Psychiatric Annals

Original Research 

Effects of Age and Anxiety on Short-Term Rehospitalization Rates in Japanese Patients with Schizophrenia

Narimasa Katsuta, MD, PhD; Tohru Ohnuma, MD, PhD; Masanobu Ito, MD, PhD; Shohei Nishimon, MD, PhD; Mayu Takeda, MD, PhD; Takahiro Sannohe, MD, PhD; Eriko Tani, MD; Yasue Miki, MD; Toru Nakamura, MD, PhD; Hiroki Yamashita, MD; Mariko Nakadaira, MD; Heii Arai, MD, PhD

Abstract

This retrospective observational study investigated the relationship between rehospitalization rates and use of antipsychotic agents. The medical records of 92 Japanese patients with acute stage schizophrenia who were admitted to Juntendo Koshigaya Hospital or Juntendo University Hospital between April 2012 and March 2014 were reviewed retrospectively. Univariate analysis indicated no significant differences in the types of antipsychotics administered to patients who were, versus those who were not, rehospitalized; however, the former group were significantly older (47.8 ± 12.4 years vs 40.2 ± 12.9 years, respectively, P = .014) and had longer durations of illness. The total score of the Brief Psychiatric Rating Scale was increased significantly in those who were rehospitalized. However, only the score for the item “anxiety” was significantly greater at the time of rehospitalization compared with that recorded at last discharge (4.00 ± 1.45 vs 2.00 ± 0.72, respectively, P < .001). Age and anxiety may be associated with rehospitalization. [Psychiatr Ann. 2020;50(7):310–316.]

Abstract

This retrospective observational study investigated the relationship between rehospitalization rates and use of antipsychotic agents. The medical records of 92 Japanese patients with acute stage schizophrenia who were admitted to Juntendo Koshigaya Hospital or Juntendo University Hospital between April 2012 and March 2014 were reviewed retrospectively. Univariate analysis indicated no significant differences in the types of antipsychotics administered to patients who were, versus those who were not, rehospitalized; however, the former group were significantly older (47.8 ± 12.4 years vs 40.2 ± 12.9 years, respectively, P = .014) and had longer durations of illness. The total score of the Brief Psychiatric Rating Scale was increased significantly in those who were rehospitalized. However, only the score for the item “anxiety” was significantly greater at the time of rehospitalization compared with that recorded at last discharge (4.00 ± 1.45 vs 2.00 ± 0.72, respectively, P < .001). Age and anxiety may be associated with rehospitalization. [Psychiatr Ann. 2020;50(7):310–316.]

Short-term rehospitalization, termed the “revolving door” phenomenon, is a common event in patients with schizophrenia.1 Thus, preventing relapses of schizophrenic episodes is important to improve prognoses, avert deterioration in social, occupational, and financial status, and avoid the increased burden of familial care.2 Although the use of monotherapy with second-generation antipsychotics (SGAs) has recently become widely accepted in Japan,3 the prescription of first-generation antipsychotics (FGAs) and/or polypharmacy for patients with schizophrenia remains common.4 SGAs are considered superior to FGAs in reducing negative symptoms and are associated with fewer extrapyramidal symptoms; however, SGAs can cause metabolic-related side effects such as weight gain.5 According to the Japanese Guidelines for Pharmacological Therapy of Schizophrenia,3 SGAs are recommended for treating first-episode of schizophrenia and for continuing antipsychotic treatment to maintain quality of life.3 In addition, the guidelines state that SGAs are superior to FGAs for preventing relapse in patients with schizophrenia.3

In other countries, the type of antipsychotic agent and various factors, including sex,6 age,7 age at onset of disease,8 and history of previous hospitalization,9,10 have been correlated with an increased risk of rehospitalization. However, it remains unclear whether the use of SGAs is associated with lower rehospitalization rates in patients with schizophrenia.8,11–20 In Japan, 30% of patients with schizophrenia are rehospitalized within 1 year after usual clinical treatment, but few studies have identified factors associated with the rehospitalization of Japanese patients with schizophrenia.4 Therefore, this retrospective observational study investigated the correlation between rehospitalization of patients with schizophrenia in Japanese and the types of antipsychotics (ie, SGA or FGA) administered in consideration of various other clinical factors.

