Changes in psychopharmacotherapy for patients with schizophrenia in a psychiatric institution in Japan: A 12-year prescription survey pre- and post-introduction of clozapine.

Psychopharmacotherapy for patients with schizophrenia in Japan has a long history of polypharmacy, which is rare worldwide but remains a critical problem. One reason for this is that clozapine was not available in Japan until 2009. We aimed to investigate the changes in psychopharmacotherapy in patients with schizophrenia over 12 years pre- and post-introduction of clozapine to clarify how psychopharmacotherapy for patients with schizophrenia has changed with the introduction of clozapine. We retrospectively collected data from the medical records of inpatients diagnosed with schizophrenia at the Okayama Psychiatric Medical Center. Chlorpromazine equivalent (CP-eq) decreased from 1276.6 mg/day in 2009 to 613.9 mg/day in 2020. The prescribed daily dose/defined daily dose (PDD/DDD) decreased from 3.0 in 2009 to 1.2 in 2020. The monotherapy rate increased from 24.4 % in 2009 to 74.6 % in 2020. Our institution began using clozapine in 2010, and the prescription rate for clozapine increased to 37.3 % in 2020. The prescription rate for more than three antipsychotics decreased from 27.8 % in 2009 to 0.8 % in 2020. The increase in clozapine prescription has contributed to an increased rate of antipsychotic monotherapy and a decreased rate of polypharmacy, promoting the optimization of schizophrenia medication. Clozapine therapy should be further promoted in Japan to reduce treatment-resistant schizophrenia due to polypharmacy as much as possible.

Ranking important predictors of the need for a high-acuity psychiatry unit among 2,064 inpatients admitted to psychiatric emergency hospitals: a random forest model.

Aims: In order to uphold and enhance the emergency psychiatric care system, a thorough comprehension of the characteristics of patients who require a high-acuity psychiatry unit is indispensable. We aimed to clarify the most important predictors of the need for a high-acuity psychiatry unit using a random forest model. Methods: This cross-sectional study encompassed patients admitted to psychiatric emergency hospitals at 161 medical institutions across Japan between December 8, 2022, and January 31, 2023. Questionnaires were completed by psychiatrists, with a maximum of 30 patients assessed per medical institution. The questionnaires included psychiatrists' assessment of the patient's condition (exposure variables) and the need for a high-acuity psychiatry unit (outcome variables). The exposure variables consisted of 32 binary variables, including age, diagnoses, and clinical condition (i.e., factors on the clinical profile, emergency treatment requirements, and purpose of hospitalization). The outcome variable was the need for a high-acuity psychiatry unit, scored from 0 to 10. To identify the most important predictors of the need for a high-acuity psychiatry unit, we used a random forest model. As a sensitivity analysis, multivariate linear regression analysis was performed. Results: Data on 2,164 patients from 81 medical institutions were obtained (response rate, 50.3%). After excluding participants with missing values, this analysis included 2,064 patients. Of the 32 items, the top-5 predictors of the need for a high-acuity psychiatry unit were the essentiality of inpatient treatment (otherwise, symptoms will worsen or linger), need for 24-hour professional care, symptom severity, safety ensured by specialized equipment, and medication management. These items were each significantly and positively associated with the need for a high-acuity psychiatry unit in linear regression analyses (p < 0.001 for all). Conversely, items on age and diagnosis were lower in the ranking and were not statistically significant in linear regression models. Conclusion: Items related to the patient's clinical profile might hold greater importance in predicting the need for a high-acuity psychiatry unit than do items associated with age and diagnosis.

Effect of smoking habits and concomitant valproic acid use on relapse in patients with treatment-resistant schizophrenia receiving clozapine: A 1-year retrospective cohort study.

