Mortality in patients with schizophrenia in Japan.

PURPOSE: Patients with schizophrenia have a higher mortality risk than the general population. However, no recent studies have investigated mortality in patients with schizophrenia in Japan. Therefore, we conducted a retrospective study to evaluate excess mortality and risk factors for mortality in patients with schizophrenia in Japan. METHODS: We included patients diagnosed with schizophrenia or schizoaffective disorder at Yamanashi Prefectural Kita Hospital between January 1, 2013, and December 31, 2017. Standardized mortality ratios (SMRs) were used to compare mortality rates between patients with schizophrenia and the general population. Logistic regression analysis was performed to estimate risk factors associated with mortality. RESULTS: Of the 1,699 patients with schizophrenia (893 men and 806 women), 104 (55 men and 49 women) died during the study period. The all-cause SMR (95% confidence interval [CI]) was 2.18 (1.76-2.60); the natural- and unnatural-cause SMRs were 2.06 (1.62-2.50) and 5.07 (2.85-7.30), respectively. Men (adjusted odds ratio [OR] = 2.24, 95% CI = 1.10-4.56), age (adjusted OR = 1.12, 95% CI = 1.09-1.16), and barbiturate use (adjusted OR = 8.17, 95% CI = 2.07-32.32) were associated with the risk of mortality. CONCLUSION: The mortality rate remains high in patients with schizophrenia in Japan. Further studies are needed to evaluate mortality trends in this population.

Appendicitis Associated With Clozapine: Analyses Based on a Spontaneous Reporting System Database in Japan.

BACKGROUND: An association between appendicitis and clozapine has recently been reported; however, few studies other than case reports have investigated this association. Therefore, we aimed to investigate the association between appendicitis and clozapine, using a large spontaneous reporting database in Japan. METHODS: Japanese Adverse Drug Event Report data were used in this study, and patients who had received clozapine or nonclozapine second-generation antipsychotics (NC-SGAs) available in Japan were included. To compare the reporting frequency of appendicitis associated with clozapine and NC-SGAs, we calculated the adjusted reporting odds ratio using logistic regression models, adjusting for age group, sex, and anticholinergic use. We conducted a time-to-event analysis to examine the time to onset of appendicitis associated with clozapine. RESULTS: In total, 8921 patients were included in this study, of whom 85 (1.0%) had appendicitis. Of these, 83 patients had received clozapine. Appendicitis was significantly more frequently reported with clozapine than with NC-SGAs. Time-to-event analysis showed that the risk of developing appendicitis associated with clozapine increased over time. CONCLUSIONS: Clozapine was associated with a higher risk of appendicitis than NC-SGAs, which increased with time. These findings suggest that clinicians need to pay greater attention to the risk of developing appendicitis during clozapine treatment.

Combination Therapy of Long-Acting Injectable Second-Generation Antipsychotics and Oral Antipsychotics: A Retrospective Chart Review and Prescribers' Attitude Survey.

BACKGROUND: Although long-acting injectable antipsychotics (LAI-APs) have been considered as a monotherapeutic option in the maintenance treatment of schizophrenia, it has been recently reported that the combination therapy of LAI-APs and oral antipsychotics (OAPs) is common. METHODS: We conducted a retrospective chart review to examine the situation of the combination therapy of LAI second-generation antipsychotics (LAI-SGAs) and OAPs, and a questionnaire survey to investigate prescribers' attitudes toward the combination therapy. We included patients who received any LAI-SGAs for 1 month or longer and classified them into monotherapy and combination therapy groups. We collected information on age, sex, primary psychiatric diagnosis, and concomitant psychotropic medications. RESULTS: Of the 132 patients, 39 (29.5%) received the combination therapy of LAI-SGAs and OAPs. Long-acting injectable risperidone was significantly associated with receiving the combination therapy compared with LAI aripiprazole. Olanzapine was the most common OAP in combination with LAI-SGAs. Only 8 patients (20.5%) concurrently received the same type of OAPs as LAI-SGAs. More than 60% of the patients received OAP polypharmacy before the initiation of LAI-SGAs. The psychiatrists in charge prescribed LAI-SGAs mainly because of a concern about adherence, and OAPs mainly because of insufficient dose of LAI-SGAs, to patients in the combination therapy group. They estimated that adherence to OAPs in two thirds of the patients in the combination therapy group was 80% or higher. CONCLUSIONS: The present study showed that the combination therapy of LAI-SGAs and OAPs is often conducted in real-world clinical practice. Considering the reason for the introduction of LAI-APs, clinicians should carefully monitor patients' adherence to OAPs concurrently used with LAI-APs.

