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 RESEARCH ARTICLE

A survey study of the satisfaction and attitude of the Korean psychiatrists toward antipsychotic polypharmacy

Jisoon Chang, MD

Department of Psychiatry, Inje University Sanggye Paik Hospital, Seoul, South Korea

Bongseog Kim, MD, PhD

Department of Psychiatry, Inje University Sanggye Paik Hospital, Seoul, South Korea

BACKGROUND: Antipsychotic polypharmacy (AP) to treat patients with schizophrenia and schizoaffective disorder is commonly prescribed in clinical practice; however, evidence supporting its use is scarce. This study surveyed South Korean psychiatrists’ rationale for AP.

METHODS: Psychiatrists were interviewed using a newly developed, semi-structured questionnaire inquiring about AP attitudes and behaviors, including frequency of use, rationale, concerns, and preferred combinations.

RESULTS: Compared with the high-prescribing AP group (≥10 patients a day; HAP group), the low-prescribing AP group (≤9 patients a day; LAP group) tended to work in a university general hospital, publish more research papers a year, attend more psychiatric conferences, prescribe more 2-antipsychotic combinations, and have more satisfaction with AP. Psychiatrists were satisfied with the therapeutic response with AP (rating 6.4±1.5). Psychiatrists felt concern about AP (rating 4.7±1.6), mostly because of its higher risk of chronic adverse effects.

CONCLUSIONS: In South Korean psychiatric practices, the LAP group seems to pay closer attention to AP than the HAP group does. However, both the HAP and LAP groups share similar attitudes toward satisfaction, concerns, and preferred combinations of AP.

KEYWORDS: antipsychotics, polypharmacy, combinations, schizophrenia

ANNALS OF CLINICAL PSYCHIATRY 2014;26(1):64-69

  INTRODUCTION

Antipsychotic polypharmacy (AP) refers to the co-prescription of >1 antipsychotic to control psychotic symptoms. Most recent practice guidelines for schizophrenia recommend antipsychotic monotherapy as a first-line treatment.1,2 However, several studies state that AP accounts for 7% to 50% of schizophrenia treatment.3-5 Research from many countries in East Asia, including Korea, shows that AP comprises 70% of all prescriptions of antipsychotics,6 and its use is growing.7,8

According to a meta-analysis of 19 studies comprising 1,229 patients, AP yielded more significant benefits than monotherapy in all aspects of treatment effect and discontinuance.9 Evidence that AP is related to an increased mortality rate calls for debate, and some reports whose results do not confirm these findings.10,11

Therefore, considering cost-effectiveness and the lack of evidence on the efficacy and safety of AP, a thorough investigation regarding its use should be done.12,13 Earlier studies demonstrated polypharmacy increased the risk for drug-drug interaction leading to increased drug concentration and side effects.14 These side effects include extrapyramidal symptoms, metabolic syndrome, cognitive dysfunction, and cardiovascular disease.

Nevertheless, it is thought that AP could ameliorate residual positive symptoms and violence,15 minimize side effects,16 and facilitate switching among antipsychotics.17 One study suggested that polypharmacy was associated with variables related to the prescribing psychiatrist, such as his (her) doubt about pharmacotherapy guidelines and participation in seminars hosted by pharmaceutical companies.18 A consensus on AP use is lacking and controversial among psychiatrists. In particular, there are few studies on Korean psychiatrists’ attitudes towards AP.

This study aimed to investigate the effectiveness, preference, and concerns about AP by asking psychiatrists to fill out questionnaires about their practice to find the gap between clinical practice and guidelines for treating schizophrenia and schizoaffective disorder with antipsychotics. We also aimed to elucidate the preferred combination of antipsychotics, the reason for its use, psychiatrists’ satisfaction with AP, observed side effects of AP, and psychiatrists’ second-line treatment plans.

  METHODS

Subjects

Psychiatrists affiliated with a psychiatric unit of university general hospitals and psychiatric hospitals in Korea were recruited. All participants had sufficient clinical experience in treating patients who met DSM-IV-TR criteria for schizophrenia and schizoaffective disorder. Participants heard the explanation about the purposes of this study and agreed to participate. Participants were interviewed between September 2012 and January 2013 by a letter or direct contact. The total number of participants was 83. The study was approved by the institutional review board of the Sanggye Paik Hospital.

Procedures

We explained the purposes of this study to the participants and distributed the questionnaire. Participants were asked to fill out the questionnaire without a time limit. Participants were interviewed using a newly developed, semi-structured questionnaire known as the Korean Psychiatrists’ Perception about AP Questionnaire. This semi-structured questionnaire covers: 1) demographic characteristics of participants (age, sex, years of practice, place of work, number of psychiatric conferences attended, number of published research papers, and the age-specific patient groups); 2) estimated number of patients on AP, reasons for their prescription, and the amount of time they considered AP before prescribing; 3) preferred antipsychotic combinations, reasons for their preference, and treatment satisfaction level (Likert scale of 0=none to 10=extreme); 4) psychiatrists’ level of concern about AP (Likert scale of 0=none to 10=extreme), the reason for concern, and the most common side effects of AP; and 5) the treatment plan after possible AP treatment failure.