INTRODUCTION: No study has investigated the impact of smoking habits and concomitant valproic acid (VPA) use on clinical outcomes in maintenance treatment with clozapine. Thus, we aimed to examine the effect of smoking habits and concomitant VPA use on relapse during the first year after discharge in patients with treatment-resistant schizophrenia (TRS) receiving clozapine. METHODS: This retrospective cohort study included patients with TRS who were initiated on clozapine during hospitalization and discharged between April 2012 and January 2021 in two tertiary psychiatric hospitals in Japan. Relapse was defined as rehospitalization due to psychiatric exacerbation during the first year after discharge. A multivariable Cox proportional hazards regression analysis was performed to analyze the effect of smoking habits and concomitant VPA use on relapse. Subgroup analyses were also conducted to examine potential interactions between smoking habits and concomitant VPA use. RESULTS: Among the included 192 patients, 69 (35.9%) met the criteria of relapse. While smoking habits (adjusted hazard ratio [aHR], 2.27; 95% confidence interval [CI], 1.28-4.01; p < 0.01) independently increased the risk of relapse, a significant interaction for relapse risk was found between smoking habits and concomitant VPA use (p-interaction = 0.015). Concomitant VPA use may be an effective modifier of the increased relapse risk associated with smoking habits. Among patients who smoked, those using VPA concomitantly exhibited a higher risk of relapse (aHR, 5.32; 95% CI, 1.68-16.9; p < 0.01) than those not using VPA (aHR, 1.41; 95% CI, 0.73-2.70; p = 0.30). CONCLUSION: The findings suggest that the combination of smoking habits and concomitant VPA use may increase the risk of relapse after discharge. Future studies are required to elucidate the mechanisms underlying these findings, such as a decrease in clozapine blood levels.

Comparison between olanzapine and aripiprazole treatment for 104 weeks after hospital discharge in schizophrenia spectrum disorders: a multicenter retrospective cohort study in a real-world setting.

RATIONALE: The long-term effectiveness of olanzapine and aripiprazole in real clinical conditions at flexible doses in patients after hospital discharge has not been evaluated yet. OBJECTIVES: This study was a multicenter retrospective cohort study. Patients with schizophrenia (n = 398) were prescribed olanzapine (n = 303) or aripiprazole (n = 95) at hospital discharge. The continuation of olanzapine or aripiprazole at 26, 52, or 104 weeks after the hospital discharge were compared using a Cox proportional hazards model and adjusted for possible confounders. RESULTS: The Kaplan-Meier survival curves revealed that the continuation of olanzapine at 26 (P = 0.001) and 52 weeks (P = 0.018) was significantly higher than that of aripiprazole but not at 104 weeks. Olanzapine was better than aripiprazole in efficacy at 26 (hazard ratio: 0.321, 95% confidence interval: 0.159-0.645, P = 0.001), 52 (hazard ratio: 0.405, 95% confidence interval: 0.209-0.786, P = 0.008), and 104 weeks (hazard ratio: 0.438, 95% confidence interval: 0.246-0.780, P = 0.005). Aripiprazole was better than olanzapine in tolerability at 104 weeks (hazard ratio: 4.574, 95% confidence interval: 1.415-14.787, P = 0.011). Rates after two years continuation of olanzapine and aripiprazole were not significantly different in patients with less than five years' duration of illness, but olanzapine was more commonly maintained for more than two years in those patients who had been ill for over five years' due to its greater efficacy. CONCLUSION: Olanzapine treatment showed better continuation rates at 26 and 52 after hospital discharge than aripiprazole, whereas maintenance with the two antipsychotics did not differ significantly at 104 weeks, due reduced tolerability of long-term olanzapine treatment.

The validity of atypical psychosis diagnostic criteria to detect anti-NMDA receptor encephalitis with psychiatric symptoms.