Olanzapine Reduction From High Dose to Standard Dose: A Retrospective Chart Review.

PURPOSE/BACKGROUND: Although high-dose olanzapine might be a treatment option in patients with treatment-resistant schizophrenia, it can be reduced to the standard dose after symptoms are stabilized. We examined the rate of olanzapine reduction from high to standard dose and whether this change was successful. METHODS/PROCEDURES: We included patients who received high-dose olanzapine (>20 mg/d) for 4 weeks or longer at our hospital. First, we retrospectively followed the patients for 6 years and estimated the percentage of those whose olanzapine was reduced from high to standard dose. Second, we followed patients who received olanzapine reduction for 1 year and estimated the rate of success based on the study-defined criteria for unsuccessful reduction. We also explored factors associated with the dose reduction and successful results. FINDINGS/RESULTS: Among 110 patients who received high-dose olanzapine treatment, 72 had their olanzapine dose reduced to the standard dose for 6 years; the duration of high-dose olanzapine treatment was significantly and negatively associated with a reduction in olanzapine (hazard ratio, 0.98; 95% confidence interval, 0.98-0.99). Among the patients whose olanzapine was reduced, 50 achieved successful reduction for 1 year. Among the reasons for the reduction, an unknown reason was significantly associated with successful reduction (hazard ratio, 4.93; 95% confidence interval, 1.55-22.8). IMPLICATIONS/CONCLUSIONS: The findings suggest that high-dose olanzapine can be reduced to the standard dose after stabilization of symptoms in most patients with schizophrenia.

Long-Acting Injectables Versus Oral Antipsychotics: A Retrospective Bidirectional Mirror-Image Study.

PURPOSE: Mirror-image studies, which compare equal periods of time before and after a new treatment is introduced, may reflect the real-world impact of that treatment. However, most mirror-image studies that have investigated the impact of long-acting injectable antipsychotics (LAIs) were unidirectional in design, for patients switching from oral antipsychotics (OAPs) to LAIs. Therefore, we conducted a bidirectional mirror-image study comparing LAIs and OAPs. METHODS: We included 126 schizophrenia or schizoaffective disorder patients' LAI treatment data from 3 psychiatric hospitals. Patients took OAPs for 6 months or more before initiating LAIs, or the reverse. We obtained data on the number of hospitalizations as a primary outcome, plus the total duration and mean duration of hospitalization as secondary outcomes during the 6 months of the patients' first treatment, and the 6 months after the patients started their second type of treatment. RESULTS: The results indicated that there was no significant difference in any outcomes between LAI and OAP treatment when going from LAIs to OAPs (n = 59). However, when patients started with OAPs and switched to LAIs (n = 67), they were hospitalized a significantly fewer number of times, and the duration of their stays was shorter in the LAI phase than in the OAP phase. When combined with bidirectional data, LAI superiority was still observed. CONCLUSIONS: The findings endorse the relative effectiveness of LAIs over OAPs in the real world, although the inherent flaws of mirror-image studies such as expectation bias and having no parallel comparator should be considered.

Effect of Clozapine vs Other Second-Generation Antipsychotics on Hospitalization and Seclusion: A Retrospective Mirror-Image Study in a Japanese Public Psychiatric Hospital.

