痴呆病人精神和行为症状的治疗

痴呆病人的精神和行为症状发生率相当高,影响病人和照料者的生活质量。本文对痴呆病人精神和行为的治疗方法及抗精神病药治疗对病人生活质量的影响做了简要介绍,重点介绍非典型抗精神病药治疗精神和行为症状的效果和不良反应。     

伴发精神行为症状的高龄痴呆患者应用抗精神病药的安全性分析

目的:分析伴精神行为症状(BPSD)的高龄痴呆患者抗精神病药使用情况。方法:采用回顾性分析方法,根据是否应用抗精神病药治疗,将住院治疗的伴BPSD的80岁以上痴呆患者分为抗精神病药组(56例)和非抗精神病药组(34例),比较两组间安全性。结果:抗精神病药组中血管性痴呆患者的比例(32.1%)明显高于非抗精神病药组(8.8%)(χ~2=6.43,P0.05);不同痴呆类型的患者间奥氮平、喹硫平、利培酮、阿立哌唑、氟哌啶醇的药物剂量比较,差异无统计学意义(P均0.05)。不同痴呆类型间发生不良事件的比较,差异无统计学意义(P均0.05)。结论:应用小剂量抗精神病药治疗伴有BPSD的高龄痴呆患者未升高不良事件发生的风险。     

上海社区阿尔茨海默病行为和精神症状的发生率及影响因素

目的调查上海社区阿尔茨海默病（AD）患者行为和精神症状（BPSD）的发生率及分析可能的相关影响因素。方法对符合美国精神障碍诊断和统计手册第4版（DSM—IV）诊断标准的378例社区AD患者,进行一般资料调查,评定简易智力状态检查（MMSE）、临床痴呆评定表（CDR）及AD病理行为评分表（BEHAVE—AD）,分析BPSD症状发生率及有关的影响因素。结果BPSD的发生率为62．2％,其中以行为紊乱发生率最高（35．4％）,幻觉及焦虑恐惧最低（均为11．4％）,在接受BPSD治疗上仅为20％～25％。重度痴呆的幻觉及行为紊乱的发生率或因子分要高于轻、中度痴呆,而中度痴呆的情感障碍因子分最高。与AD患者BPSD有关的影响因素为病前生活事件、MMSE总分、年龄及CDR评分。结论社区AD患者的BPSD有较高的发生率,与BPSD发生的可能危险因素有生活事件、年龄及认知功能损害程度,需要引起足够的重视。     

氟哌啶醇与利培酮治疗痴呆患者精神行为症状的随机双盲对照研究

目的 比较氟哌啶醇与利培酮治疗痴呆患者精神行为症状(BPSD)的疗效及安全性。方法 116例伴精神行为症状的痴呆患者随机入组,双盲对照治疗8周,评定疗效和不良反应并记录用药量。结果 氟哌啶醇组和利培酮组的最高平均治疗剂量分别为(2.5±1.0)mg/d和(1.2±0.6)mg/d;治疗后痴呆病理行为评定表减分率>30％者分别为84％和85％;不良反应发生率分别为31％和21％,合并应用安坦频度分别为19％和6％;两组不良反应的差异以第4周最为明显,利培酮组无严重不良反应发生。结论 较低剂量氟哌啶醇或利培酮可以显著改善BPSD,利培酮的安全性和耐受性优于氟哌啶醇。     

中日两国痴呆老人患病类型及精神行为症状的比较

目的比较探讨中日两国痴呆老人患病类型及精神行为症状（BPSD）发生率的差异。方法以辽宁省沈阳市苏家屯地区3432例65岁以上老年人为调查对象进行痴呆的流行病学调查，并与在日本新渴县丝鱼川地区调查结果比较。结果（1）调查地区痴呆的患病率为8．13％，低于日方调查结果10．6％。其中阿尔茨海默病（AD）占23．9％（日本为57．1％），血管性痴呆（VD）为56．6％（日本为22．6％）。（2）痴呆患者的精神行为症状（BPSD）的发生率两国之间无明显性差异，但不安症状、忧郁、烦躁、依赖等情感方面的变化以及大小便失禁症状方面，中方的发生率明显高于日方。结论老年痴呆已经成为当今中国的一个重大社会问题，中日两国痴呆患者患病类型及BPSD发生率出现差异的原因与两国之间的医疗保障制度以及生活水平不同相关。     

