Antipsychotics for the Treatment of Behavioral and Psychological Symptoms of Dementia (BPSD)

Centro di Medicina dell'Invecchiamento, Dipartimento di Scienze Gerontologiche, Geriatriche e Fisiatriche, Università Cattolica del Sacro Cuore, Largo A. Gemelli, I-00168 Rome, Italy.
Current Neuropharmacology (Impact Factor: 3.05). 07/2008; 6(2):117-24. DOI: 10.2174/157015908784533860
Source: PubMed


Behavioral and psychological symptoms of dementia (BPSD), i.e. verbal and physical aggression, agitation, psychotic symptoms (hallucinations and delusions), sleep disturbances, oppositional behavior, and wandering, are a common and potentially severe problem complicating dementia. Their prevalence is very high and it is estimated that up to 90% of patients with Alzheimer's disease (AD) may present at least one BPSD. Beside the obvious impact on the quality of life of people with dementia, BPSD are responsible for increased risk of patient institutionalization and increased costs. Furthermore, they are associated with caregivers' stress and depression. Drugs used include antipsychotics, antidepressants, anticonvulsivants, anxiolytics, cholinesterase inhibitors and N-methyl-D-aspartate receptor modulators. Among these, the most commonly used are anti-psychotics. These drugs have been used for many decades, but in the last years new compounds have been marketed with the promise of comparable efficacy but less frequent adverse effects (especially extra-pyramidal side effects). Their safety, however, has been challenged by data showing a potential increase in adverse cerebrovascular side effects and mortality. This review will summarize the pathophysiology and neuropharmacology of BPSD, it will describe the characteristics of the anti-psychotics most commonly used focusing on their efficacy and safety in BPSD.