BACKGROUND: Clozapine has been regarded as the gold standard for patients with treatment-resistant schizophrenia, but a recent network meta-analysis has questioned its relative superiority over other second-generation antipsychotics (SGAs) such as olanzapine and risperidone. PURPOSE: We conducted a retrospective mirror-image study of clozapine vs other SGAs to evaluate real-world effectiveness of clozapine in terms of the duration of hospitalization and seclusion, both of which represent a critical outcome. METHODS: We included all patients who initiated clozapine at the Yamanashi Prefectural KITA Hospital and had continued to take any SGA(s) other than clozapine for at least 1 year before the initiation of clozapine. We obtained data on hospitalization and seclusion during 1 year of SGA treatment (SGA phase) and 1 year after the treatment was switched to clozapine (clozapine phase). RESULTS: The study included 35 patients (21 men, 31 with schizophrenia, 4 with schizoaffective disorder) with the average ± SD age of 37.3 ± 11.1 years. The results indicated that total hospitalization days did not differ significantly between SGA and clozapine treatment. However, total duration of seclusion was significantly shorter in the clozapine phase than in the SGA phase. Furthermore, the number of patients who were secluded at least once was significantly smaller in the clozapine phase than in the SGA phase. The results were essentially unchanged when outlier patients were excluded and only when patients taking olanzapine and/or risperidone during the SGA phase were considered. CONCLUSIONS: Although the findings from this retrospective analysis need to be further tested in prospective trials, they endorse the relative effectiveness of clozapine over other SGAs in the real world.

[What Lessons Should We Learn from the Death of Patients on Xeplion?].

From the launch of the long-acting injectable antipsychotic paliperidone palmitate (XEPLION) on November 19, 2013, 32 fatal cases had been reported up to May 18, 2014 (estimated number of users is approximately 11,000 patients) in the Early Post-marketing Phase Vigilance. The most common cause of death was sudden death (12 cases were sudden death defined by ICD-10 codes 96.0 and 96.1 and 4 cases suspected sudden death), followed by suicide (7 cases), and neuroleptic malignant syndrome (4 cases). Several deaths occurred involving patients with serious somatic disorder, such as a malignant tumor or pneumonia. The risk of all-cause mortality on XEPLION was not high in comparison with other investigations; the sudden death risk on XEPLION may be higher than on ZODIAC. According to many reports from foreign countries, mortality rates associated with schizophrenia are two to three times higher than those of the general population, corresponding to a 10-25-year reduction in life expectancy. Natural deaths account for about 60% of the excess mortality of schizophrenia patients, and such patients are more likely to die from ischemic heart disease. Since it has been suggested that more than half of sudden deaths in schizophrenic patients have a cardiac origin, sudden cardiac deaths are chiefly responsible for their reduced life expectancy. This sudden death-related problem of patients with schizophrenia has been forgotten or ignored in the psychiatric care of Japan. Taking advantage of this opportunity, we should tackle this problem seriously, and make an effort to reduce the mortality gap.

Reintroduction of clozapine after perforation of the large intestine--a case report and review of the literature.

OBJECTIVE: To report on a patient who was successfully rechallenged with clozapine after perforation of the large intestine and pulmonary embolism post operatively, and provide a literature review on clozapine rechallenge. CASE SUMMARY: A 46-year-old Japanese man with treatment-resistant schizophrenia developed constipation and slight abdominal discomfort while taking clozapine 275 mg/day. He developed appendicitis, leading to perforation of the large intestine. During the postsurgery period, a partial embolism of the pulmonary artery was revealed. The patient's constipation was relieved when clozapine was discontinued, but other antipsychotics failed to control his delusions well. After thorough discussion, it was decided to rechallenge with clozapine. The low dose of clozapine 200 mg/day was tolerable for his delusion, and his constipation was managed with laxatives and exercises until 8 months after the accident. DISCUSSION: Clozapine is a gold standard medication in treatment-resistant schizophrenia but is associated with various adverse effects, some of which are life-threatening. Reintroduction of clozapine after severe adverse drug effects when other medications are not effective almost always poses a clinical dilemma for mental health professionals. A PubMed search (to January 25, 2013) using the key words clozapine and rechallenge found 50 articles. There were only sporadic positive case reports regarding the rechallenge after clozapine-related serious gastrointestinal problems. CONCLUSIONS: From the currently available evidence, most psychiatrists appear to avoid reintroduction of clozapine. However, the evidence is too weak to draw a definitive conclusion about reintroduction of this drug. Reintroduction of clozapine after initial adverse effects in patients with treatment-resistant schizophrenia may warrant case-by-case judgment, but needs to be further investigated.