利培酮维持治疗痴呆患者的行为和精神症状的初步研究

目的　了解抗精神病药维持治疗痴呆患者的行为和精神症状 (BPSD)的必要性。方法　采用随机对照研究方法将 15例经 8周利培酮或氟哌啶醇急性期治疗后BPSD得到缓解的病例继续服利培酮 1mg/d ,14例同类病人不服任何抗精神病药 ,两组病人均随访 2 4周。随访中 ,定期进行阿尔茨海默病病理行为评分表 (BEHAVE AD)和Cohen Mansfield激越问卷 (CMAI)的评定。病人随访中如BPSD复发 (BEHAVE AD评分≥ 8分 )则作为复发病例。结果　利培酮组复发率 2 6 .6 7% (4/ 15 ) ,不服药组复发率 5 7.14 % (8/ 14 ) ;经Kalan Meier生存分析两组无显著性差异 (P >0 .0 5 )。通过复发因素的Cox回归分析 ,是否用药维持因素无显著性 (P >0 .0 5 )。结论　尽管短期用抗精神病药治疗BPSD有效 ,但长期用药维持是不必要的     

残疾精神分裂症患者综合医疗干预效果研究

目的：了解青岛市残疾精神分裂症患者综合医疗干预的效果。方法：对500例残疾精神分裂症患者在综合医疗干预前后进行精神卫生调查表、社会功能缺陷筛选量表（SDSS），治疗中出现的症状量表（TESS），阳性与阴性症状量表（PANSS）进行评定。结果：残疾精神分裂症患者在综合医疗干预后，其疗效、药物不良反应、服药依从性、社会功能均有改善，用药种类非典型抗精神病药使用增多，典型抗精神病药的使用减少。结论：对残疾精神分裂症患者的综合医疗干预有利于患者的全面康复。     

典型和非典型抗精神病药合并碳酸锂治疗双相情感障碍躁狂发作的对照研究

目的探讨典型和非典型抗精神病药物合并碳酸锂治疗双相情感障碍躁狂发作患者的疗效。方法将94例双相情感障碍躁狂发作患者分为典型抗精神病药物组（43例）和非典型抗精神病药物组（51例），进行为期8周的疗效比较。采用Bech-Rafaelsen躁狂量表（BRMS）、临床大体印象量表（CGI）、副反应量表（TESS）以及药物依从性量表分别于入组前和入组第1、2、4、6和8周末时进行评定。结果治疗结束时，两组BRMS评分较入组时均显著减低（P〈0．01）；临床总有效率：典型抗精神病药物组83．7％，非典型抗精神病药物组82．3％；两组疗效差异无显著性。非典型药物组的不良反应较典型组少，药物依从性较典型组高。结论非典型抗精神病药物治疗双相情感障碍躁狂发作的疗效肯定，不良反应较少，安全性高，依从性好，适合临床应用。     

利培酮治疗老年期痴呆患者的精神和行为障碍的疗效分析

1996年世界老年精神病学会一致决定将痴呆的精神障碍统一称之为“痴呆行为和精神症状”(be havioraland psychologicalsymptomsofdementia ,BPSD) [1] ,并认为与痴呆的认知功能相比 ,痴呆的精神症状显然是可以治疗的[2 ] 。但在选用适合治疗BPSD的抗精神病药物及其剂量方面的报道却并不多见。为此 ,我们选用利培酮在这方面进行了一些探索 ,现报道于后。1　对象与方法1 1　对象　系杨浦区精神卫生中心 2 0 0 1年 4月～2 0 0 2年 7月首次前来门诊者 ,其诊断符合CCMD -2 -R老年期痴呆诊断标准 ,并同时伴有精神和行为症状的患者共计 31例…     

