The cost of behavioral and psychological symptoms of dementia (BPSD) in community dwelling Alzheimer's disease patients

INTRODUCTION: Behavioral and psychological symptoms of dementia (BPSD) are highly prevalent in Alzheimer's disease (AD) patients. They are a source of distress for the caregivers and one of the main reasons for nursing home placement, which is the major component of the cost of Alzheimer's disease. The aim of the present study was to assess the direct and indirect cost related to the care of BPSD within a prospective study examining the overall cost of AD in Israel. METHODS: Seventy-one community dwelling AD patients were interviewed. Interviews covered information about the number of caregivers' hours invested in caring for the patient and amount of expenditure such as in-house paid help and payments for day care. Effort devoted to BPSD was defined as the number of hours spent by primary and secondary caregivers in a typical week dealing with BPSD (managing aggression, pacing, attempts to leave the house under inappropriate circumstances, or comforting a hallucinating, depressed or anxious patient). RESULTS: The annual indirect cost for management of BPSD in an AD patient was approximately 2665 dollars -over 25% of the total annual indirect cost of care ($10 520). The annual direct cost of BPSD of an AD patient was approximately 1450 dollars -over 35% of the total annual direct cost of care (3900 dollars). CONCLUSIONS: Approximately 30% (4115 dollars) of the total annual cost of AD (14420 dollars) is invested in the direct management of BPSD. Given the importance of BPSD as one of the main components of the cost of AD, future cost studies should be designed to measure the cost of specific components of BPSD and verify which are the most costly aspects of the disease. Despite the considerable methodological difficulties in disentangling the costs of the specific symptoms of AD, cost effectiveness studies of different interventions should be conducted in order to determine the optimal intervention with relation to cost.     

Post‐marketing survey of donepezil hydrochloride in Japanese patients with Alzheimer's disease with behavioral and psychological symptoms of dementia (BPSD)

Background: To investigate the efficacy and safety of donepezil hydrochloride (Aricept^®; Eisai Co., Ltd, Tokyo, Japan), we conducted a post‐marketing survey in Japanese patients with Alzheimer's disease (AD) who also had behavioral and psychological symptoms of dementia (BPSD), such as hallucinations/delusions, wandering, and aggression, which cause the greatest burden on caregivers. Methods: A prospective, centrally registered investigation was conducted through regular clinical settings with patients diagnosed as mild to moderate AD presenting with hallucinations/delusions, wandering, and/or aggression. The treatment period was 12 weeks and no restrictions were placed on concomitant medications. Results: The BPSD improvement rates at last‐observation‐carried‐forward (LOCF) were 60.1% for hallucinations/delusions, 59.6% for wandering, and 65.6% for aggression. For all symptoms, improvement rates increased with the duration of the treatment period. The BPSD deterioration rates at LOCF were 1.3% for hallucinations/delusions, 3.4% for wandering, and 1.6% for aggression. Assessment of cognitive function with both the revised Hasegawa Dementia Scale (HDS‐R) and Mini‐Mental State Examination (MMSE) indicated significant improvements after treatment. There were significant differences in the changes in HDS‐R scores between patients whose hallucinations/delusions or wandering were improved and patients whose symptoms were not improved. Moreover, the data suggested a possible correlation between changes in hallucinations/delusions and HDS‐R scores, changes in hallucinations/delusions and MMSE scores, and changes in wandering and MMSE scores. Patients in whom BPSD improved also demonstrated a greater improvement in cognitive function compared with patients in whom no improvement in BPSD was noted. Nursing burden on caregivers at LOCF showed 3.6% for ‘No burden’, 54.1% for ‘Burden decreased’, and 4.5% for ‘Burden increased.’ There was an increase in the combined ratio of ‘No burden’ and ‘Burden decreased’ in proportion with prolonged treatment period. Patients with improved BPSD had a significantly greater ratio (88.5–94.4%) of ‘No burden’ plus ‘Burden decreased’ than those patients in whom no improvement in BPSD was noted. Conclusions: These results suggest that donepezil not only improves the cognitive dysfunction of AD patients, but may also relieve BPSD in these patients. Treatment with donepezil was also found to alleviate the burden of caregivers for approximately 60% of patients. Moreover, the results indicate that donepezil is unlikely to trigger potential risks of excessive deterioration of BPSD, which would result in a heavier burden of nursing care.     