Methods

Approval

The study protocol was approved by the Ethics Committee of the Juntendo University Faculty of Medicine (approval no. 2015014). Each patient provided written informed consent after receiving a complete description of the study. The use of drug therapy was not controlled due to ethical considerations.

Patients

The study cohort was limited to Japanese patients with schizophrenia according to the criteria in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV).21 The diagnosis of schizophrenia was based on clinical interviews conducted by at least three experienced psychiatrists. The patients were admitted to Juntendo Koshigaya Hospital (Saitama, Japan) or Juntendo University Hospital (Tokyo, Japan) due to worsening of symptoms over a 2-year period between April 2012 and March 2014. Patients with other schizophrenia spectrum disorders (ie, schizophreniform disorder, schizoaffective disorder, psychosis not otherwise specified, and schizoid personality disorder) were excluded from the analysis. In addition, 1-year follow-up examinations of the admitted patients were conducted from the time of the last discharge until December 31, 2015.

Evaluation of Symptoms at Discharge

Clinical symptoms were evaluated using the Brief Psychiatric Rating Scale (BPRS); each item was rated on a scale from 1 to 7.22 In addition, the degree of psychosis was evaluated using the Scale to Assess Unawareness of Mental Disorder (SUMD); each item was rated on a scale from 0 to 5.23 The SUMD provides separate assessments of mental disorders, social consequences, need for treatment, perception of each present symptom, and attribution of symptoms to the disorder. A top priority of the Juntendo University Schizophrenia Project is to improve patient symptoms in the most effective manner.24 The antipsychotic equivalent dose (milligrams) was converted to equivalent doses of chlorpromazine, as is routinely done in Japan.25

Statistical Analysis

The chi-squared test was used to assess differences in the distribution of frequencies of patient characteristics (eg, sex). Differences in clinical variables were identified using the two-tailed Mann-Whitney U test for comparisons of two groups or the Kruskal-Wallis test for comparisons of three or more groups. The correlations between each clinical feature, such as duration of hospitalization and age, were analyzed using the Pearson's correlation coefficient or Spearman's rank correlation coefficient. Conditional logistic regression analyses were performed to calculate relative risk estimates as odds ratios with 95% confidence intervals (CI). All statistical analyses were conducted using SPSS version 22.0 software (IBM Corp., Armonk, NY). A P value of < 0 denoted statistical significance.

Results

Clinical Variables in Patients with Schizophrenia

The 92 Japanese patients with schizophrenia (51 women and 41 men) were divided into two groups based on the incidence of rehospitalization within 1 year, and clinical variables were compared (Table 1). Univariate analysis showed that there were no significant differences in the types of antipsychotics administered to patients who were or were not rehospitalized during the observation period. However, patients who were hospitalized were significantly older (47.8 ± 12.4 years vs 40.2 ± 12.9 years, respectively; P = 0.014) and had longer durations of illness (21.7 ± 11.2 years vs 15.3 ± 10.8 years, respectively; P = 0.022). There were no significant differences in other clinical variables (eg, living alone) between the groups. After classifying patients into three groups based on the types of antipsychotics prescribed (ie, FGA, SGA, and a combination of the two), we found no significant differences noted in the frequencies of the different agents between the two groups (Table 1).

Clinical Variables of Patients with Schizophrenia Classified Based on Rehospitalization at Dischargea

Table 1.