Anti-NMDAR encephalitis has a psychotic presentation that is difficult to distinguish from primary psychosis. An atypical psychosis that is similar to schizophrenia, mood disorder, and epilepsy is unique, and the original diagnostic criteria exist only in Japan. The clinical symptoms and courses of anti-NMDAR encephalitis and atypical psychosis are very similar. We investigated whether the diagnostic criteria of atypical psychosis are useful to increase the detection rate of anti-NMDAR encephalitis with psychiatric symptoms. The presence of anti-NR1/NR2B IgG antibodies in the cerebrospinal fluid of 218 newly admitted inpatients initially diagnosed with schizophrenia (n = 151), mood disorder (n = 47), or epilepsy with psychiatric symptoms (n = 20) was assessed by cell-based assay. Of 218 patients, 123 (36.3 years ± SD 17.2, 69.9 % females) fulfilled the diagnostic criteria of category B for atypical psychosis. All 12 patients (9.8 %, 12/123) with anti-NR1/NR2B IgG antibodies fulfilled category B of atypical psychosis statistically better than the patients without anti-NR1/NR2B IgG antibodies (P = 0.0009). Of the 12 patients with anti-NMDAR antibodies, two did not fulfill either criteria of catatonia (DSM-5) or Graus' diagnostic criteria of anti-NMDAR encephalitis during the time course, and 11 patients showed good prognosis with early immunotherapies. In ROC analysis, abnormal electroencephalogram findings showed the highest sensitivity (0.833) for detection of anti-NR1/NR2B IgG antibodies, and 31.3 % of patients with category B atypical psychosis and abnormal electroencephalogram findings had anti-NMDAR antibodies. Lumbar puncture and detection of anti-NMDAR antibodies should be considered for patients who fulfill atypical psychosis diagnosis criteria with an abnormal electroencephalogram.

Changes in Plasma Clozapine Levels after Smoking Cessation in Japanese Inpatients with Schizophrenia: A Retrospective Cohort Study.

Although reported for Caucasians, changes in plasma clozapine levels after smoking cessation in East Asians remain unclear. We here investigated plasma clozapine levels before and after smoking cessation in Japanese inpatients with schizophrenia. We conducted a retrospective chart review of 14 inpatients with schizophrenia who were being treated with clozapine between June 1, 2019, and July 31, 2019 and who were smokers as of July 1, 2019, the day on which a smoking ban was instituted in the tertiary public psychiatric hospital. The primary outcome was individual differences in plasma clozapine levels between before and after the smoking ban, which were compared using paired t-tests. The mean plasma clozapine level was significantly increased, by 213.4 ng/mL (95% CI 119.9-306.8; p<0.01) or 53.2%. Four of the 14 inpatients experienced clinically significant side effects, such as myoclonus, drooling, and amnesia, due to the development of high plasma clozapine levels. Our findings indicated that close monitoring of plasma clozapine levels before and after smoking cessation and prior dose adjustment of clozapine may be necessary, to prevent a significant risk of developing high plasma clozapine levels, even in Japanese patients.

Clinical moderators of response to nalmefene in a randomized-controlled trial for alcohol dependence: An exploratory analysis.

BACKGROUND: Nalmefene is the only medication marketed to reduce the consumption of alcohol in patients with alcohol dependence, but it remains unclear which patients could most benefit from it. This study aimed to identify clinical moderators that affect treatment response to nalmefene in patients with alcohol dependence. METHODS: In a multicenter, randomized, controlled, double-blind, phase 3 study of nalmefene on Japanese patients with alcohol dependence, the relationship between the reduction of heavy drinking days (HDD) and total alcohol consumption (TAC) at 12 and 24 weeks of treatment and baseline variables of the participants were analyzed in a linear regression and multiple adjusted analysis. RESULTS: Age < 65, no family history of problem drinking, age at onset of problem drinking ≥ 25, and not currently smoking were possible positive moderators. Nalmefene showed a significant HDD reduction in patients with age < 65 or no family history of problem drinking, and a significant TAC reduction in patients with age at onset of problem drinking ≥ 25 or who were not currently smoking. After multiple adjusted analyses, age < 65 (p = .028), no family history of problem drinking (p = .047), and age at onset of problem drinking ≥ 25 (p = .030) were statistically significant. Not currently smoking (p = .071) was marginally significant. In combination, these moderators indicated synergistic effects. CONCLUSIONS: Alcohol-dependent patients with favorable prognostic factors such as non-smoking status, no family history of problem drinking, and a late-onset of problem drinking selectively benefit from nalmefene. Further research is needed to validate these exploratory results.

