Factors correlated with initiating antipsychotics among dementia patients in Korean long-term care facilities: National Health Insurance Service-Senior Cohort (2002-2013)

Sunghye Kim1, Hangseok Choi2, Jinho Yoo1, Sunyoung Kim3, Byung-sung Kim1, Hyunrim Choi1, Nari Bu1, *Chang Won Won1

1Department of Family Medicine, College of Medicine, Kyung Hee University, Seoul, Korea

2College of Pharmacy, Chung-Ang University, Seoul, Korea

3Department of Medicine, Graduate School, Kyung Hee University, Seoul, Korea

DOI: 10.24816/jcgg.2017.v8i4.03

 

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Abstract

Background/Objectives

This study aimed to identify the pattern of initial antipsychotic prescriptions among dementia patients in Korean long-term care facilities (LTCFs), despite safety issues, and to investigate various factors correlated with their use.

Methods

We used a population-based senior cohort database of the Korean National Health Insurance Service (2002-2013) to target dementia patients newly admitted to LTCFs with no history of schizophrenia or bipolar disorder, and no history of antipsychotic use within six months prior to institutionalization (N=1,986). The sociodemographic, clinical, and facility-related characteristics were compared between the antipsychotic prescription and non-prescription groups. We used multivariate logistic regression models to identify factors that may affect the prescription of antipsychotics.

Results

The mean initial prescription rate of antipsychotics was 38.1%. A higher prescription rate of antipsychotics during institutionalization was correlated with male gender, use of memantine, schizophrenia, bipolar disorder, sleep disorder, depression, anxiety disorder, a greater number of pre-admission BPSD, and lower pre-admission functional dependence. A total of 59.4% of cases with antipsychotic prescriptions presented with psychotic symptoms, aggression, and agitation, of which 20.8%, and 19.8% presented with other behavioral and psychological symptoms of dementia (BPSD), and no BPSD, respectively.

Conclusions

The rate of initial antipsychotic prescriptions in Korean LTCF residents with dementia was high, and the prescription of antipsychotics was more strongly affected by the clinical characteristics of the patients than by sociodemographic or facility-related factors. Notably, more than 40% of the dementia patients in LTCFs received antipsychotics without appropriate indications.

Keywords

long-term care facilities, dementia, antipsychotics

2210-8335/Copyright © 2017, Asia Pacific League of Clinical Gerontology & Geriatrics. Published by Full Universe Integrated Marketing Limited.

Article Outline

  1. Introduction
  2. Case presentation2.1 Source Data
    2.2 Study Population
    2.3 Korean Long-term Care Insurance and Long-term Care Facilities
    2.4 Variables of Interest
    2.5 Antipsychotic Prescription Rate
    2.6 Missing and Void Data
    2.7 Statistical Analysis
    2.8 Subgroup Analysis
    2.9 Ethics Statement
  3. Discussion
  4. Conflicts of interest statement4.1 Strengths and Limitations
  5. Conclusions
  6. References

Abstract

Background/Objectives

This study aimed to identify the pattern of initial antipsychotic prescriptions among dementia patients in Korean long-term care facilities (LTCFs), despite safety issues, and to investigate various factors correlated with their use.

Methods

We used a population-based senior cohort database of the Korean National Health Insurance Service (2002-2013) to target dementia patients newly admitted to LTCFs with no history of schizophrenia or bipolar disorder, and no history of antipsychotic use within six months prior to institutionalization (N=1,986). The sociodemographic, clinical, and facility-related characteristics were compared between the antipsychotic prescription and non-prescription groups. We used multivariate logistic regression models to identify factors that may affect the prescription of antipsychotics.

Results

The mean initial prescription rate of antipsychotics was 38.1%. A higher prescription rate of antipsychotics during institutionalization was correlated with male gender, use of memantine, schizophrenia, bipolar disorder, sleep disorder, depression, anxiety disorder, a greater number of pre-admission BPSD, and lower pre-admission functional dependence. A total of 59.4% of cases with antipsychotic prescriptions presented with psychotic symptoms, aggression, and agitation, of which 20.8%, and 19.8% presented with other behavioral and psychological symptoms of dementia (BPSD), and no BPSD, respectively.

Conclusions

The rate of initial antipsychotic prescriptions in Korean LTCF residents with dementia was high, and the prescription of antipsychotics was more strongly affected by the clinical characteristics of the patients than by sociodemographic or facility-related factors. Notably, more than 40% of the dementia patients in LTCFs received antipsychotics without appropriate indications.

 

1. Introduction

Over 90% of dementia patients exhibit various behavioral and psychological symptoms of dementia (BPSD), such as anxiety, agitation, aggression, depression, delusion, and hallucinations. These are the most disruptive symptoms of dementia that occur, regardless of disease stage. BPSD decrease the quality of life in both patients and their caregivers, ultimately increasing the likelihood of admission to long-term care facilities (LTCFs).12

There is no standardized management of BPSD, but antipsychotics have been the main pharmacological treatment of BPSD. Although typical antipsychotics have long been the most commonly used, severe adverse side effects, such as extrapyramidal symptoms, including tardive dyskinesia,3,4,5steered the trend toward more active use of atypical antipsychotics.6However, subsequent randomized clinical trials and observational studies reported that atypical antipsychotics increased the risk of mortality and cerebrovascular events among patients with dementia. Based on these findings, the U.S. Food and Drug Administration (FDA) issued black-box warnings against atypical antipsychotics in 2005, which was extended to typical antipsychotics in 2008.7In keeping with the current FDA advisory, the Korean government also issued additional warnings intended to increase awareness of the potential harm associated with antipsychotics use and mandated labeling to indicate that no antipsychotics have been approved for treating dementia.8

Although BPSD treatment guidelines recommend non-pharmacological treatment as the first line of treatment, antipsychotics are still used in the treatment of dementia worldwide.2 It has been reported that the prescription rates of antipsychotics were higher in LTCF residents than in community dwellers.7,9

One study reported that approximately 80% of dementia patients placed in LTCFs exhibit BPSD.10The trend in Korea shows an increasing number of dementia patients placed in LTCFs nationwide,11and it highlights the growing need for appropriate BPSD management.

