|Year : 2021 | Volume
| Issue : 2 | Page : 70-75
Psychotropic drug prescription patterns and their predictors among older adult patients with schizophrenia in a tertiary-referral psychiatric hospital
Mu- Chun Lin1, Hsing- Kang Chen2
1 Department of Geriatric Psychiatry, Yuli Hospital, Ministry of Health and Welfare, Hualien; Department of Psychiatry, Cathay General Hospital, Taipei, Taiwan
2 Department of Geriatric Psychiatry, Yuli Hospital, Ministry of Health and Welfare, Hualien, Taiwan
|Date of Submission||15-Dec-2020|
|Date of Decision||12-Jan-2021|
|Date of Acceptance||15-Jan-2021|
|Date of Web Publication||22-Jun-2021|
M.D., M.P.H Hsing- Kang Chen
No. 448, Chung-Hwa Road, Yuli Township, Hualien County 981
Source of Support: None, Conflict of Interest: None
Objective: Medical treatments for patients with refractory schizophrenia can be roughly divided into three strategies – clozapine administration, adjuvant use of mood stabilizers, and antipsychotic polypharmacy. Few studies exist on older adult patients with schizophrenia. In this study, we intended to assess the prevalence of clozapine administration, adjuvant use of mood stabilizers, and antipsychotic polypharmacy, and to find their predictors in those patients with schizophrenia. Methods: In this cross-sectional study, we collected information of patients' sociodemographic and clinical details. Their psychotic symptoms were evaluated using a clinical interview with a positive and negative syndrome scale (PANSS). Results: We enrolled 240 study participants, with 74 patients (30.8%) receiving clozapine, 40 patients (16.7%) receiving adjuvant use of mood stabilizers, and 42 patients (17.5%) receiving antipsychotic polypharmacy. Younger age (p < 0.05), higher PANSS general symptoms subscales (p < 0.001), and higher dosage of antipsychotics (p < 0.01) were significantly related to patients with clozapine administration. As to patients with adjuvant therapy with mood stabilizers, only younger age (p < 0.01) and male gender (p < 0.05) showed significant association. Finally, patients receiving antipsychotic polypharmacy were significantly related to lower body mass index (BMI) (p < 0.05), higher PANSS positive symptoms subscale (p < 0.05), and higher dosage of antipsychotics (p < 0.001). Conclusions: Our findings showed that patients with clozapine prescription were 30.8% in prevalence which is higher than other studies in Asia. The prevalence of adjuvant mood stabilizers and antipsychotic polypharmacy were 16.7% and 17.5%, respectively. Those two findings are lower than those in other studies in Asia.
Keywords: antipsychotic polypharmacy, clozapine, mood stabilizer, Research on Asian Psychotropic Prescription Pattern
|How to cite this article:|
Lin MC, Chen HK. Psychotropic drug prescription patterns and their predictors among older adult patients with schizophrenia in a tertiary-referral psychiatric hospital. Taiwan J Psychiatry 2021;35:70-5
|How to cite this URL:|
Lin MC, Chen HK. Psychotropic drug prescription patterns and their predictors among older adult patients with schizophrenia in a tertiary-referral psychiatric hospital. Taiwan J Psychiatry [serial online] 2021 [cited 2021 Sep 22];35:70-5. Available from: http://www.e-tjp.org/text.asp?2021/35/2/70/318960
| Introduction|| |
Schizophrenia is a chronic and disabling psychiatric disorder. Even under adequate treatment, around two-thirds of the patients with schizophrenia still have persistent or fluctuating symptoms ,,,. Those symptoms impair patients' daily life function and shorten their life expectancy ,. Due to the advancement of psychiatric medical care and new medications, the life expectancy of patients with schizophrenia has been prolonged remarkably over the past decades . But as these patients get older, they become more susceptible to the adverse effects of antipsychotics and have more medical comorbidities ,. Thus, the reasonable use of antipsychotics in older adult patients with schizophrenia is a critical issue in recent years .
Many current guidelines for treating patients with schizophrenia unanimously recommend antipsychotic monotherapy. If a patient does not respond to a second kind of antipsychotic drug, he/she is called a patient with treatment-refractory schizophrenia . Clinically, medical treatment for treatment-refractory schizophrenia can be divided into three strategies – administration clozapine ,,, add-on therapy with mood stabilizers ,, and the use of antipsychotic polypharmacy ,.