Risk factors for clozapine-induced central nervous system abnormalities in Japanese patients with treatment-resistant schizophrenia.

The purpose of this study was to assess the risk factors for clozapine-induced central nervous system (CNS) abnormalities (i.e., electroencephalogram [EEG] abnormalities, myoclonus, and seizures). We retrospectively analyzed data from 106 patients with schizophrenia who received clozapine treatment through our hospital. A review of the EEG recordings showed that 71 of these patients (67.0 %) developed CNS abnormalities after initiating clozapine treatment. EEG abnormalities, myoclonus, and seizures occurred in 53.8 %, 38.7 %, and 8.5 % of the patients, respectively. Multivariate logistic regression analysis showed that the risk factors for clozapine-induced CNS abnormalities were concomitant lithium usage (odds ratio, 4.560; 95 % confidence interval, 1.750-11.900) and shorter illness durations before clozapine initiation (odds ratio, 0.796; 95 % confidence interval, 0.649-0.976). However, plasma clozapine levels and the usage of antiepileptics did not exhibit associations with the risks of CNS abnormalities. Clinicians should monitor their patients for incident CNS abnormalities when administering lithium in combination with clozapine regardless of plasma clozapine levels or the usage of antiepileptics. This is especially true for patients with short illness durations.

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.

The relationship between plasma clozapine concentration and clinical outcome: a cross-sectional study.

OBJECTIVE: There is no report that statistically evaluates the therapeutic reference (350-600 ng/ml) and adverse drug reaction (ADR) range (>1000 ng/ml) of clozapine (CLZ) recommended by the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) consensus guidelines in an isolated and large sampling study. METHODS: We administered CLZ to 131 Japanese patients with treatment-resistant schizophrenia in a multicenter cross-sectional study. Plasma CLZ concentrations were assayed by high-performance liquid chromatography using trough sampling. The Brief Psychiatric Rating Scale (BPRS) and severe dose-dependent ADR (sedation, myoclonus, and seizures) were analyzed statistically after adjusting for possible confounders. RESULTS: The daily CLZ dosage showed a moderately positive relationship with the plasma concentration (r = 0.49, p < 0.001). Every 100 ng/ml increase in plasma CLZ concentration improved the total BPRS score 1.95% (95% CI: 0.89-3.01, p < 0.001) and the odds ratio (OR) 1.38 (95% CI: 1.14-1.66, p = 0.001) for BPRS response. Compared with concentrations below 350 ng/ml CLZ, 350-600 ng/ml (11.12%; 95% CI: 2.52-19.72, p = 0.012) and 600-1000 ng/ml (11.05%; 95% CI: 2.40-19.71, p = 0.013) showed significant improvement in the total BPRS score. Dosages above 1000 ng/ml showed greater improvement (25.36%; 95% CI: 13.08-37.64, p < 0.001) of the total BPRS score but more severe ADRs than dosages below 1000 ng/ml (OR: 31.72; 95% CI: 1.04-968.81, p = 0.048). CONCLUSION: The AGNP therapeutic reference range (350-600 ng/ml) is useful, and a dose above 1000 ng/ml is potentially more effective but carries the risk of severe ADRs in the central nervous system.

Clinical Utility and Safety of Slower-than-Recommended Titration of Clozapine for Treatment-Resistant Schizophrenia: a Retrospective Cohort Study.

Slow titration of clozapine is recommended given the risk of serious adverse effects. However, the utility and safety of slower-than-recommended titration of clozapine remain unclear. Consequently, we aimed to investigate the clinical utility and safety of slower-than-recommended titration of clozapine for treatment-resistant schizophrenia. We conducted a retrospective chart review of 152 inpatients with treatment-resistant schizophrenia who had been newly started on clozapine in a tertiary psychiatric public hospital between April 2012 and March 2018. The primary outcome was clozapine continuation for the first 18 weeks. We performed multivariate logistic regression to identify the association between the rate of clozapine dose titration and clozapine continuation for the first 18 weeks. Among the 152 inpatients, 122 (80%) could continue clozapine for the first 18 weeks. There was no significant association between the rate of clozapine dose titration and clozapine continuation for the first 18 weeks (adjusted odds ratio 1.23; 95% CI 0.29-5.26; p = 0.78). Our findings indicate that slower-than-recommended titration of clozapine may not improve toward clozapine continuation for the first 18 weeks. Therefore, it may not be a beneficial option in terms of safe clozapine continuation when starting clozapine for treatment-resistant schizophrenia.