The aim of this study was to identify the pattern of initial antipsychotic prescriptions for dementia patients in long-term care facilities, and to investigate the sociodemographic, clinical, and facility-related characteristics correlated with their use.

2. Methods

2.1 Source Data

The National Health Insurance Service–National Sample Cohort (NHIS-NSC) is a population-based cohort established by the National Health Insurance Service (NHIS) in South Korea, which is open to the public, ensuring its applicability in research.12 The National Health Insurance Service-Senior Cohort (NHIS-SC), a subtype of NHIS-NSC, was established to provide useful and representative information for academic studies pertaining to geriatric diseases. The NHIS-SC was constructed from a simple random selection of 558,147 elderly Koreans aged 60 years and older, approximately 10% of the nation’s 5.5 million elderly population eligible for health insurance and coverage as of December 2002. Information regarding their insurance eligibility, income, use of healthcare services, and health check-ups was collected from 2002 to 2013, and LTCF data regarding the requests for and use of LTCFs were collected from July 2008 to 2013.

2.2 Study Population

We included patients with dementia who were newly admitted to LTCFs between July 1, 2008, and June 30, 2013. Participants were defined as having dementia if they had a primary or subsidiary diagnosis of dementia, and had one or more prescriptions for anti-dementia drugs during their LTCF stay. Participants with a diagnosis of schizophrenia or bipolar disorder between 2002 and their LTCF admission, and those diagnosed with alcohol withdrawal or alcohol-induced psychosis during their LTCF stay were excluded from analyses to minimize the possibility of antipsychotic prescriptions for reasons other than BPSD. Participants with a history of antipsychotic prescription within six months prior to LTCF admission were also excluded. However, participants newly diagnosed with schizophrenia or bipolar disorder during their LTCF stay were included, because antipsychotics cannot be prescribed without adequate diagnoses.

Patients were divided into two groups for comparison. Patients with a record of one or more antipsychotic prescriptions were classified as the antipsychotics group, and patients with no record of antipsychotic prescriptions were classified as the non-antipsychotics group. The Anatomical Therapeutic and Chemical (ATC) codes for typical and atypical antipsychotics included in this study were N05AA01, N05AA02, N05AB03, N05AB06, N05AD01, N05AD06, N05AE02, N05AE04, N05AF03, N05AF04, N05AF05, N05AG02, N05AH02, N05AH03, N05AH04, N05AL01, N05AL05, N05AX08, N05AX11, N05AX12, and N05AX13.

2.3 Korean Long-term Care Insurance and Long-term Care Facilities

National Long-term Care Insurance (LTCI) was introduced in July 2008 for all individuals aged 65 years and older and for individuals less than 65 years of age with geriatric diseases. Under the LTCI program, the applicant requesting services is assessed for his or her care needs by well-trained nurses or social workers based on 52 items across the five domains of physical and cognitive function, behavioral changes, rehabilitation, and nursing care. Results of the assessment are used to determine the applicant’s level of care needs. LTCI was initially graded into three levels, and was later expanded to include five levels in July 2013. Applicants with greater need for care are assigned lower grades. Applicants graded at levels one or two are eligible for placement in LTCFs, and applicants graded three to five can only apply for LTCF in case of poor living conditions, general condition unfit for home care, or lack of family support.11,13

The applicants who receive LTCI grades are issued LTCI certification. The valid period of the initial LTCI certification is one year, after which the valid period differs depending on individual circumstances. The beneficiaries who want to enter LTCFs must apply during the valid period, and those without valid LTCI certification within one year prior to admission were excluded.

2.4 Variables of Interest

Sociodemographic, neuropsychiatric, and facility-related characteristics were included as independent variables. Functional dependence level, BPSD, and cognitive impairment were based on the results of the LTCI certification. Functional dependence assessment, which consists of 13 assessment items, is conceptually comparable to the basic activities of daily living (ADLs). Each item is scored on a scale of one to three, with one indicating complete independence, two indicating partial dependence, and three indicating complete dependence, rendering the total score of 13 to 39 points. A higher functional score indicates poorer performance of basic daily activities. Complete independence was categorized as “not dependent,” whereas partial dependence and complete dependence were categorized as “dependent” for the analysis of functional dependence level. BPSD and cognitive impairment consisted of 22 and 10 assessment items, respectively. Each item was rated as one (yes) or zero (no), and the total score was calculated as the sum of the items rated one (yes).

Diagnostic codes used in the analysis were according to the Korean Standard Classification of Diseases, 5th and 6th Revisions (KCD-5 and KCD-6). Types of dementia included Alzheimer’s disease (F00, G30), vascular dementia (F01), Lewy body dementia (KCD-5: G31.8, KCD-6: G31.82) and others or unspecified (F02, F03). Comorbidities included diabetes (E10, E11, E12, E13, E14), hypertension (I10, I15), Parkinson’s disease (G20, G21, G22), congestive heart failure (I50), ischemic heart disease (I20, I21, I22, I23, I24, I25), cerebrovascular disease (I60, I61, I62, I63, I64, I65, I66, I67, I68, I69), chronic lung disease (J40, J41, J42, J43, J44), osteoporosis (M80, M81, M82), and chronic renal disease (N18). Regarding accompanying psychiatric diseases, depression (F32, F33), bipolar disorder (F30, F31), other mood disorders (F34, F38, F39), anxiety disorder (F40, F41, F42, F43), sleep disorder (F51), schizophrenia (F20) and other psychiatric illnesses (F21, F22, F23, F24, F25, F28, F29) were included.

2.5 Antipsychotic Prescription Rate

The antipsychotic prescription rate was defined as the proportion of participants in the antipsychotics group relative to the total number of participants. The rate of each specific antipsychotic administered during the participants’ LTCF stay was also calculated, which was the proportion of participants who submitted claims for a specific antipsychotic medication during their LTCF stay relative to the overall number of participants in the antipsychotic prescription group. In cases where multiple medications were prescribed, duplicates were allowed for each medication.

2.6 Missing and Void Data

Information regarding the number of beds, functional training rooms, and program rooms are not a requirement when registering for facility approval, and there were some missing or void data. Patients admitted to LTCFs with no beds or missing data regarding the number of beds were excluded from the study. Patients with missing data regarding functional training rooms and program rooms were included in the study, but were excluded from the corresponding analyses.