Statistical analysis

In addition to descriptive statistics analyses of variance, we divided study participants into high prescribing AP group (≥10 patients per day; HAP group) vs low prescribing AP group (≤9 patients per day; LAP group) according to the median split number of patients receiving AP per day. Chi-square tests and independent t tests were used to compare variables regarding clinicians’ characteristics and their perceptions of AP between the HAP and LAP groups. We used Fisher exact test if the tests did not satisfy the smallest expected frequencies. Statistical significance was set at a two-tailed P < .05, using SAS enterprise guide 4.1 (SAS Institute Inc., Cary, North Carolina, USA).

  RESULTS

Demographic characteristics

Of the 83 participants, 51.8% (n=43) were professors in psychiatric clinics of university general hospitals, 47.0% (n=39) were in their 40s, and 73.5% (n=61) were male. The average number of years of clinical practice as a psychiatrist was 13.9±8.5 and the mean number of attended academic conferences or seminars was 4.5±2.7 per year. The average number of published research papers was 2.4±2.8 per year. Additionally, 83.1% (n=69) of participants treated adult patients and 10.8% (n=9) of participants treated children (TABLE 1).


TABLE 1

Participants’ demographics and antipsychotic treatment characteristics

Characteristics Total (N=83) HAP (n=48) LAP (n=35) F/χ2 P
University hospital (%) 43 (51.8) 13 (27.1) 30 (85.7) 27.868 .000
Age 40 to 49 (%) 39 (47.0) 21 (43.8) 18 (51.4) 2.51 .471
Male (%) 61 (73.5) 40 (83.3) 21 (60.0) 5.657 .024
Years of practice (M±SD) 13.9±8.5 14.4±8.3 13.3±8.8 0.004 .574
Number of attended psychiatric conferences/year (M±SD) 4.5±2.7 4.0±2.5 5.3±2.8 1.039 .032
Number of published research papers/year (M±SD) 2.4±2.8 1.7±2.5 3.3±2.8 0.403 .010
Adult patients (%) 69 (83.1) 46 (95.8) 23 (65.7) 12.815 .001
Treatment setting, inpatient (%) 60 (72.3) 40 (83.3) 20 (57.1) 6.885 .017
HAP: high prescribing antipsychotic polypharmacy; LAP: low prescribing antipsychotic polypharmacy; M: mean; SD: standard deviation.
Differences in frequency of prescribing AP

When comparing the 2 groups according to frequency of AP prescriptions, the LAP group tended to work in university hospitals (P < .001) and attend more psychiatric conferences (P=.032). Clinicians in the LAP group also showed a tendency to prescribe AP more frequently to inpatients than to outpatients (P=.017) (TABLE 1). The combination of 2 second-generation antipsychotics (SGAs) was most preferred (P=.001) of the antipsychotic combinations (TABLE 2).


TABLE 2

Prescribing patterns and reasons for preferring antipsychotic polypharmacy

  Total (n=83) HAP (n=48) LAP (n=35) F/χ2 P
Number of patients with AP/d (M±SD) 14.1±13.1 21.5±12.5 3.6±2.1 40.392 .000
Time for consideration of AP (M±SD)          
  6 months ≤ time < 12 months (%) 38 (45.8) 22 (45.8) 16 (45.7) 0 1.000
Preferred antipsychotic combinations (%)          
  SGA + SGA (%) 48 (57.8) 20 (41.7) 28 (80.0) 12.44 .001
Prescriber satisfaction (rating 0 to 10) (M±SD) 6.4±1.5 6.1±1.4 6.9±1.6 1.242 .019
Preference reasons       9.033 .135
  Controlling the target symptoms (%) 33 (39.8) 18 (37.5) 15 (42.9)    
  Augmentation after failed clozapine (%) 27 (32.5) 18 (37.5) 9 (25.7)    
  Speed up effect than antipsychotic monotherapy (%) 8 (9.6) 7 (14.6) 1 (2.9)    
AP: antipsychotic polypharmacy; HAP: high prescribing antipsychotic polypharmacy; LAP: low prescribing antipsychotic polypharmacy; M: mean; SD: standard deviation; SGA: second-generation antipsychotic.
Prescription of AP

Participants administered AP to 14.1±13.1 patients with schizophrenia and schizoaffective disorder per day. Specifically, 57.8% (n=48) of the participants prescribed 2 SGAs (TABLE 2). Among antipsychotics, the most preferred medication was risperidone (26.5%, n=36) followed by quetiapine (17.6%, n=24), and aripiprazole (14.7%, n=20). Risperidone + chlorpromazine showed the highest frequency of prescription (15.7%, n=13), followed by risperidone + quetiapine (14.5%, n=12), and risperidone + haloperidol (14.5%, n=12).