多发性脑梗死性痴呆的精神症状及治疗

目的：探讨多发性脑硬死性痴呆（ＭＩＤ）精神症状出现率及特点，以及对抗精神病药物治疗的反应。方法：回顾性分析５６例ＭＩＤ患者的临床资料，并与４８例精神分裂症（ＳＣ）对照。结果：ＭＩＤ有５５．４％出现精神病性症状。多风的症状是意志减退，情感淡漠，妄想和幼觉。抗精神病药治疗阳性症状效果较好，与ＳＣ组无显著差异。副反应并不比ＳＣ病人多。结论：ＭＩＤ伴发精神症状相当常见，其阳性症状抗精神病药治疗可得到很好控     

Influence of the FDA Talk Paper upon the use of atypical antipsychotics for psychotic symptoms in older patients with dementia in Japan

Background: Atypical antipsychotic medications have often been used in the treatment of behavioral and psychological symptoms of dementia (BPSD). Recently, the US Food and Drug Administration (FDA) issued new safety information concerning atypical antipsychotic drugs, indicating that their use may increase the risk of cardiovascular adverse events among elderly adults with BPSD. Based on this information, the Japanese Ministry of Health, Labor and Welfare issued a similar warning against the use of atypical antipsychotic drugs licensed in Japan. We then sought to determine whether or not the use of typical antipsychotics should be recommended to replace atypical antipsychotics. In this paper, we discuss the influence of these warnings on the withholding of use of risperidone exemplified in seven case histories. Methods: Seven inpatients who exhibited BPSD received risperidone monotherapy in our hospital. In response to the FDA notice, the atypical antipsychotics used to treat these patients were replaced with typical antipsychotic agents. Results: During the period of risperidone administration, all patients exhibited clinical improvement compared with their baseline results and showed no adverse events. Two of our seven patients developed psychotic exacerbation and exhibited extrapyramidal symptoms coinciding with the replacement of risperidone with conventional antipsychotics. Conclusion: To the best of our knowledge, this is the first clinical report on the influence of the FDA alert on the use of atypical antipsychotics for psychotic symptoms in older patients with dementia in Japan. In two of our seven BPSD cases, there was no benefit from taking conventional antipsychotics. Our results lead to the conclusion that the use of typical antipsychotics should not be recommended to replace atypical antipsychotics. Although close attention should be paid to the FDA alert, clinicians must take into consideration the balance of benefits and risks when evaluating the appropriate use of antipsychotics in older patients with dementia.     

Stopping antipsychotic drug therapy in demented nursing home patients: a randomized, placebo-controlled study--the Bergen District Nursing Home Study (BEDNURS)

BACKGROUND: Despite modest efficacy, unpredictable individual utility, and a high rate of adverse effects, behavioural and psychological symptoms of dementia (BPSD) are common determinants for antipsychotic drug therapy in nursing home patients. AIMS: To explore the impact on BPSD of stopping long-term antipsychotic treatment in nursing home patients with dementia. METHODS: Fifty-five patients (43 women; mean age 84.1) taking haloperidol, risperidone, or olanzapine for BPSD were randomly assigned to cessation (intervention group, n = 27) or continued treatment with antipsychotic drugs (reference group, n = 28) for 4 consecutive weeks. The Neuropsychiatric Inventory (NPI) Questionnaire was used to examine changes in behavioural and psychological symptoms. RESULTS: By study completion, 23 of the 27 intervention group patients were still off antipsychotics. Symptom scores (NPI) remained stable or even improved in 42 patients (intervention group, 18 out of 27; reference group, 24 out of 28; p = 0.18). As compared to patients with stable or improved symptom scores, patients with behavioural deterioration after antipsychotic cessation used higher daily drug doses at baseline (p = 0.42). CONCLUSION: A large share of elderly nursing home patients on long-term treatment with antipsychotics for BPSD, do well without this treatment. Standardized symptom evaluations and drug cessation attempts should therefore be undertaken at regular intervals. Copyright (c) 2008 John Wiley & Sons, Ltd.     