Clinical Variables of Patients with Schizophrenia Classified Based on Rehospitalization at Discharge

Clinical Factors Related to Rehospitalization Within 1 Year

Logistic regression analysis was performed with multiple categories as outcome variables (ie, daily antipsychotic dose) to identify correlations among the various clinical factors. Prior to performing logistic regression analysis, the correlations among clinical variables of 24 rehospitalized patients were analyzed through single correlation analysis. The durations of illness and untreated symptoms were correlated with other items and thus excluded from the logistic regression analysis. The results showed that, unlike the type of administered antipsychotic, age was significantly correlated with rehospitalization within 1 year (odds ratio of 1.042; 95% CI: 1.00–1.09) (Table 2).

Factors Related to Rehospitalization Within 1 Year

Table 2.

Factors Related to Rehospitalization Within 1 Year

Most Changed Symptoms in Rehospitalized Patients

There were no significant differences between the groups' total BPRS scores at the time of last discharge. Therefore, changes in each BPRS item in the re-hospitalization group were investigated to determine the cause of rehospitalization (Table 3). The total BPRS score was increased significantly, but only the score of the item “anxiety” was significantly greater at the time of rehospitalization compared with that recorded at the time of last discharge (4.00 ± 1.45 vs. 2.00 ± 0.72, respectively, P < 0.001). The item “anxiety” was evaluated according to the perceived degree of anxiety through each patient's linguistic expression.

Changes in BRPS Scores in Rehospitalized Patients with Schizophrenia from the Last Discharge to Rehospitalization

Table 3.

Changes in BRPS Scores in Rehospitalized Patients with Schizophrenia from the Last Discharge to Rehospitalization

Discussion

The results of the present study did not reveal significant differences in short-term prognoses among the FGA, SGA, and combination treatment groups up to December 31, 2015. These findings suggest that SGAs are not superior to FGAs with regard to the rehospitalization rate within a short follow-up period of 1 year. The previous studies' results are contradictory, as some studies reported lower rehospitalization rates of patient with schizophrenia treated with SGAs.11–13 Patel et al.15 reported lower rehospitalization rates among patients treated with FGAs, whereas others reported no differences between patients receiving SGAs or FGAs.8,16–20 Moreover, a meta-analysis conducted by De Hert et al.26 found no significant effects of the type of medication on the relapse of schizophrenia. The present study showed that patient age was significantly correlated with rehospitalization of Japanese patients with schizophrenia within 1 year. Previous studies suggested that the use of SGAs may be associated with lower rehospitalization rates of patients with schizophrenia.11–13 In the 1990s, there was a tendency to treat older adult patients with schizophrenia using FGAs, as opposed to SGAs. However, all studies investigating the rehospitalization of patients treated with SGAs were published prior to 2001, whereas those published after 2002 failed to confirm this relationship (Table 4). Thus, early studies reporting SGAs' preventive effects on rehospitalization may only reflect the frequent prescription of FGAs in older adult patients. In this study, logistic regression analysis that considered the type of antipsychotic and daily dosage found that only age was a relative risk factor for the rehospitalization of Japanese patients with schizophrenia.

Observational Studies Comparing Patients with Schizophrenia Treated with Antipsychotics

Table 4.

Observational Studies Comparing Patients with Schizophrenia Treated with Antipsychotics

Previous studies suggested that the course of illness involves three phases: (1) an early phase, marked by deterioration; (2) a middle phase, characterized by a relatively stable disease course; and (3) a late phase, characterized by gradual improvement of symptoms.27 After treatment, the symptoms of schizophrenia tend to become less severe, and mental health often improves.

In 24 rehospitalized patients, the frequencies of positive symptoms (eg, hallucinations and suspiciousness) did not significantly decrease after rehospitalization. Moreover, several long-term Japanese studies28 reported that certain symptoms improved with age. In contrast, the present study's results showed that the severity of anxiety among rehospitalized patients deteriorated with age (Table 3). The lack of adequate services and community residential care facilities for treating anxiety in patients with schizophrenia remains a serious obstacle to destigmatizing mental disorders in Japan, contributing to the heavy burden and stress experienced by patients' families. Notably, more than 80% of Japanese patients with schizophrenia return to live with their families, who may not be prepared to provide the supportive services required for the patients' re-entry into the community;29 therefore, it is important to address the symptoms of anxiety appropriately.