Switching strategies for antipsychotic monotherapy in schizophrenia: a multi-center cohort study of aripiprazole.

RATIONALE: Changing antipsychotics of patients with chronic schizophrenia involves several risks. Switching to aripiprazole is especially difficult. We investigated switching methods and related factors for successful switching patients with chronic schizophrenia to aripiprazole. OBJECTIVES: This study was a multi-center historical cohort study and approved by the research ethics committee of Okayama University Hospital and Okayama Psychiatric Medical Center. We compared survival proportions of 178 chronic schizophrenia patients who continued aripiprazole monotherapy for 6 months after non-direct switching (add-on switching (n = 45), cross switching (n = 62)) or direct switching (n = 71). We adjusted possible confounders using a Cox proportional hazards model. RESULTS: Of patients with chronic schizophrenia, 56.7% (101/178) were switched to aripiprazole monotherapy, and 55.0% (98/178) showed improvement in symptoms as demonstrated by the Clinical Global Impression Severity score. Kaplan-Meier survival curves showed that non-direct switching had a higher survival proportion than direct switching (log-rank test, p = 0.012). Even after adjusting for several variables using a Cox proportional hazards model, add-on switching had a significantly lower hazard at 6 months than direct switching (hazard ratio 0.42, 95% confidence interval 0.21-0.82, P = 0.01). In cases of switching to aripiprazole for psychiatric symptoms, non-direct switching had a lower hazard than direct switching (hazard ratio 0.41, 95% confidence interval 0.21-0.81, P = 0.01) but was not significant for adverse reaction. When aripiprazole was switched from olanzapine, add-on switch showed the lowest hazard ratio for continuation (hazard ratio 0.29, 95% confidence interval 0.07-1.11, P = 0.07). CONCLUSIONS: Flexibility in strategies when switching to aripiprazole may induce a better outcome for patients with chronic schizophrenia.

Change in smoking cessation stage over 1 year in patients with schizophrenia: a follow up study in Japan.

BACKGROUND: We performed a follow up study about willingness and behaviors to quit smoking among smokers with schizophrenia in Japan. METHODS: Participants were outpatients with schizophrenia aged 20-69 years who had been visiting the hospital for ≥1 year as of April 1, 2016, and had visited the hospital more than once in the previous 6 months. A baseline survey on smoking behaviors including current smoking status and smoking cessation stage, was administered in 420 participants that were randomly extracted from a patient pool (n = 680) in 2016, and a follow-up survey was administered in 2017. We calculated the distribution and change in smoking cessation stage, number of smokers and nonsmokers after 1 year, and quitting rate from a naturalistic 1-year smoking-cessation follow up. RESULTS: The number of baseline respondents was 350; 113 current smokers and 68 former smokers. Among the 113 current smokers, 104 (92.0%) were followed for 1 year, 79 (70.0%) were interested in smoking cessation, and only 7 had received smoking cessation treatments at baseline. Among the tracked 104 participants, only 6 (5.8%) stopped smoking after 1 year. Among the 25 participants who had intentions to quit smoking within 6 months at baseline, 6 (24.0%) maintained their intention to quit smoking for 1 year, and 16 (64.0%) did not maintain their intention to quit smoking. CONCLUSIONS: Our findings showed that many smokers with schizophrenia were interested in quitting smoking, but few patients received treatment and actually quit smoking. Timely intervention, including the option to receive smoking cessation treatment, is necessary for those patients with schizophrenia who smoke. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN000023874, registered on August 31, 2016).

Anti-NMDA-receptor antibody in initial diagnosis of mood disorder.

