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Keywords:

  • Alzheimer's disease;
  • atypical psychotics;
  • behavioral and psychological symptoms of dementia (BPSD);
  • pharmacotherapy;
  • vascular dementia

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES

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.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES

As dementia progresses, various behavioral and psychological symptoms of dementia (BPSD) can occur, such as agitation, depression, and wandering. BPSD increases the burden of caregivers.1 Low doses of antipsychotics and antidepressants had been recommended for the treatment of BPSD.2 In pharmacotherapy of the elderly, changes to in vivo pharmacokinetics and somatic complications can often occur. Therefore, the use of atypical antipsychotics had been recommended because they were considered to have a low incidence of side-effects.3 For example, the effectiveness of both risperidone and olanzapine has been reported in the treatment of BPSD and, although extrapyramidal symptoms (EPS) and abnormal gait can occur as side-effects, very few serious side-effects have been observed.4 However, in April 2004, the US Food and Drug Administration (FDA) issued a warning stating that the use of atypical antipsychotics in the elderly increased their mortality rate. In accordance with this warning, it was widely announced in Japan that antipsychotics were not indicated as a treatment for dementia. However, there are patients with severe BPSD in whom antipsychotics are still used after the patients have been informed of the adverse effects of these drugs and after they have provided informed consent to be treated with them. The present paper is based on the results of a survey of pharmacotherapy for BPSD performed at National Hospital Organization Hanamaki Hospital in 2004. A discussion of recent findings regarding the use of antipsychotics for the treatment of BPSD is also included.

METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES

The National Hospital Organization Hanamaki Hospital is a mid-size hospitalization facility with 250 beds in its Psychiatric Ward. Patients 65 years or older account for 40% of outpatients and inpatients, and 45% of these patients have dementia. In July 2004, a survey was performed on patients with Alzheimer's disease (AD; ICD-10: F00) or vascular dementia (VaD; ICD-10: F01) who were being treated with risperidone for BPSD.

Variables recorded were patient's age, sex, scores on the revised Hasegawa Dementia Scale (HDS-R; a rating scale of cognitive and memory disorders), and BPSD that were the reason for antipsychotic treatment. In terms of pharmacotherapy, we examined the dose of risperidone (chlorpromazine (CP) equivalents) used at the beginning of treatment and 3 months after the initiaion of treatment. In addition, we examined the frequency of use of antiparkinsonian agents and laxatives in combination with the antipsychotic 3 months after initation of antipsychotic therapy. Finally, over the 3-month period, any adverse effects and improvements in BPSD, as rated by the physicians in charge, were documented. Changes in BPSD were classified as improved, unchanged, or aggravated. Mean values were compared using t-tests.

The present study was conducted with the approval of the National Hospital Organization Hanamaki Hospital's ethics committee. Identifying information for the individuals involved in the study was removed in advance before their data was used.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES

A survey was conducted on 23 patients, 18 with Alzheimer's disease (AD) and five with VaD (six men and 17 women; mean age 81.9 ± 7.7 years). The HDS-R was 11.4 ± 7.5. The BPSD seen at the beginning of treatment with risperidone were delusion (11 subjects; 48%), violence (five patients; 22%), insomnia (five patients; 22%), offensive language (four patients; 17%), hallucinations (three patients; 13%), wandering (three patients; 13%), and resistance against care (three patients; 13%).

At the beginning of the treatment period, the mean dose of risperidone administered was 0.62 ± 0.30 mg (62 ± 30 mg CP equivalents). After 3 months treatment, the mean dose of risperidone had increased significantly to 0.99 ± 0.49 mg (99 ± 49 mg CP equivalents; < 0.01). An antiparkinsonian agent was used in combination with the antipsychotic medication in 4.3% of patients; laxatives were used in 11.0%. Over the 3-month period since the initation of antipsychotic treatment, BPSD improved in 78% of subjects. However, there was no improvement in delusions in three patients and no improvement in violence, offensive language, and wandering in one patient.

During the 3-month period of antipsychotic treatment, there was some type of adverse event reported by 65% of patients. Most commonly, patients reported being unsteady on their feet (39%); of these patients, 26% reported falls. Dysphasia was seen in 22% of patients and 13% exhibited EPS. There were no deaths or cardiovascular complications.

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES

In the initial development of dementia, short-term memory and temporal orientation are impaired; thereafter, remote memory and spatial orientation are impaired. During this process, BPSD appear and advanced cognitive and memory disorders progress.5 In the present study, risperidone pharmacotherapy for BPSD was investigated. Reversal of days and nights became evident as a BPSD, and led to the initiation of antipsychotic treatment. Reversal of days and nights has been reported to have a high correlation with the sense of burden felt by caregivers.1 It has also been reported that delusions and offensive language (excitement) are seen frequently during the emergency hospitalization of patients with dementia.6 These BPSD require intensive intervention. An increase burden on caregivers led to the start of atypical antipsychotic drug treatment. Onor et al. administered risperidone to an AD patient starting at a dose of 0.5 mg/day.7 The dose of risperidone was increased 0.5 mg/day every 3 days to improve symptoms, with the patient receiving a final dose of 1 mg/day risperidone.7 This treatment regimen is comparable with that of the present study.

In terms of adverse events, the incidence of EPS has been reported to be 15.6% following BPSD treatment with atypical antipychotics.8 This is consistent with the incidence of EPS observed in patients in the present study. The percentage of patients who fall in geriatric health service facilities has been reported to be approximately 20%.9 Again, this is similar to the rate of falls recorded for patients in the present study. Therefore, it is unlikely that the effect of the antipsychotic specifically on falls is large. A previous report indicated that there was no difference in the fall rate between patients being treated with risperidone and placebo.10

In the present study, there were no deaths or cardiovascular events. As mentioned previously, the FDA issued a warning that the mortality rate increased in elderly patients treated with antipsychotics. However, subsequent to this and after a review of the literature, it has been reported that there is no randomized controlled trial fully supporting the FDA's warning.11 Other reports have indicated that the mortality rate does not increase in patient groups treated with an antipsychotic compared with those being treated with a placebo.12–14

There has been a study conducted investigating the minimization of the dose of drugs for the treatment of BPSD used by combining pharmacotherapy with environmental adjustment and a behavioral therapy approach.15 Another study reported on the effectiveness of rivastigmine, a cholinesterase inhibitor, in the treatment of moderate or milder BPSD.12 However, atypical antipsychotics are thought to be effective for serious BPSD, including physical harm to oneself or to others. Guidelines have been issued indicating that thorough risk assessments of the cardiovascular and metabolic systems should be performed prior to commencement of therapy.16

In the present study, the dose of atypical antipsychotics for BPSD treatment was low and no serious side-effects were encountered. Thus, an atypical antipsychotic could be a treatment option for BPSD if a cardiovascular risk assessment is performed thoroughly and if informed consent can be obtained.

ACKNOWLEDGMENTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES

This study was funded by a research grant (19A-1) for Nervous and Mental Disorders from the Ministry of Health, Labour and Welfare.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES
  • 1
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