曲唑酮治疗阿尔茨海默病伴发精神行为症状的临床研究

目的比较曲唑酮与奥氮平治疗阿尔茨海默病伴发精神行为症状的疗效及不良反应。方法将71例伴发精神行为症状的阿尔茨海默病患者随机分为两组,分别以曲唑酮（36例）和奥氮平（35例）治疗,疗程均为8周;分别于治疗前后采用痴呆行为量表（BRSD）及治疗时出现的症状量表（TESS）评定两组疗效及不良反应,并进行比较。结果曲唑酮和奥氮平治疗阿尔茨海默病伴发精神行为症状的显效率分别为52.8%和54.3%,两组间差异无统计学意义（P〉0.05）;曲唑酮组和奥氮平组不良反应发生率分别为13.9%和37.1%,曲唑酮组不良反应的发生率明显低于奥氮平组,差异有统计学意义（P〈0.05）。结论曲唑酮和奥氮平对阿尔茨海默病伴发精神行为症状均有明显疗效,但曲唑酮不良反应发生率更低、安全性更高。     

Behavioral and psychological symptoms of dementia in untreated Alzheimer's disease patients

Background: To ascertain the prevalence of psychotic symptoms and behavioral disturbances of dementia patients is useful for families and health care professionals in order to anticipate the progression of Alzheimer’s disease (AD) and to recognize deterioration. This study aimed to determine whether behavioral and psychological symptoms of dementia (BPSD) are related to severity of untreated AD. Methods: Two hundred and two patients were classified into three groups by Functional Assessment Staging score as follows: mild group (n = 92) was at stages 3 or 4; moderate group (n = 80) was at stage 5; and severe group (n = 30) was at stages 6 or 7. We then compared the prevalence of BPSD among the groups. Psychiatric symptoms of BPSD were defined as including hallucinations, delusions, delusional misidentification syndrome and depressive mood; while behavioral disturbances included physical aggression, wandering, adverse sleep and hyperphagia. Results: In our study, depressive mood, physical aggression and wandering were statistically associated with the severity of AD. Conclusion: These results are meaningful for caregivers in helping them to understand the anticipated progression of AD and to recognize deterioration. In the care of AD patients, it is necessary to be aware of characteristics of each BPSD.     

曲唑酮治疗慢性功能性疼痛的双盲对照研究

目的：探讨曲唑酮与止痛剂对慢性功能性疼痛的疗效和副反应。方法：140例患者随机分为2组双盲对照，分别进行曲唑酮与去痛剂治疗4周，采用汉密尔顿抑郁量表（HAMD）和四级临床疗效评定标准进行评定，采用副反应量表（TESS）评定副反应。结果：曲唑酮的疗效明显好于去痛剂，有效率分别为92.85％、62.85％，副反应不严重。结论：曲唑酮对慢性功能性疼痛疗效肯定，副反应轻。     

Trazodone for the treatment of sleep disorders in dementia: an open-label, observational and review study

Sleep disorders (SD) in patients with dementia are very common in clinical practice. The use of antidepressants with hypnotic actions, such as trazodone, plays an important role in these cases. The aim of this study is to present a profile of the use of trazodone in demented patients with SD, as well as a review of trazodone hydrochloride in SD. We evaluated 178 elderly patients with Alzheimer's disease and other dementias, clinically presenting SD and treated with hypnosedative medications. In the one-year period comprising the study, 68 (38.2%) of the 178 had sleep disorders. Most patients (114; 64%) had a diagnosis of Alzheimer's disease. Approximately 85% of patients with SD used hypnosedative drugs. Trazodone was the most commonly used drug among patients (N = 35), with an effectiveness of 65.7%. Trazodone has been shown to be a good option for treatment of the elderly with dementia and associated SD.     