Anti-NMDAR encephalitis is increasingly recognized as one etiology of psychiatric symptoms, but there is not enough evidence on patients with mood disorder. We assayed anti-NR1/NR2B IgG antibodies in serum and/or cerebrospinal fluid of 62 patients initially diagnosed with mood disorder by a cell-based assay. We also investigated the specific patient characteristics and psychotic symptoms. At first admission, the patients showed only psychiatric symptoms without typical neurological signs or abnormal examination findings. Four of the 62 patients had anti-NR1/NR2B IgG antibodies. The anti-NR1/NR2B IgG antibody-positive patients showed more super- or abnormal sensitivity (P = 0.00088), catatonia (P = 0.049), and more conceptual disorganization (P < 0.0001), hostility (P = 0.0010), suspiciousness (P < 0.0001), and less emotional withdrawal (P < 0.0001) and motor retardation (P < 0.0001) on the Brief Psychiatric Rating Scale than the antibody-negative patients. During the clinical course, anti-NR1/NR2B IgG antibody-positive patients showed more catatonia (P = 0.0042) and met Graus's criteria for diagnosis of anti-NMDAR encephalitis, but negative patients did not. Immunotherapy was effective for anti-NR1/NR2B IgG antibody-positive patients, and there was the weak relationship (R²â€¯= 0.318) between the anti-NR1/NR2B IgG antibody titer in the cerebrospinal fluid and the Brief Psychiatric Rating Scale score.

Associations between readmission and patient-reported measures in acute psychiatric inpatients: a study protocol for a multicenter prospective longitudinal study (the ePOP-J study).

BACKGROUND: Several previous observational studies have reported the risk factors associated with readmission in people with mental illness. While patient-reported experiences and outcomes have become increasingly important in healthcare, only a few studies have examined these parameters in terms of their direct association with readmission in an acute psychiatric setting. This project will investigate multiple factors associated with readmission and community living in acute psychiatric patients in Japan. This study will primarily investigate whether patient-reported experiences at discharge, particularly quality of life (QoL), are associated with future readmission and whether readmission after the index hospitalization is associated with changes in patient-reported outcomes during the study period. Here, we describe the rationale and methods of this study. METHODS: This multicenter prospective cohort study is being conducted in 21 participating Japanese hospitals, with a target sample of approximately 600 participants admitted to the acute psychiatric ward. The study has four planned assessment points: time of index admission (T1), time of discharge (from the index admission) (T2), 6 months after discharge from the index admission (T3), and 12 months after discharge from the index admission (T4). Participants will complete self-reported measures including a QoL scale, a subjective disability scale, and an empowerment- and self-agency-related scale at each assessment point; additionally, service satisfaction, subjective view of need for services, and subjective relationships with family members will be assessed at T2 and T3. We will assess the participants' hospitalization during the study period and evaluate several potential individual- and service-level factors associated with readmission and patient-reported experiences and outcomes. Multivariate analyses will be conducted to identify potential associations between readmission and patient-reported experiences and outcomes. DISCUSSION: The present study may produce evidence on how patient-reported experiences at discharge influence readmission and on the influence of readmission on the course of patient-reported outcomes from admission to community living after discharge. The study may contribute to improving care for both patients' subjective views of their own health conditions and their community lives in an acute psychiatric setting.Trial registration University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) UMIN000034220. Registered on September 20, 2018.

A randomized controlled trial of comprehensive early intervention care in patients with first-episode psychosis in Japan: 1.5-year outcomes from the J-CAP study.

