for the treatment of BPSD and studies are urgently needed to evaluate BPSD treatments in non-Alzheimer dementias.

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    • "Two first-generation antipsychotics (haloperidol, chlorpromazine ) were compared with well-established secondgeneration atypical antipsychotics (clozapine, olanzapine, risperidone , aripiprazole) and with lurasidone and asenapine, which have been recently introduced to the market (Ishibashi et al. 2010; Schatzberg and Nemeroff 2009). As stated above, a lack of clear-cut separation between doses producing antidepressant and antipsychotic effects and doses leading to deterioration of cognitive and motor functions can limit the use of antipsychotic drugs for BPSD (Ballard et al. 2009; Jeste et al. 2008; Potenza and McDougle 1998). Therefore , a key aim of the present study was to asses the relationship between antipsychotic, antidepressant, motor impairing, and amnestic doses of a wide range of antipsychotic drugs. "
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    ABSTRACT: Many dementia patients exhibit behavioral and psychological symptoms (BPSD), including psychosis and depression. Although antipsychotics are frequently prescribed off-label, they can have marked side effects. In addition, comparative preclinical studies of their effects are surprisingly scarce, and strategies for discovery of novel pharmacotherapeutics are lacking. We therefore compared eight antipsychotics in rat behavioral tests of psychosis, antidepressant-like activity, and cognitive impairment as a basis for preclinical evaluation of new drug candidates. The methods used in this study include inhibition of MK-801-induced hyperactivity, forced swim test (FST), passive avoidance (PA), spontaneous locomotor activity, and catalepsy. The drugs exhibited antipsychotic-like activity in the MK-801 test but with diverse profiles in the other models. Risperidone impaired PA performance, but with some dose separation versus its actions in the MK-801 test. In contrast, clozapine, olanzapine, lurasidone, and asenapine showed little or no dose separation in these tests. Aripiprazole did not impair PA performance but was poorly active in the MK-801 test. Diverse effects were also observed in the FST: chlorpromazine was inactive and most other drugs reduced immobility over narrow dose ranges, whereas clozapine reduced immobility over a wider dose range, overlapping with antipsychotic activity. Although the propensity of second-generation antipsychotics to produce catalepsy was lower, they all elicited pronounced sedation. Consistent with clinical data, most currently available second-generation antipsychotics induced cognitive and motor side effects with little separation from therapeutic-like doses. This study provides a uniform in vivo comparative basis on which to evaluate future early-stage drug candidates intended for potential pharmacotherapy of BPSD.
    Archiv für Experimentelle Pathologie und Pharmakologie 03/2014; 387(6). DOI:10.1007/s00210-014-0966-4 · 2.47 Impact Factor
    • "Behavioral and psychological symptoms of dementia (BPSD) occur frequently in people with the condition , affecting 90% of people with the condition at some point (Ballard et al., 2009). In particular, agitation , aggression, psychosis, and depression are major causes of distress for people with dementia and those caring for them, presenting a significant challenge for treatment and care. "
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    ABSTRACT: Background: Several important systematic reviews and meta-analyses focusing on psychosocial interventions have been undertaken in the last decade. However, they have not focused specifically on the treatment of individual behavioral and psychological symptoms of dementia (BPSD) with personalized interventions. This updated systematic review will focus on studies reporting the effect of personalized psychosocial interventions on key BPSD in care homes. Methods: Systematic review of the evidence for psychosocial interventions for BPSD, focusing on papers published between 2000 and 2012. All care home and nursing home studies including individual and cluster randomized controlled trials (RCTs) and pre-/post-test studies with control conditions were included. Results: 641 studies were identified, of which 40 fulfilled inclusion and exclusion criteria. There was good evidence to support the value of personalized pleasant activities with and without social interaction for the treatment of agitation, and reminiscence therapy to improve mood. The evidence for other therapies was more limited. Conclusions: There is a growing body of evidence indicating specific effects of different personalized psychosocial interventions on individual BPSD and mood outcomes.
    International Psychogeriatrics 02/2014; 26(7):1-16. DOI:10.1017/S1041610214000131 · 1.93 Impact Factor
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    • "Nevertheless, the prevalence of psychotropic drug use (PDU) among nursing home patients with dementia is high with rates ranging from 48 to 66% [8-10]. Moreover, there is a risk for long-term use of psychotropic drugs whereas prescription for only a short period of time is recommended [4,11]. For instance, 74% of the nursing home patients with dementia use antipsychotics, anxiolytics, hypnotics, or sedatives for 83% of the duration of their stay [12], and 31% continue the use of antipsychotics, antidepressants, anxiolytics, hypnotics, anticonvulsants, or anti-dementia drugs throughout a 2-year period [9]. "
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    ABSTRACT: Neuropsychiatric symptoms are highly prevalent in nursing home patients with dementia. Despite modest effectiveness and considerable side effects, psychotropic drugs are frequently prescribed for these neuropsychiatric symptoms. This raises questions whether psychotropic drugs are appropriately prescribed. The aim of the PROPER (PRescription Optimization of Psychotropic drugs in Elderly nuRsing home patients with dementia) II study is to investigate the efficacy of an intervention for improving the appropriateness of psychotropic drug prescription in nursing home patients with dementia.Methods/design: The PROPER II study is a multi-center cluster randomized controlled, pragmatic trial using parallel groups. It has a duration of eighteen months and four six-monthly assessments. Six nursing homes will participate in the intervention and six will continue care as usual. The nursing homes will be located throughout the Netherlands, each participating with two dementia special care units with an average of fifteen patients per unit, resulting in 360 patients. The intervention consists of a structured and repeated multidisciplinary medication review supported by education and continuous evaluation. It is conducted by pharmacists, physicians, and nurses and consists of three components: 1) preparation and education, 2) conduct, and 3) evaluation/guidance. The primary outcome is the proportion of patients with appropriate psychotropic drug use. Secondary outcomes are the overall frequency of psychotropic drug use, neuropsychiatric symptoms, quality of life, activities of daily living, psychotropic drug side effects and adverse events (including cognition, comorbidity, and mortality). Besides, a process analysis on the intervention will be carried out. This study is expected to improve the appropriateness of psychotropic drug prescription for neuropsychiatric symptoms in nursing home patients with dementia by introducing a structured and repeated multidisciplinary medication review supported by education and continuous evaluation.Trial registration: Netherlands Trial Registry (NTR): NTR3569.
    BMC Psychiatry 11/2013; 13(1):280. DOI:10.1186/1471-244X-13-280 · 2.21 Impact Factor
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