Consideration of AP

The most common amount of time clinicians reported considering AP was 6 months to 12 months after each treatment was initiated (n=38, 45.8%). There was no significant difference between the HAP and LAP groups regarding the reason for trying AP (TABLE 2). When asked about their preference of certain combinations of antipsychotics, most of the participants expected to maximize the therapeutic effects of antipsychotics on positive and negative symptoms, considered the receptor profile of antipsychotics, and hoped to control target symptoms such as violence, anxiety, and agitation (n=33, 39.8%). Regarding the estimated level of perceived concern when prescribing AP, by numerical Likert scale from 0 (none) to 10 (extreme), psychiatrists rated values of 4.74±1.61, and there was no significant difference between groups regarding the reason for concern (TABLE 3). Respondents were asked to select the 3 most common adverse effects of prescribing AP, and answered weight gain, sedation, and extrapyramidal symptoms concurrently (n=16, 20.5%). Sedation (n=28, 34.1%) accounted for the highest number of adverse effects of AP among all the participants. The HAP group answered that sedation was the most common adverse effect of AP, while the LAP group selected weight gain (TABLE 3). Regarding the treatment plan after possible AP failure, the most common answer of all the participants in both groups was increasing the drug to the highest dose.


TABLE 3

Expected effects and prescribers’ concerns about AP

  Total (n=83) HAP (n=48) LAP (n=35) F/χ2 P
Expected effect       11.936 .011
  Controlling the target symptoms (%) 40 (48.2) 23 (47.9) 17 (48.6)    
  Speed up effect than antipsychotic monotherapy (%) 30 (36.6) 22 (45.8) 8 (22.9)    
  Reduce dose of 1st AP for reducing side effects (%) 8 (9.6) 2 (4.2) 6 (17.6)    
Prescriber’s level of concern about AP (M±SD) 4.74±1.61 4.50±1.82 5.07±1.22 11.18 .111
The reason for concern       7.242 .250
  Increased possibility of chronic side effects (%) 41 (49.4) 24 (50.0) 17 (48.6)    
  Lack of evidence base (%) 19 (22.9) 12 (25.0) 7 (20.0)    
  Higher total dosage of antipsychotics (%) 9 (10.8) 3 (6.3) 6 (17.1)    
Clinical scenario       9.338 .158
  Sedation (%) 28 (34.1) 21 (43.8) 7 (20.6)    
  Weight gain (%) 26 (31.7) 11 (22.9) 15 (44.1)    
  Extrapyramidal adverse effects (%) 14 (17.1) 9 (18.8) 5 (14.7)    
AP: antipsychotic polypharmacy; HAP: high prescribing antipsychotic polypharmacy; LAP: low prescribing antipsychotic polypharmacy; M: mean; SD: standard deviation.

  DISCUSSION

Although there was not enough evidence on the effects of AP for treating schizophrenia and schizoaffective disorder, AP is the most commonly used pharmacotherapy in Korean clinical situations. On a daily basis, clinicians prescribed AP to 14.1±13.1 patients diagnosed with schizophrenia and schizoaffective disorder. Considering the daily numbers of patients with schizophrenia and schizoaffective disorder (10 < n ≤ 20), we presumed that AP is used frequently. Therefore, there might be a gap between known treatment guidelines and a clinician’s tendency to prescribe AP, as has been reported previously in the literature.19,20

Korean guidelines for treating schizophrenia released in 200621 recommended using SGA monotherapy for the initial treatment of schizophrenia. AP was on the 5th level of algorithm and was recommended for patients with treatment-resistant schizophrenia. However, the guidelines indicated that in specific clinical situations, psychiatrists could immediately initiate combination antipsychotic therapy, regardless of its level in the algorithm.

The American Psychiatric Association’s (APA) 2004 practice guideline for treating schizophrenia19 described evidence regarding the use of antipsychotic combinations with clozapine. In addition, it pointed out the lack of evidence about other antipsychotic combinations, but acknowledged that psychiatrists frequently prescribed a combination of ≥2 antipsychotics in clinical practice, especially when managing patients with treatment-resistant schizophrenia. Furthermore, the APA practice guidelines recommended that practitioners be aware of problems related to combination therapy, including higher risk of side effects and drug-drug interactions, increased costs, and decreased adherence.22