Tardive Dyskinesia and Long-Acting Injectable Antipsychotics: Analyses Based on a Spontaneous Reporting System Database in Japan.

Objective: This study compared the reporting frequency of tardive dyskinesia (TD) between long-acting injectable antipsychotics (LAI-APs) and the equivalent oral antipsychotics (O-APs), LAI first-generation antipsychotics (LAI-FGAs) and LAI second-generation antipsychotics (LAI-SGAs), and individual LAI-APs.Methods: The Japanese Adverse Drug Event Report was used in this study, and data were obtained from April 2004 to February 2021. Patients who received LAI-APs available in Japan (LAI haloperidol, LAI fluphenazine, LAI aripiprazole, LAI risperidone, and LAI paliperidone) or the equivalent O-APs were included in this study. We calculated the adjusted reporting odds ratios (aRORs) to compare the reporting frequency of TD.Results: A total of 8,425 patients were included in the study. TD was reported significantly less frequently with LAI paliperidone than with oral paliperidone (aROR [95% confidence interval (CI)] = 0.13 [0.05-0.36]). Other LAI-APs were associated with a numerically lower reporting frequency of TD than the equivalent oral SGAs. The reporting frequency of TD associated with LAI-SGAs was significantly lower than that of LAI-FGAs (aROR [95% CI] = 0.18 [0.08-0.43]). All LAI-SGAs were significantly associated with a lower reporting frequency of TD than that of LAI fluphenazine (aROR [95% CI]: LAI aripiprazole, 0.11 [0.04-0.35]; LAI risperidone, 0.09 [0.03-0.32]; LAI paliperidone, 0.02 [0.005-0.09]). and LAI haloperidol, 8.58 [1.85-39.72]). LAI fluphenazine was significantly associated with a higher reporting frequency of TD than LAI haloperidol (aROR [95% CI] = 8.58 [1.85-39.72]). The reporting frequency of TD associated with LAI paliperidone was significantly lower than that with LAI aripiprazole (aROR [95% CI] = 0.18 [0.05-0.73]).Conclusions: Compared to O-APs, LAI-APs, particularly LAI-SGAs, may be associated with a lower risk of TD.

Is antipsychotic polypharmacy associated with metabolic syndrome even after adjustment for lifestyle effects?: a cross-sectional study.

BACKGROUND: Although the validity and safety of antipsychotic polypharmacy remains unclear, it is commonplace in the treatment of schizophrenia. This study aimed to investigate the degree that antipsychotic polypharmacy contributed to metabolic syndrome in outpatients with schizophrenia, after adjustment for the effects of lifestyle. METHODS: A cross-sectional survey was carried out between April 2007 and October 2007 at Yamanashi Prefectural KITA hospital in Japan. 334 patients consented to this cross-sectional study. We measured the components consisting metabolic syndrome, and interviewed the participants about their lifestyle. We classified metabolic syndrome into four groups according to the severity of metabolic disturbance: the metabolic syndrome; the pre-metabolic syndrome; the visceral fat obesity; and the normal group. We used multinomial logistic regression models to assess the association of metabolic syndrome with antipsychotic polypharmacy, adjusting for lifestyle. RESULTS: Seventy-four (22.2%) patients were in the metabolic syndrome group, 61 (18.3%) patients were in the pre-metabolic syndrome group, and 41 (12.3%) patients were in visceral fat obesity group. Antipsychotic polypharmacy was present in 167 (50.0%) patients. In multinomial logistic regression analyses, antipsychotic polypharmacy was significantly associated with the pre-metabolic syndrome group (adjusted odds ratio [AOR], 2.348; 95% confidence interval [CI], 1.181-4.668), but not with the metabolic syndrome group (AOR, 1.269; 95%CI, 0.679-2.371). CONCLUSIONS: These results suggest that antipsychotic polypharmacy, compared with monotherapy, may be independently associated with an increased risk of having pre-metabolic syndrome, even after adjusting for patients' lifestyle characteristics. As metabolic syndrome is associated with an increased risk of cardiovascular mortality, further studies are needed to clarify the validity and safety of antipsychotic polypharmacy.