Behavioral and psychological symptoms assessed with the BEHAVE-AD-FW are differentially associated with cognitive dysfunction in Alzheimer's disease.

To assess the possible neurological basis of behavioral and psychological symptoms of dementia (BPSD), the relationships between BPSD and cognitive function were evaluated in 40 patients with Alzheimer's disease (AD). BPSD was assessed using the Behavioral Pathology in Alzheimer's Disease Frequency Weighted Severity Scale (BEHAVE-AD-FW) for behavioral symptoms and psychological symptoms separately, and cognitive function was also assessed using the Cognitive Abilities Screening Instrument (CASI). We found that only behavioral symptoms were associated with cognitive function based on the CASI total score and the score for the CASI attention domain. Administration of risperidone, an atypical anti-psychotic drug, for one month, improved the behavioral symptoms and the scores for the CASI attention and orientation domains. Our data suggest that BPSD in AD may reflect two largely independent pathophysiological processes: one associated with behavioral symptoms partly overlapping with attention, and the other associated with psychological symptoms predominantly unrelated to cognitive function.     

How to treat behavioral and psychological symptoms of dementia (BPSD): Do not treat patients exhibiting symptoms like BPSD with neuroleptics from the beginning

The present report details the case of three patients who had symptoms like behavioral and psychological symptoms of dementia (BPSD). In all three cases, other factors contributing to the disease were hidden behind the symptoms resembling BPSD. These cases exhibited symptoms like BPSD following acute or subacute onset. Before starting medication with antipsychotic drugs, the underlying causes of the symptoms, especially those with an acute or subacute onset, should be considered.     

New therapeutic strategies for behavioral and psychological symptoms of dementia]

Interventional studies, with the aim of reducing the burden of care through drug or non-drug therapies of behavioral and psychological symptoms of dementia (BPSD), have been scarce. However, we are now able to do pharmacological management for BPSD with new drugs such as atypical neuroleptics, SSRIs, and cholinesterase inhibitors. Delusions of theft are one of the most frequently observed BPSD in patients with AD. In addition, the delusions and ensuing aggression and anxiety are major factors that increase the burden of caregivers. Delusions of theft in patients with AD were eliminated or reduced with low-dose atypical neuroleptics (risperidone). This significantly reduced the burden of care overall for caregivers. New therapeutic strategies such as cholinesterase inhibitors for visual hallucinations in DLB and SSRIs for overeating and stereotyped behavior in FTLD might also remarkably reduce the burden of care for these patients. For many dementia patients, there are still no drugs that offer a principal cure. It is, therefore, important to evaluate their BPSD correctly at the earliest possible time, so that the burden of caring can be reduced through appropriate drug treatment. This reduction is critical for the continuation of satisfactory at-home care and might contribute to the health economics.     

Beneficial and adverse effects of pharmacotherapy with risperidone on behavioral and psychological symptoms of dementia (BPSD)

Background: Behavioral and psychological symptoms of dementia (BPSD) increase the burden of caregiving. In 2004, the US Food and Drug Administration issued a warning on an increase in the mortality rate in elderly patients using antipsychotics. Thereafter, although the need for antipsychotics for BPSD has increased, discussions regarding their indication have continued. Methods: The present study was performed in 18 patients with Alzheimer's disease (AD) and patients with vascular dementia (VaD) who were treated with risperidone because of BPSD. Changes in the dose of risperidone and the beneficial and adverse effects of risperidone were evaluated for 3 months after the start of antipsychotic therapy. Results: The mean starting dose of risperidone was 0.62 ± 0.30 mg (62 ± 30 mg chlorpromazine (CP) equivalents), which, after 3 months, increased to 0.99 ± 0.49 mg risperidone (99 ± 49 mg CP equivalents). The symptoms of BPSD at the beginning of treatment were delusions (48% of patients) and violence (22% of patients). In the 3‐month treatment period, an improvement in BSPD symptoms was recorded in 78% of patients. During the study period, adverse effects were observed in 65% of patients: 26% of patients reported falling and extrapyramidal symptoms were seen in 13%. There were no cardiovascular events or deaths. Conclusion: In the present study, low doses of risperidone were used for the treatment of BPSD and no serious side‐effects were observed. An atypical antipsychotic can be one of the treatment options if a thorough risk assessment of the cardiovascular system is made and informed consent is obtained.     