In the past, many papers exist discussing the above strategies for managing treatment-refractory schizophrenia, but still, no clear conclusion exists. But, those studies have mainly focused on adult patients with schizophrenia and those on inpatient units. In this study, we intended to find the prevalences of clozapine use, adjuvant use of mood stabilizers, and antipsychotic polypharmacy in older adults with schizophrenia. In addition, we also wanted to recognize the associated predictors of the above prescription patterns.
| Methods|| |
Study design and participants
This was a cross-sectional study. Between January 1 and December 31, 2014, we recruited 240 stable older adult patients aged 50 years or older who fulfilled the DSM-IV diagnostic criteria for schizophrenia or schizoaffective disorder from our therapeutic community in Yuli Hospital, Ministry of Health and Welfare, where is located in eastern Taiwan rural area and was established in 1966. This governmental hospital aims at being a long-term care unit of homeless or chronic psychiatric patients . The majority of patients have been diagnosed with schizophrenia and the average age has been over 50 years . The patients were referred from counties all over Taiwan due to identified poor response to psychotropics, long-standing residual psychiatric symptoms, and low socioeconomic status. Currently, more than 2,000 psychiatric patients stay in the hospital, and are provided with humanistic, patient-centered, and professional care. Compared with patients in acute or chronic ward treatment settings, patients in the therapeutic community are relatively stable in psychiatric symptoms. Therefore, even though they are sheltered by Yuli Hospital, they are encouraged to get into temporary workers and contract employees either inside or outside the hospital (i.e., working in the nearby Yuli Township). This promotion has been intended to enhance patients' recovery, well-being, and purpose of life .
Participants were excluded from this study if (a) they had neurocognitive brain diseases, (b) received electroconvulsive therapy in the last three months, or (c) had intellectual disability or dementia which made them unable to write consent form.
We did clinical assessments and laboratory tests on study participants. Their psychotic symptoms were evaluated using a clinical interview with a positive and negative syndrome scale  (PANSS; range, 30 to 210; higher scores indicating more severe psychotic symptoms). At the same time, we collected patients' sociodemographic details, including age, gender, education level, duration of illness, age of onset, body mass index (BMI), medical comorbidity, mood stabilizers, first- and second-generation antipsychotics, and dosage of antipsychotics (being converted to chlorpromazine equivalents ). Besides, concomitant anticholinergic agents and benzodiazepines were also surveyed.
This study was approved by the institutional review board of Yuli Hospital, Ministry of Health and Welfare, Hualien (IRB protocol number = YLH-IRB-10210 and date of approval = January 21, 2014). All patients gave written informed consent before their participating in this research.
The demographic and clinical characteristics of samples were presented as means ± standard deviation for continuous and normally distributed data and frequencies (percentages) for categorical variables.
Forward stepwise logistic regression analysis was conducted to determine the predictors of clozapine administration, adjuvant use of mood stabilizers, and antipsychotic polypharmacy. The independent variables were age, gender, educational level, duration of illness, age of onset, BMI, medical comorbidity, dosage of antipsychotics, and PANSS general and positive and negative symptoms subscales.
Data were analyzed using the Statistical Package for the Social Science version 11.5 for Windows (SPSS Inc., Chicago, Illinois, USA). The differences between the groups were considered significant if p < 0.05.
| Results|| |
A total of 245 patients fulfilled the inclusion criteria during the study period. Three patients refused to sign a consent form, 2 patients had severe systemic diseases, and another 2 patients could not receive further evaluation. We enrolled 240 patients with a complete rate of 98.0%.
In those patients, the median age was 60.5 ± 7.2 years, and 70.4% were males [Table 1]. The average education level was 9.4 ± 3.5 years, the average age of onset was 26.1 ± 9.7 years, the average duration of illness was 34.2 ± 10.9 years, and the average BMI was 24.3 ± 4.0. A total of 186 patients (77.5%) had medical comorbidity. As to the psychotic symptoms, the average score of PANSS total was 74.3 ± 18.0, of PANSS general was 37.0 ± 9.5, of PANSS positive was 14.0 ± 4.3, and of PANSS negative was 23.2 ± 6.7.