Apolipoprotein E polymorphism and behavioral and psychological symptoms of dementia in patients with Alzheimer disease

The aims of this study were to identify subsyndromes of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer disease (AD), and to investigate whether the apolipoprotein E (ApoE) gene confers a risk of distinct BPSD subsyndromes. BPSD of 96 patients with AD were assessed using the Neuropsychiatric Inventory. Factor analysis with principal component analysis and varimax rotation was used to construct the BPSD subsyndromes. ApoE genotypes were determined using the TaqMan technology. The results showed that the 5 subsyndromes can be determined, including: agitation/aggression-delusion, euphoria-disinhibition, depression-apathy, hallucination-nighttime behavior, and appetite. ApoE ε4 carriers had higher factor scores in the agitation/aggression-delusion subsyndrome. We demonstrated that ApoE ε4 confers a higher risk for the subsyndrome of agitation/aggression delusion in AD.     

曲唑酮与阿米替林治疗抑郁症对照研究

目的:探讨曲唑酮对抑郁症的疗效。方法:将80例患者随机平分为两组,分别给予曲唑酮和阿米替林治疗,疗程4周。用汉密尔顿抑郁量表(HAMD)和副反应量表(TESS)评定疗效和不良反应。结果:治疗4周后,两药对抑郁症均有良好疗效,疗效近似(P>0.05);但曲唑酮不良反应小,程度轻(P<0.05或P<0.01)。结论:曲唑酮治疗抑郁症安全,疗效确切。     

Role of serotonin transporter polymorphisms in the behavioural and psychological symptoms in probable Alzheimer disease patients

BACKGROUND/AIMS: Alzheimer disease (AD) patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to BPSD development in AD has been demonstrated. This is an investigation of whether the linked polymorphic region and variable number tandem repeat variants of the serotonin transporter (SERT) are associated with BPSD. METHODS: The longitudinal measures of BPSD of our large cohort of 367 AD patients were assessed by the Neuropsychiatric Inventory. Measures with good evidence of serotonergic involvement (delusions, hallucinations, depression, anxiety, agitation/aggression and irritability) were related to genotype and allele frequencies of the linked polymorphic region and variable number tandem repeat variants. RESULTS: Analysis revealed significant relationships between the linked polymorphic region variant long allele with irritability and the variable number tandem repeat 10-repeat allele with psychosis, but no associations were found with depression, anxiety or agitation/aggression. CONCLUSION: Our data and review of previous studies suggest SERT could play a minor role in development of psychosis and aggressive/irritable tendencies; however, further investigations are required in large, well-characterized cohorts.     

Survey on the usefulness of trazodone in patients with PTSD with insomnia or nightmares

BACKGROUND: Trazodone is commonly used in the treatment of insonmia and nightmares in patients with PTSD. There is little evidence in the literature for this practice. METHOD: Seventy-four patients from the Palo Alto Veterans Affairs Health Care System in California who were admitted to a specialized 8 week inpatient treatment program for PTSD were surveyed regarding their use of trazodone in the treatment of insomnia or nightmares. Patients were asked to complete a questionnaire regarding trazodone's effectiveness, side effects, and optimal doses. RESULTS: Of 74 patients surveyed, 60 patients were able to maintain an effective dose of trazodone. The other 14 patients were unable to tolerate the medication. Seventy-two percent of the 60 patients assessed found trazodone helpful in decreasing nightmares, from an average of 3.3 to 1.3 nights per week (p<.005). Ninety-two percent found it helped with sleep onset, and 78% reported improvement with sleep maintenance. There was a significant correlation between the effectiveness in decreasing nightmares and improving sleep (r= .57, p < .005). The effective dose range of trazodone for 70% of patients was 50 to 200 mg nightly. Of the 74 patients surveyed, 9 (12%) reported priapism. CONCLUSION: Trazodone appears effective for the treatment of insomnia and nightmares associated with chronic PTSD. However, controlled trials are needed before any definite conclusions can be drawn. The higher than expected occurrence of priapism warrants clinicians asking directly about this side effect.     