2.7 Statistical Analysis

The primary assessment in the present study concerned comparing the variables between dementia patients newly admitted to LTCFs who subsequently received antipsychotics and their counterparts who did not receive antipsychotics. When testing the statistical significance of the basic demographic distribution and clinical factors, two-sample t-tests or two-sample Wilcoxon tests were used for continuous variables, whereas Fisher’s exact tests were used for categorical variables. In addition, the odds ratio (OR) was calculated from a multiple regression analysis model adjusted for sex, psychiatric

disease, memantine use, total length of stay, and certification assessment items according to clinical evaluation. Significance level was set at 0.05. To correct potential errors due to multiple comparisons, a Bonferroni test was used. All statistical analysis was performed with R version 3.3.3 (R Foundation for Statistical Computing, Vienna, Austria). For data exploration and conversion, SAS version 9.3 (SAS Institute Inc., Cary, NC, USA) was used.

2.8 Subgroup Analysis

A subgroup analysis was performed to examine the relationship between the BPSD items of LTCI certification and antipsychotic prescription rate. We only included participants with antipsychotic prescriptions within one month after admission, due to the higher likelihood of new manifestation of BPSD with passage of time in LTCFs.

To assess the adequacy of the prescription, the following three BPSD categories were selected as independent variables: 1) presence of BPSD symptoms that are known to be alleviated by antipsychotics, including psychiatric symptoms, aggression, and agitation (as shown in Table 2, delusion, visual/auditory hallucination, agitation, violent behaviors and language, destroying items, and shouting),14 2) other BPSD; and 3) no BPSD.

2.9 Ethics Statement

This study was approved by the Institutional Review Board of Kyung Hee University Hospital, Seoul, Korea (Approval ID: KHUH 2016-02-108-008).

3. RESULTS

Of 3,619 elderly dementia patients in the NHIS-SC database who were newly admitted into LTCFs between July 1, 2008, and June 30, 2013, 1,986 were included in the study after excluding 1,324 patients who had prescriptions of antipsychotics within six months prior to admission to the LTCFs, diagnoses of bipolar disorder or schizophrenia before admission to the LTCFs, were diagnosed with alcohol withdrawal or alcohol-induced psychosis during their stay in the LTCFs, or had no LTCI certification for the admission year or the year prior. Additional 309 patients who were admitted to LTCFs with no beds or missing data regarding the number of beds were excluded from the study.

Of the remaining patients, 756 patients with antipsychotic prescriptions during their admission were assigned to the antipsychotics group, and 1,230 patients with no prescriptions for antipsychotics were assigned to the non-antipsychotics group to compare and analyze the various factors potentially influencing the decision for antipsychotic prescriptions (Figure 1).

Figure 1. Flow chart showing the distribution of participants throughout the trial.

 

3.1 Characteristics of LTCFs and Dementia Patients

The mean age of the participants was 81.5 ± 6.5 years, and 77.3% of the participants were females. The mean length of stay was 647.6 ± 559.3 days. The difference in mean age between the groups was not statistically significant, but the proportion of women was significantly higher in the non-antipsychotics group, with women accounting for 74.1% of the participants in the antipsychotics group and 79.4% in the non-antipsychotics group (p-value=0.007). The antipsychotics group had a significantly longer mean total length of stay of 725.3 days compared to 599.9 days for the non-antipsychotics group (p-value <0.001). The non-antipsychotics group had a higher functional dependence score (26.0 points) than the antipsychotics group (24.7 points; p-value <0.001). However, there were no significant differences between the groups in terms of facility characteristics (Table 1).

The antipsychotics group had a higher rate of all psychiatric diseases of interest relative to the non-antipsychotics group. In the antipsychotics group, 90% of the participants had Alzheimer’s disease, compared to 84.6% in the non-antipsychotics group. Acetylcholinesterase inhibitor (AChEI), memantine, and both AChEI and memantine were prescribed to 1,554 (78.3%), 540 (27.2%), and 108 (5.4%) patients, respectively. There was no statistically significant difference in the prescription rate of AChEI, but the prescription rate for memantine was significantly higher in the antipsychotics group (33.5%) than in the non-antipsychotics group (23.3%). The average number of BPSD prior to LTCF admission in the total population was 2.61, and was higher in the antipsychotics group (3.44) than in the non-antipsychotics group (2.1). Regarding cognitive impairment, person disorientation was the sole item that showed a statistically significant group difference, found in 26.2% of the antipsychotics group and 22.1% of the non-antipsychotics group (p-value=0.039; Table 2).

3.2 Factors Influencing the Decision for Antipsychotics Prescription

Multivariate logistic regression revealed that a higher prescription rate of antipsychotics during institutionalization was correlated with male gender, use of memantine, schizophrenia, bipolar disorder, sleep disorder, depression, anxiety disorder, a greater number of pre-admission BPSD, and lower pre-admission functional dependence. Among these, schizophrenia and bipolar disorder had the highest ORs of 7.96 (95% confidence interval [CI] 4.51 to 14.08) and 7.30 (95% CI 5.01 to 10.63), respectively (Table 3).

3.3 Antipsychotic Prescription Rate in LTCFs Residents with Dementia

The antipsychotic prescription rate among dementia patients in LTCFs was 38.1%. Of the 756 patients in the antipsychotics group, 158 (20.9%) received typical antipsychotics, whereas 675 (89.3%) received atypical antipsychotics. The most frequently prescribed antipsychotic was quetiapine, followed by risperidone, haloperidol, perphenazine, olanzapine, and chloropromazine (Table 4).

In the antipsychotics group, antipsychotics were prescribed for 35% of the total length of stay in LTCFs, with the number of days with a prescription averaging 201.9. Up to 6.2% of patients received antipsychotics for more than 80% of the total length of their LTCF stay.


3.4 BPSD and Antipsychotic Prescription

Antipsychotics were first prescribed one to 1,762 days after admission. A total of 207 participants received antipsychotics within one month of admission; of these, 59.4% presented with psychotic symptoms, aggression, and agitation, while only 41.5% of the non-antipsychotics group presented these symptoms. Other BPSD and no BPSD were reported more frequently in the non-antipsychotics group. In the antipsychotics group, 20.8%, and 19.8% presented other BPSD, and no BPSD, respectively (p-value <0.001; Table 5).