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    • "Overall, 25–50% of patients with dementia show symptoms of psychosis (Jeste et al., 2008) and 40–60% experience significant depressive symptoms at some stage of the disease (Hersch and Falzgraf, 2007). BPSD are usually treated with psychotropic drugs, often second-generation antipsychotics (SGA) that produce less extrapyramidal symptoms (EPS) and have better efficacy against negative symptoms than classical ones (Liperoti et al., 2008). However, a recent meta-analysis based on 14 placebocontrolled trials of elderly patients with BPSD revealed only modest effects for three SGA, that is, risperidone, aripiprazole and olanzapine (Maher et al., 2011). "
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    ABSTRACT: Many dementia patients exhibit behavioural and psychological symptoms (BPSD) that include psychosis, aggressivity, depression and anxiety. Antipsychotic drugs are frequently prescribed but fail to significantly attenuate mood deficits, may interfere with cognitive function and are associated with motor and cardiac side-effects which are problematic in elderly patients. A need therefore exists for drugs that are better suited for treatment of BPSD. we used in vitro cellular and in vivo behavioural tests to characterize ADN-1184, a novel arylsulfonamide ligand with potential utility for treatment of BPSD. ADN-1184 exhibits substantial 5-HT6 /5-HT7 /5-HT2A /D2 receptor affinity and antagonist properties in vitro. In tests of antipsychotic-like activity, it reversed MK-801-induced hyperactivity and stereotypies, and inhibited Conditioned Avoidance Response (CAR) (MED = 3 mg/kg i.p.). Remarkably, ADN-1184 also reduced immobility time in the forced swim test at low doses (0.3 and 1 mg/kg i.p.; higher doses were not significantly active). Notably, up to 30 mg/kg ADN-1184 did not impair memory performance in the passive avoidance test or elicit significant catalepsy and only modestly inhibited spontaneous locomotor activity (MED = 30 mg/kg i.p.). ADN-1184 combines antipsychotic-like with antidepressant-like properties without interfering with memory function or locomotion. This profile is superior to that of commonly-used atypical antipsychotics tested under the same conditions (Kołaczkowski et al., submitted) and suggests that it is feasible to identify drugs that improve behavioural and psychological symptoms without exacerbating cognitive deficit or movement impairment which are of particular concern in dementia patients.
    British Journal of Pharmacology 11/2013; 171(4). DOI:10.1111/bph.12509 · 4.84 Impact Factor
    • "Behavioral and Psychological Symptoms of Dementia (BPSD) is the term applied to the various problems that complicate dementia and prevalence is high. It is estimated that up to 90% of patients with Alzheimer’s disease may present at least one BPSD during the course of the disease [2]. BPSD include behaviors such as aggression, screaming, restlessness, and also symptoms such as anxiety, hallucinations and depressive mood [3]. "
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    ABSTRACT: Antipsychotic drugs are widely used for the treatment of Behavioral and Psychological Symptoms of Dementia (BPSD), despite their limited efficacy and concerns about safety. The aim of this study was to describe antipsychotic drug therapy among people with dementia living in specialized care units in northern Sweden. This study was conducted in 40 specialized care units in northern Sweden, with a total study population of 344 people with dementia. The study population was described in regard to antipsychotic drug use, ADL function, cognitive function and BPSD, using the Multi-Dimensional Dementia Assessment Scale (MDDAS). These data were collected at baseline and six months later. Detailed data about antipsychotic prescribing were collected from prescription records. This study showed that 132 persons (38%) in the study population used antipsychotic drugs at the start of the study. Of these, 52/132 (39%) had prescriptions that followed national guidelines with regard to dose and substance. After six months, there were 111 of 132 persons left because of deaths and dropouts. Of these 111 people, 80 (72%) were still being treated with antipsychotics, 63/111 (57%) with the same dose. People who exhibited aggressive behavior (OR: 1.980, CI: 1.515-2.588), or passiveness (OR: 1.548, CI: 1.150-2.083), or had mild cognitive impairment (OR: 2.284 CI: 1.046-4.988), were at increased risk of being prescribed antipsychotics. The prevalence of antipsychotic drug use among people with dementia living in specialized care units was high and inappropriate long-term use of antipsychotic drugs was common.
    BMC pharmacology & toxicology 02/2013; 14(1):10. DOI:10.1186/2050-6511-14-10
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    • "Behavioural and psychological symptoms of dementia (BPSD) comprise a broad spectrum of non-cognitive symptoms including physical aggression, agitation, hallucinations, depression, delusions , wandering and sleep disturbances (Petrovic et al., 2007; Liperoti et al., 2008). Up to 80% of patients with Alzheimer's dementia may develop periodic episodes or chronic behavioural and psychological symptoms in their course of illness (Lyketsos et al., 2002). "
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    ABSTRACT: Within the treatment of dementia, management of behavioural and psychological symptoms (BPSD) is a complex component. We wanted to offer a pragmatic synthesis of existing specific practice recommendations for managing BPSD, based on agreement among systematically appraised dementia guidelines. We conducted a systematic search in MEDLINE and guideline organisation databases, supplemented by a hand search of web sites. Fifteen retrieved guidelines were eligible for quality appraisal by the Appraisal of Guidelines Research and Evaluation instrument (AGREE), performed by 2 independent reviewers. From the 5 included guidelines, 18 specific practice recommendations for BPSD were extracted and compared for their level of evidence and strength. No agreement was found among dementia guidelines for the majority of specific practice recommendations with regard to non-pharmacological interventions, although these were recommended as first-line treatment. Pharmacological specific practice recommendations were proposed as second-line treatment, with agreement for the use of a selection of antipsychotics based on strong supporting evidence, but with guidance for timely discontinuation. The appraisal of the level of agreement between guidelines for each specific practice recommendation was complicated by variation in grading systems, and was performed with criteria developed a posteriori. Despite the limited number of recommendations for which agreement was found, guidelines did agree on careful antipsychotic use for BPSD. Adverse events might outweigh the supporting evidence of efficacy, weakening the recommendation. More pivotal trials on the effectiveness of non-pharmacological interventions, as well as guidelines specifically focusing on BPSD, are needed.
    Ageing research reviews 08/2011; 11(1):78-86. DOI:10.1016/j.arr.2011.07.002 · 4.94 Impact Factor
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