|Table 1: Demographic and clinical characteristics in patients with schizophrenia (n = 240)|
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Regarding the prescription pattern [Table 2], 4 patients did not receive any antipsychotic, 67 patients (27.9%) received only one first-generation antipsychotic, 127 patients (52.9%) received only one second-generation antipsychotic, and 42 patients (17.5%) two kinds of antipsychotic. Totally, 74 patients (30.8%) received clozapine either as monotherapy or for combination use. The average antipsychotic dosage was 285 ± 226 mg, calculated based on chlorpromazine equivalents. In total, 40 patients (16.7%) received adjuvant mood stabilizers while 103 patients (42.9%) and 101 patients (42.1%) received concomitant anticholinergic agents or benzodiazepines, respectively.
|Table 2: The psychotropics prescription patterns in patients with schizophrenia (n=240)|
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In the regression analysis [Table 3], younger age (B = −0.051, p < 0.05), higher average subscales of general symptoms (B = 0.069, p < 0.001), and higher average dosage of antipsychotics (B = 0.002, p < 0.01) were significantly related to administration clozapine (single use or combination). As to patients with adjuvant therapy with mood stabilizers, only younger age (B = −0.092, p < 0.01) and female gender (B = −0.908, p < 0.05) showed significant association. Finally, patients with many antipsychotics were related to significantly lower BMI (B = −0.113, p < 0.05), significantly higher positive symptoms subscale (B = 0.087, p < 0.05), and significantly higher average dosage of antipsychotics (B = 0.004, p < 0.001). The three models were considered well-adjusted, according to the Hosmer–Lemeshow test (p > 0.05).
|Table 3: Multiple logistic regression analysis of patients with schizophrenia (n = 240)|
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| Discussion|| |
The results of our study [Table 2] showed that the prevalence of clozapine prescription was 30.8%, and of adjuvant use of mood stabilizers and antipsychotic polypharmacy was 16.7% and 17.5%, respectively, in older adult patients with schizophrenia. Intuitively, our treatment community setting may make the results different from other studies. The results were discussed below.
Administration of clozapine
Our study [Table 2] showed the prevalence of 30.8% of clozapine use either as monotherapy or combination usage. This finding is higher than that in some studies in the Asian area. Research based on hospitalized patients with schizophrenia aged over 50 years from the database of the Research on Asian Psychotropic Prescription Pattern project (REAP, including China, Hong Kong, Japan, Korea, Singapore, and Taiwan) has shown a clozapine prescription rate as low as 20.6% in 2001–2009  and 18.4% in 2016 . In the multiple logistic regression analysis of their study, patients taking clozapine have a longer duration of illness, more negative symptoms, and are less likely to receive first-generation antipsychotics and anticholinergic drugs, but more likely to report weight gain compared to those not receiving clozapine . In our study [Table 3], younger age (p < 0.05), higher PANSS general subscales (p < 0.001), and higher antipsychotic dosage (p < 0.01) were significantly related to more clozapine prescription. The discrepancy between the two studies may be due to different treatment settings . In our study, we included patients from our therapeutic community. But their patients have been collected from acute ward units . In our therapeutic community locating in eastern Taiwan, patients were generally chronically ill, poorly responding to antipsychotics, lack of social support, being referred from different counties or cities in Taiwan. The characteristics of chronicity, longer duration of illness, and being treatment refractory in our study population may lead to the earlier prescription of clozapine .
Adjuvant use of mood stabilizers
In our study [Table 2], the prevalence of adjuvant use of mood stabilizers was 16.7%. This finding is much lower than that other studies worldwide. For instance, in Asian countries, the from REAP project in 2012 showed 26.7% in the prevalence of adjuvant use of mood stabilizers . Also, a study surveying inpatient from nine Asian regions in 2001–2008 has reported a rate of 20.4% . In the more recent REAP survey in 2016, the prevalence of adjuvant use of mood stabilizers was dropped to 13.7% . Regarding studies from Westerner countries, the prevalence of adjunctive mood stabilizers among hospitalized schizophrenic patients is 26.2%–43.4% from a New York State Cohort (United States) report .
Our lower prevalence of adjuvant mood stabilizers may be due to the relative stability of therapeutic community patients. As to the predictors, younger age (p < 0.01) and male gender (p < 0.05) showed a significantly higher rate of adjuvant therapy with mood stabilizers. This result is in consistent with the previous REAP study  and could be explained that young, male patients often present with more aggressive and impulsive behaviors .