Table 1. General characteristics of dementia patients in long-term care facilities (LTCFs), number (%)
Characteristics Total

(N=1,986)

AP group

(N=756)

Non-AP group

(N=1,230)

p-value
Age, mean (SD), years 81.5 (6.5) 81.5 (6.4) 81.5 (6.5) 0.875
Sex

Male

Female

 

450 (22.7)

1,536 (77.3)

 

196 (25.9)

560 (74.1)

 

254 (20.7)

976 (79.4)

0.007
LTCI grades

1

2

3

 

279 (14.1)

652 (32.8)

1,055 (53.1)

 

102 (13.5)

261 (34.5)

393 (52.0)

 

177 (14.4)

391 (31.8)

662 (53.8)

0.443
Comorbidity

Diabetes

Hypertension

Parkinson’s disease

Congestive heart failure

Ischemic heart disease

Cerebrovascular disease

Chronic lung disease

Osteoporosis

Chronic renal disease

 

705 (35.5)

1,412 (71.1)

262 (13.2)

243 (12.2)

388 (19.5)

1,010 (50.9)

767 (38.6)

616 (31.0)

69 (3.5)

 

282 (37.3)

527 (69.7)

99 (13.1)

90 (11.9)

162 (21.4)

366 (48.4)

299 (39.6)

235 (31.1)

29 (3.8)

 

423 (34.4)

885 (72.0)

163 (13.3)

153 (12.4)

226 (18.4)

644 (52.4)

468 (38.1)

381 (31.0)

40 (3.3)

 

0.193

0.285

0.946

0.778

0.103

0.096

0.507

0.960

0.529

Living with a partner (spouse)

Main caregiver (spouse)

257 (13.0)

227 (11.4)

107 (14.2)

93 (12.3)

150 (12.2)

134 (10.9)

0.216

0.346

Insurance coverage

Health insurance

Medical-aid

 

1,446 (72.8)

540 (27.2)

 

558 (73.8)

198 (26.2)

 

888 (72.2)

342 (27.8)

0.437
Functional dependence

Total scores, mean (SD)

Dressing

Washing face

Brushing teeth

Bathing

Eating

Turning in bed

Sitting up in bed

Transferring from bed to chair

Walking out of the room

Toileting

Bowel control

Bladder control

Washing hair

 

25.5 (6.3)

1,902 (95.8)

1,670 (84.1)

1,742 (87.6)

1,981 (99.8)

744 (37.5)

470 (23.7)

682 (34.3)

810 (40.8)

1,333 (67.1)

1,779 (89.6)

979 (49.3)

1,222 (61.5)

1,945 (98.0)

 

24.7 (6.1)

721 (95.4)

626 (82.8)

656 (86.8)

752 (99.5)

263 (34.8)

146 (19.3)

214 (28.3)

263 (34.8)

448 (59.3)

652 (86.2)

353 (46.7)

432 (57.1)

733 (97.0)

 

26.0 (6.4)

1,181 (96.0)

1,044 (84.9)

1,086 (88.3)

1,229 (99.9)

481 (39.1)

324 (26.3)

468 (38.1)

547 (44.5)

885 (72.0)

1,127 (91.6)

626 (50.9)

790 (64.2)

1,212 (98.5)

 

<0.001

0.493

0.230

0.325

0.073

0.056

<0.001

<0.001

<0.001

<0.001

<0.001

0.072

0.002

0.022

Ownership of LTCFs

Local government agency

Corporate

Private

Others

 

141 (7.1)

1208 (60.8)

635 (32.0)

2 (0.1)

 

56 (7.4)

458 (60.6)

240 (31.8)

2 (0.3)

 

85 (6.9)

750 (61.0)

395 (32.1)

0 (0.0)

0.395
Residence Location of LTCFs

Seoul

6 metropolitan citiesa

Others

 

136 (6.9)

396 (20.0)

1454 (73.2)

 

50 (6.6)

133 (17.6)

573 (75.8)

 

86 (7.0)

263 (21.4)

881 (71.6)

0.101
Bed capacity, mean (SD)

≥30

10-29

≤9

22.0 (17.5)

414 (20.9)

1121 (56.5)

451 (22.7)

21.5 (15.0)

159 (21.0)

434 (57.4)

163 (21.6)

22.3 (18.9)

255 (20.7)

687 (55.9)

288 (23.4)

0.800

0.633

 

 

Functional training roomb

Program roomc

1615 (87.6)

1802 (94.2)

628 (89.3)

691 (94.9)

987 (86.6)

1111 (93.8)

0.094

0.315

Total length of stay in mean number of days (SD) 647.6 (559.3) 725.2 (578.8) 599.9 (541.7) <0.001
LTCF, long-term care facility; AP, antipsychotics; LTCI, long-term care insurance; SD, standard deviation.
LTCI grades: lower grades mean higher dependency.
a 6 metropolitan cities: Busan, Incheon, Daejeon, Daegu, Gwangju, and Ulsan.
b 143 missing values of functional training room excluded from analysis; N=1,843 (AP group: N=703; Non-AP group: N=1,140).
c 73 missing values of program room excluded from analysis; N=1913 (AP group: N=728; Non-AP group: N=1,185)

 

4. DISCUSSION

The prescription rate of antipsychotics among dementia patients in Korean LTCFs was 38.1% in our study, which is high, considering the safety warnings for antipsychotic use in dementia patients. The actual prescription rate of antipsychotics is expected to be higher in real practice, since we excluded patients who were taking antipsychotics before LTCF admission, as well as patients diagnosed with schizophrenia and bipolar disorder. This rate is similar to the 41.1% prescription rate of antipsychotics for dementia patients in American LTCFs reported in 2006.15

A recent Korean study of 20 LTCFs reported a lower antipsychotic prescription rate of 27%, which is much lower than the results of our study. However, the previous study targeted only LTCFs with visiting geriatricians, and there is difficulty in interpreting that data to represent the overall LTCF situation in Korea. The prescription rate of antipsychotics for dementia patients was reported to be 32.8% in 57 LTCFs in seven European countries and Israel, and 31% in 20 LTCFs in the Netherlands.16 However, these studies also targeted a limited number of select LTCFs, and are not free of selection bias. Foebel et al. studied dementia patients admitted to LTCFs in Ontario, Canada from 2003 to 2011 and verified the prescription rate of antipsychotics within six months after admission to be 26.1%, which decreased to 7.0% when targeting only patients without a prior history of antipsychotics.17 Of the 1,986 participants in our study, only 435 (21.9%) received antipsychotics for the first time within six months of admission, which is also higher than the results of the Canadian study.