Neuroleptic malignant syndrome associated with long-acting injectable versus oral second-generation antipsychotics: Analyses based on a spontaneous reporting system database in Japan.

Long-acting injectable antipsychotics (LAI-APs) remain underutilized. One reason is the concern that LAI-APs might cause serious adverse events such as neuroleptic malignant syndrome (NMS) and lead to prolonged symptoms compared with oral treatment. Because the risk of NMS associated with LAI second-generation antipsychotics (LAI-SGAs) remains unclear, we compared reporting frequency, time to onset, and mortality of NMS between LAI- and oral SGAs using data from a Japanese spontaneous adverse event reporting database between April 2004 and September 2019. Of 5791 patients reporting adverse events due to LAI-SGAs or the equivalent oral SGAs, 768 (13%) developed NMS. LAI aripiprazole and LAI paliperidone were associated with a significantly lower reporting frequency of NMS than the equivalent oral SGAs (adjusted reporting odds ratio [95% confidence interval]: 0.35 [0.19-0.63] and 0.40 [0.27-0.59], respectively). Between 42% and 62% of the NMS associated with LAI- and oral SGAs other than LAI risperidone occurred within 30 days after initiation. The proportion of mortality due to NMS associated with oral aripiprazole was 13.1% and no deaths occurred in patients with NMS associated with LAI aripiprazole. The proportions of mortality due to NMS associated with oral risperidone/paliperidone, LAI risperidone, and LAI paliperidone were 8.8%, 4.2%, and 3.4%, respectively. Our findings showed that LAI-SGAs were not associated with a higher reporting frequency and mortality of NMS compared with oral SGAs, although clinicians need to closely monitor the occurrence of NMS not only during oral SGA treatment, but also, and in particular, in the early stage of LAI-SGA treatment.

Clinical outcomes after clozapine discontinuation in responders versus nonresponders: a retrospective chart review.

No studies have compared clinical outcomes after discontinuation of clozapine between patients who responded to clozapine and those who did not. Therefore, we examined 1-year clinical outcomes after clozapine discontinuation in responders and nonresponders. We reviewed data on patients who discontinued clozapine and retrospectively followed them for 1 year. Clinical information was collected from medical records starting at the initiation of clozapine administration, at discontinuation and at 1 year after discontinuation. In addition, clinical status was assessed using the Clinical Global Impression - Severity (CGI-S) and Clinical Global Impression - Improvement (CGI-I) scales. We classified the patients into clozapine responder and nonresponder groups according to the CGI-I score. Thirty-nine patients were enrolled in this study. Olanzapine was the most common antipsychotic prescribed after clozapine discontinuation in both the responder and nonresponder groups. The mean CGI-S score significantly increased 1 year after clozapine discontinuation in the responder group and significantly decreased in the nonresponder group; there was a significant difference in changes in the CGI-S scores between the groups. The difference remained significant after controlling for clozapine dose and duration of treatment. The findings suggest that clinicians may consider continuing and discontinuing clozapine treatment for patients who responded to clozapine and those who did not, respectively.

Risk of withdrawal of consent for treatment with long-acting injectable versus oral antipsychotics: A meta-analysis of randomized controlled trials.