Quetiapine treatment for behavioural and psychological symptoms of dementia in Alzheimer's disease patients: a 6-week, double-blind, placebo-controlled study

SETTING: Treating elderly patients with Alzheimer's disease (AD) and behavioral and psychological symptoms of dementia (BPSD) is challenging due to the increased risk of iatrogenic movement disorders with old neuroleptics and the seemingly increasing risk of cardiovascular events with newer atypical agents. Quetiapine is an atypical antipsychotic agent that warrants further investigation. OBJECTIVES: To assess tolerability, safety, and clinical benefit of quetiapine in AD patients with BPSD. PARTICIPANTS AND DESIGN: AD patients with BPSD participated in a 6-week randomized, double-blind, placebo-controlled trial. Quetiapine was increased on the basis of clinical response and tolerability. Primary efficacy assessments included the Neuropsychiatric Inventory (NPI) and Clinical Global Impression of Change (CGI-C). Secondary efficacy measures included the Mini-Mental State Examination (MMSE), the Simpson-Angus Scale (SAS) and the Abnormal Involuntary Movement Scale (AIMS). RESULTS: Forty patients (26 women), mean age 82.2 (SD 6.4) years were enrolled, 27 completed treatment. Median dose of quetiapine was 200 mg/day. Significant NPI total scores reductions (79% for placebo and 68.5% for quetiapine) were observed. The CGI-C score decreased significantly in the quetiapine group (p = 0.009 at 6 weeks) and did not change significantly in the placebo group (p = 0.48). The MMSE, AIMS, SAS scores and adverse events did not differ significantly between the two arms. CONCLUSIONS: Quetiapine did not significantly improve psychosis scores. It did not cause cognitive and motor deterioration. These results might possibly be due to small sample size.     

Anticonvulsant mood stabilizers in the treatment of behavioral and psychological symptoms of dementia (BPSD)