The first episode of psychosis represents a critical period wherein comprehensive early intervention in psychosis (EIP) may alter the course of illness. However, evidence from randomized controlled trials that have examined the impact of comprehensive EIP care on clinical and functional recovery assessed by independent blinded raters is limited. The objective of this study was to conduct a single-blinded multicenter trial comparing comprehensive EIP care and standard care in young patients with first-episode psychosis (FEP) in Japan (J-CAP Study). A total of 77 participants with FEP (aged 15-35 years) were randomized to receive standard care or specialized comprehensive EIP care and were followed up for 1.5 years (trial no.: UMIN000005092). Function (measured with the Global Assessment of Functioning) and clinical remission (defined by internationally standardized criteria proposed by the Remission in Schizophrenia Working Group) were evaluated by independent raters who were blinded to group assignment. Dropout rate and other secondary outcomes were also examined. The specialized EIP care group had a higher clinical remission rate (odds ratio, 6.3; 95% confidence interval, 1.0-37.9) and lower treatment dropout rate (odds ratio, 0.038; 95% confidence interval, 0.002-0.923) than the standard care group, even after adjusting for baseline characteristics. Functional improvement in the specialized EIP care group was slightly higher than that in the standard care group, but this difference was not statistically significant (p = 0.195). From the results, we conclude that comprehensive EIP care may provide advantages over standard care in patients with FEP.

Two-year effectiveness of risperidone and aripiprazole in the maintenance treatment of patients with recent-onset or chronic schizophrenia and related psychotic disorders: a retrospective multicenter study.

This study aimed to assess the comparative effectiveness of risperidone (RIS) versus aripiprazole (ARP) in patients with recent-onset or chronic schizophrenia during maintenance treatment and to examine the interaction between illness duration and the effectiveness of the treatment. All adult patients with schizophrenia and related disorders discharged from four psychiatric hospitals between 2006 and 2012 were screened and the 2-year continuation rates of monotherapy using RIS or ARP after discharge were examined retrospectively. The treatment continuation of the two drugs in patients with recent-onset (illness duration <5 years) or chronic schizophrenia (illness duration ≥5 years) and the moderator effect of illness duration on the effectiveness of the treatment were analyzed. Of 328 patients, 233 received RIS and 95 received ARP. No significant difference was found between the two drugs in the treatment continuation for the entire sample. However, there was a significant difference favoring ARP in the recent-onset subgroup mainly because of differences in tolerability, whereas RIS tended to present better outcomes in patients with chronic illness. Furthermore, there was a significant variation in the effectiveness of the treatment between recent-onset and chronic schizophrenia. Our results suggest that illness duration is an important moderator in terms of the long-term effectiveness of the two drugs.

Optimal Dosing of Risperidone and Olanzapine in the Maintenance Treatment for Patients With Schizophrenia and Related Psychotic Disorders: A Retrospective Multicenter Study.

OBJECTIVES: This study aims to determine the optimal tolerability dose ranges of risperidone (RIS) and olanzapine (OLZ) administered during schizophrenia maintenance phase. METHODS: Two-year continuation rates of prescription at discharge were examined using a retrospective cohort study method. Adult patients with schizophrenia and related psychotic disorders, receiving antipsychotic monotherapy with RIS or OLZ at discharge, were included. The primary outcome measures were the time to treatment discontinuation and 2-year continuation rates at 4 modal dose ranges of each drug. We estimated the optimal tolerability dose ranges by comparing the continuation rates at various modal doses. RESULTS: Of 648 patients, 344 received RIS and 304 received OLZ. The RIS 2-year continuation rates at 4 daily modal dose ranges were significantly different (0.5-2.5 mg: 46.0%, 3.0-5.0 mg: 40.0%, 5.5-7.5 mg: 30.0%, and 8.0-10.0 mg: 28.0%), with the difference favoring RIS at lower doses (0.5-5.0 mg) more than higher doses (5.5-10.0 mg). In contrast, there were no significant differences among OLZ 4 modal dose ranges (2.5-7.5 mg: 49.1%, 10.0-15.0 mg: 42.6%, 17.5-22.5 mg: 40.9%, and 25.0-30.0 mg: 39.0%). The time to treatment discontinuation significantly favored OLZ over RIS. However, it did not significantly differ between RIS and OLZ at lower doses. CONCLUSIONS: It is suggested that the optimal tolerability dose range during maintenance treatment is 0.5 to 5.0 mg/d for RIS and 2.5 to 30 mg/d for OLZ, and that RIS at lower doses is comparable with OLZ at lower doses.