BACKGROUND: Despite the clinical importance of antipsychotic long-acting injections (LAIs) in the treatment of schizophrenia, their use may be limited by patients' reluctance to accept the injections. No studies to date have investigated whether patients are more likely to withdraw their consent to treatment with LAIs than to treatment with oral antipsychotics (OAPs). Therefore, we performed a meta-analysis of randomized controlled trials (RCTs) to compare the risk of withdrawal of consent between the 2 routes of administration. METHODS: PubMed, the Cochrane Library, PsycINFO, and CINAHL were systematically searched. RCTs with open-label or rater-masked design that compared LAIs with OAPs were selected. Data on study discontinuation due to withdrawal of consent and/or loss to follow-up were extracted. RESULTS: A total of 16 studies (4815 patients) that met the study eligibility criteria were included in the meta-analysis. There was no significant difference between the LAI and OAP groups in the risk of cessation of treatment because of withdrawal of consent. Similarly, there was no significant difference in the risk of study discontinuation because of withdrawal of consent plus loss to follow-up. CONCLUSIONS: These findings were unexpected and suggest that patients may not be more hesitant to continue LAIs than OAPs after consenting to or receiving treatment. Nevertheless, patients should be provided detailed explanations about the use of LAIs and a support system that encourages them to continue treatment.

Development of diagnostic criteria and severity scale for polydipsia: A systematic literature review and well-experienced clinicians' consensus.

Despite the clinical importance of polydipsia, no diagnostic criteria or severity scales that comprehensively assess this condition are available. Thus, we aimed to develop diagnostic criteria and a severity scale for polydipsia based on a systematic review and well-experienced clinicians' consensus. We performed a systematic review, identified 27 studies related to diagnostic criteria or severity classification for polydipsia, and extracted items used to assess polydipsia in these studies. Ten well-experienced clinicians-5 psychiatrists and 5 nurses-participated in the Delphi method. They evaluated 39 items extracted based on the results of the systematic review regarding (1) their necessity in diagnosing and assessing the severity of polydipsia, and (2) their relative importance rated on 7-point scale among the items included in the severity scale. The Polydipsia Diagnostic Criteria (PDC) included 4 essential items-excessive drinking, low serum sodium level or low serum osmolality, abnormal normalized diurnal weight gain, and low urine specific gravity-based on consensus reached using the Delphi method. The Polydipsia Severity Scale (PSS) included 13 items with a maximum score of 59. The first diagnostic criteria and symptom scale for polydipsia were developed based on the findings of a systematic review and well-experienced clinicians' consensus.

Longitudinal changes in antipsychotic dose in patients treated with long-acting injectable second-generation antipsychotics.

Only a few studies have investigated changes in the dose of long-acting injectable second-generation antipsychotics (LAI-SGAs) over the long term in the maintenance treatment of schizophrenia. In this retrospective cohort study, we examined longitudinal changes in antipsychotic dose over a 3-year period in patients with schizophrenia who had been taking LAI-SGAs for at least 1 year. We compared the total daily chlorpromazine equivalent dose of antipsychotics at 12, 24 and 36 months with the baseline dose at 3 months after initiation of LAI-SGAs. We also performed multiple regression analysis to explore factors associated with change in total daily dose 12 months after treatment initiation. A total of 154 patients fulfilled the inclusion criteria. There was no significant difference in total daily antipsychotic dose between 3 months and 12, 24 or 36 months after treatment initiation. Total daily dose was increased in 43 (27.9%), 31 (34.8%) and 22 patients (36.7%) at 12, 24 and 36 months, respectively. Age and total antipsychotic dose at 3 months were significantly negatively associated with change in total daily dose. Antipsychotic dose was basically unchanged during long-term treatment in patients treated with LAI-SGAs in the maintenance phase, although there was an increase in some patients.

Relationship between polydipsia and antipsychotics: A systematic review of clinical studies and case reports.