INTRODUCTION: Dementia, besides the dominant cognitive disorders that define it, is associated with behavioral disturbances, the consequences of which are, on various levels, a determining factor for the handling of these patients. The treatment of behavioral and psychological symptoms is essential and although, to date, no therapeutic solution is satisfactory, it is necessary to look for an alternative to the neuroleptics usually employed, which raise real problems of tolerance in this geriatric population. BACKGROUND: For several years, anticonvulsants, among which some have shown mood stabilizing activity, have been the object of research in this indication. The purpose of this review of the literature is to assess the interest and the limits of anticonvulsant mood stabilizers (carbamazepine, valproic acid, gabapentin, lamotrigine, topiramate, oxcarbazepine) in the treatment of the so-called "noncognitive" symptoms of dementia. Their mechanism of action in mood disorders is not well known, but it would appear to be via the modulation of glutamate-mediated excitatory synaptic transmission and gamma-aminobutyric acid (GABA)-mediated inhibitory synaptic transmission that anticonvulsants might reduce behavioral symptoms in demented patients. METHODS: The method employed in this work was a systematic bibliographic review, in which only the double-blind placebo-controlled studies or the clinically detailed enough open-labelled studies using validated scales were retained. RESULTS: Among these medications, only carbamazepine demonstrated its efficacy in behavioral and psychological symptoms of dementia (BPSD) in controlled studies, notably that of Tariot et al. [J Am Geriatr Soc 42 (1994) 1160-1166 and Am J Psychiatry 155 (1998) 54-61] and Olin et al. [Am J Geriatr Psychiatry 9 (2001) 400-405], but with significant adverse events (sedation, hyponatremia, cardiac toxicity), particularly in the elderly and, being a strong enzymatic inducer, with a high likelihood of drug-drug interactions. Valproic acid showed some interesting results in BPSD within a large number of open studies and case reports. However, among the five controlled studies that have been published [Curr Ther Res 62 (2001) 51-67; Am J Geriatr Psychiatry 9 (2001) 58-66; Int J Geriatr Psychiatry 17 (2002) 579-585; Curr Alzheimer Res 2 (2005) 553-558 and Am J Geraitr Psychiatry 13 (2005) 942-945], none confirmed its efficacy on these symptoms. Regarding its tolerability in the geriatric population, no notable major side effect was reported (haematologic and hepatic effects are not more frequent than in the general population), except possible excessive sedation. Moreover, it appears that valproic acid could have neuroprotective effects, even if the contrary has been observed in a recent study. More studies need to be (and are being) conducted, notably on the interest of valproic acid in prophylaxis of BPSD. Gabapentin seems to be worthwhile and well tolerated in this indication, but no controlled study has been conducted to prove its efficacy, even if a quite important number of case reports and open studies have shown encouraging results. Concerning lamotrigine, which may potentially induce severe cutaneous side effects when administered with valproic acid, this drug has shown its efficacy in bipolar disorders and two recent case reports seem to indicate some interest in BPSD. Furthermore, lamotrigine appears to have neuroprotective effects. Although topiramate has shown interesting results in one open study in BPSD, its use in demented patients cannot be recommended because of its deleterious effect on cognitive functions. Oxcarbazepine, theoretically, could be an alternative to carbamazepine, which is, as aforesaid, the only anticonvulsant that proved its interest in BPSD. However, no clinical study has yet been published to support this hypothesis. This drug is better tolerated than carbamazepine, but induces severe and more frequent hyponatremia. DISCUSSION AND CONCLUSION: Finally, although we all know that antipsychotics should no longer be prescribed in the elderly, the treatment of behavioral and psychological symptoms of dementia remains a difficult problem, considering the lack of a real alternative to these medications. Anticonvulsant mood stabilizers are an interesting solution but none of them, other than carbamazepine, which did, but which is not better tolerated than the usual drugs in this population - was able to prove its efficacy in this indication. Among these medications, valproic acid, gabapentin and lamotrigine should be studied further, and the neuroprotective effect of some of them is an interesting route for research.     

Half a century of antipsychotics and still a central role for dopamine D2 receptors

A review of the history of antipsychotics reveals that while the therapeutic effects of chlorpromazine and reserpine were discovered and actively researched almost concurrently, subsequent drug development has been restricted to drugs acting on postsynaptic receptors rather than modulation of dopamine release. The fundamental property of atypical antipsychotics is their ability to produce an antipsychotic effect in the absence of extrapyramidal side effects (EPS) or prolactin elevation. Modulation of the dopamine D2 receptor remains both necessary and sufficient for antipsychotic drug action, with affinity to the D2-receptor being the single most important discriminator between a typical and atypical drug profile. Most antipsychotics, including atypical antipsychotics, show a dose-dependent threshold of D2 receptor occupancy for their therapeutic effects, although the precise threshold is different for different drugs. Some atypical antipsychotics do not appear to reach the threshold for EPS and prolactin elevation, possibly accounting for their atypical nature. To link the biological theories of antipsychotics to their psychological effects, a hypothesis is proposed wherein psychosis is a state of aberrant salience of stimuli and ideas, and antipsychotics, via modulation of the mesolimbic dopamine system, dampen the salience of these symptoms. Thus, antipsychotics do not excise psychosis: they provide the neurochemical platform for the resolution of symptoms. Future generations of antipsychotics may need to move away from a "one-size-fits-all polypharmacy-in-a-pill" approach to treat all the different aspects of schizophrenia. At least in theory a preferred approach would be the development of specific treatments for the different dimensions of schizophrenia (e.g., positive, negative, cognitive, and affective) that can be flexibly used and titrated in the service of patients' presenting psychopathology.