A 2-year follow-up of behavioural and psychological symptoms in Alzheimer's disease

BACKGROUND: The aim was to examine the longitudinal occurrence and persistence of behavioural and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD). METHODS: Following 60 patients with mild to severe AD over a period of 2 years with annual evaluations, the prospective occurrence and persistence of BPSD in AD were determined by using the Behavioural Abnormalities in AD Rating scale (BEHAVE-AD). Clinical and demographic features of the AD patients were analysed for their association with course features of these symptoms. RESULTS: All of the 60 AD patients experienced BPSD at some point during the 2-year period, particularly agitation was present in every patient within this period. 2-year persistence of BPSD in AD was frequently observed in patients with agitation and with depressiveness, with less frequency in patients with anxiety and aggressiveness, but not in patients with delusions or hallucinations. 2-year persistent aggressiveness was associated with older age and more functional impairment. More functional impairment was also related to 2-year non-persistent hallucinations. CONCLUSIONS: Counselling AD patients and their families and tailoring therapeutic strategies should take into account the different modi of BPSD in AD occurring and persisting longitudinally and interacting with functional disturbances.     

A longitudinal evaluation of behavioural and psychological symptoms of probable Alzheimer's disease

BACKGROUND: Non-cognitive symptoms are a frequent feature of Alzheimer's disease (AD). Much of the literature that has accumulated pertains to cross-sectional prevalence of these symptoms. There has been relatively little attention paid to the longitudinal course of Behavioural and Psychological Symptoms of Dementia (BPSD). AIMS: The purpose of this study is to examine the longitudinal course of BPSD in a group of patients with mild AD. METHODS: A retrospective review of a database was performed to identify patients with NINCDS/ADRDA criteria for probable AD and who had been evaluated three times at yearly interval over a two-year period. Fifty-two subjects were identified with probable AD that had completed follow-up for 24 months. The BEHAVE-AD was used to evaluate BPSD and data was analysed using a Markov analysis. RESULTS: Activity disturbance is a common and relatively persistent symptom in the mild stages of AD. Anxiety, paranoid ideation, and aggression were moderately persistent. Affective symptoms were not persistent with less than half the patients having the symptoms a year later. CONCLUSIONS: Activity disturbance is common and persistent in early AD. Paranoid and delusional ideation shows moderate persistence and depressive symptoms infrequently last longer than a year. These findings may have clinical relevance for the pharmacological and non-pharmacological management of BPSD.     

曲唑酮联合银杏叶提取物治疗血管性抑郁症的疗效对照分析

目的探讨曲唑酮联合银杏叶提取物治疗血管性抑郁症的疗效与不良反应.方法 73例血管性抑郁症患者随机分为曲唑酮联合银杏叶提取物治疗(治疗组)和常规活血化瘀治疗(对照组),疗程8周.采用汉密尔顿抑郁量表(HAMD)、不良反应量表(TESS)评价临床疗效和不良反应.结果曲唑酮联合银杏叶提取物治疗血管性抑郁症在第2周起效,在第8周治疗结束时总有效率为80.6%;不良反应少而轻.结论曲唑酮联合银杏叶提取物治疗血管性抑郁症安全有效.     

Trazodone. A comparative clinical and predictive study

The clinical efficacy and tolerability of trazodone and amitriptyline were compared in 74 hospital patients suffering from depressive illness. The daily doses of trazodone and amitriptyline were 150-300 mg and 75-225 mg, respectively, with half-strength capsules for patients over the age of 65 years. Twenty-five and 29 patients receiving trazodone and amitriptyline, respectively, completed the 6 week treatment period. Antidepressant activity was measured using the Hamilton Depression Rating Scale (HDRS), the Zung Scale of Depression, visual analogue scales and a Global Assessment Scale. Trazodone and amitriptyline were both effective but not statistically different from each other in terms of antidepressant action. Moreover, patients with neurotic or endogenous depression responded equally well on either treatment. Trazodone was less troublesome in respect of the persistent dry mouth and severe adverse psychiatric reactions which occurred with amitriptyline. Patients should be advised to take trazodone after meals.     

Neuropsychiatric profiles in patients with Alzheimer's disease and vascular dementia

Background/Aims:

The aim of the following study is to compare the behavioral and psychological symptoms of dementia (BPSD) in patients of Alzheimer disease (AD) and vascular dementia (VaD).