OBJECTIVE: This systematic review aimed to elucidate the relationship between polydipsia and antipsychotics. METHODS: We systematically searched MEDLINE, Embase, and PsycINFO, and included clinical studies and case reports on polydipsia induced or improved by antipsychotics. RESULTS: We identified 61 articles: 1 double-blind randomized controlled trial (RCT), 4 single-arm trials, 1 cross-sectional study, 3 case series, and 52 case reports. The double-blind RCT demonstrated no significant difference in improvement in polydipsia between olanzapine and haloperidol. Two single-arm trials showed that polydipsia improved during clozapine treatment, whereas the other 2 showed that risperidone did not improve polydipsia. The cross-sectional study showed the prevalence of hyponatremia with first-generation antipsychotics (FGAs: 26.1%) and second-generation antipsychotics (SGAs: 4.9%). Two case series reported that clozapine improved polydipsia; the other one indicated that patients with polydipsia who were treated with FGAs had schizophrenia (70.4%) and mental retardation (25.9%). Of 90 cases in the case reports, 67 (75.3%) were diagnosed with schizophrenia. Of 83 cases in which antipsychotic treatment started before the onset of polydipsia, 75 (90.3%) received FGAs, particularly haloperidol (n = 24, 28.9%), and 11 (13.3%) received risperidone. Among 40 cases in which polydipsia was improved following antipsychotic treatment, 36 (90.0%) received SGAs, primarily clozapine (n = 14, 35.0%). CONCLUSIONS: Although the causal relationship between polydipsia and antipsychotics remains unclear because of the paucity of high-quality studies, antipsychotics with high affinity to dopamine D2 receptors may be associated with an increased risk of polydipsia while clozapine may be effective for treating polydipsia.

[Burden on designated hospitals when they receive inpatients from distant places in accordance with the Medical Treatment and Supervision Act].

OBJECTIVE: The current Medical Treatment and Supervision Act places a burden on designated psychiafric hospitals with forensic wards. We aimed to clarify the rate of discharge beyond the jurisdictional catchment area, for which overnight training becomes quite cost-ineffective, as hospital staff must accompany the patients home. SUBJECTS: On September 30, 2008, there were 16 designated hospitals in Japan, and 447 inpatients in these hospitals. They were the subjects of this study. METHOD: We collected information on the 447 subjects regarding the postdischarge administrative division, the nearest railway station to the postdischarge residential location, "treatment stage", "overnight training" at the postdischarge residential location, and trouble during "overnight training". We analyzed the collected data using the "designated bed sufficiency ratio". We divided the 447 subjects into three groups: (1) Home inpatient group (home group); the administrative division of his/her postdischarge residential area is the same administrative division as the designated hospital. (2) Inpatient within a jurisdiction group (within group) ; the administrative division of his/her postdischarge residential area is not the same as the designated hospital but is in any administrative division within a jurisdiction of the Japanese Regional Bureau of Health and Welfare. (3) Inpatient outside a jurisdiction group (outside group) ; the administrative division of his/her postdischarge residential area is not the same as the designated hospital but is any administrative division outside a jurisdiction of the Japanese Regional Bureau of Health and Welfare. We compared: (1) the time required to travel to the railway station nearest the postdischarge residential location (time required), (2) traveling expenses, and (3) the distance from the railway station nearest the designated hospital to that of the postdischarge residential location (distance) between the three groups. We also analyzed staff comments regarding "overnight training". RESULTS: The lack of designated beds was a serious problem in two jurisdictions of Kinki and the Hokkaido Regional Bureau of Health and Welfare, with a "designated bed sufficient ratio" of 0.08 and 0.00, respectively. Twenty-four Japanese administrative divisions had no designated beds, while 37 administrative divisions had less than 10 inpatients at the time of the survey. The numbers of people in the "home group", "within group", and "outside group" were 125 (28.0%), 166 (37.1%), and 145 (32.4%), respectively. The "time required", traveling expenses, and distance were 1: 00, Yen 735, and 29.8 km in the "home group", 2: 51, Yen 5,764, and 165.3 km in the "within group", and 4: 14, Yen 20,565, and 694.6 km in the "outside group". Seventy-nine (59.4%) of 133 subjects who were at the "return to community stage" had already experienced "overnight training". No difference was found in the rate of "overnight training" between the "home group", "within group", and "outside group". Staff comments included difficulties in providing staff for "overnight training", responsibilities during "overnight training", and difficulties in finding places of residence in the inpatients' hometowns. DISCUSSION: Because of the lack and maldistribution of designated beds in Japan, many patients are reluctantly admitted to designated hospitals far from their postdischarge residential areas, burdening not only hospital staff but also families and the inpatients themselves. Increasing the number of designated beds will solve this problem. An effective way would be to set up a ward with a small-scale designated unit (less than 15 beds) in the 24 administrative divisions where there are no designaed beds at present.