A greater number of BPSD prior to admission was associated with an increased prescription rate of antipsychotics. The subgroup analysis on patients (N=207) who received antipsychotics within a month of admission revealed noteworthy results that 20.8% received antipsychotics for BPSD without appropriate indication, and 19.8% received antipsychotics without any BPSD. Similarly, 39.4% of dementia patients in U.S. LTCFs were reported to receive antipsychotics without appropriate indication.18

Facility-related factors, including the number of beds, location, ownership, and establishment of functional training and program rooms of LTCFs did not show a statistically significant difference in the antipsychotic prescription rate. Previous studies in the U.S., the Netherlands, and Canada reported that the prescription rates of antipsychotics in LTCFs differ according to the characteristics and culture at the facility level, independent of individual characteristics, even in the same country.15Chen, Y, Briesacher, BA, Field, TS, et al. Unexplained variation across US nursing homes in antipsychotic prescribing rates. Archives of internal medicine 2010;170(1):89-95.,16Kleijer, BC, van Marum, RJ, Frijters, DH, et al. Variability between nursing homes in prevalence of antipsychotic use in patients with dementia. International Psychogeriatrics 2014;26(03):363-371.,19Rochon, PA, Stukel, TA, Bronskill, SE, et al. Variation in nursing home antipsychotic prescribing rates. Archives of internal medicine 2007;167(7):676-683.,20 However, there are no residing physicians in Korean LTCFs. Physician visits occur every two weeks, but prescriptions within the institution are prohibited by law, and necessary prescriptions can only be issued in external hospitals. Therefore, the culture of the facility is not likely to affect medical prescription rates.

Lower pre-admission functional dependence was associated with an increased prescription of antipsychotics in this study. Bed-ridden patients with high functional dependence have a decreased possibility of being a threat to others or raising self-inflicted harm, even if BPSD are manifested. Therefore, the low rate of antipsychotic prescriptions among bed-ridden patients can be interpreted as diminished use of antipsychotics as chemical restraints, which is a positive phenomenon. The results of a Canadian study are in accord with our study,17 but a study on 31 LTCFs in Finland discovered no association between dependence of ADLs and the use of antipsychotics.21 Another recent study reported that moderate functional disability increases antipsychotic prescriptions among dementia patients in LTCFs, but is not related to serious functional damage.7In our study, antipsychotic prescriptions were higher in patients who were accompanied by the diagnostic codes of schizophrenia, bipolar disorder, sleep disorder, or anxiety disorder during LTCF admission. The rate of antipsychotic prescriptions was more than seven times higher among patients with schizophrenia and bipolar disorder, whose prevalence was reported to be 0.2% in a 2011 Korean epidemiologic investigation of psychiatric diseases among 6,000 indiviuals.22 Both diseases have a lower prevalence and incidence in older age groups,23,24 and most antipsychotics are covered by insurance only in case of the two diseases in Korea. Therefore, there is high possibility of intentional entry of incorrect diagnostic codes to prescribe antipsychotics under insurance or inaccurate diagnoses by physicians in external hospitals. It would also explain the unrealistically high incidence of these two diseases among elderly dementia patients.

The rate of antipsychotic prescriptions also increased with the use of memantine, which can be claimed only in moderate or greater severity dementia patients, as evidenced by a Mini-Mental State Examination (MMSE) score of 20 and less, a Clinical Dementia Rating (CDR) of two or three, or a Global Deterioration Scale (GDS) of four and above. Therefore, more severe states of dementia can be interpreted to be related to the claim for memantine, and higher rate of prescription of antipsychotics. A previous study using the Cognitive Performance Scale (CPS) to assess the severity of dementia reported that antipsychotic prescriptions were associated with severe dementia (CPS five and above), but not with moderate dementia (CPS two-four).7 Another study reported CPS three and above to be associated with the antipsychotic prescription.17

Foebel et al. reported that antipsychotic prescriptions in European LTCFs are likely to continue once started.17 The antipsychotics group received antipsychotics on average of 35% (201.9 days) of their stays in our study, with the long-term antipsychotic prescription rates reaching 6.2%. Lack of physicians and difficulty with day-to-day medical control in Korean LTCFs may lead to long-term antipsychotic use in absence of appropriate consideration of individual symptoms.

Table 2. Neuropsychiatric characteristics of dementia patients in long-term care facilities, number (%)

Characteristics Total

(N =1986)

AP group

(N=756)

Non-AP group

(N=1230)

p-value
Psychiatric diseases

Depression

Bipolar disorder

Other mood disorder

Anxiety disorder

Sleep disorder

Schizophrenia

Other psychiatric illnesses

 

688 (34.6)

210 (10.6)

58 (2.9)

549 (27.6)

353 (17.8)

113 (5.7)

110 (5.5)

 

341 (45.1)

168 (22.2)

33 (4.4)

271 (35.9)

197 (26.1)

97 (12.8)

93 (12.3)

 

347 (28.2)

42 (3.4)

25 (2.0)

278 (22.6)

156 (12.7)

16 (1.3)

17 (1.4)

 

<0.001

<0.001

0.004

<0.001

<0.001

<0.001

<0.001

Type of dementia

Alzheimer’s disease

Vascular dementia

Lewy body dementia

Others or unspecified

 

1721 (86.7)

445 (22.4)

8 (0.4)

875 (44.1)

 

680 (90.0)

167 (22.1)

5 (0.7)

377 (49.9)

 

1041 (84.6)

278 (22.6)

3 (0.2)

498 (40.5)

 