Materials and Methods:

We used National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer''s Disease and Related Disorders Association criteria for diagnosing AD and National Institute of Neurological Disorders and Stroke-Association International pour la Recherche et l’Enseignement en Neurosciences Criteria for diagnosing VaD. VaD cohort was further subcategorized into small vessel and large vessel disease. The severity of cognitive impairment and the BPSD were studied by means of the Clinical Dementia Rating Scale (CDR) and the Neuropsychiatric Inventory respectively.

Results:

We studied 50 AD and 50 VaD patients of whom 38 were small vessels and 12 were large vessels VaD. The severity of dementia was comparable in both groups. The agitation/aggression, depression/dysphoria, anxiety, apathy/indifference, irritability, aberrant motor behavior, appetite and eating behavior and night-time behaviors occurred significantly more frequently in patients with VaD than AD. We found a weak positive correlation between the CDR score and the number of neuropsychiatric symptoms per patient in both cohorts. Elation/euphoria, agitation/aggression was significantly more frequent in patients with large vessel in comparison to small vessel VaD.

Conclusions:

BPSD are common in both types of dementia and they are more severe in VaD than AD when the groups have similar levels of cognitive impairment.     

The effects of trazodone on sleep in patients treated with stimulant antidepressants

BACKGROUND AND PURPOSE: To evaluate the effects of trazodone on subjective and objective measures of sleep in depressed insomnia patients treated with selective serotonin reuptake inhibitors (SSRIs). SSRIs can exacerbate or cause new insomnia while alleviating other symptoms of depression. Trazodone has been reported to be an effective hypnotic for patients with antidepressant-associated insomnia. PATIENTS AND METHODS: Twelve female patients were given either 100 mg trazodone or placebo for 7 days in a double-blind crossover design with a 7-day washout period. Polysomnographic recordings were repeated on the 3rd, 9th and 17th, 23rd nights after treatment with trazodone or placebo. Sleep was assessed by Pittsburgh sleep quality index (PSQI) at the beginning and end of the study. Psychological evaluation was done by Hamilton depression rating scale (HDRS). RESULTS: Trazodone significantly increased total sleep time, percentage of stages 3+4, sleep efficiency index, sleep continuity index and decreased percentage of stage 1, number of awakenings, stage shifts compared to the baseline. This improvement was also obtained after 7 days of treatment. The PSQI score was reduced to 5+/-1.6 at the end of the study. HDRS was reduced to 11.5+/-4.5 with trazodone and to 12.2+/-3 with placebo. CONCLUSION: Trazodone is effective in the treatment of antidepressant-associated insomnia.     

曲唑酮与阿普唑仑治疗广泛性焦虑症的对照研究

目的　比较曲唑酮与阿普唑仑治疗广泛性焦虑症的疗效及副作用。方法　选择符合CCMD 2 R诊断标准的广泛性焦虑症病例 6 3例 ,随机分为曲唑酮组 (34例 )和阿普唑仑组 (2 9例 )。分别用曲唑酮 5 0～ 15 0mg/日 ,阿普唑仑 0 8～ 2 4mg/日 ,治疗观察 12周。用汉密尔顿焦虑量表(HAMA)和药物副反应量表 (TESS) ,评定疗效和药物的不良反应。结果　曲唑酮与阿普唑仑疗效相当 ,起效稍慢于阿普唑仑 ,但中长期疗效更持久 ,没有严重副反应及药物依赖性。结论　曲唑酮治疗广泛性焦虑症疗效好 ,副反应轻 ,患者服药依从性好     

Successful treatment of alcohol withdrawal with trazodone

Trazodone, a second generation antidepressant, is helpful in the treatment of lasting alcohol withdrawal symptoms, such as sleep disturbances and craving. We report a case suggesting that trazodone is also efficient for the treatment of the acute phase of alcohol withdrawal treatment. A 30-year-old male patient with severe alcohol withdrawal symptoms was successfully treated with an adjuvant administration of 600 mg trazodone per day, while he had remained symptomatic for several days under high doses of diazepam and clomethiazolum. Controlled trials with trazodone for this indication could be useful.     

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.