The World Federation of Societies of Biological Psychiatry (WFSBP) Guideline for Biological Treatment of Schizophrenia 201223,24 provided evidence supporting the effectiveness of AP with more diverse combinations than previous practice guidelines. The most recent WFSBP guideline includes strong evidence on AP from numerous studies. One study shows that almost one-half of patients receiving long-acting injectable antipsychotics are concomitantly treated with oral antipsychotics.25 This form of combination treatment needs to be investigated in future prospective studies to identify the benefits and risks of this strategy. The WFSBP guideline suggested that combining clozapine with other SGAs (possibly risperidone) might have some advantages compared with monotherapy. Additionally, it has been suggested that there are several lines of evidences supporting switching from AP to antipsychotic monotherapy and that this switch may be associated with significant weight loss.26

In this study, we observed that Korean psychiatrists preferred the choice of 2 SGAs in antipsychotic combinations. The most frequently type of AP used in clinical practice was risperidone + chlorpromazine and risperidone + haloperidol. This might be because psychiatrists in Korea preferred treating schizophrenia patients with SGAs. Additionally, we presumed that clinicians have a tendency to choose a combination of typical antipsychotics and SGAs rather than a combination of 2 SGAs, considering the economic issue based on the medical insurance system in Korea. Nevertheless, typical antipsychotics have an increased burden of extrapyramidal side effects and tardive dyskinesia than SGAs, and have an similar effect on the positive and negative symptoms of schizophrenia.27 Therefore, there are more requirements for maximizing the treatment effect of these antipsychotic combinations, and for minimizing side effects of antipsychotics when treating schizophrenia.

Inconsistent with a previous report,28 our results show that psychiatrists in the LAP group (≤9 patients per day) usually were working as professors in university general hospitals, publishing more research papers, and prescribing AP more frequently to inpatients than the psychiatrists in the HAP group (≥10 patients per day). However, in comparing the HAP and LAP groups, there was no difference in the reasons for considering AP. In clinical practice, it seems that Korean psychiatrists decide whether to prescribe AP based on clinical experience, and consider the purpose of treatment and the target receptor profiles of antipsychotics. The participants in this study considered AP-related side effects such as sedation, weight gain, and extrapyramidal symptoms. Psychiatrists prescribing AP with high frequency indicated that they would increase the dosage of antipsychotics if AP failed. We think this suggests that these psychiatrists have high expectations regarding AP efficacy.

This study has several limitations. First, the findings cannot be generalized to all psychiatrists in South Korea or other Asian countries. This mainly is because our study only included psychiatrists affiliated as professors in university general hospitals or as staff in the psychiatric hospitals and excluded private practitioners in psychiatric clinics. We also did not take into account the regional characteristics of the hospitals. However, considering that professors, staff in psychiatric hospitals, and private practitioners commonly treat both outpatients and inpatients with schizophrenia under the same medical insurance system in Korea, we assume that our participants’ practice might represent the actual clinical situation of psychiatry in Korea. Second, there might be an inconsistency between decisions based on theory and those based on clinical experience with AP, because this study relied on each psychiatrist’s recall about prescribing AP and did not investigate real case reports. Therefore, further research is required to elucidate the correlation between participants’ subjectively perceived tendencies and actual practice patterns with AP through investigating clinical data. Third, although long-acting injectable antipsychotics have been developed, this study did not reflect recent clinical applications of these drugs. Future studies are needed to address this issue.

There are several reports that AP has been prescribed frequently despite the lack of strong evidence of its efficacy in treating schizophrenia and schizoaffective disorder.20 Korean psychiatrists also prescribe AP based on their clinical experiences and the receptor profile of the medication. However, AP is not officially accepted as a standard treatment for schizophrenia in the Korean medical insurance system. Therefore, this study is significant because it is one of the first studies to show psychiatrists’ perceptions of AP and the frequency with which AP is prescribed.

The accumulation of supportive evidences from future systematic and well-designed studies on AP will bring expert groups to a consensus regarding use of AP and eventually may bridge the gap between clinical situations and clinical guidelines of AP. Furthermore, we expect to improve the quality of life of patients with schizophrenia and schizoaffective disorder through the comprehensive understanding of pharmacotherapy based on objective and reasonable evidence.

DISCLOSURE: The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

ACKNOWLEDGEMENTS: Dr. Kim designed the study and wrote the protocol. Drs. Chang and Kim collected the data. Dr. Kim conducted the statistical analyses and the interpretation of data. Both of the authors contributed to and revised the final manuscript. Both of the authors have no conflict of interest. We thank to all the participants who contributed to this study. This study was supported by the 2012 Inje University research grant (#20120728).

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CORRESPONDENCE: Bongseog Kim, MD, PhD Department of Psychiatry Inje University Sanggye Paik Hospital Dongil-ro 1342, Nowon-gu Seoul, South Korea E-MAIL: psy.jschang@gmail.com, kimbs328@paik.ac.kr