0.001

0.825

0.272

<0.001

Anti-dementia drugs

AChEI

Donepezil

Rivastigmine

Galantamine

Memantine

Both AChEI and memantine

 

1554 (78.3)

1425 (71.8)

66 (3.3)

108 (0.1)

540 (27.2)

108 (5.4)

 

577 (76.3)

531 (70.2)

27 (3.6)

42 (5.6)

253 (33.5)

74 (9.8)

 

977 (79.4)

894 (72.7)

39 (3.2)

66 (5.4)

287 (23.3)

34 (2.8)

 

0.105

0.259

0.699

0.919

<0.001

<0.001

BPSD

Total number, mean (SD)

Delusion

Visual or auditory hallucination

Depression

Irregular sleep

Resisting care

Anxiety or restlessness

Being lost

Verbal or physical violence

Wandering outside

Breaking objects

Inappropriate behavior

Hiding objects

Dressing inappropriately

Unsanitary behavior

Inappropriate handling of fire

Separation anxiety

Shouting

Inappropriate sexual behavior

Eating inappropriate objects

Interfering or meddling

Refusing meals

Sticking to someone

 

2.6 (2.8)

498 (25.1)

482 (24.3)

143 (7.2)

566 (28.5)

241 (12.1)

166 (8.4)

340 (17.1)

414 (20.9)

301 (15.2)

87 (4.4)

568 (28.6)

285 (14.4)

384 (19.3)

225 (11.3)

325 (16.4)

106 (5.3)

22 (1.1)

2 (0.1)

6 (0.3)

8 (0.4)

7 (0.4)

5 (0.3)

 

3.4(3.1)

256 (33.9)

243 (32.1)

68 (9.0)

292 (38.6)

124 (16.4)

88 (11.6)

178 (23.5)

218 (28.8)

158 (20.9)

55 (7.3)

271 (35.9)

142 (18.8)

195 (25.8)

83 (11.0)

147 (19.4)

54 (7.1)

14 (1.9)

0 (0.0)

5 (0.7)

4 (0.5)

3 (0.4)

4 (0.5)

 

2.1(2.5)

242 (19.7)

239 (19.4)

75 (6.1)

274 (22.3)

117 (9.5)

78 (6.3)

162 (13.2)

196 (16.0)

143 (11.6)

32 (2.6)

297 (24.2)

143 (11.6)

189 (15.4)

142 (11.5)

178 (14.5)

52 (4.2)

8 (0.6)

2 (0.2)

1 (0.1)

4 (0.3)

4 (0.3)

1 (0.1)

 

<0.001

<0.001

<0.001

0.020

<0.001

<0.001

<0.001

<0.001

<0.001

<0.001

<0.001

<0.001

<0.001

<0.001

0.716

0.004

0.007

0.016

0.528

0.033

0.489

1.000

0.073

Cognitive impairment

Short-term memory impairment

Time disorientation

Place disorientation

Person disorientation

Long-term memory impairment

Misunderstanding instructions

Lack of situational judgement

Communication problem

Calculation problem

Failure to understand daily routine

 

1928 (97.1)

1837 (92.5)

1458 (73.4)

470 (23.7)

1442 (72.6)

689 (34.7)

1441 (72.6)

378 (19.0)

1807 (91.0)

713 (35.9)

 

738 (97.6)

709 (93.8)

561 (74.2)

198 (26.2)

550 (72.8)

271 (35.9)

550 (72.8)

152 (20.1)

695 (91.9)

285 (37.7)

 

1190 (96.8)

1128 (91.7)

897 (72.9)

272 (22.1)

892 (72.5)

418 (34.0)

891 (72.4)

226 (18.4)

1112 (90.4)

428 (34.8)

 

0.276

0.096

0.565

0.039

0.918

0.409

0.918

0.347

0.260

0.194

AP, antipsychotics; AChEI, acetylcholinesterase inhibitor; BPSD, behavioral and psychological symptoms of dementia 



Table 3.
Correlates of new antipsychotic prescriptions among Korean long-term care facility residents with dementia (N=1986): multivariate logistic regression models

Correlates p-value OR 95% CI
Female 0.017 0.74 0.58 0.95
Depression <0.001 1.64 1.32 2.04
Bipolar disorder <0.001 7.30 5.01 10.63
Anxiety disorder 0.009 1.37 1.08 1.73
Sleep disorder <0.001 2.04 1.56 2.65
Schizophrenia <0.001 7.96 4.51 14.08
Alzheimer’s disease 0.280 1.19 0.87 1.63
Memantine use <0.001 1.81 1.44 2.28
Functional dependence scores 0.041 0.98 0.96 1.00
BPSD scores <0.001 1.17 1.12 1.21
Person disorientation 0.796 0.97 0.75 1.25
Total length of stay 0.233 1.00 1.00 1.00

OR, odds ratio; CI, confidence interval; BPSD, behavioral and psychological symptoms of dementia


 

Table 4. Prescription rates for each antipsychotic among antipsychotics users (N=756) in Korean long-term care facility residents with dementia

Type of antipsychotics Number (%)
Typical antipsychotics

Chlorpromazine (N05AA01) Levomepromazine (N05AA02)   Trifluoperazine (N05AB06)

Perphenazine (N05AB03),  Bromperidol (N05AD06)

Haloperidol (N05AD01) Pimozide (N05AG02)

Sulpiride (N05AL01) Chlorprothixene (N05AF03) Thiothixene (N05AF04) Zuclopenthixol (N05AF05)

158 (20.9)

18 (2.4)

5 (0.7)

0 (0.0)

44 (5.8)

2 (0.3)

94 (12.4)

0 (0.0)

10 (1.3)

0 (0.0)

0 (0.0)

0 (0.0)

Atypical antipsychotics

Clozapine (N05AH02) Quetiapine (N05AH04) Olanzapine (N05AH03)  Zotepine (N05AX11)

Molindone (N05AE02) Paliperidone (N05AX13),  Risperidone (N05AX08)  Amisulpride (N05AL05) Aripiprazole (N05AX12) Ziprasidone (N05AE04)

675 (89.3)

2 (0.3)

424 (56.1)

33 (4.4)

2 (0.3)

2 (0.3)

2 (0.3)

330 (43.7)

5 (0.7)

4 (0.5)

0 (0.0)

Prescription rate = (Number of patients with one or more prescription of the corresponding drug during their LTCF stay)/756

The main strength of this study is the representativeness of the sample, since we used the cohort data sampling of more than 10% of all the older adults in Korea. In addition, the acquisition of most independent variables ahead of an antipsychotic prescription contributes to the causal relationship with the outcome.