Social anxiety due to aging may be related to the incidence of rehospitalization. Studies addressing this hypothesis reported that assertive community treatment could effectively prevent the “revolving door” phenomenon. However, the availability of community-based mental health treatment for patients after discharge, including assertive community treatment, remains insufficient in Japan.30 It is also desirable to use community resources and educational institutions to support patients with schizophrenia in reducing and preventing recurrence. Although none of the patients in the rehospitalization group lived alone (Table 1), a previous long-term rehospitalization study found that living alone may worsen the symptoms of anxiety.31

Study Limitations

This study was characterized by two limitations that should be addressed. First, the number of patients was relatively small; thus, larger prospective studies are needed to confirm these results. Second, the details of patient support and the periods between hospitalizations were not included in the medical records.

Conclusion

The present study showed that the use of SGAs had no significant effect on short-term rehospitalization within 1 year compared with FGAs. Age and the degree of anxiety may be associated with the rehospitalization of Japanese patients with schizophrenia.

References

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Clinical Variables of Patients with Schizophrenia Classified Based on Rehospitalization at Dischargea

Variable Rehospitalization
Total (N = 92) No (n = 68) Yes (n = 24) X2 P
Sex (M/F), n 41/51 30/38 11/13 0.02 .88
Age, years 42.1 ± 13.1 40.2 ± 12.9 47.8 ± 12.4 −0.12 .01b
Age at onset, years 25.2 ± 8.8 25.6 ± 9.3 24.2 ± 6.9 −0.27 .79
Duration of untreated, months 34.3 ± 61.6 32.7 ± 60.6 39.5 ± 65.8 −0.12 .90
Duration of illness, years 16.9 ± 11.2 15.3 ± 10.8 21.7 ± 11.2 −2.41 .02b
Level of education, years 12.8 ± 2.2 12.9 ± 2.3 12.5 ± 2.1 −1.00 .32
Number. of hospitalizations 2.4 ± 3.2 2.0 ± 1.7 3.6 ± 5.4 −1.92 .06
CP dose, mg/day 791.3 ± 550.3 774.0 ± 551.4 840.4 ± 555.9 −0.49 .62
BPRS, total score 39.8 ± 9.6 40.0 ± 10.0 39.4 ± 8.7 −0.13 .90
SUMD, total score 19.5 ± 7.2 19.2 ±7.4 20.2 ± 6.6 −0.76 .45
Living alone (yes/no), n 5/87 5/63 0/24 1.87 .31
Antipsychotic




  FGA group, n (%) 34 (37.0) 24 (35.3) 10 (41.7)

  SGA group, n (%) 42 (45.7) 32 (47.1) 10 (41.7) 0.32 .85
  Combination group, n (%) 16 (17.4) 12 (17.6) 4 (16.7)

Factors Related to Rehospitalization Within 1 Year

Factor Odds ratio 95% CI P value
Sex


  Male 1.000
  Female 0.818 0.29–2.34 0.709

Age, years 1.042 1.00–1.09 0.047a

Number of hospitalizations 1.168 0.89–1.53 0.257

CP dose, mg/day 1.001 1.00–1.00 0.362

BPRS, total score 0.992 0.94–1.05 0.768

Antipsychotic


  FGA 2.133 0.34–13.33 0.418
  SGA 1.577 0.32–7.85 0.578
  Combination 1.000

Changes in BRPS Scores in Rehospitalized Patients with Schizophrenia from the Last Discharge to Rehospitalization