Our result [Table 2] revealed that the prevalence of antipsychotic polypharmacy was 17.5%. This finding is much lower than that in other studies in the Asian area. The result from REAP database has reported a prevalence of antipsychotic polypharmacy as high as 40.5% in a schizophrenic population aged 50 years or more in 2016 ,. But differences exist between countries – Singapore and Japan as high as 60%, and Taiwan the lowest, only 17.5%, which are consistent with the result of our study . Health-care systems, financial structures, medical traditions, socioeconomic, cultural backgrounds, and personal preferences of patients may contribute to these results . When comparing previous REAP studies (51.6% in 2001-2009), a decreasing trend of antipsychotic polypharmacy is reported. Growing awareness among psychiatrists in the region about inappropriate use of antipsychotic polypharmacy may contribute to this phenomenon .
Regarding the associated predictive factors, our study [Table 3] showed that antipsychotic dosage (p < 0.05) and the severity of positive symptoms (p < 0.001) were significantly related to the prevalence of antipsychotic polypharmacy. This finding is in accordance with that a previous study in East Asia in 2004 .
Furthermore, our study's result was also consistent with that studies in the United States ,. In another middle-aged global systemic review of antipsychotic polypharmacy, the pooled median prevalence of antipsychotic polypharmacy is 19.6% . In its Asian subgroup analysis, the prevalence of antipsychotic polypharmacy is 19.2%, which is also close to that in our study result .
It is worth mentioning that the subjects of our study were older adult patients with schizophrenia; however, up to 42.9% of them were using anticholinergic agents, and 42.1% were under sedatives and hypnotics (i.e., benzodiazepines) [Table 3]. Past studies showed that long-term use of those drugs in older adult patients can cause remarkable cognitive decline, falling, and delirium, which are also associated with increased morbidity and mortality ,,,,. A possible explanation for this phenomenon is that our therapeutic community residents have both relatively longer duration of illness and higher PANSS scores comparing to chronically ill patients in other studies ,. Therefore, a certain prevalence of anticholinergic agents is needed for the management of extrapyramidal symptoms (EPS), caused by psychotropics . Nevertheless, our prevalence of anticholinergic agents was lower than those other surveys from acute ward settings in the Asian area (66.3% in 2001, 52.8% in 2004, 54.6% in 2009, 45.6% in 2016 REAP surveys ,). Also, benzodiazepines are frequent adjunctive medications for aggression and irritability in schizophrenia, especially male, inpatient patients . Our study subjects had 70.4% of men, which may cause the preferred use of benzodiazepines. Still, the prevalence of benzodiazepines of our patients was lower than or close that to the general prevalence in Taiwan (69.4% in 2001–2008, 40.7% in 2016 REAP surveys ,). The older age and relatively alleviated symptoms of our patients may interpret those two comparative findings above. Despite of this, continual evaluation for dosage adjustment is crucial to minimize the adverse effect burden ,.
The readers are warned against overinterpreting the study results because our study has four limitations.
- This cross-sectional study design could not provide a causal relationship.
- The generalizability of the result in this study is limited because all participants in the study were from a long-term care unit.
- We did not include antidepressant prescription in our study because the rate of depressive symptoms was too low to ignore in our clinical experience.
- Residual confounding factors in this study could exist even though most confounding factors were adjusted in this study.
Our findings showed that the prevalence of clozapine prescription was 30.8%. This number is higher than that in other studies in Asia. The prevalence of adjuvant use of mood stabilizers and antipsychotic polypharmacy was 16.7% and 17.5%, respectively. Both the numbers are lower than those in other studies in Asia.
Up to date, no clear conclusion exists in optimal treatment strategies for managing patients with treatment-refractory schizophrenia. Our examination in this study on the associated predictors of prescription patterns may benefit further treatment selection. Nevertheless, the efficacies of adjuvant use of mood stabilizers and antipsychotic polypharmacy for patients with chronic schizophrenia have not been fully established, and they should be used with caution. Future studies are needed to explore this issue in more detail.
| Acknowledgment|| |
MC Lin and HK Chen all contributed to the design and writing of this paper.
| Financial Support and Sponsorship|| |
This work was supported by clinical research grant YLH-IRP-10309, Yuli Hospital, Ministry of Health and Welfare, Taiwan.
| Conflicts of Interest|| |
The authors disclose no conflicts of interest related to this study.
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[Table 1], [Table 2], [Table 3]