4.1 Strengths and Limitations

An important limitation of our study is the lack of clinical information, as the data are based on the claims database provided by the NHIS. Therefore, it cannot be discerned whether the diagnostic codes truly represent patients’ conditions or if the codes were entered for the purpose of claiming insurance. The reasons for antipsychotic prescriptions cannot be ascertained accurately for the same reason.

5. Conclusions

Antipsychotics were newly prescribed to 38.1% of dementia patients after admission to LTCFs in Korea, and the prescription of antipsychotics was more strongly affected by the clinical characteristics of the patients than by sociodemographic or facility-related factors. A higher prescription rate of antipsychotics during institutionalization was correlated with male gender, use of memantine, schizophrenia, bipolar disorder, sleep disorder, depression, anxiety disorder, a greater number of pre-admission BPSD, and lower pre-admission functional dependence. It is also notable that 40.6% of the patients received antipsychotics without appropriate indications. Furthermore, there is concern for prolongation of indiscrete prescription of antipsychotics to dementia patients in LTCFs with the current method of delivering healthcare to the residents of LTCFs in Korea.

Table 5. Behavioral and psychological symptoms of dementia (BPSD) related to antipsychotic prescription within one month of institutionalization, number (%)

BPSD AP group

N=207

Non-AP group

N=1230

p-value
Any BPSD of psychotic symptoms,  aggression, agitationa 123 (59.4) 511 (41.5) <0.001
other BPSD 43 (20.8) 273 (22.2)
No BPSD 41 (19.8) 446 (36.3)

AP, antipsychotics; BPSD, behavioral and psychological symptoms of dementia
a Delusion, visual or auditory hallucination, anxiety/restlessness, verbal or physical violence, breaking items, shouting are included

 

Conflict of interest

The authors declare no conflicts of interest.

Acknowledgement

This study used a senior cohort database offered by the National Health Insurance Service, but did not receive any specific grants from any foundations.

References

1. Cohen‐Mansfield J, Billig N. Agitated behaviors in the elderly: I. A conceptual review. J Am Geriatr Soc. 1986;34(10):711-21.

2. Herrmann N. Recommendations for the management of behavioral and psychological symptoms of dementia. Can J Neurol Sci. 2001;28(S1):S96-S107.

3. Arana GW. An overview of side effects caused by typical antipsychotics. J Clin Psychiatry. 2000;61 Suppl 8:5-11; discussion 12-13.

4. Schneider LS, Pollock VE, Lyness SA. A metaanalysis of controlled trials of neuroleptic treatment in dementia. J Am Geriatr Soc. 1990;38(5):553-63.

5. Jeste DV, Blazer D, Casey D, Meeks T, Salzman C, Schneider L, et al. ACNP White Paper: update on use of antipsychotic drugs in elderly persons with dementia. Neuropsychopharmacology 2008;33(5):957-70.

6. Lee PE, Gill SS, Freedman M, Bronskill SE, Hillmer MP, Rochon PA. Atypical antipsychotic drugs in the treatment of behavioural and psychological symptoms of dementia: systematic review. BMJ 2004;329(7457):75.

7. Foebel, AD, Liperoti, R, Onder, G, Finne-Soveri H, Henrard JC, Lukas A, et al. Use of antipsychotic drugs among residents with dementia in European long-term care facilities: results from the SHELTER study. J Am Med Dir Assoc. 2014;15(12):911-7.

8. Ahn SH, Jung SY, Kim YJ, Seong JM, Choi NK, Shin JY, et al. Patterns of prescription of atypical antipsychotics in elderly ambulatory patients with dementia in Korea. J Pharmacoepidemiol Risk Manag 2009;2:97104.

9. Maguire A, Hughes C, Cardwell C, O’Reilly D. Psychotropic medications and the transition into care: a national data linkage study. J Am Geriatr Soc. 2013;61(2):215-21.

10. Margallo‐Lana M, Swann A, O’Brien J, Fairbairn A, Reichelt K, Potkins D, et al. Prevalence and pharmacological management of behavioural and psychological symptoms amongst dementia sufferers living in care environments. Int J Geriatr Psychiatry. 2001;16(1):39-44.

11. Won, CW. Elderly long-term care in Korea. Journal of Clinical Gerontology and Geriatrics 2013;4(1):4-6.

12. Lee J, Lee JS, Park SH, Shin SA, Kim K. Cohort profile: The national health insurance service–national sample cohort (NHIS-NSC), South Korea. Int J Epidemiol. 2017;46(2):e15.

13. Kim H, Kwon S, Yoon NH, Hyun KR. Utilization of long-term care services under the public long-term care insurance program in Korea: implications of a subsidy policy. Health Policy 2013;111(2):166-74.

14. Edge L. Antipsychotic drugs for dementia: a balancing act. 2009.

15. Chen Y, Briesacher BA, Field TS, Tjia J, Lau DT, Gurwitz JH. Unexplained variation across US nursing homes in antipsychotic prescribing rates. Arch Intern Med. 2010;170(1):89-95.

16. Kleijer BC, van Marum RJ, Frijters DH, Jansen PA, Ribbe MW, Egberts AC, et al. Variability between nursing homes in prevalence of antipsychotic use in patients with dementia. Int Psychogeriatr. 2014;26(03):363-71.

17. Foebel A, Ballokova A, Wellens NI, Fialova D, Milisen K, Liperoti R, et al. A retrospective, longitudinal study of factors associated with new antipsychotic medication use among recently admitted long-term care residents. BMC Geriatr. 2015;15(1):128.

18. Volicer, L. Antipsychotics do not have to be used “off label” in dementia. Elsevier; 2012.

19. Rochon PA, Stukel TA, Bronskill SE, Gomes T, Sykora K, Wodchis WP, et al. Variation in nursing home antipsychotic prescribing rates. Arch Intern Med. 2007;167(7):676-83.