Item At last discharge At rehospitalization Wilcoxon test Z Wilcoxon test P
Somatic concern 2.00 ± 0.72 2.50 ± 1.47 −1.24 0.22
Anxiety 2.00 ± 0.72 4.00 ± 1.45 −4.20 0.00004a
Emotional withdrawal 3.33 ± 1.13 3.25 ± 1.15 −0.49 0.62
Conceptual disorganization 2.83 ± 1.13 2.96 ± 0.81 −0.58 0.56
Guilt 1.54 ± 0.83 1.63 ± 0.92 −0.65 0.52
Tension 1.88 ± 0.74 2.25 ± 0.74 −1.94 0.05
Bizarre behavior 2.04 ± 1.00 2.38 ± 1.10 −1.17 0.24
Grandiosity 1.54 ± 0.88 1.75 ± 1.22 −0.74 0.46
Depression 1.42 ± 0.78 1.42 ± 0.83 −0.61 0.95
Hostility 1.75 ± 0.68 2.04 ± 0.86 −1.71 0.09
Suspiciousness 2.54 ± 1.21 2.67 ± 0.82 −0.51 0.61
Hallucinations 2.67 ± 1.20 3.46 ± 1.64 −1.63 0.10
Motor retardation 2.75 ± 1.42 2.71 ± 1.23 −0.14 0.89
Uncooperativeness 2.38 ± 1.01 2.42 ± 0.93 −0.32 0.75
Unusual thought content 2.79 ± 1.18 2.63 ± 0.77 −0.41 0.68
Blunted affect 3.13 ± 1.57 3.08 ± 1.02 −0.39 0.70
Excitement 1.46 ± 0.66 1.46 ± 0.72 −0.66 0.51
Disorientation 1.33 ± 0.64 1.46 ± 0.72 −0.66 0.51
Total score 39.38 ± 8.73 44.33 ± 4.94 −2.13 0.03a

Observational Studies Comparing Patients with Schizophrenia Treated with Antipsychotics

Study (year) Antipsychotics Patients, n Follow-up period, years Better rehospitalizationrates
Tran et al.11 (1998) Olanzapine vs haloperidol 807 1 SGA > FGA
Conley et al.12 (1999) Risperidone or clozapine vs FGA 124 1 SGA > FGA
Rabinowitz et al.13 (2001) Risperidone or olanzapine vs FGA 1,039 2 SGA > FGA
Patel et al.15 (2002) Risperidone or olanzapine vs FGA 305 1 SGA < FGA
Strasser et al.16 (2004) SGA vs FGA 76 1 SGA = FGA
Lin et al.8 (2006) Risperidone or clozapine vs FGA 382 2 SGA = FGA
Castro and Elkis19 (2007) Risperidone vs haloperidol 96 3 SGA = FGA
Herceg et al.14 (2008) Olanzapine, risperidone, or clozapine vs haloperidol or fluphenazine 533 2 SGA = FGA
Werneck et al.17 (2011) Olanzapine or clozapine vs FGA 242 3 SGA = FGA
Aziri et al.20 (2012) SGA vs FGA 1,400 1 SGA = FGA
Huang et al.18 (2013) Risperidone vs FGA 10,552 1 SGA = FGA
Authors

Narimasa Katsuta, MD, PhD, is an Associate Professor. Tohru Ohnuma, MD, PhD, is a Senior Associate Professor. Masanobu Ito, MD, PhD, is an Associate Professor. Shohei Nishimon, MD, PhD, is an Assistant Professor. Mayu Takeda, MD, PhD, is an Assistant Professor. Takahiro Sannohe, MD, PhD, is an Assistant Professor. Eriko Tani, MD, is a Graduate Student. Yasue Miki, MD, is a Graduate Student. Toru Nakamura, MD, PhD, is an Assistant Professor. Hiroki Yamashita, MD, is a Graduate Student. Mariko Nakadaira, MD, is a Graduate Student. Heii Arai, MD, PhD, is a Professor. All authors are affiliated with the Department of Psychiatry, Juntendo University Faculty of Medicine.

Address correspondence to Tohru Ohnuma, MD, PhD, Department of Psychiatry, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113–8421, Japan; email: otoru@juntendo.ac.jp.

Disclosure: The authors have no relevant financial relationships to disclose.

10.3928/00485713-20200603-01

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