20. Kamble P, Chen H, Sherer JT, Aparasu RR. Use of antipsychotics among elderly nursing home residents with dementia in the US. Drugs Aging. 2009;26(6):483-92.

21. Pekkarinen L, Elovainio M, Sinervo T, Finne-Soveri H, Noro A. Nursing working conditions in relation to restraint practices in long-term care units. Med Care. 2006;44(12):1114-20.

22. Ministry of Health and Welfare. The Epidemiological Survey of Mental. Disorders in Korea; 2012. http://www.index.go.kr/potal/main/EachDtlPageDetail.do?idx_cd=1441. Accessed August 5 2017.

23. Depp CA, Jeste DV. Bipolar disorder in older adults: a critical review. Bipolar Disord. 2004;6(5):343-67.

24. Jeste DV, Alexopoulos GS, Bartels SJ, Cummings JL, Gallo JJ, Gottlieb GL, et al. Consensus statement on the upcoming crisis in geriatric mental health: research agenda for the next 2 decades. Arch Gen Psychiatry. 1999;56(9):848-53.

1. Cohen‐Mansfield J, Billig N. Agitated behaviors in the elderly: I. A conceptual review. J Am Geriatr Soc. 1986;34(10):711-21.

2. Herrmann N. Recommendations for the management of behavioral and psychological symptoms of dementia. Can J Neurol Sci. 2001;28(S1):S96-S107.

3. Arana GW. An overview of side effects caused by typical antipsychotics. J Clin Psychiatry. 2000;61 Suppl 8:5-11; discussion 12-13.

4. Schneider LS, Pollock VE, Lyness SA. A metaanalysis of controlled trials of neuroleptic treatment in dementia. J Am Geriatr Soc. 1990;38(5):553-63.

5. Jeste DV, Blazer D, Casey D, Meeks T, Salzman C, Schneider L, et al. ACNP White Paper: update on use of antipsychotic drugs in elderly persons with dementia. Neuropsychopharmacology 2008;33(5):957-70.

6. Lee PE, Gill SS, Freedman M, Bronskill SE, Hillmer MP, Rochon PA. Atypical antipsychotic drugs in the treatment of behavioural and psychological symptoms of dementia: systematic review. BMJ 2004;329(7457):75.

7. Foebel, AD, Liperoti, R, Onder, G, Finne-Soveri H, Henrard JC, Lukas A, et al. Use of antipsychotic drugs among residents with dementia in European long-term care facilities: results from the SHELTER study. J Am Med Dir Assoc. 2014;15(12):911-7.

8. Ahn SH, Jung SY, Kim YJ, Seong JM, Choi NK, Shin JY, et al. Patterns of prescription of atypical antipsychotics in elderly ambulatory patients with dementia in Korea. J Pharmacoepidemiol Risk Manag 2009;2:97104.

9. Maguire A, Hughes C, Cardwell C, O’Reilly D. Psychotropic medications and the transition into care: a national data linkage study. J Am Geriatr Soc. 2013;61(2):215-21.

10. Margallo‐Lana M, Swann A, O’Brien J, Fairbairn A, Reichelt K, Potkins D, et al. Prevalence and pharmacological management of behavioural and psychological symptoms amongst dementia sufferers living in care environments. Int J Geriatr Psychiatry. 2001;16(1):39-44.

11. Won, CW. Elderly long-term care in Korea. Journal of Clinical Gerontology and Geriatrics 2013;4(1):4-6.

12. Lee J, Lee JS, Park SH, Shin SA, Kim K. Cohort profile: The national health insurance service–national sample cohort (NHIS-NSC), South Korea. Int J Epidemiol. 2017;46(2):e15.

13. Kim H, Kwon S, Yoon NH, Hyun KR. Utilization of long-term care services under the public long-term care insurance program in Korea: implications of a subsidy policy. Health Policy 2013;111(2):166-74.

14. Edge L. Antipsychotic drugs for dementia: a balancing act. 2009.

15. Chen Y, Briesacher BA, Field TS, Tjia J, Lau DT, Gurwitz JH. Unexplained variation across US nursing homes in antipsychotic prescribing rates. Arch Intern Med. 2010;170(1):89-95.

16. Kleijer BC, van Marum RJ, Frijters DH, Jansen PA, Ribbe MW, Egberts AC, et al. Variability between nursing homes in prevalence of antipsychotic use in patients with dementia. Int Psychogeriatr. 2014;26(03):363-71.

17. Foebel A, Ballokova A, Wellens NI, Fialova D, Milisen K, Liperoti R, et al. A retrospective, longitudinal study of factors associated with new antipsychotic medication use among recently admitted long-term care residents. BMC Geriatr. 2015;15(1):128.

18. Volicer, L. Antipsychotics do not have to be used “off label” in dementia. Elsevier; 2012.

19. Rochon PA, Stukel TA, Bronskill SE, Gomes T, Sykora K, Wodchis WP, et al. Variation in nursing home antipsychotic prescribing rates. Arch Intern Med. 2007;167(7):676-83.

20. Kamble P, Chen H, Sherer JT, Aparasu RR. Use of antipsychotics among elderly nursing home residents with dementia in the US. Drugs Aging. 2009;26(6):483-92.

21. Pekkarinen L, Elovainio M, Sinervo T, Finne-Soveri H, Noro A. Nursing working conditions in relation to restraint practices in long-term care units. Med Care. 2006;44(12):1114-20.

22. Ministry of Health and Welfare. The Epidemiological Survey of Mental. Disorders in Korea; 2012. http://www.index.go.kr/potal/main/EachDtlPageDetail.do?idx_cd=1441. Accessed August 5 2017.

23. Depp CA, Jeste DV. Bipolar disorder in older adults: a critical review. Bipolar Disord. 2004;6(5):343-67.

24. Jeste DV, Alexopoulos GS, Bartels SJ, Cummings JL, Gallo JJ, Gottlieb GL, et al. Consensus statement on the upcoming crisis in geriatric mental health: research agenda for the next 2 decades. Arch Gen Psychiatry. 1999;56(9):848-53.